Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid pathology reduces ELP3 expression and tRNA modifications leading to impaired proteostasis in Alzheimer’s disease models

Alzheimer’s Disease (AD) is a progressive and irreversible neurodegenerative disorder, characterized by the accumulation of abeta-amyloid aggregates, which triggers tau hyperphosphorylation and neuronal loss. While the precise mechanisms underlying neurodegeneration in AD are not entirely understood, it is known that loss of proteostasis is implicated in this process. Maintaining neuronal proteostasis requires proper transfer RNA (tRNA) modifications, which are crucial for optimal translation. However, research into tRNA epitranscriptome in AD is limited, and it is not yet clear how alterations in tRNA modifying enzymes and tRNA modifications might contribute to disease progression. Here, we report that expression of the tRNA modifying enzyme ELP3 is reduced in the brain of AD patients and amyloid AD mouse models, suggesting ELP3 is implicated in proteostasis dysregulation observed in AD. To investigate the role of ELP3 specifically in neuronal proteostasis impairments in the context of amyloid pathology, we analyzed SH-SY5Y neuronal cells carrying the amyloidogenic Swedish familial AD mutation in the APP gene (SH-SWE) or the wild-type gene (SH-WT). Similarly to the amyloid mouse models, SH-SWE exhibited reduced levels of ELP3 which was associated with tRNA hypomodifications and reduced abundance, as well as proteostasis impairments. Furthermore, the knock-down of ELP3 in SH-WT recapitulated the proteostasis impairments observed in SH-SWE cells. Importantly, the correction of tRNA deficits due to ELP3 reduction rescued and reverted proteostasis impairments of SH-SWE and SH-WT knock-down for ELP3, respectively. Additionally, SH-WT exposed to the secretome of SH-SWE or synthetic amyloid aggregates recapitulate the SH-SWE phenotype, characterized by reduced ELP3 expression, tRNA hypomodification and increased protein aggregation. Taken together, our data suggest that amyloid pathology dysregulates neuronal proteostasis through the reduction of ELP3 and tRNA modifications. This study highlights the modulation of tRNA modifications as a potential therapeutic avenue to restore neuronal proteostasis in AD and preserve neuronal function. Graphical Abstract
Flexible terahertz optics: light beam profile engineering via C-shaped metallic metasurface

The potential of terahertz (THz) imaging implementation in a large variety of applications requires compact, reliable, and relatively low-cost solutions in systems constituents. Here we focus on the development of passive optical elements and demonstrate flexible and reliable THz beam profile engineering for imaging aims via mechanical bending of a stainless steel-based C-shaped metasurface. The designed and laser-ablation technology fabricated metasurface provides compact THz focusing and enables THz light engineering as well as polarization control ability in THz imaging. Focusing, light profile engineering, and polarization control performances of the metasurfaces with different focal distances and C-shape designs are presented. Experimental data are well supported by simulations, using Finite Difference Time Domain (FDTD) method. THz images of different objects at ∼ 94 GHz using InP Gunn diode, bow-tie sensors, and exclusively metasurfaces-based optics are exposed. Further routes in the development of low-cost multicolor and polarization-sensitive THz imaging are discussed.
Climate change-related warming-induced shifts in leaf chemical traits favor nutrition of the specialist herbivore Battus polydamas archidamas

One of the major impacts of climate change is increasing global temperatures. Because warming is expected to affect plant morphological and chemical traits, it may therefore also influence plant interactions with other trophic levels, including herbivores. Here, we simulated a climate warming scenario of +2.7°C in the field using open-top chambers and assessed the effects of warming on plant performance (growth, leaf area, and chlorophyll), leaf nutrients (nitrogen and carbon), and primary (amino acids and carbohydrates) and secondary (toxic aristolochic acids) metabolites in the plant Aristolochia chilensis. We performed untargeted metabolomics analyses for estimating general changes in foliar metabolites between ambient control and warming-treated plants. Bioassays were additionally conducted to evaluate how changes in host plant chemistry affected growth and nutritional parameters in first-instar larvae of the specialist lepidopteran herbivore Battus polydamas archidamas. We found that warming did not significantly affect plant performance, but did result in significant changes in leaf nutrients, and primary and secondary metabolites, although in opposite directions. While primary metabolites (specifically, nitrogen-containing compounds) decreased in response to treatment, aristolochic acids increased. Untargeted metabolomics analyses showed that, of a total of 824 features, 50 were significantly different between ambient control and warming-treated plants; some of these were identified by MS/MS spectra as amino acids. Larvae feeding on warming-treated plants, showed significantly enhanced growth, food conversion efficiency, and lipid concentration. Our study contributes to current understanding of climate change impacts on trophic interactions, showing that projected temperature increases lead to changes in the resistance phenotype of the host plant, favoring nutrition and growth of a unique specialist herbivore.
Informed consent in minor and intermediate pediatric elective surgery: results of an in-house questionnaire

Background The aim of this study was to evaluate the quality of our surgical informed consent and parents'/guardians' late recall of surgical procedures and risks of elective day surgery after pre-operative interview with surgeons. Methods All parents/guardians of patients <18 years of age undergoing minor and intermediate elective procedures from January 15th to September 1st, 2022, were prospectively enrolled in the study. Before discharge, parents/guardians were asked to complete an in-house questionnaire regarding the duration of the consent procedure, duration of the interview, quality of the informative handouts, and their ability to recall the type of disease, type of surgical procedure, and surgical risks. Results One hundred and two questionnaires were returned. In all cases, informed consent was obtained between 24 and 72 h prior to surgery. The following responses were collected: 98/102 (96%) parents/guardians reported that the duration of the consent process was adequate; 95/102 (93%) reported that the handouts were fully informative, and 7/102 (7%) reported that they were partially informative regarding explanation of the disease and surgical procedure; regarding complications, 93/102 (91%) perceived the handouts to be fully/partially informative, while 4/102 (4%) perceived the handouts to be poorly/non-informative, and 5/102 (5%) did not provide a response; 94/102 (92%) stated that they remembered the pathology, but only 87/94 (93%) recalled it correctly; 90/102 (88%) stated that they remembered the type of procedure, but only 76/90 (84%) recalled it correctly; and 53/102 (52%) stated that they remembered the surgical risks, but only 20/53 (38%) could recall more than one complication. Conclusions Late recall of surgical complications by parents was poor despite the high perceived quality of the surgical risk handouts and medical interview. Implementation of expedient methods may improve overall comprehension and satisfaction of parents/guardians regarding the IC process. Further, more efforts should be made to develop standardized guidelines for an optimal IC process.
Neurotransmitters: promising immune modulators in the tumor microenvironment

The tumor microenvironment (TME) is modified by its cellular or acellular components throughout the whole period of tumor development. The dynamic modulation can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Hence, the focus of cancer research and intervention has gradually shifted to TME components and their interactions. Accumulated evidence indicates neural and immune factors play a distinct role in modulating TME synergistically. Among the complicated interactions, neurotransmitters, the traditional neural regulators, mediate some crucial regulatory functions. Nevertheless, knowledge of the exact mechanisms is still scarce. Meanwhile, therapies targeting the TME remain unsatisfactory. It holds a great prospect to reveal the molecular mechanism by which the interplay between the nervous and immune systems regulate cancer progression for laying a vivid landscape of tumor development and improving clinical treatment.
Effects of E-health-based interventions on glycemic control for patients with type 2 diabetes: a Bayesian network meta-analysis

The high disease burden of type 2 diabetes seriously affects the quality of life of patients, and with the deep integration of the Internet and healthcare, the application of electronic tools and information technology to has become a trend for disease management. The aim of this study was to evaluate the effectiveness of different forms and durations of E-health interventions in achieving glycemic control in type 2 diabetes patients. PubMed, Embase, Cochrane, and Clinical Trials.gov were searched for randomized controlled trials reporting different forms of E-health intervention for glycemic control in type 2 diabetes patients, including comprehensive measures (CM), smartphone applications (SA), phone calls (PC), short message service (SMS), websites (W), wearable devices (WD), and usual care. The inclusion criteria were as follows: (1) adults (age≥18) with type 2 diabetes mellitus; (2) intervention period ≥1 month; (3) outcome HbA1c (%); and (4) randomized control of E-health based approaches. Cochrane tools were used to assess the risk of bias. R 4.1. 2 was used to conduct the Bayesian network meta-analysis. A total of 88 studies with 13,972 type 2 diabetes patients were included. Compared to the usual care group, the SMS-based intervention was superior in reducing HbA1c levels (mean difference (MD)-0.56, 95% confidence interval (CI): -0.82 to -0.31), followed by SA (MD-0.45, 95% CI: -0.61 to -0.30), CM (MD-0.41, 95% CI: -0.57 to -0.25), W (MD-0.39, 95% CI: -0.60 to -0.18) and PC (MD-0.32, 95% CI: -0.50 to -0.14) (p < 0.05). Subgroup analysis revealed that intervention durations of ≤6 months were most effective. All type of E-health based approaches can improve glycemic control in patients with type 2 diabetes. SMS is a high-frequency, low-barrier technology that achieves the best effect in lowering HbA1c, with ≤6 months being the optimal intervention duration. Systematic review registration https://www.crd. york.ac. uk/prospero, identifier CRD42022299896.
microRNA-dependent regulation of gene expression in GABAergic interneurons

Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal and local inhibitory interneurons within those circuits. Gamma-aminobutyric acid (GABA)ergic inhibitory interneurons are a remarkably heterogeneous population, comprising subclasses based on their morphological, electrophysiological, and molecular features, with differential connectivity and activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for neuronal development and plasticity. miRNAs are a large group of small non-coding RNAs (21–24 nucleotides) acting as negative regulators of mRNA translation and stability. However, while miRNA-dependent gene regulation in principal neurons has been described heretofore in several studies, an understanding of the role of miRNAs in inhibitory interneurons is only beginning to emerge. Recent research demonstrated that miRNAs are differentially expressed in interneuron subclasses, are vitally important for migration, maturation, and survival of interneurons during embryonic development and are crucial for cognitive function and memory formation. In this review, we discuss recent progress in understanding miRNA-dependent regulation of gene expression in interneuron development and function. We aim to shed light onto mechanisms by which miRNAs in GABAergic interneurons contribute to sculpting neuronal circuits, and how their dysregulation may underlie the emergence of numerous neurodevelopmental and neuropsychiatric disorders.
Evaluation of triple negative breast cancer with heterogeneous immune infiltration

Introduction Tumor infiltrating lymphocytes (TILs) are known to be a prognostic and predictive biomarker in breast cancer, particularly in triple negative breast cancer (TNBC) patients. International guidelines have been proposed to evaluate them in the clinical setting as a continuous variable, without a clear defined cut-off. However, there are scenarios where the immune infiltration is heterogeneous that some areas of the patient’s tumour have high numbers of TILs while other areas completely lack them. This spontaneous presentation of a heterogeneous immune infiltration could be a great opportunity to study why some tumours present TILs at diagnosis but others do not, while eliminating inter patient’s differences. Methods In this study, we have identified five TNBC patients that showed great TIL heterogeneity, with areas of low (≤5%) and high (≥50%) numbers of TILs in their surgical specimens. To evaluate immune infiltration heterogeneity, we performed and analyzed bulk RNA-sequencing in three independent triplicates from the high and low TIL areas of each patient. Results Gene expression was homogeneous within the triplicates in each area but was remarkable different between TILs regions. These differences were not only due to the presence of TILs as there were other non-inflammatory genes and pathways differentially expressed between the two areas. Discussion This highlights the importance of intratumour heterogeneity driving the immune infiltration, and not patient’s characteristics like the HLA phenotype, germline DNA or immune repertoire.
Analyzing the use of videoconference by and for older adults in nursing homes: an interdisciplinary approach to learn from the pandemic

Introduction During the Covid-19 pandemic and the resulting visitation restrictions, digital tools were used in many nursing homes in France to allow the older adults and their relatives to maintain social contact via videoconferencing. This article adopts an interdisciplinary approach to analyze the processes that affect the use of digital technologies. Methods Drawing on the concept of “mediation,” it seeks to shed light on how individuals embrace these tools in a relational situation. The interviews and observations undertaken among residents, their relatives, professionals, and the management head of seven nursing homes in 2021, make it possible to outline the different forms of practices and uses and to identify the factors leading to the variations observed. Results While the key objective of these technical and technological tools is to compensate – on a functional level – for the communication problems and the isolation of individuals in order to promote residents’ “quality of life” by maintaining “social contact,” our study reveals that these tools’ uses and practices largely differ. It also shows considerable inequalities in terms of residents’ acquisition of subjective feelings of ownership of the tools. These are never attributed to isolated physical, cognitive, psychic, and social difficulties, but are influenced by specific organizational, interactional, and psychic configurations. Some of the structures analyzed revealed situations in which mediation failed, occasionally exposing the risk associated with seeking “ties at all costs,” or revealing a disturbing strangeness when residents were placed in front of screens. Some configurations, however, showed that it was possible to set up an intermediate space for the experience to unfold, which in turn opened up a space where individuals, groups, and institutions could experiment, allowing them to develop subjective feelings of ownership of this experience. Discussion This article discusses how the configurations that failed to promote the mediation process reveal the need to assess the representations of care and assistance in the relationships between older adults, their loved ones, and nursing home professionals. Indeed, in certain situations, the use of videoconferencing, while seeking to produce a positive effect, risks displacing and increasing the effects of the “negative” associated with dependency, which may worsen individuals’ difficulties within nursing homes. The risks associated with the failure to take into account residents’ requests and consent explain why it is important to discuss how certain uses of digital tools may renew the dilemma between concerns for protection, on the one hand, and respect for autonomy on the other.
Modeling inducible neuropathologies of the retina with differential phenotypes in organoids

Neurodegenerative diseases remain incompletely understood and therapies are needed. Stem cell-derived organoid models facilitate fundamental and translational medicine research. However, to which extent differential neuronal and glial pathologic processes can be reproduced in current systems is still unclear. Here, we tested 16 different chemical, physical, and cell functional manipulations in mouse retina organoids to further explore this. Some of the treatments induce differential phenotypes, indicating that organoids are competent to reproduce distinct pathologic processes. Notably, mouse retina organoids even reproduce a complex pathology phenotype with combined photoreceptor neurodegeneration and glial pathologies upon combined (not single) application of HBEGF and TNF, two factors previously associated with neurodegenerative diseases. Pharmacological inhibitors for MAPK signaling completely prevent photoreceptor and glial pathologies, while inhibitors for Rho/ROCK, NFkB, and CDK4 differentially affect them. In conclusion, mouse retina organoids facilitate reproduction of distinct and complex pathologies, mechanistic access, insights for further organoid optimization, and modeling of differential phenotypes for future applications in fundamental and translational medicine research.
The roles of heme oxygenase-1 in renal disease

Heme oxygenase (HO), a heat shock protein containing hemoglobin, is an important enzyme in heme catabolism. It is involved in cell homeostasis and has anti-inflammatory, antioxidant, anti-apoptosis, immunomodulation, and other functions. It is expressed at a modest level in most normal tissues. When the body suffers from ischemia hypoxia, injury, toxins, and other nociceptive stimuli, the expression increases, which can transform the oxidative microenvironment into an antioxidant environment to promote tissue recovery from damage. In recent years, research has continued to verify its value in a variety of human bodily systems. It is also regarded as a key target for the treatment of numerous disorders. With the advancement of studies, its significance in renal disease has gained increasing attention. It is thought to have a significant protective function in preventing acute kidney injury and delaying the progression of chronic renal diseases. Its protective mechanisms include anti-inflammatory, antioxidant, cell cycle regulation, apoptosis inhibition, hemodynamic regulation, and other aspects, which have been demonstrated in diverse animal models. Furthermore, as a protective factor, its potential therapeutic efficacy in renal disease has recently become a hot area of research. Although a large number of preclinical trials have confirmed its therapeutic potential in reducing kidney injury, due to the problems and side effects of HO-1 induction therapy, its efficacy and safety in clinical application need to be further explored. In this review, we summarize the current state of research on the mechanism, location, and treatment of HO and its relationship with various renal diseases.
Feasibility study on the use of “Qi-tonifying medicine compound” as an anti-fatigue functional food ingredient based on network pharmacology and molecular docking

Introduction Fatigue has attracted broad attention in recent years due to its high morbidity rates. The use of functional foods to relieve fatigue-associated symptoms is becoming increasingly popular and has achieved relatively good results. In this study, network pharmacology and molecular docking strategies were used to establish the material basis and mechanisms of Chinese herbal compounds in fatigue treatment. According to traditional medicine theories and relevant guidance documents published by the Chinese Ministry of Health, four herbal medicines, including Eucommia ulmoides Oliver bark, Eucommia ulmoides Oliver male flower, Panax notoginseng, and Syzygium aromaticum (EEPS), were selected to constitute the anti-fatigue herbal compound that may be suitable as functional food ingredients. Methods The major active ingredients in EEPS were identified via comprehensive literature search and Traditional Chinese Medicine Systems Pharmacology database search. Corresponding targets for these ingredients were predicted using SwissTargetPrediction. The network was constructed using Cytoscape 3.9. 1 to obtain key ingredients. Prediction of absorption, distribution, metabolism, excretion and toxicity properties was performed using the ADMETIab 2.0 database. The anti-fatigue targets were retrieved from GeneCards v5.13, OMIM, TTD and DisGeNET 7.0 databases. Then, the potential targets of EEPS in fatigue treatment were screened through a Venn diagram. A protein–protein interaction (PPI) network of these overlapping targets was constructed, and the hub targets in the network selected through topological screening. Gene Ontology and KEGG pathway enrichment analyses were performed using the DAVID database and the bioinformatics online platform. Finally, AutoDock tools were used to verify the binding capacity between the key active ingredients and the core targets. Results and Discussion This study identified the active ingredients and potential molecular mechanisms of EEPS in fatigue treatment, which will provide a foundation for future research on applications of herbal medicines in the functional food industry.
Perceptual training modifies temporal sensitivity and a sense of agency

Perceptual training has been argued to be a potential means to modify temporal sensitivity (the ability to detect a time-based discrepancy between two stimuli) with previous studies providing preliminary evidence that perceptual training can lead to increased temporal sensitivity. However, previous studies have not employed a control group and therefore cannot rule out the possibility that the observed effects are due to repeated completion of the task, rather than the training itself. Moreover, despite temporal sensitivity being suggested to be an important aspect of the sense of agency, the effects of perceptual training on the sense of agency have not been explored. Therefore, this study aimed to explore the effects of perceptual training on the sense of agency and replicate previously observed effects on temporal sensitivity while utilizing a more rigorous methodology. Given the existing literature, it was predicted that the sense of agency and temporal sensitivity will be enhanced following perceptual training. Temporal sensitivity was only weakly modified by perceptual training when compared to the control condition. Sense of agency was significantly modulated by perceptual training, over and above the control condition. This study's findings present novel evidence indicating that perceptual training can influence high-level processes such as the sense of agency and temporal sensitivity.