Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant Limb Assay as in Vivo Organoid Model

Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled in vitro by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an in vivo organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties in vivo from these cells for the first time.
Dietary Supplementation of Ferrous Glycine Chelate Improves Growth Performance of Piglets by Enhancing Serum Immune Antioxidant Properties, Modulating Microbial Structure and Its Metabolic Function in the Early Stage

The present research aimed to explore the effect of dietary ferrous glycine chelate supplementation on performance, serum immune-antioxidant parameters, fecal volatile fatty acids, and microbiota in weaned piglets. A total of 80 healthy piglets (weaned at 28 day with an initial weight of 7.43 ± 1.51 kg) were separated into two treatments with five replicates of eight pigs each following a completely randomized block design. The diet was a corn-soybean basal diet with 2,000 mg/kg ferrous glycine chelates (FGC) or not (Ctrl). The serum and fecal samples were collected on days 14 and 28 of the experiment. The results indicated that dietary FGC supplementation improved (p < 0.05) the average daily gain and average daily feed intake overall, alleviated (p < 0.05) the diarrhea rate of piglets at the early stage, enhanced (p < 0.05) the levels of superoxide dismutase and catalase on day 14 and lowered (p < 0.05) the MDA level overall. Similarly, the levels of growth hormone and serum iron were increased (p < 0.05) in the FGC group. Moreover, dietary FGC supplementation was capable of modulating the microbial community structure of piglets in the early period, increasing (p < 0.05) the abundance of short-chain fatty acid-producing bacteria Tezzerella, decreasing (p < 0.05) the abundance of potentially pathogenic bacteria Slackia, Olsenella, and Prevotella as well as stimulating (p < 0.05) the propanoate and butanoate metabolisms. Briefly, dietary supplemented FGC ameliorates the performance and alleviated the diarrhea of piglets by enhancing antioxidant properties, improving iron transport, up-regulating the growth hormone, modulating the fecal microbiota, and increasing the metabolism function. Therefore, FGC is effective for early iron supplementation and growth of piglets and may be more effective in neonatal piglets.
Ectomycorrhizal Fungal Transformation of Dissolved Organic Matter: Consequences for Reductive Iron Oxide Dissolution and Fenton-Based Oxidation of Mineral-Associated Organic Matter

Recent studies have shown that dissolved organic matter (DOM) decomposed by ectomycorrhizal (ECM) fungi increases adsorptive properties of organic matter towards soil mineral surfaces. Concomitantly, ECM fungi secrete secondary metabolites with iron reducing capacity that are thought to participate in non-enzymatic Fenton-based decomposition of DOM. The aim of this study was to investigate if the iron reduction induced by the ECM fungus Paxillus involutus during organic matter decomposition was conserved in the decomposed DOM. We explored how the modified DOM reductively dissolved ferrihydrite and goethite nanoparticles and how these processes affected the reactions with H2O2 and the Fenton-based oxidation of mineral-associated organic matter. Culture filtrates were obtained from incubation of the ECM fungus on DOM from forest litter of a spruce forest. This modified DOM was separated by extraction into an ethyl acetate and a water fraction. These fractions were reacted with ferrihydrite and goethite in absence and presence of H2O2. Dissolved Fe2+ and HO• were measured and the reactions at the iron oxide-water interfaces were monitored in real-time with in-situ IR spectroscopy. Experiments showed that decomposition of DOM by P. involutus generated a modified DOM that displayed an increased and persistent reductive capacity. Most of the reductants were isolated in the aromatic- and carboxyl-dominated ethyl acetate fraction but some reduction capacity was also captured in the water fraction mainly containing carbohydrates. Reductive dissolution was more extensive for ferrihydrite than goethite, and this process generated significant oxidation of the DOM-ferrihydrite associations. Oxidation of adsorbed DOM was triggered by H2O2 via heterogenous and homogeneous Fenton reactions. These oxidation processes were favored by ferrihydrite because of a high reduction potential and a high efficiency of heterogeneous Fenton as compared to goethite. An optimal timing between the heterogeneous and homogeneous Fenton processes triggered extensive radical oxidation of the DOM-ferrihydrite associations generating a high concentration of surface-associated oxalate. Overall, the results show that organic matter associated with ferrihydrite may be more susceptible to radical oxidation than on goethite, and that fungal decomposition of DOM in general may have consequences for other important soil processes such as mineral dissolution, adsorption and initiation of radical reactions.
Trans-Spinal Direct Current Stimulation Targets Ca2+ Channels to Induce Persistent Motor Unit Responses

Trans-spinal direct current stimulation (tsDCS) is a neuromodulatory approach to augment spinal cord activity to improve function after neurological disease and injury. Little is known about the mechanisms underlying tsDCS actions on the motor system. The purpose of this study is to determine the role for a persistent inward current (PIC)-like response in motoneurons in mediating tsDCS actions. We recorded single motor units from the extensor and flexor carpi radialis muscles in healthy sedated rats and measured unit activity changes produced by cervical enlargement cathodal and anodal tsDCS (c-tsDCS; a-tsDCS). Both c-tsDCS and a-tsDCS immediately increased spontaneous motor unit firing during stimulation. After c-tsDCS was stopped, spontaneous firing persisted for a substantial period (165 ± 5s), yet after a-tsDCS activity shortly returned to baseline (27 ± 7s). Administration of the L-type calcium channel blocker Nimodipine reduced spontaneous motor unit firing during c-tsDCS and blocked the persistent response. By contrast, Nimodipine did not change unit firing during a-tsDCS but the short persistent response was blocked. Computer simulation using a two-compartment neuronal model replicated the main experimental observations: larger and more persistent responses during and after c-tsDCS than a-tsDCS. Using reduced Ca2+ conductance to model Nimodipine action, a reduced response during c-tsDCS and elimination of the persistent response was observed. Our experimental findings, supported by computer simulation, show that c-tsDCS can target Ca2+ conductances to augment motoneuron activity. As tsDCS is well-tolerated in humans, this knowledge informs therapeutic treatment strategies to achieve rehabilitation goals after injury; in particular, to increase muscle force.
Bacteriocin-Like Inhibitory Substances in Staphylococci of Different Origins and Species With Activity Against Relevant Pathogens

Bacteriocins are antimicrobial peptides with relevance in the modulation of human and animal microbiota that have gained interest in biomedical and biotechnological applications. In this study, the production of bacteriocin-like inhibitory substances (BLIS) was tested among a collection of 890 staphylococci of different origins (humans, animals, food, and the environment) and species, both coagulase-positive (CoPS, 238 isolates of 3 species) and coagulase-negative staphylococci (CoNS, 652 isolates of 26 species). Of the 890 staphylococci, 60 (6.7%) showed antimicrobial activity by the spot-on-lawn method against at least one of the 25 indicator bacteria tested. BLIS-producer (BLIS+) isolates were detected in 8.8% of CoPS and 6.0% of CoNS. The staphylococcal species with the highest percentages of BLIS+ isolates were S. chromogenes (38.5%), S. pseudintermedius (26.7%), and S. warneri (23.1%). The production of BLIS was more frequently detected among isolates of pets, wild animals, and food. Moreover, 13 BLIS+ isolates showed wide antimicrobial activiy spectrum, and 7 of these isolates (of species S. aureus, S. pseudintermedius, S. sciuri, and S. hominis) demonstrated antimicrobial activity against more than 70% of the indicator bacteria tested. The genetic characterization (by PCR and sequencing) of the 60 BLIS+ isolates revealed the detection of (a) 11 CoNS and CoPS isolates carrying putative lantibiotic-like genes; (b) 3 S. pseudintermedius isolates harboring the genes of BacSp222 bacteriocin; and (c) 2 S. chromogenes isolates that presented the gene of a putative cyclic bacteriocin (uberolysin-like), being the first report in this CoNS species. Antimicrobial susceptibility testing was performed in BLIS+ isolates and one-third of the CoNS isolates showed susceptibility to all antibiotics tested, which also lacked the virulence genes studied. These BLIS+ CoNS are good candidates for further characterization studies.
Multiple-Allele MHC Class II Epitope Engineering by a Molecular Dynamics-Based Evolution Protocol

Epitopes that bind simultaneously to all human alleles of Major Histocompatibility Complex class II (MHC II) are considered one of the key factors for the development of improved vaccines and cancer immunotherapies. To engineer MHC II multiple-allele binders, we developed a protocol called PanMHC-PARCE, based on the unsupervised optimization of the epitope sequence by single-point mutations, parallel explicit-solvent molecular dynamics simulations and scoring of the MHC II-epitope complexes. The key idea is accepting mutations that not only improve the affinity but also reduce the affinity gap between the alleles. We applied this methodology to enhance a Plasmodium vivax epitope for multiple-allele binding. In vitro rate-binding assays showed that four engineered peptides were able to bind with improved affinity toward multiple human MHC II alleles. Moreover, we demonstrated that mice immunized with the peptides exhibited interferon-gamma cellular immune response. Overall, the method enables the engineering of peptides with improved binding properties that can be used for the generation of new immunotherapies.
Determination of the Effects of Duodenal Infusion Soy Protein Hydrolysate on Hepatic Glucose and Lipid Metabolism in Pigs Through Multi-Omics Analysis

High animal protein intake increases hepatic lipid deposition and the risk of diabetes. However, the effects of high plant protein (HPP) intake on glycaemic responses and hepatic lipid metabolism in healthy people, as well as the underlying mechanisms, remain unclear. The current study explored the metabolomic and transcriptomic responses in the livers of pigs to assess the effects of HPP intake on host glucose and lipid metabolism. Sixteen pigs were infused with sterile saline or soy protein hydrolysate (SPH; 70 g/day) through a duodenal fistula twice daily during a 15 days experimental period. Hepatic metabolomic and transcriptomic analyses were performed, and the serum and hepatic biochemical parameters were measured. The results revealed that SPH infusion decreased serum glucose, hepatic triglyceride (TG), total cholesterol and low-density lipoprotein cholesterol levels, while it increased serum urea and eight hepatic amino acid levels (P < 0.05). Hepatic metabolomics displayed that SPH treatment produced seven different metabolites, four of which were related to lipid metabolism and one was related to glucose metabolism. In particular, lower (P < 0.05) glycocholic acid and glucose 1-phosphate levels and higher (P < 0.05) phosphatidylethanolamine (PE), arachidonic acid, prostaglandin F2α, l-carnitine and indole-3 acetic acid levels were observed following SPH infusion. A further metabolic pathway enrichment analysis found that these differential metabolites were mainly enriched in pathways related to lipid and glucose metabolism. Hepatic transcriptomics also demonstrated that multiple genes related to glucose and lipid metabolism were affected by SPH (P < 0.05). Together, SPH infusion reduced the hepatic TG levels by accelerating fatty acid β-oxidation and inhibiting TG synthesis. In addition, SPH infusion reduced the serum glucose levels by promoting hepatic glucose uptake and glycolysis. This study's result demonstrated that HPP intake regulated glycaemic responses and hepatic lipid metabolism in pigs without increasing the risk of hepatic lipid deposition and hyperglycaemia.
Supporting Cells and Their Potential Roles in Cisplatin-Induced Ototoxicity

Cisplatin is a known ototoxic chemotherapy drug, causing irreversible hearing loss. Evidence has shown that cisplatin causes inner ear damage as a result of adduct formation, a proinflammatory environment and the generation of reactive oxygen species within the inner ear. The main cochlear targets for cisplatin are commonly known to be the outer hair cells, the stria vascularis and the spiral ganglion neurons. Further evidence has shown that certain transporters can mediate cisplatin influx into the inner ear cells including organic cation transporter 2 (OCT2) and the copper transporter Ctr1. However, the expression profiles for these transporters within inner ear cells are not consistent in the literature, and expression of OCT2 and Ctr1 has also been observed in supporting cells. Organ of Corti supporting cells are essential for hair cell activity and survival. Special interest has been devoted to gap junction expression by these cells as certain mutations have been linked to hearing loss. Interestingly, cisplatin appears to affect connexin expression in the inner ear. While investigations regarding cisplatin-induced hearing loss have been focused mainly on the known targets previously mentioned, the role of supporting cells for cisplatin-induced ototoxicity has been overlooked. In this mini review, we discuss the implications of supporting cells expressing OCT2 and Ctr1 as well as the potential role of gap junctions in cisplatin-induced cytotoxicity.
EEG-TNet: An End-To-End Brain Computer Interface Framework for Mental Workload Estimation

The mental workload (MWL) of different occupational groups' workers is the main and direct factor of unsafe behavior, which may cause serious accidents. One of the new and useful technologies to estimate MWL is the Brain computer interface (BCI) based on EEG signals, which is regarded as the gold standard of cognitive status. However, estimation systems involving handcrafted EEG features are time-consuming and unsuitable to apply in real-time. The purpose of this study was to propose an end-to-end BCI framework for MWL estimation. First, a new automated data preprocessing method was proposed to remove the artifact without human interference. Then a new neural network structure named EEG-TNet was designed to extract both the temporal and frequency information from the original EEG. Furthermore, two types of experiments and ablation studies were performed to prove the effectiveness of this model. In the subject-dependent experiment, the estimation accuracy of dual-task estimation (No task vs. TASK) and triple-task estimation (Lo vs. Mi vs. Hi) reached 99.82 and 99.21%, respectively. In contrast, the accuracy of different tasks reached 82.78 and 66.83% in subject-independent experiments. Additionally, the ablation studies proved that preprocessing method and network structure had significant contributions to estimation MWL. The proposed method is convenient without any human intervention and outperforms other related studies, which becomes an effective way to reduce human factor risks.
Integrating Lipidomics and Transcriptomics Reveals the Crosstalk Between Oxidative Stress and Neuroinflammation in Central Nervous System Demyelination

Multiple sclerosis (MS) is an incurable and progressive neurodegenerative disease that affects more than 2.5 million people worldwide and brings tremendous economic pressures to society. However, the pathophysiology of MS is still not fully elucidated, and there is no effective treatment. Demyelination is thought to be the primary pathophysiological alteration in MS, and our previous study found abnormal lipid metabolism in the demyelinated corpus callosum. Growing evidence indicates that central nervous system (CNS) demyelinating diseases never result from one independent factor, and the simultaneous participation of abnormal lipid metabolism, oxidative stress, and neuroinflammation could potentiate each other in the pathogenesis of MS. Therefore, a single omics analysis cannot provide a full description of any neurodegenerative disease. It has been demonstrated that oxidative stress and neuroinflammation are two reciprocal causative reasons for the progression of MS disease. However, the potential crosstalk between oxidative stress and neuroinflammation remains elusive so far. With an integrated analysis of targeted lipidomics and transcriptomics, our research presents the potential interaction between abnormalities of lipid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in CNS demyelinating diseases. The findings of this paper may be used to identify possible targets for the therapy of CNS demyelinating diseases.
Effectiveness and Success Factors of Bilateral Arm Training After Stroke: A Systematic Review and Meta-Analysis

Bilateral arm training (BAT) presents as a promising approach in upper extremity (UE) rehabilitation after a stroke as it may facilitate neuroplasticity. However, the effectiveness of BAT is inconclusive, and no systematic reviews and meta-analyses have investigated the impact of different factors on the outcomes of BAT. This systematic review and meta-analysis aimed to (1) compare the effects of bilateral arm training (BAT) with unilateral arm training (UAT) and conventional therapy (CT) on the upper limb (UL) motor impairments and functional performance post-stroke, and (2) investigate the different contributing factors that may influence the success of BAT. A comprehensive literature search was performed in five databases. Randomized control trials (RCTs) that met inclusion criteria were selected and assessed for methodological qualities. Data relating to outcome measures, characteristics of participants (stroke chronicity and severity), and features of intervention (type of BAT and dose) were extracted for meta-analysis. With 25 RCTs meeting the inclusion criteria, BAT demonstrated significantly greater improvements in motor impairments as measured by Fugl-Meyer Assessment of Upper Extremity (FMA-UE) than CT (MD = 3.94, p = < 0.001), but not in functional performance as measured by the pooled outcomes of Action Research Arm Test (ARAT), Box and Block Test (BBT), and the time component of Motor Function Test (WMFT-time) (SMD = 0.28, p = 0.313). The superior motor impairment effects of BAT were associated with recruiting mildly impaired individuals in the chronic phase of stroke (MD = 6.71, p < 0.001), and applying a higher dose of intervention (MD = 6.52, p < 0.001). Subgroup analysis showed that bilateral functional task training (BFTT) improves both motor impairments (MD = 7.84, p < 0.001) and functional performance (SMD = 1.02, p = 0.049). No significant differences were detected between BAT and UAT for motor impairment (MD = −0.90, p = 0.681) or functional performance (SMD = −0.09, p = 0.457). Thus, our meta-analysis indicates that BAT may be more beneficial than CT in addressing post-stroke UL motor impairment, particularly in the chronic phase with mild UL paresis. The success of BAT may be dose-dependent, and higher doses of intervention may be required. BFTT appears to be a valuable form of BAT that could be integrated into stroke rehabilitation programs. BAT and UAT are generally equivalent in improving UL motor impairments and functional performance.
Uremic Toxin-Producing Bacteroides Species Prevail in the Gut Microbiota of Taiwanese CKD Patients: An Analysis Using the New Taiwan Microbiome Baseline

Rationale and Objective Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota. Study Design This was a cross-sectional cohort study. Settings and Participants Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients. Results Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was Bacteroides, and at the species level hemodialysis patients showed significant abundance in B. ovatus, B. caccae, B. uniformis, and peritoneal dialysis patients showed higher abundance in Blautia producta (p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment. Conclusion This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients’ condition.