Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Microbiota Sensing – Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-β Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis

Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer’s disease (AD)—a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from short chain fatty acids (SCFAs) produced by microbiota. The abundance of SCFAs, is often low in the gut of older adults with AD. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists using an in-silico library of more than 144,000 natural compounds and selected 15 of them based on binding with FFAR2-agonist active sites. Fenchol (a natural compound commonly present in basil) was recognized as a potential FFAR2 stimulator in neuronal cells and demonstrated protective effects against Aβ-stimulated neurodegeneration in an FFAR2-dependent manner. In addition, Fenchol reduced AD-like phenotypes, such as Aβ-accumulation, and impaired chemotaxis behavior in Caenorhabditis (C.) elegans and mice models, by increasing Aβ-clearance via the promotion of proteolysis and reduced senescence in neuronal cells. These results suggest that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while the activation of FFAR2 by Fenchol ameliorates these abnormalities by promoting proteolytic Aβ-clearance and reducing cellular senescence. Thus, stimulation of FFAR2 signaling by Fenchol as a natural compound can be a therapeutic approach to ameliorate AD pathology.
Personal Resources and Organizational Outcomes: Sex as a Moderator of the Complex Relationships Between Self-Esteem, Heart Rate Variability, and Work-Related Exhaustion

Global self-esteem represents a protective personal resource lowering the risk of psychological distress. Research conducted in the work setting has confirmed the psychosocial benefits of high self-esteem. However, research linking self-esteem to neurobiological adaptability appears quite scarce. In this study, we propose a theoretical model in which self-esteem predicts work-related exhaustion indirectly, through the mediation of heart rate variability (HRV) and negative affect at work. Moreover, we explore the relationship between self-esteem and HRV. From one side, one would expect a positive link between self-esteem and HRV, signaling higher autonomic adaptability. However, recent studies have shown that in women, such associations become more complex, with even reversed patterns as compared with that in men. Thus, we included sex as a moderator of the relationship between HRV and self-esteem. The model was tested on a sample of 110 individuals working in the relational professions (54% males; Mage = 42.6, SD = 13.73), observed for an entire workday. Results confirmed the protective role of self-esteem against the experience of negative affect and (indirectly) work-related exhaustion. Symptoms of exhaustion at work were also negatively predicted by HRV, and both HRV and negative affect acted as mediators of the relationship between self-esteem and work-related exhaustion. Notably, sex differences emerged in the association between global self-esteem and cardiac vagal tone at work: in women, self-esteem was negatively related to HRV, which in turn led to higher work-related exhaustion, whereas in men, no evidence of this indirect effect appeared. Burnout prevention programs should not ignore important sex differences in how individuals respond to work-related stress.
Experience resetting in reinforcement learning facilitates exploration–exploitation transitions during a behavioral task for primates

The exploration–exploitation trade-off is a fundamental problem in re-inforcement learning. To study the neural mechanisms involved in this problem, a target search task in which exploration and exploitation phases appear alternately is useful. Monkeys well trained in this task clearly understand that they have entered the exploratory phase and quickly acquire new experiences by resetting their previous experiences. In this study, we used a simple model to show that experience resetting in the exploratory phase improves performance rather than decreasing the greediness of action selection, and we then present a neural network-type model enabling experience resetting.
Tapping to Music Predicts Literacy Skills of First-Grade Children

The ability to synchronise one’s movements to the sound of a regular beat has been found to be associated with children’s language and reading abilities. Sensorimotor synchronisation or tapping performance can among other factors [e.g., working memory and rapid automatized naming (RAN)] predict phonological awareness and word reading accuracy and fluency of first graders. While tapping tasks that use a simple metronome sound are more often used, applying musical stimuli has the potential advantage of being more engaging and motivating for children. In the present study, we investigated whether tapping to a metronome beat or complex musical stimuli would predict phonological awareness and reading outcomes of Hungarian 6-7-year olds (N=37). We also measured participants’ general cognitive abilities (RAN, non-verbal intelligence and verbal working memory). Our results show that phonological awareness, spelling and reading accuracy were associated with the musical tasks while reading fluency was predicted by the metronome trials. Our findings suggest that complex musical tasks should be considered when investigating this age group, as they were, in general, more effective in predicting literacy outcomes.
Smoothelin-Like Protein 1 Regulates Development and Metabolic Transformation of Skeletal Muscle in Hyperthyroidism

Hyperthyroidism triggers a glycolytic shift in skeletal muscle (SKM) by altering the expression of metabolic proteins, which is often accompanied by peripheral insulin resistance. Our previous results show that smoothelin-like protein 1 (SMTNL1), a transcriptional co-regulator, promotes insulin sensitivity in SKM. Our aim was to elucidate the role of SMTNL1 in SKM under physiological and pathological 3,3′,5-Triiodo-L-thyronine (T3) concentrations. Human hyper- and euthyroid SKM biopsies were used for microarray analysis and proteome profiler arrays. Expression of genes related to energy production, nucleic acid- and lipid metabolism was changed significantly in hyperthyroid samples. The phosphorylation levels and activity of AMPKα2 and JNK were increased by 15% and 23%, respectively, in the hyperthyroid samples compared to control. Moreover, SMTNL1 expression showed a 6-fold decrease in the hyperthyroid samples and in T3-treated C2C12 cells. Physiological and supraphysiological concentrations of T3 were applied on differentiated C2C12 cells upon SMTNL1 overexpression to assess the activity and expression level of the elements of thyroid hormone signaling, insulin signaling and glucose metabolism. Our results demonstrate that SMTNL1 selectively regulated TRα expression. Overexpression of SMTNL1 induced insulin sensitivity through the inhibition of JNK activity by 40% and hampered the non-genomic effects of T3 by decreasing the activity of ERK1/2 through PKCδ. SMTNL1 overexpression reduced IRS1 Ser307 and Ser612 phosphorylation by 52% and 53%, respectively, in hyperthyroid model to restore the normal responsiveness of glucose transport to insulin. SMTNL1 regulated glucose phosphorylation and balances glycolysis and glycogen synthesis via the downregulation of hexokinase II by 1.3-fold. Additionally, mitochondrial respiration and glycolysis were measured by SeaHorse analysis to determine cellular metabolic function/phenotype of our model system in real-time. T3 overload strongly increased the rate of acidification and a shift to glycolysis, while SMTNL1 overexpression antagonizes the T3 effects. These lines of evidence suggest that SMTNL1 potentially prevents hyperthyroidism-induced changes in SKM, and it holds great promise as a novel therapeutic target in insulin resistance.
Why can we detect lianas from space?

Lianas, woody vines acting as structural parasites of trees, have profound effects on the composition and structure of tropical forests, impacting tree growth, mortality, and forest succession. Remote sensing offers a powerful tool for quantifying the scale of liana infestation, provided the availability of robust detection methods. We analyze the consistency and global specificity of spectral signals from liana-infested tree crowns and forest stands, examining the underlying mechanisms. We compiled a database, including leaf reflectance spectra from 5424 leaves, fine-scale airborne reflectance data from 999 liana-infested canopies, and coarse-scale satellite reflectance data covering hectares of liana-infested forest stands. To unravel the mechanisms of the liana spectral signal, we applied mechanistic radiative transfer models across scales, corroborated by field data on liana leaf chemistry and canopy structure. We find a consistent liana spectral signature at canopy and stand scales across sites. This signature mainly arises at the canopy level due to direct effects of leaf angles, resulting in a larger apparent leaf area, and indirect effects from increased light scattering in the NIR and SWIR regions, linked to lianas’ less costly leaf construction compared to trees. The existence of a consistent global spectral signal for lianas suggests that large-scale quantification of liana infestation is feasible. However, because the traits identified are not exclusive to lianas, accurate large-scale detection requires rigorously validated remote sensing methods. Our models highlight challenges in automated detection, such as potential misidentification due to leaf phenology, tree life-history, topography, and climate, especially where the scale of liana infestation is less than a single remote sensing pixel. The observed cross-site patterns also prompt ecological questions about lianas’ adaptive similarities across environments, indicating possible convergent evolution due to shared constraints on leaf biochemical and structural traits. Open data statement Of the 17 datasets used, 10 are published and publicly accessible, with links provided in this submission (Appendix S1: Section S1). Upon acceptance, remaining seven datasets will be provided via Smithsonian’s Dspace. The open-source model code is available as R-package ccrtm (https://cran.r-project.org/web/packages/ccrtm/index.html) and on github (https://github.com/MarcoDVisser/ccrtm). Code will be archived in Zenodo should the manuscript be accepted for publication
A Nomogram for Predicting Pathological Complete Response to Neoadjuvant Chemoradiotherapy Using Semiquantitative Parameters Derived From Sequential PET/CT in Locally Advanced Rectal Cancer

We evaluated the predictive value of semiquantitative volumetric parameters derived from sequential PET/CT and developed a nomogram to predict pathological complete response (pCR) in patients with rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). From April 2008 to December 2013, among the patients who underwent nCRT, those who were taken sequential PET/CT before and after nCRT were included. MRI-based staging and semiquantitative parameters of PET/CT including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated before and after nCRT. Multivariable analysis was performed to select significant predictors to construct a nomogram. Sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve (AUC) of the model were evaluated to determine its performance. Among 137 eligible patients, 17 (12.4%) had pCR. All post-PET/CT parameters showed significant differences between pCR and non-pCR groups. Patients were randomly assigned to a training group (91 patients) and a validation group (46 patients). In multivariable analysis with the training group, post-CEA, post-MRI T staging, post-SUVmax, and post-MTV were significantly associated with pCR. There was no significant pre-nCRT variable for predicting pCR. Using significant predictors, a nomogram was developed. Sensitivity, specificity, accuracy, and AUC of the nomogram were 0.882, 0.808, 0.848, and 0.884 with the training group and 0.857, 0.781, 0.783, and 0.828 with the validation group, respectively. This model showed the better performance than other predictive models that did not contain PET/CT parameters. A nomogram containing semiquantitative post-PET/CT could effectively select candidates for organ-sparing strategies.
Efficient fluorescence‐based localization technique for real‐time tracking endophytes route in host‐plants colonization

Bacterial isolates that enhance plant growth and suppress plant pathogens growth are essential tools for reducing pesticide applications in plant production systems. The objectives of this study were to develop a reliable fluorescence-based technique for labeling bacterial isolates selected as biological control agents (BCAs) to allow their direct tracking in the host-plant interactions, understand the BCA localization within their host plants, and the route of plant colonization. Objectives were achieved by developing competent BCAs transformed with two plasmids, pBSU101 and pANIC-10A, containing reporter genes eGFP and pporRFP, respectively. Our results revealed that the plasmid-mediated transformation efficiencies of antibiotic-resistant competent BCAs identified as PSL, IMC8, and PS were up 84%. Fluorescent BCA-tagged reporter genes were associated with roots and hypocotyls but not with leaves or stems and were confirmed by fluoresence microscopy and PCR analyses in colonized Arabidopsis and sorghum. This fluorescence-based technique’s high resolution and reproducibility make it a platform-independent system that allows tracking of BCAs spatially within plant tissues, enabling assessment of the movement and niches of BCAs within colonized plants. Steps for producing and transforming competent fluorescent BCAs, as well as the inoculation of plants with transformed BCAs, localization, and confirmation of fluorescent BCAs through fluorescence imaging and PCR, are provided in this manuscript. This study features host-plant interactions and subsequently biological and physiological mechanisms implicated in these interactions. The maximum time to complete all the steps of this protocol is approximately three months. SENTENCE SUMMARY We describe a novel fluorescence localization technique as a powerful tool to directly visualize and determine the route in-situ of BCAs in host-plants interaction. The study features the host-plant interactions, biological and physiological responses implicated.
Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma

Background: Metallothioneins (MTs) play crucial roles in the modulation of zinc/copper homeostasis, regulation of neoplastic growth and proliferation, and protection against apoptosis. The present study attempted to visualize the prognostic landscape of MT functional isoforms and identify potential prognostic biomarkers in hepatocellular carcinoma (HCC). Methods: The transcriptional expression, comprehensive prognostic performances, and gene–gene interaction network of MT isoforms in HCC were evaluated via Oncomine, GEPIA, Kaplan–Meier plotter, and GeneMANIA databases. Characterized by good prognostic value in three external cohorts, MT1H was specifically selected as a potential prognostic biomarker in HCC with various clinicopathological features. Functional and pathway enrichment analyses of MT1H status were performed using cBioPortal, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and ssGSVA method. Results: MT1E/1F/1G/1H/1M/1X/2A was greatly downregulated in HCC. Prognostic analyses elucidated the essential correlations between MT1A/1B/1H/1X/2A/4 attenuation and poor overall survival, between MT1B/1H/4 downregulation and worse relapse-free survival, and between MT1A/1B/1E/1H/1M/2A/4 downregulation and diminished progression-free survival in HCC. Taken together, these results indicated the powerful prognostic value of MT1H among MTs in HCC. In-depth analyses suggested that MT1H may be more applicable to alcohol-derived HCC and involved in the downregulation of the inflammatory pathway, Jak–STAT pathway, TNF pathway, and Wnt signaling pathway. Conclusion: MT-specific isoforms displayed aberrant expression and varying prognostic value in HCC. MT1H repression in HCC was multi-dimensionally detrimental to patient outcomes. Therefore, MT1H was possibly associated with carcinogenesis and exploited as a novel prognostic biomarker and candidate therapeutic target for HCC.
Bariatric Surgery Induces a Differential Effect on Plasma Aldosterone in Comparison to Dietary Advice Alone

Background and Objectives The pathophysiological mechanisms linking weight loss to blood pressure (BP) reduction are not completely understood. The objective of this study was to compare the effect of weight loss after Roux-en-Y gastric bypass (RYGB) on BP, renin-angiotensin-aldosterone system (RAAS), and urinary electrolytes excretion to those of dietary advice. Methods This was a case-control prospective study including obese patients referred for RYGB (cases) and obese receiving diet advice only (controls). Ambulatory BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary electrolytes were measured before (M0) and after intervention (M3: 3 months and M12: 12 months). Results Twenty-five patients were included in the RYGB group and twelve patients in the control group. After 12 months, weight loss (-42 ± 11.5 vs -12.3 ± 6.3 kg in the control group, p=0.001) and decrease in PAC were more pronounced in the RYGB group (-34 ± 76 vs +14 ± 45 pg/ml in the control group, p=0.002). There was no difference in PRA between both groups (-0.08 ± 1.68 vs 0.01 ± 0.37 ng/ml/h, p=0.31). Sodium excretion was more marked in the RYGB group after 3 months only (-89 ± 14.9 vs -9.9 ± 27.9 mmol/day, p=0.009). The decrease in SBP was similar between both groups (-6.9 ± 9.9 vs -7.1 ± 11.9 mmHg in the control group, p=0.96). Conclusions Bariatric-induced weight loss induces a progressive decrease in PAC independently of PRA and sodium excretion. Whether this decrease in PAC affects target organ damage in the long term remains to be determined. Clinical Trial Registration ClinicalTrials.gov, identifier NCT02218112.
Prognostic Signatures of Alternative Splicing Events in Esophageal Carcinoma Based on TCGA Splice-Seq Data

An alternative splicing (AS) event is a highly complex process that plays an essential role in post-transcriptional gene expression. Several studies have suggested that abnormal AS events were the primary element in the pathological process of cancer. However, few works are dedicated to the study of AS events in esophageal carcinoma (EC). In the present study, clinical information and RNA-seq data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The percent spliced in (PSI) values of AS events were acquired from the TCGA Splice-seq. A total of 183 EC patients were enrolled in this study, and 2,212 AS events were found significantly associated with the overall survival of these patients by univariate Cox regression analysis. The prognostic signatures based on AS events were built by multivariate Cox analysis. Receiver operating characteristic (ROC) curves displayed that the area under the curve (AUC) of the following prognostic signatures, including exon skip (ES), alternate terminator (AT), alternate acceptor site (AA), alternate promoter (AP), alternate donor site (AD), retained intron (RI), and total events, was greater than 0.8, suggesting that these seven signatures had valuable prognosis prediction capacity. Finally, the risk score of prognostic signatures was indicated as an independent risk factor of survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function of splicing factors (SFs) that were associated with AS events. Also, the interactive network between AS events and SFs identified several hub genes and AS events which need further study. This was a comprehensive study that explored prognosis-related AS events and established valuable prognosis signatures in EC patients. The network of interactions between AS events and SFs might offer novel insights into the fundamental mechanisms of tumorigenesis and progression of EC.
Balance of osmotic pressures determines the volume of the cell nucleus

The volume of the cell nucleus varies across cell-types and species, and is commonly thought to be determined by the size of the genome and degree of chromatin compaction. However, this notion has been challenged over the years by multiple experimental evidence. Here, we consider the physical condition of mechanical force balance as a determining condition of the nuclear volume and use quantitative, order-of-magnitude analysis to estimate the forces from different sources of nuclear and cellular pressure. Our estimates suggest that the dominant pressure within the nucleus and cytoplasm originates from the osmotic pressure of proteins and RNA molecules that are localized to the nucleus or cytoplasm by out-of-equilibrium, active nucleocytoplasmic transport rather than from chromatin or its associated ions. This motivates us to formulate a physical model for the ratio of the cell and nuclear volumes in which osmotic pressures of localized proteins determine the relative volumes. In accordance with unexplained observations that are century-old, our model predicts that the ratio of the cell and nuclear volumes is a constant, robust to a wide variety of biochemical and biophysical manipulations, and is changed only if gene expression or nucleocytoplasmic transport are modulated.
Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review

Apatinib is a multitarget tyrosine kinase inhibitor marketed in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It has also been used off-label for the treatment of many other malignancies. To comprehensively evaluate the efficacy of apatinib as a targeted therapy in the treatment of malignancies, we conducted systematic online and manual searches of the literature on apatinib in the treatment of malignancies. In this review, we first summarized the efficacy of apatinib against various malignancies based on clinical trials where results have been reported. In prospectively registered trials, apatinib has been proven to be effective against GC, HCC, lung cancer, breast cancer, sarcoma, esophageal cancer, colorectal cancer, ovarian cancer, cervical cancer, cholangiocarcinoma, diffuse large B-cell lymphoma, nasopharyngeal carcinoma, and differentiated thyroid cancer. The response biomarkers for apatinib were also reviewed. This review will serve as a good reference for the application of apatinib in clinical studies and the design of clinical trials.