Miracle-dz/UniFAR-FTUs huggingface dataset:
Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway

Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis after acute myocardial infarction (AMI). This study investigated the protective effect of myocardial ischemic postconditioning (IPo) on intestinal barrier injury induced by myocardial IR and the underlying cellular signaling mechanisms with a focus on the DJ-1. Adult SD rats were subjected to unilateral myocardial IR with or without ischemic postconditioning. After 30 min of ischemia and 120 min of reperfusion, heart tissue, intestine, and blood were collected for subsequent examination. The outcome measures were (i) intestinal histopathology, (ii) intestinal barrier function and inflammatory responses, (iii) apoptosis and oxidative stress, and (iv) cellular signaling changes. IPo significantly attenuated intestinal injury induced by myocardial IR. Furthermore, IPo significantly increased DJ-1, nuclear Nrf2, NQO1, and HO-1 expression in the intestine and inhibited IR-induced apoptosis and oxidative stress. The protective effect of IPo was abolished by the knockdown of DJ-1. Conversely, the overexpression of DJ-1 provided a protective effect similar to that of IPo. Our data indicate that IPo protects the intestine against myocardial IR, which is likely mediated by the upregulation of DJ-1/Nrf2 pathway.
Tracking Animal-Dispersed Seedlings Using 15N Xylem Injection Method

Although various seed-marking methods have been developed for seed dispersal, it remains difficult to track the actual patterns of seed dispersal and seedling recruitment. Thus, new labeling methods that accurately track seedling establishment along with seed movement would help us better understand seed dispersal. Here, we developed a new nondestructive method using 15N xylem injection to track seed dispersal and seedling recruitment based on the enriched isotopic signals in the mature seeds. Our results first showed that xylem injection of 15N successfully enriched 15N both in the acorns and seedlings of Quercus variabilis. By marking acorns and seedlings with 15N stable isotopes, we successfully tracked seedlings established from acorns dispersed by seed-eating animals in the field. Our xylem 15N injection caused little alteration to seeds and showed no significant effects on seed selection by seed-eating animals as well as seed germination and seedling establishment, verifying the validity of the 15N xylem injection method to track seedling establishment. Our xylem 15N injection method is expected to be a powerful tool for tracking seed dispersal and seedling recruitment mediated by seed-eating animals in seed dispersal ecology.
Identifying New Hybrid Insulin Peptides (HIPs) in Type 1 Diabetes

In 2016 Delong et al. discovered a new type of neoepitope formed by the fusion of two unrelated peptide fragments. Remarkably these neoepitopes, called hybrid insulin peptides, or HIPs, are recognized by pathogenic CD4+ T cells in the NOD mouse and human pancreatic islet-infiltrating T cells in people with type 1 diabetes. Current data implicates CD4+ T-cell responses to HIPs in the immune pathogenesis of human T1D. Because of their role in the immune pathogenesis of human T1D it is important to identify new HIPs that are recognized by CD4+ T cells in people at risk of, or with, T1D. A detailed knowledge of T1D-associated HIPs will allow HIPs to be used in assays to monitor changes in T cell mediated beta-cell autoimmunity. They will also provide new targets for antigen-specific therapies for T1D. However, because HIPs are formed by the fusion of two unrelated peptides there are an enormous number of potential HIPs which makes it technically challenging to identify them. Here we review the discovery of HIPs, how they form and discuss approaches to identifying new HIPs relevant to the immune pathogenesis of human type 1 diabetes.
Ultra-High Dose Rate FLASH Irradiation Induced Radio-Resistance of Normal Fibroblast Cells Can Be Enhanced by Hypoxia and Mitochondrial Dysfunction Resulting From Loss of Cytochrome C

Ultra-high dose rate FLASH irradiation (FLASH-IR) has got extensive attention since it may provide better protection on normal tissues while maintain tumor killing effect compared with conventional dose rate irradiation. The FLASH-IR induced protection effect on normal tissues is exhibited as radio-resistance of the irradiated normal cells, and is suggested to be related to oxygen depletion. However, the detailed cell death profile and pathways are still unclear. Presently normal mouse embryonic fibroblast cells were FLASH irradiated (∼109 Gy/s) at the dose of ∼10–40 Gy in hypoxic and normoxic condition, with ultra-fast laser-generated particles. The early apoptosis, late apoptosis and necrosis of cells were detected and analyzed at 6, 12, and 24 h post FLASH-IR. The results showed that FLASH-IR induced significant early apoptosis, late apoptosis and necrosis in normal fibroblast cells, and the apoptosis level increased with time, in either hypoxic or normoxic conditions. In addition, the proportion of early apoptosis, late apoptosis and necrosis were significantly lower in hypoxia than that of normoxia, indicating that radio-resistance of normal fibroblast cells under FLASH-IR can be enhanced by hypoxia. To further investigate the apoptosis related profile and potential pathways, mitochondria dysfunction cells resulting from loss of cytochrome c (cyt c–/–) were also irradiated. The results showed that compared with irradiated normal cells (cyt c+/+), the late apoptosis and necrosis but not early apoptosis proportions of irradiated cyt c–/– cells were significant decreased in both hypoxia and normoxia, indicating mitochondrial dysfunction increased radio-resistance of FLASH irradiated cells. Taken together, to our limited knowledge, this is the first report shedding light on the death profile and pathway of normal and cyt c–/– cells under FLASH-IR in hypoxic and normoxic circumstances, which might help us improve the understanding of the FLASH-IR induced protection effect in normal cells, and thus might potentially help to optimize the future clinical FLASH treatment.
Vaginal Microbiome Composition in Early Pregnancy and Risk of Spontaneous Preterm and Early Term Birth Among African American Women

Objective To evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women. Methods Vaginal samples collected in early pregnancy (8-14 weeks’ gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231). Results Nearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%. Conclusions In this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.
How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS

Background: Gouty arthritis (GA) is a common metabolic disease caused by a long-term disorder of purine metabolism and increased serum levels of uric acid. The processed product of dried root of Aconitum carmichaeli Debeaux (Aconiti Radix cocta, ARC) is used often in traditional Chinese medicine (TCM) to treat GA, but its specific active components and mechanism of action are not clear. Methods: First, we used ultra-performance liquid chromatography-quadrupole/time-of-flight tandem mass spectrometry to identify the chemical spectrum of ARC. Based on this result, we explored the active components of ARC in GA treatment and their potential targets and pathways. Simultaneously, we used computer simulations, in vitro cell experiments and animal experiments to verify the prediction results of systems pharmacology. In vitro, we used aurantiamide acetate (AA) to treat monosodium urate (MSU)-stimulated THP-1 cells and demonstrated the reliability of the prediction by western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). ELISAs kit were used to measure changes in levels of proinflammatory factors in rats with GA induced by MSU to demonstrate the efficacy of ARC in GA treatment. Results: Forty-three chemical constituents in ARC were identified. ARC could regulate 65 targets through 29 active components, and then treat GA, which involved 1427 Gene Ontology (GO) terms and 146 signaling pathways. Signaling pathways such as proteoglycans in cancer, C-type lectin receptor signaling pathway, and TNF signaling pathway may have an important role in GA treatment with ARC. In silico results showed that the active components songoramine and ignavine had high binding to mitogen-activated protein kinase p38 alpha (MAPK14) and matrix metallopeptidase (MMP)9, indicating that ARC treatment of GA was through multiple components and multiple targets. In vitro experiments showed that AA in ARC could effectively reduce expression of MAPK14, MMP9, and cyclooxygenase2 (PTGS2) in THP-1 cells stimulated by MSU, whereas it could significantly inhibit the mRNA expression of Caspase-1, spleen tyrosine kinase (SYK), and PTGS2. Animal experiments showed that a ARC aqueous extract could significantly reduce expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intereleukin (IL)-18 in the serum of GA rats stimulated by MSU. Hence, ARC may inhibit inflammation by regulating the proteoglycans in cancer-associated signaling pathways. Conclusion: ARC treatment of GA may have the following mechanisms, ARC can reduce MSU crystal-induced joint swelling, reduce synovial tissue damage, and reduce the expression of inflammatory factors in serum. AA in ARC may inhibit inflammation by regulating the protein expression of MAPK14, MMP9, and PTGS2 and the mRNA expression of caspase-1, SYK, and PTGS2.
Superresolution Microscopy Reveals Distinct Phosphoinositide Subdomains Within the Cilia Transition Zone

Primary cilia are evolutionary conserved microtubule-based organelles that protrude from the surface of most mammalian cells. Phosphoinositides (PI) are membrane-associated signaling lipids that regulate numerous cellular events via the recruitment of lipid-binding effectors. The temporal and spatial membrane distribution of phosphoinositides is regulated by phosphoinositide kinases and phosphatases. Recently phosphoinositide signaling and turnover has been observed at primary cilia. However, the precise localization of the phosphoinositides to specific ciliary subdomains remains undefined. Here we use superresolution microscopy (2D stimulated emission depletion microscopy) to map phosphoinositide distribution at the cilia transition zone. PI(3,4,5)P3 and PI(4,5)P2 localized to distinct subregions of the transition zone in a ring-shape at the inner transition zone membrane. Interestingly, the PI(3,4,5)P3 subdomain was more distal within the transition zone relative to PtdIns(4,5)P2. The phosphoinositide effector kinase pAKT(S473) localized in close proximity to these phosphoinositides. The inositol polyphosphate 5-phosphatase, INPP5E, degrades transition zone phosphoinositides, however, studies of fixed cells have reported recombinant INPP5E localizes to the ciliary axoneme, distant from its substrates. Notably, here using live cell imaging and optimized fixation/permeabilization protocols INPP5E was found concentrated at the cilia base, in a distribution characteristic of the transition zone in a ring-shaped domain of similar dimensions to the phosphoinositides. Collectively, this superresolution map places the phosphoinositides in situ with the transition zone proteins and reveals that INPP5E also likely localizes to a subdomain of the transition zone membrane, where it is optimally situated to control local phosphoinositide metabolism.
Tremor-Suppression Orthoses for the Upper Limb: Current Developments and Future Challenges

Introduction: Pathological tremor is the most common motor disorder in adults and characterized by involuntary, rhythmic muscular contraction leading to shaking movements in one or more parts of the body. Functional Electrical Stimulation (FES) and biomechanical loading using wearable orthoses have emerged as effective and non-invasive methods for tremor suppression. A variety of upper-limb orthoses for tremor suppression have been introduced; however, a systematic review of the mechanical design, algorithms for tremor extraction, and the experimental design is still missing. Methods: To address this gap, we applied a standard systematic review methodology to conduct a literature search in the PubMed and PMC databases. Inclusion criteria and full-text access eligibility were used to filter the studies from the search results. Subsequently, we extracted relevant information, such as suppression mechanism, system weights, degrees of freedom (DOF), algorithms for tremor estimation, experimental settings, and the efficacy. Results: The results show that the majority of tremor-suppression orthoses are active with 47% prevalence. Active orthoses are also the heaviest with an average weight of 561 ± 467 g, followed by semi-active 486 ± 395 g, and passive orthoses 191 ± 137 g. Most of the orthoses only support one DOF (54.5%). Two-DOF and three-DOF orthoses account for 33 and 18%, respectively. The average efficacy of tremor suppression using wearable orthoses is 83 ± 13%. Active orthoses are the most efficient with an average efficacy of 83 ± 8%, following by the semi-active 77 ± 19%, and passive orthoses 75 ± 12%. Among different experimental setups, bench testing shows the highest efficacy at 95 ± 5%, this value dropped to 86 ± 8% when evaluating with tremor-affected subjects. The majority of the orthoses (92%) measured voluntary and/or tremorous motions using biomechanical sensors (e.g., IMU, force sensor). Only one system was found to utilize EMG for tremor extraction. Conclusions: Our review showed an improvement in efficacy of using robotic orthoses in tremor suppression. However, significant challenges for the translations of these systems into clinical or home use remain unsolved. Future challenges include improving the wearability of the orthoses (e.g., lightweight, aesthetic, and soft structure), and user control interfaces (i.e., neural machine interface). We also suggest addressing non-technical challenges (e.g., regulatory compliance, insurance reimbursement) to make the technology more accessible.
A Review on Virtual Reality Skill Training Applications

This study aimed to discuss the research efforts in developing virtual reality (VR) technology for different training applications. To begin with, we describe how VR training experiences are typically created and delivered using the current software and hardware. We then discuss the challenges and solutions of applying VR training to different application domains, such as first responder training, medical training, military training, workforce training, and education. Furthermore, we discuss the common assessment tests and evaluation methods used to validate VR training effectiveness. We conclude the article by discussing possible future directions to leverage VR technology advances for developing novel training experiences.
Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

Biomarkers that can guide cancer therapy based on patients’ individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.
Prosthetic Embodiment and Body Image Changes in Patients Undergoing Bionic Reconstruction Following Brachial Plexus Injury

Brachial plexus injuries with multiple-root involvement lead to severe and long-lasting impairments in the functionality and appearance of the affected upper extremity. In cases, where biologic reconstruction of hand and arm function is not possible, bionic reconstruction may be considered as a viable clinical option. Bionic reconstruction, through a careful combination of surgical augmentation, amputation, and prosthetic substitution of the functionless hand, has been shown to achieve substantial improvements in function and quality of life. However, it is known that long-term distortions in the body image are present in patients with severe nerve injury as well as in prosthetic users regardless of the level of function. To date, the body image of patients who voluntarily opted for elective amputation and prosthetic reconstruction has not been investigated. Moreover, the degree of embodiment of the prosthesis in these patients is unknown. We have conducted a longitudinal study evaluating changes of body image using the patient-reported Body Image Questionnaire 20 (BIQ-20) and a structured questionnaire about prosthetic embodiment. Six patients have been included. At follow up 2.5–5 years after intervention, a majority of patients reported better BIQ-20 scores including a less negative body evaluation (5 out of 6 patients) and higher vital body dynamics (4 out of 6 patients). Moreover, patients described a strong to moderate prosthesis embodiment. Interestingly, whether patients reported performing bimanual tasks together with the prosthetic hand or not, did not influence their perception of the prosthesis as a body part. In general, this group of patients undergoing prosthetic substitution after brachial plexus injury shows noticeable inter-individual differences. This indicates that the replacement of human anatomy with technology is not a straight-forward process perceived in the same way by everyone opting for it.
Direct numerical simulation of ‘short’ laminar separation bubbles with turbulent reattachment

Direct numerical simulation of the incompressible Navier-Stokes equations is used to study flows where laminar boundary-layer separation is followed by turbulent reattachment forming a closed region known as a laminar separation bubble. In the simulations a laminar boundary layer is forced to separate by the action of a suction profile applied as the upper boundary condition. The separated shear layer undergoes transition via oblique modes and Λ-vortex-induced breakdown and reattaches as turbulent flow, slowly recovering to an equilibrium turbulent boundary layer. Compared with classical experiments the computed bubbles may be classified as ‘short’, as the external potential flow is only affected in the immediate vicinity of the bubble. Near reattachment budgets of turbulence kinetic energy are dominated by turbulence events away from the wall. Characteristics of near-wall turbulence only develop several bubble lengths downstream of reattachment. Comparisons are made with two-dimensional simulations which fail to capture many of the detailed features of the full three-dimensional simulations. Stability characteristics of mean flow profiles are computed in the separated flow region for a family of velocity profiles generated using simulation data. Absolute instability is shown to require reverse flows of the order of 15–20%. The three-dimensional bubbles with turbulent reattachment have maximum reverse flows of less than 8% and it is concluded that for these bubbles the basic instability is convective in nature.