Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic effect of modified zengye decoction on primary Sjogren’s syndrome and its effect on plasma exosomal proteins

Background: Modified Zengye Decoction (MZD), a traditional Chinese medicine, is an effective treatment for patients with primary Sjögren’s syndrome (pSS). Purpose: To evaluate the efficacy of MZD and investigate its effect on plasma exosomal proteins. Methods: Eighteen pSS patients were treated with MZD for 2 weeks. The therapeutic effect was evaluated by observing the changes in clinical symptoms, laboratory parameters, and plasma cytokines before and after treatment. Then, the differentially expressed proteins (DEPs) in the plasma exosomes before and after treatment were identified via label-free proteomics, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the possible biological functions and signaling pathways involved in the exosomal DEPs. Results: MZD can effectively relieve the clinical symptoms of pSS patients, downregulate the plasma IgG and IgM levels, and inhibit plasma cytokine production. Thirteen DEPs were identified via label-free proteomics in the plasma exosomes before and after MZD treatment, of which 12 were downregulated proteins. GO analysis showed that these downregulated proteins were mainly related to the insulin response involved in dryness symptoms and the Gram-negative bacterial defense response and proteoglycan binding involved in infection. KEGG enrichment analysis showed that these downregulated proteins were primarily associated with the porphyrin metabolism involved in oteoarthrosis and the NF-κB and TLR4 pathways involved in infection. Conclusion: MZD can effectively alleviate SS symptoms, while its mechanism may be associated with the reduced protein expression in insulin response, porphyrin metabolism, and the TLR4/NF-κB pathway.
The contribution of pain and disability on the transition from acute to chronic pain-related TMD: A 3-month prospective cohort study

Although most cases of pain-related temporomandibular disorders (TMD) are mild and self-limiting, about 10% of TMD patients develop severe disorders associated with chronic pain and disability. It has been suggested that pain intensity contributes to the transition from acute to chronic pain-related TMD. Therefore, the aims of this current prospective cohort study were to assess if pain intensity, pain always being present, pain or stiffness on awakening, jaw activities, and interference, were associated with the transition from acute to chronic pain-related TMD at 3 months of follow-up. One hundred and nine participants, recruited from four clinics in Montreal and Ottawa, received examinations and completed the required instruments at baseline and at the 3rd month of follow-up. In a multivariable analysis including sex, age, characteristic pain index (CPI) (OR = 1.03, 95%CI = 1.01–1.06, P = 0.005), moderate to severe average pain intensity (OR = 3.51, 95%CI = 1.24–9.93, P = 0.02), disability points score (OR = 1.29, 95%CI = 1.06–1.57, P = 0.01), interferences (ORs = 1.30–1.32, P = 0.003–0.005), screening score (OR = 1.37, 95%CI = 1.08–1.76, P = 0.01), and pain always present (OR = 2.55, 95%CI = 1.08–6.00, P = 0.03) assessed at first-visit were related to the transition outcome at the 3rd month of follow-up. Further, we found that if 4 patients with acute pain-related TMD on average were exposed to these risk factors at baseline, 1 would have the transition from acute to chronic pain at 3 months of follow-up. Results indicate that these factors are associated with the transition from acute to chronic pain-related TMD, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with pain-related TMD.
Inflammatory bowel disease-associated Escherichia coli strain LF82 in the damage of gut and cognition of honeybees

Patients with inflammatory bowel disease (IBD) are often accompanied with some cognitive impairment, but the mechanism is unclear. By orally exposing honeybees (Apis mellifera) to IBD-associated Escherichia coli LF82 (LF82), and non-pathogenic Escherichia coli MG1655 (MG1655) as the normal strain, we investigated whether and how LF82 induces enteritis-like manifestations and cognitive behavioral modifications in honeybees using multiparametric analysis. LF82 significantly increased gut permeability, impaired learning and memory ability in olfactory proboscis extension response conditioning, and shortened the lifespan of honeybees. Compared to MG1655, LF82 reduced the levels of tryptophan metabolism pathway substances in the honeybee gut. LF82 also upregulated genes involved in immune and apoptosis-related pathways and downregulated genes involved in G protein-coupled receptors in the honeybee brain. In conclusion, LF82 can induce enteritis-like manifestations and cognition impairment through gut metabolites and brain transcriptome alteration in honeybees. Honeybees can serve as a novel potential model to study the microbiota-gut-brain interaction in IBD condition.
Is LysM-Cre a good candidate Cre for knocking out Atg5 gene in mice?

COPYRIGHT © 2022 Wen, Li, Liang and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Opinion PUBLISHED 26 August 2022 DOI 10.3389/fimmu.2022. 964496
Characteristics of members of IGT family genes in controlling rice root system architecture and tiller development

Root system architecture (RSA) and tiller are important agronomic traits. However, the mechanisms of the IGT family genes regulate RSA and tiller development in different rice varieties remain unclear. In this study, we demonstrated that 38 rice varieties obtained from Yuanyang Hani’s terraced fields with different RSA and could be classified into six groups based on the ratio of root length and width. We found a positive correlation between RSA (including root width, length, and area) and tiller number in most of rice varieties. Furthermore, the IGT family genes Deeper Rooting 1 (DRO1), LAZY1, TAC1, and qSOR1 showed different expression patterns when rice grown under irrigation and drought conditions. Moreover, the qSOR1 gene had higher levels in the roots and tillers, and accompanied with higher levels of PIN1b gene in roots when rice grown under drought environmental condition. DRO1 gene had two single nucleotide polymorphisms (SNPs) in the exon 3 sequences and showed different expression patterns in the roots and tillers of the 38 rice varieties. Overexpression of DRO1 with a deletion of exon 5 caused shorter root length, less lateral roots and lower levels of LAZY1, TAC1, and qSOR1. Further protein interaction network, microRNA targeting and co-expression analysis showed that DRO1 plays a critical role in the root and tiller development associated with auxin transport. These data suggest that the RSA and tiller development are regulated by the IGT family genes in an intricate network way, which is tightly related to rice genetic background in rice adapting to different environmental conditions.
Acute changes in free and extracellular vesicle-associated circulating miRNAs and myokine profile in professional sky-runners during the Gran Sasso d’Italia vertical run

The modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of molecules associated with skeletal muscle activity and energy metabolism—such as myokines—as well as those involved in their transcriptional regulation, like microRNA. This study aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokine response. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1,000 m gain, 3,600 m length). Circulating total (t-miRNA) and extracellular vesicle-associated (EV-miRNA) miRNAs were extracted from the pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6 normalized on the global mean. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated for each single subject. Target prediction on MirWalk v3.0, Gene-Ontology, and pathway enrichment analysis on Panther v17.0 were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. In whole plasma, five miRNAs were upregulated and two were downregulated; in the EV fraction, five miRNAs were upregulated and three were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of the post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirmed these results. This study provides an example of a systemic response to acute endurance exercise, in which circulating miRNAs play a pivotal role.
Tourists’ apprehension toward choosing the next destination: A study based on the learning zone model

The current research is based on Senninger’s Learning Zone Model applied to the tourists’ comfort zone. This model was created in 2000 and it proved to be useful in many applied areas: Psychology, Sociology, Marketing and Management. This modes is a behavioral one and shows how a person can justify his action based on previous tested experiences (comfort zone) or dares to step beyond in fear, learn or growth zone. Our research is extending the existent area of expertise to tourism. We aimed at exploring whether the tourists’ apprehension toward choosing their next destination from a comfort zone perspective or rather from the other zones’ perspectives such as fear, learning or growth. To meet this purpose we conducted a mixed method: firstly a qualitative one, an in-depth interview based on Delphi method with 10 tourism specialists and secondly an online survey on 208 Generation Z tourists. The interviews were meant to help developing a 20 items scale (5 items for each level of the model) to measure from which of the 4 zones are the respondents making the choice of the future travel destination. Our conclusions show that Gen Z tourists display behaviors that can be associated with learning or growth zones rather than the comfort zone. This is relevant when choosing the next travel destination, because our findings could bring about a new approach to promoting tourist destinations as part of various products. As a result, a large range of managerial tools can better adapt the promotion messages to the target market from a new psychological perspective.
Neural Decoders Using Reinforcement Learning in Brain Machine Interfaces: A Technical Review

Creating flexible and robust brain machine interfaces (BMIs) is currently a popular topic of research that has been explored for decades in medicine, engineering, commercial, and machine-learning communities. In particular, the use of techniques using reinforcement learning (RL) has demonstrated impressive results but is under-represented in the BMI community. To shine more light on this promising relationship, this article aims to provide an exhaustive review of RL’s applications to BMIs. Our primary focus in this review is to provide a technical summary of various algorithms used in RL-based BMIs to decode neural intention, without emphasizing preprocessing techniques on the neural signals and reward modeling for RL. We first organize the literature based on the type of RL methods used for neural decoding, and then each algorithm’s learning strategy is explained along with its application in BMIs. A comparative analysis highlighting the similarities and uniqueness among neural decoders is provided. Finally, we end this review with a discussion about the current stage of RLBMIs including their limitations and promising directions for future research.
Presence of chondroitin sulphate and requirement for heparan sulphate biosynthesis in the developing zebrafish inner ear

Epithelial morphogenesis to form the semicircular canal ducts of the zebrafish inner ear depends on the production of the large glycosaminoglycan hyaluronan, which is thought to contribute to the driving force that pushes projections of epithelium into the lumen of the otic vesicle. Proteoglycans are also implicated in otic morphogenesis: several of the genes coding for proteoglycan core proteins, together with enzymes that synthesise and modify their polysaccharide chains, are expressed in the developing zebrafish inner ear. In this study, we demonstrate the highly specific localisation of chondroitin sulphate to the sites of epithelial projection outgrowth in the ear, present before any morphological deformation of the epithelium. Staining for chondroitin sulphate is also present in the otolithic membrane, whereas the otoliths are strongly positive for keratan sulphate. We show that heparan sulphate biosynthesis is critical for normal epithelial projection outgrowth, otolith growth and tethering. In the ext2 mutant ear, which has reduced heparan sulphate levels, but continues to produce hyaluronan, epithelial projections are rudimentary, and do not grow sufficiently to meet and fuse to form the pillars of tissue that normally span the otic lumen. Staining for chondroitin sulphate and expression of versican b, a chondroitin sulphate proteoglycan core protein gene, persist abnormally at high levels in the unfused projections of the ext2 mutant ear. We propose a model for wild-type epithelial projection outgrowth in which hyaluronan and proteoglycans are linked to form a hydrated gel that fills the projection core, with both classes of molecule playing essential roles in zebrafish semicircular canal morphogenesis.
Lactobacillus mucosae exerted different antiviral effects on respiratory syncytial virus infection in mice

Respiratory syncytial virus (RSV) infection is a constant threat to the health of young children, and this is mainly attributed to the lack of effective prevention strategies. This study aimed to determine whether Lactobacillus (L.) mucosae, a potential probiotic, could protect against respiratory viral infection in a mouse model. Naive 3–4-week-old BALB/c mice were orally administered with three L. mucosae strains (2.5 × 108 CFU/mouse) 7 days before RSV infection (105 TCID50/mouse). Results showed that all three strains inhibited RSV replication and reduced the proportions of inflammatory cells, including granulocytes and monocytes in the blood. The L. mucosae M104R01L3 treatment maintained stable weight in mice and increased interferon (IFN)-β and tumor necrosis factor (TNF)-α levels. The L. mucosae DCC1HL5 treatment increased interleukin (IL)-1β and IL-10 levels. Moreover, the M104R01L3 and DCC1HL5 strains increased the proportions of Akkermansia, Alistipes, and Anaeroplasma which contributed to the advantageous modulation of the gut microbiota. Besides, L. mucosae affected the gut levels of short-chain fatty acids (SCFAs) that are important for the antiviral response. L. mucosae 1,025 increased acetate, propionate, and butyrate levels, whereas L. mucosae M104R01L3 increased the level of acetate in the gut. L. mucosae M104R01L3 may protect against viral infection by upregulating the IFN-β levels in the lungs and its antiviral effect may be related to the increase of acetate levels in the gut. In conclusion, the three L. mucosae strains exerted antiviral effects against RSV infection by differentially regulating immune responses and intestinal micro-ecological balance. This study can provide a reference for studying the mechanisms underlying the antiviral effects of L. mucosae.
Emerging role of different DNA methyltransferases in the pathogenesis of cancer

DNA methylation is one of the most essential epigenetic mechanisms to regulate gene expression. DNA methyltransferases (DNMTs) play a vital role in DNA methylation in the genome. In mammals, DNMTs act with some elements to regulate the dynamic DNA methylation patterns of embryonic and adult cells. Conversely, the aberrant function of DNMTs is frequently the hallmark in judging cancer, including total hypomethylation and partial hypermethylation of tumor suppressor genes (TSGs), which improve the malignancy of tumors, aggravate the ailment for patients, and significantly exacerbate the difficulty of cancer therapy. Since DNA methylation is reversible, currently, DNMTs are viewed as an important epigenetic target for drug development. However, the impression of DNMTs on cancers is still controversial, and therapeutic methods targeting DNMTs remain under exploration. This review mainly summarizes the relationship between the main DNMTs and cancers as well as regulatory mechanisms and clinical applications of DNMTs in cancer and highlights several forthcoming strategies for targeting DNMTs.
TaNAC020 homoeologous genes are associated with higher thousand kernel weight and kernel length in Chinese wheat

NAC proteins constitute one of the largest plant-specific transcription factor (TF) families and play significant roles in plant growth and development. In the present study, three TaNAC020 homoeologous genes located on chromosomes 7A, 7B, and 7D were isolated from wheat (Triticum aestivum L.). TaNAC020s were predominantly expressed in developing grains. The developed transgenic rice lines for TaNAC020-B showed higher starch density and lower amylose contents than those of the wild type (WT). Sequence polymorphism studies showed seven and eight SNPs in TaNAC020-A/B, making three and two haplotypes, respectively. No sequence polymorphism was identified in TaNAC020-D. Association analysis revealed that HAP-2 of TaNAC020-A and TaNAC020-B was the favored haplotype for higher thousand kernel weight and length. Geographic distribution and allelic frequency showed that our favored haplotype experienced strong selection in China, and likewise, diversity increased in TaNAC020s during wheat polyploidization. The results obtained in this study demonstrate that TaNAC020s positively influence starch synthesis and accumulation and are one of the key regulators of the kernel (seed) size and kernel number and have the potential for utilization in wheat breeding to improve grain yield. Molecular markers developed in this study stand instrumental in marker-assisted selection for genetic improvement and germplasm enhancement in wheat.
Whole-brain monosynaptic outputs and presynaptic inputs of GABAergic neurons in the vestibular nuclei complex of mice

GABAergic neurons in the vestibular nuclei (VN) participate in multiple vital vestibular sensory processing allowing for the maintenance and rehabilitation of vestibular functions. However, although the important role of GABA in the central vestibular system has been widely reported, the underlying neural circuits between VN GABAergic neurons and other brain functional regions remain elusive, which limits the further study of the underlying mechanism. Hence, it is necessary to elucidate neural connectivity based on outputs and inputs of GABAergic neurons in the VN. This study employed a modified rabies virus retrograde tracing vector and cre-dependent adeno-associated viruses (AAVs) anterograde tracing vector, combined with a transgenic VGAT-IRES-Cre mice, to map the inputs and outputs of VN GABAergic neurons in the whole brain. We found that 51 discrete brain regions received projections from VN GABAergic neurons in the whole brain, and there were 77 upstream nuclei innervating GABAergic neurons in the VN. These nuclei were mainly located in four brain regions, including the medulla, pons, midbrain, and cerebellum. Among them, VN GABAergic neurons established neural circuits with some functional nuclei in the whole brain, especially regulating balance maintenance, emotion control, pain processing, sleep and circadian rhythm regulation, and fluid homeostasis. Therefore, this study deepens a comprehensive understanding of the whole-brain neural connectivity of VN, providing the neuroanatomical information for further research on the neural mechanism of the co-morbidities with vestibular dysfunction.
On and off signaling pathways in the retina and the visual system

Visual processing starts at the retina of the eye, and signals are then transferred primarily to the visual cortex and the tectum. In the retina, multiple neural networks encode different aspects of visual input, such as color and motion. Subsequently, multiple neural streams in parallel convey unique aspects of visual information to cortical and subcortical regions. Bipolar cells, which are the second-order neurons of the retina, separate visual signals evoked by light and dark contrasts and encode them to ON and OFF pathways, respectively. The interplay between ON and OFF neural signals is the foundation for visual processing for object contrast which underlies higher order stimulus processing. ON and OFF pathways have been classically thought to signal in a mirror-symmetric manner. However, while these two pathways contribute synergistically to visual perception in some instances, they have pronounced asymmetries suggesting independent operation in other cases. In this review, we summarize the role of the ON–OFF dichotomy in visual signaling, aiming to contribute to the understanding of visual recognition.
The application value of CT radiomics features in predicting pressure amplitude correlation index in patients with severe traumatic brain injury

Purpose To explore the application value of a machine learning model based on CT radiomics features in predicting the pressure amplitude correlation index (RAP) in patients with severe traumatic brain injury (sTBI). Methods Retrospectively analyzed the clinical and imaging data in 36 patients with sTBI. All patients underwent surgical treatment, continuous ICP monitoring, and invasive arterial pressure monitoring. The pressure amplitude correlation index (RAP) was collected within 1 h after surgery. Three volume of interest (VOI) was selected from the craniocerebral CT images of patients 1 h after surgery, and a total of 93 radiomics features were extracted from each VOI. Three models were established to be used to evaluate the patients' RAP levels. The accuracy, precision, recall rate, F1 score, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were used to evaluate the predictive performance of each model. Results The optimal number of features for three predicting models of RAP was five, respectively. The accuracy of predicting the model of the hippocampus was 77.78%, precision was 88.24%, recall rate was 60%, the F1 score was 0.6, and AUC was 0.88. The accuracy of predicting the model of the brainstem was 63.64%, precision was 58.33%, the recall rate was 60%, the F1 score was 0.54, and AUC was 0.82. The accuracy of predicting the model of the thalamus was 81.82%, precision was 88.89%, recall rate was 75%, the F1 score was 0.77, and AUC was 0.96. Conclusions CT radiomics can predict RAP levels in patients with sTBI, which has the potential to establish a method of non-invasive intracranial pressure (NI-ICP) monitoring.