bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simo decoction curing spleen deficiency constipation was associated with brain-bacteria-gut axis by intestinal mucosal microbiota
Authors: Yi Xin , Zhou Kang , Deng Na , Cai Ying , Peng Xinxin , Tan Zhoujin 
Published: February 2023

BackgroundSimo decoction (SMD) is a traditional prescription for treating gastrointestinal diseases. More and more evidences prove that SMD can treat constipation by regulating intestinal microbiota and related oxidative stress indicators, but the specific mechanism is still unclear.MethodsA network pharmacological analysis was used to predict the medicinal substances and potential targets of SMD to alleviate constipation. Then, 15 male mice were randomly divided into normal group (MN group), natural recovery group (MR group), and SMD treatment group (MT group). Constipation model mice were constructed by gavage of Folium sennae decoction and control of diet and drinking water, and SMD was used for intervention after successful modeling. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), superoxide dismutase (SOD), malondialdehyde (MDA), and fecal microbial activities were measured, and the intestinal mucosal microbiota was sequenced.ResultNetwork pharmacology analysis showed that a total of 24 potential active components were obtained from SMD, and 226 target proteins were obtained after conversion. Meanwhile, we obtained 1,273 and 424 disease-related targets in the GeneCards database and the DisGeNET database, respectively. After combination and deduplication, the disease targets shared 101 targets with the potential active components of SMD. When the mice were intervened with SMD, the 5-HT, VIP, MDA, SOD content, and microbial activity in MT group were close to MN group, and Chao 1 and ACE in MT group were significantly higher than that in MR group. In the Linear discriminant analysis Effect Size (LEfSe) analysis, the abundance of beneficial bacteria such as Bacteroides, Faecalibacterium, Alistipes, Subdoligranulum, Lactiplantibacillus, and Phascolarctobacterium in MT group increased. At the same time, there were some associations between microbiota and brain-gut peptides and oxidative stress indicators.ConclusionSMD can promote intestinal health and relieve constipation through brain-bacteria-gut axis associating with intestinal mucosal microbiota and alleviate oxidative stress.
Bacillus subtilis vector based oral rabies vaccines induced potent immune response and protective efficacy in mice
Authors: Zhang Ying , Mo Ruo , Sun Sheng , Cui Zhanding , Liang Bo , Li Entao , Wang Tiecheng , Feng Ye , Yang Songtao , Yan Feihu , Zhao Yongkun , Xia Xianzhu 
Published: February 2023

IntroductionRabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine.MethodsWe constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice.ResultsThe results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.
Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Authors: Minaya Miguel A. , Mahali Sidhartha , Iyer Abhirami K. , Eteleeb Abdallah M. , Martinez Rita , Huang Guangming , Budde John , Temple Sally , Nana Alissa L. , Seeley William W. , Spina Salvatore , Grinberg Lea T. , Harari Oscar , Karch Celeste M. 
Published: February 2023

Introduction: More than 50 mutations in the MAPT gene result in heterogeneous forms of frontotemporal lobar dementia with tau inclusions (FTLD-Tau). However, early pathogenic events that lead to disease and the degree to which they are common across MAPT mutations remain poorly understood. The goal of this study is to determine whether there is a common molecular signature of FTLD-Tau.Methods: We analyzed genes differentially expressed in induced pluripotent stem cell–derived neurons (iPSC-neurons) that represent the three major categories of MAPT mutations: splicing (IVS10 + 16), exon 10 (p.P301L), and C-terminal (p.R406W) compared with isogenic controls. The genes that were commonly differentially expressed in MAPT IVS10 + 16, p.P301L, and p.R406W neurons were enriched in trans-synaptic signaling, neuronal processes, and lysosomal function. Many of these pathways are sensitive to disruptions in calcium homeostasis. One gene, CALB1, was significantly reduced across the three MAPT mutant iPSC-neurons and in a mouse model of tau accumulation. We observed a significant reduction in calcium levels in MAPT mutant neurons compared with isogenic controls, pointing to a functional consequence of this disrupted gene expression. Finally, a subset of genes commonly differentially expressed across MAPT mutations were also dysregulated in brains from MAPT mutation carriers and to a lesser extent in brains from sporadic Alzheimer disease and progressive supranuclear palsy, suggesting that molecular signatures relevant to genetic and sporadic forms of tauopathy are captured in a dish. The results from this study demonstrate that iPSC-neurons capture molecular processes that occur in human brains and can be used to pinpoint common molecular pathways involving synaptic and lysosomal function and neuronal development, which may be regulated by disruptions in calcium homeostasis.
Coupled binding and folding of disordered SPIN N-terminal region in myeloperoxidase inhibition
Authors: Zhang Yumeng , Liu Xiaorong , Chen Jianhan 
Published: February 2023

Gram-positive pathogenic bacteria Staphylococcus express and secret staphylococcal peroxidase inhibitor (SPIN) proteins to help evade neutrophil-mediated immunity by inhibiting the activity of the main oxidative-defense player myeloperoxidase (MPO) enzyme. SPIN contains a structured 3-helix bundle C-terminal domain, which can specifically bind to MPO with high affinity, and an intrinsically disordered N-terminal domain (NTD), which folds into a structured β-hairpin and inserts itself into the active site of MPO for inhibition. Mechanistic insights of the coupled folding and binding process are needed in order to better understand how residual structures and/or conformational flexibility of NTD contribute to the different strengths of inhibition of SPIN homologs. In this work, we applied atomistic molecular dynamics simulations on two SPIN homologs, from S. aureus and S. delphini, respectively, which share high sequence identity and similarity, to explore the possible mechanistic basis for their different inhibition efficacies on human MPO. Direct simulations of the unfolding and unbinding processes at 450 K reveal that these two SPIN/MPO complexes systems follow surprisingly different mechanisms of coupled binding and folding. While coupled binding and folding of SPIN-aureus NTD is highly cooperative, SPIN-delphini NTD appears to mainly utilize a conformational selection-like mechanism. These observations are in contrast to an overwhelming prevalence of induced folding-like mechanisms for intrinsically disordered proteins that fold into helical structures upon binding. Further simulations of unbound SPIN NTDs at room temperature reveal that SPIN-delphini NTD has a much stronger propensity of forming β-hairpin like structures, consistent with its preference to fold and then bind. These may help explain why the inhibition strength is not well correlated with binding affinity for different SPIN homologs. Altogether, our work establishes the relationship between the residual conformational stability of SPIN-NTD and their inhibitory function, which can help us develop new strategies towards treating Staphylococcal infections.
The impact of iron deposition on the fear circuit of the brain in patients with Parkinson’s disease and anxiety
Authors: Chen Kaidong , Zhang Li , Mao Haixia , Chen Kefei , Shi Yachen , Meng Xiangpan , Wang Feng , Hu Xiaoyun , Fang Xiangming 
Published: February 2023

ObjectiveAnxiety is one of the most common psychiatric symptoms of Parkinson’s disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit.MethodsSixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed.ResultsPD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p &lt; 0.01; hippocampus: r = 0.496, p &lt; 0.01).ConclusionOur findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.
Toward neural health measurements for cochlear implantation: The relationship among electrode positioning, the electrically evoked action potential, impedances and behavioral stimulation levels
Authors: Lambriks Lars , van Hoof Marc , Debruyne Joke , Janssen Miranda , Hof Janny , Hellingman Katja , Devocht Elke , George Erwin 
Published: February 2023

IntroductionEstimating differences in neural health across different sites within the individual cochlea potentially enables clinical applications for subjects with a cochlear implant. The electrically evoked compound action potential (ECAP) is a measure of neural excitability that possibly provides an indication of a neural condition. There are many factors, however, that affect this measure and increase the uncertainty of its interpretation. To better characterize the ECAP response, its relationship with electrode positioning, impedances, and behavioral stimulation levels was explored.MethodsA total of 14 adult subjects implanted with an Advanced Bionics cochlear electrode array were prospectively followed up from surgery to 6 months postoperative. Insertion depth, distance to the modiolus, and distance to the medial wall were assessed for each electrode by postoperative CT analysis. ECAPs were measured intraoperatively and at three visits postoperatively on all 16 electrodes using the NRI feature of clinical programming software and characterized using multiple parameters. Impedances and behavioral stimulation levels were measured at every fitting session.ResultsPatterns in ECAPs and impedances were consistent over time, but high variability existed among subjects and between different positions in the cochlea. Electrodes located closer to the apex of the cochlea and closer to the modiolus generally showed higher neural excitation and higher impedances. Maximum loudness comfort levels were correlated strongly with the level of current needed to elicit a response of 100 μV ECAP.ConclusionMultiple factors contribute to the ECAP response in subjects with a cochlear implant. Further research might address whether the ECAP parameters used in this study will benefit clinical electrode fitting or the assessment of auditory neuron integrity.
A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol
Authors: Zhao Jia-ling , Ai Chi-bo , Wang Li , Yang Shao-jie , Wang Jian , Yang Wei , Tang Jie , Zhang Ling , Li Yan , Yan Ting-qi , Gou Shu , Xie Gui-gui , Xiang Yang 
Published: February 2023

BackgroundLow serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs.AimThe Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs.Methods and designThis is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China.OutcomesCHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up.DiscussionThe primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice.Clinical trial registrationClinicaltrials.gov, identifier: NCT05589454.
Cognitive and motor cortex activation during robot-assisted multi-sensory interactive motor rehabilitation training: An fNIRS based pilot study
Authors: Zheng Jinyu , Ma Qiqi , He Wanying , Huang Yanping , Shi Ping , Li Sujiao , Yu Hongliu 
Published: February 2023

ObjectiveThis study aimed to evaluate the effects of multiple virtual reality (VR) interaction modalities based on force-haptic feedback combined with visual or auditory feedback in different ways on cerebral cortical activation by functional near-infrared spectroscopy (fNIRS). Methods: A modular multi-sensory VR interaction system based on a planar upper-limb rehabilitation robot was developed. Twenty healthy participants completed active elbow flexion and extension training in four VR interaction patterns, including haptic (H), haptic + auditory (HA), haptic + visual (HV), and haptic + visual + auditory (HVA). Cortical activation changes in the sensorimotor cortex (SMC), premotor cortex (PMC), and prefrontal cortex (PFC) were measured.ResultsFour interaction patterns all had significant activation effects on the motor and cognitive regions of the cerebral cortex (p &lt; 0.05). Among them, in the HVA interaction mode, the cortical activation of each ROI was the strongest, followed by HV, HA, and H. The connectivity between channels of SMC and bilateral PFC, as well as the connectivity between channels in PMC, was the strongest under HVA and HV conditions. Besides, the two-way ANOVA of visual and auditory feedback showed that it was difficult for auditory feedback to have a strong impact on activation without visual feedback. In addition, under the condition of visual feedback, the effect of fusion auditory feedback on the activation degree was significantly higher than that of no auditory feedback.ConclusionsThe interaction mode of visual, auditory, and haptic multi-sensory integration is conducive to stronger cortical activation and cognitive control. Besides, there is an interaction effect between visual and auditory feedback, thus improving the cortical activation level. This research enriches the research on activation and connectivity of cognitive and motor cortex in the process of modular multi-sensory interaction training of rehabilitation robots. These conclusions provide a theoretical basis for the optimal design of the interaction mode of the rehabilitation robot and the possible scheme of clinical VR rehabilitation.
Effects of whole-body vibration training on cognitive function: A systematic review
Authors: Wen Jiayi , Leng Lu , Hu Min , Hou Xiaohui , Huang Junhao 
Published: February 2023

BackgroundWhole-body vibration (WBV) training is a novel training method that stimulates the human neuromuscular system by the use of vibration, the frequency and amplitude of which are controlled, thereby inducing adaptive changes in the body. WBV training is widely used as a clinical prevention and rehabilitation tool in physical medicine and neuro-rehabilitation as a clinical prevention and rehabilitation tool.ObjectivesThe aim of the present study was to review the effects of WBV on cognitive function, provide an evidence-based foundation for future research on WBV training, and promote additional popularization and use of the methodology in clinical practice.MethodsA systematic review of articles extracted from the following six databases was conducted: PubMed, Web of Science, China National Knowledge Infrastructure, Embase, Cochrane, and Scopus. A literature search was performed on articles in which the effects of WBV on cognitive function were evaluated.ResultsInitially, a total of 340 studies were initially identified, among which 18 articles that satisfied the inclusion criteria were selected for inclusion in the systematic review. Participants were allocated into two groups: patients with cognitive impairment and healthy individuals. The results demonstrated that WBV was both positive and ineffective in its influence on cognitive function.ConclusionThe majority of studies suggested that WBV may be a useful strategy for the management of cognitive impairment and should be considered for inclusion in rehabilitation programs. However, the impact of WBV on cognition requires additional, larger, and adequately powered studies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=376821, identifier CRD42022376821.
Effects of primary angle-closure glaucoma on interhemispheric functional connectivity
Authors: Shu Yongqiang , Huang Yuying , Chen Jingting , Chen Liting , Cai Guoqian , Guo Yu , Li Shenghong , Gao Junwei , Zeng Xianjun 
Published: February 2023

BackgroundPrevious studies on primary angle-closure glaucoma (PACG) primarily focused on local brain regions or global abnormal brain activity; however, the alteration of interhemispheric functional homotopy and its possible cause of brain-wide functional connectivity abnormalities have not been well-studied. Little is known about whether brain functional alteration could be used to differentiate from healthy controls (HCs) and its correlation with neurocognitive impairment.MethodsForty patients with PACG and 40 age- and sex-matched healthy controls were recruited for this study; resting-state functional magnetic resonance imaging (rs-fMRI), and clinical data were collected. We used the voxel-mirrored homotopic connectivity (VMHC) method to explore between-group differences and selected brain regions with statistically significant differences as regions of interest for whole-brain functional connectivity analysis. Partial correlation was used to evaluate the association between abnormal VMHC values in significantly different regions and clinical parameters, with with age and sex as covariates. Finally, the support vector machine (SVM) model was performed in classification prediction of PACG.ResultsCompared with healthy controls, patients with PACG exhibited significantly decreased VMHC values in the lingual gyrus, insula, cuneus, and pre- and post-central gyri; no regions exhibited increased VMHC values. Subsequent functional connectivity analysis revealed extensive functional changes in functional networks, particularly the default mode, salience, visual, and sensorimotor networks. The SVM model showed good performance in classification prediction of PACG, with an area under curve (AUC) of 0.85.ConclusionAltered functional homotopy of the visual cortex, sensorimotor network, and insula may lead to impairment of visual function in PACG, suggesting that patients with PACG may have visual information interaction and integration dysfunction.
Evaluation of preoperative visual pathway impairment in patients with non-functioning pituitary adenoma using diffusion tensor imaging coupled with optical coherence tomography
Authors: Pang Yanhua , Tan Zhi , Chen Xinxin , Liao Zhihui , Yang Xin , Zhong Qin , Huang Baqi , Zhong Qianshuo , Zhong Jingxiang , Mo Wei 
Published: February 2023

ObjectiveOptic chiasma compression and associated visual impairment induced by a non-functioning pituitary adenoma (NFPA) is commonly assessed by the optic disk and retina but is inadequate to understand the entire visual pathway impairment. We aim to evaluate the use of optical coherence tomography (OCT) coupled with diffusion tensor imaging (DTI) for the preoperative evaluation of visual pathway impairment.MethodsFifty-three patients with NFPA (categorized into mild and heavy compression subgroups) were subjected to OCT to calculate the thickness of the circumpapillary retinal nerve fiber layer (CP-RNFL), macular ganglion cell complex (GCC), macular ganglion cell layer (GCL), and macular inner plexus layer (IPL), as well as to DTI to calculate the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsCompared to mild compression, heavy compression caused decreased FA value, increased ADC value of several segments of the visual pathway, thin temporal CP-RNFL, and quadrant macular GCC, IPL, and GCL. Average CP-RNFL thickness, inferior-macular inner-ring IPL and GCC thicknesses, inferior CP-RNFL thickness, and superior CP-RNFL thickness were the best indicators of the impairment of the optic nerve, optic chiasma, optic tract, and optic radiation, respectively.ConclusionDTI and OCT parameters can effectively evaluate visual pathway impairment and are beneficial for the objective preoperative evaluation of visual pathway impairment in patients with NFPA.