Miracle-dz/UniFAR-FTUs huggingface dataset:
Size dependence of the surface plasmon enhanced second harmonic response of gold colloids: towards a new calibration method

Hyper Rayleigh scattering in solution is used for the determination of the first order hyperpolarizability β colloid of gold colloids in the size range 5–22 nm; these hyperpolarizabilities are found to range from 0.60 × 10–25 esu for 5 nm diameter colloids to up to 16.6 × 10–25 esu for 22 nm diameter colloids at the second harmonic wavelength of 532 nm; the strong size dependence of the hyperpolarisabilities reported here suggests that hyper Rayleigh scattering experiments can efficiently be used to calibrate the particle diameter of colloidal suspensions.
Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3

Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival.
Antiplatelet Therapy in the Secondary Prevention of Non-cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Mini-Review

The aim of this mini-review is to discuss the main antiplatelet agents that have been successfully used in the secondary prevention of non-cardioembolic ischemic stroke and transient ischemic attacks (TIA). The methodology is based on a literature review of available peer-reviewed English studies listed in PubMed. The findings reveal that aspirin remains a reliable antiplatelet agent in the secondary prevention of acute non-cardioembolic ischemic stroke and TIA. Nevertheless, currently, there are also other agents, i.e., ticagrelor, clopidogrel, and cilostazol, that can be applied. In addition, the results indicate that time is significant not only in severe stroke but also in non-severe stroke and TIA, which suggests that antiplatelet therapy should be applied within 24 h after the first symptoms because early treatment can lead to an improvement in neurological outcomes and reduce the chance of an early subsequent stroke.
The Impact of Epstein-Barr Virus Infection on Epigenetic Regulation of Host Cell Gene Expression in Epithelial and Lymphocytic Malignancies

Epstein-Barr virus (EBV) infection is associated with a variety of malignancies including Burkitt’s lymphoma (BL), Hodgkin’s disease, T cell lymphoma, nasopharyngeal carcinoma (NPC), and ∼10% of cases of gastric cancer (EBVaGC). Disruption of epigenetic regulation in the expression of tumor suppressor genes or oncogenes has been considered as one of the important mechanisms for carcinogenesis. Global hypermethylation is a distinct feature in NPC and EBVaGC, whereas global reduction of H3K27me3 is more prevalent in EBVaGC and EBV-transformed lymphoblastoid cells. In BL, EBV may even usurp the host factors to epigenetically regulate its own viral gene expression to restrict latency and lytic switch, resulting in evasion of immunosurveillance. Furthermore, in BL and EBVaGC, the interaction between the EBV episome and the host genome is evident with respectively unique epigenetic features. While the interaction is associated with suppression of gene expression in BL, the corresponding activity in EBVaGC is linked to activation of gene expression. As EBV establishes a unique latency program in these cancer types, it is possible that EBV utilizes different latency proteins to hijack the epigenetic modulators in the host cells for pathogenesis. Since epigenetic regulation of gene expression is reversible, understanding the precise mechanisms about how EBV dysregulates the epigenetic mechanisms enables us to identify the potential targets for epigenetic therapies. This review summarizes the currently available epigenetic profiles of several well-studied EBV-associated cancers and the relevant distinct mechanisms leading to aberrant epigenetic signatures due to EBV.
Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

Objective To probe markers and molecular mechanisms of the hypoplastic left heart (HLH) by single-cell RNA sequencing (scRNA-seq) and quantitative proteomics analysis. Methods Following data preprocessing, scRNA-seq data of pluripotent stem cell (iPSC)-derived cardiomyocytes from one HLH patient and one control were analyzed by the Seurat package in R. Cell clusters were characterized, which was followed by a pseudotime analysis. Markers in the pseudotime analysis were utilized for functional enrichment analysis. Quantitative proteomics analysis was based on peripheral blood samples from HLH patients without heart failure (HLH-NHF), HLH patients with heart failure (HLH-HF), and healthy controls. Hub genes were identified by the intersection of pseudotime markers and differentially expressed proteins (DE-proteins), which were validated in the GSE77798 dataset, RT-qPCR, and western blot. Results Cardiomyocytes derived from iPSCs were clustered into mesenchymal stem cells, myocardium, and fibroblast cells. Pseudotime analysis revealed their differentiation trajectory. Markers in the three pseudotime clusters were significantly associated with distinct biological processes and pathways. Finally, three hub genes (MMP2, B2M, and COL5A1) were identified, which were highly expressed in the left (LV) and right (RV) ventricles of HLH patients compared with controls. Furthermore, higher expression levels were detected in HLH patients with or without HF than in controls. Conclusion Our findings elucidate marker genes and molecular mechanisms of HLH, deepening the understanding of the pathogenesis of HLH.
Neurotransmitters, Cell Types, and Circuit Mechanisms of Motor Skill Learning and Clinical Applications

Animals acquire motor skills to better survive and adapt to a changing environment. The ability to learn novel motor actions without disturbing learned ones is essential to maintaining a broad motor repertoire. During motor learning, the brain makes a series of adjustments to build novel sensory–motor relationships that are stored within specific circuits for long-term retention. The neural mechanism of learning novel motor actions and transforming them into long-term memory still remains unclear. Here we review the latest findings with regard to the contributions of various brain subregions, cell types, and neurotransmitters to motor learning. Aiming to seek therapeutic strategies to restore the motor memory in relative neurodegenerative disorders, we also briefly describe the common experimental tests and manipulations for motor memory in rodents.
Cerebrovascular Reactivity Measurement Using Magnetic Resonance Imaging: A Systematic Review

Cerebrovascular reactivity (CVR) magnetic resonance imaging (MRI) probes cerebral haemodynamic changes in response to a vasodilatory stimulus. CVR closely relates to the health of the vasculature and is therefore a key parameter for studying cerebrovascular diseases such as stroke, small vessel disease and dementias. MRI allows in vivo measurement of CVR but several different methods have been presented in the literature, differing in pulse sequence, hardware requirements, stimulus and image processing technique. We systematically reviewed publications measuring CVR using MRI up to June 2020, identifying 235 relevant papers. We summarised the acquisition methods, experimental parameters, hardware and CVR quantification approaches used, clinical populations investigated, and corresponding summary CVR measures. CVR was investigated in many pathologies such as steno-occlusive diseases, dementia and small vessel disease and is generally lower in patients than in healthy controls. Blood oxygen level dependent (BOLD) acquisitions with fixed inspired CO2 gas or end-tidal CO2 forcing stimulus are the most commonly used methods. General linear modelling of the MRI signal with end-tidal CO2 as the regressor is the most frequently used method to compute CVR. Our survey of CVR measurement approaches and applications will help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.
Genome-Wide Scans for Ghanaian Plasmodium falciparum Genes Under Selection From Local and Chinese Host Populations

Initial malarial infection mostly causes symptomatic illness in humans. Infection that is not fatal induces complete protection from severe illness and death, and thus complete protection from severe illness or death is granted with sufficient exposure. However, malaria parasite immunity necessitates constant exposure. Therefore, it is important to evaluate lowered immunity and recurrent susceptibility to symptomatic disease in lower transmission areas. We aimed to investigate selection pressure based on transmission levels, antimalarial drug use, and environmental factors. We whole genome sequenced (WGS) P. falciparum clinical samples from Chinese hosts working in Ghana and compared the results with the WGS data of isolates from native Ghanaians downloaded from pf3k. The P. falciparum samples were generally clustered according to their geographic origin, and Chinese imported samples showed a clear African origin with a slightly different distribution from the native Ghanaian samples. Moreover, samples collected from two host populations showed evidence of differences in the intensity of selection. Compared with native Ghanaian samples, the China-imported isolates exhibited a higher proportion of monoclonal infections, and many genes associated with RBC invasion and immune evasion were found to be under less selection pressure. There was no significant difference in the selection of drug-resistance genes due to a similar artemisinin-based combination therapy medication profile. Local selection of malarial parasites is considered to be a result of differences in the host immunity or disparity in the transmission opportunities of the host. In China, most P. falciparum infections were imported from Africa, and under these circumstances, distinct local selective pressures may be caused by varying acquired immunity and transmission intensity. This study revealed the impact of host switching on the immune system, and it may provide a better understanding of the mechanisms that enable clinical immunity to malaria.
Chemotranscriptomic Profiling Defines Drug-Specific Signatures of the Glycopeptide Antibiotics Dalbavancin, Vancomycin and Chlorobiphenyl-Vancomycin in a VanB-Type-Resistant Streptomycete

Dalbavancin, vancomycin and chlorobiphenyl-vancomycin share a high degree of structural similarity and the same primary mode of drug action. All inhibit bacterial cell wall biosynthesis through complexation with intermediates in peptidoglycan biosynthesis mediated via interaction with peptidyl-d-alanyl–d-alanine (d-Ala–d-Ala) residues present at the termini of the intermediates. VanB-type glycopeptide resistance in bacteria encodes an inducible reprogramming of bacterial cell wall biosynthesis that generates precursors terminating with d-alanyl–d-lactate (d-Ala–d-Lac). This system in Streptomyces coelicolor confers protection against the natural product vancomycin but not dalbavancin or chlorobiphenyl-vancomycin, which are semi-synthetic derivatives and fail to sufficiently activate the inducible VanB-type sensory response. We used transcriptome profiling by RNAseq to identify the gene expression signatures elucidated in S. coelicolor in response to the three different glycopeptide compounds. An integrated comparison of the results defines both the contribution of the VanB resistance system to the control of changes in gene transcription and the impact at the transcriptional level of the structural diversity present in the glycopeptide antibiotics used. Dalbavancin induces markedly more extensive changes in the expression of genes required for transport processes, RNA methylation, haem biosynthesis and the biosynthesis of the amino acids arginine and glutamine. Chlorobiphenyl-vancomycin exhibits specific effects on tryptophan and calcium-dependent antibiotic biosynthesis and has a stronger repressive effect on translation. Vancomycin predictably has a uniquely strong effect on the genes controlled by the VanB resistance system and also impacts metal ion homeostasis and leucine biosynthesis. Leaderless gene transcription is disfavoured in the core transcriptional up- and down-regulation taking place in response to all the glycopeptide antibiotics, while HrdB-dependent transcripts are favoured in the down-regulated group. This study illustrates the biological impact of peripheral changes to glycopeptide antibiotic structure and could inform the design of future semi-synthetic glycopeptide derivatives.
Identification of an Immune-Related Signature for Predicting Prognosis in Patients With Pancreatic Ductal Adenocarcinoma

Purpose Pancreatic ductal adenocarcinoma (PDAC) is one of the highest fatality rate cancers with poor survival rates. The tumor microenvironment (TME) is vital for tumor immune responses, leading to resistance to chemotherapy and poor prognosis of PDAC patients. This study aimed to provide a comprehensive evaluation of the immune genes and microenvironment in PDAC that might help in predicting prognosis and guiding clinical treatments. Methods We developed a prognosis-associated immune signature (i.e., PAIS) based on immune-associated genes to predict the overall survival of patients with PDAC. The clinical significance and immune landscapes of the signature were comprehensively analyzed. Results Owing to gene expression profiles from TCGA database, functional enrichment analysis revealed a significant difference in the immune response between PDAC and normal pancreas. Using transcriptome data analysis of a training set, we identified an immune signature represented by 5 genes (ESR2, IDO1, IL20RB, PPP3CA, and PLAU) related to the overall survival of patients with PDAC, significantly. This training set was well-validated in a test set. Our results indicated a clear association between a high-risk score and a very poor prognosis. Stratification analysis and multivariate Cox regression analysis revealed that PAIS was an important prognostic factor. We also found that the risk score was positively correlated with the inflammatory response, antigen-presenting process, and expression level of some immunosuppressive checkpoint molecules (e.g., CD73, PD-L1, CD80, and B7-H3). These results suggested that high-risk patients had a suppressed immune response. However, they could respond better to chemotherapy. In addition, PAIS was positively correlated with the infiltration of M2 macrophages in PDAC. Conclusions This study highlighted the relationship between the immune response and prognosis in PDAC and developed a clinically feasible signature that might serve as a powerful prognostic tool and help further optimize the cancer therapy paradigm.
Grafting Delays Watermel on Fruit Ripening by Altering Gene Expression of ABA Centric Phytohormone Signaling

Grafting cultivation is implemented worldwide mainly to resist abiotic and biotic stresses and is an effective method to improve watermelon production. However, grafting may affect fruit development and quality. In our experiment, pumpkin-grafted (PG) watermelon fruits developed slower and the ripening period was extended compared to self-grafted (SG) fruits. We found that the concentrations of abscisic acid (ABA) among endogenous phytohormones were dramatically reduced by pumpkin grafting. In order to understand these changes at the gene expression level, we performed a comprehensive analysis of the fruit flesh transcriptomes between PG and SG during fruit development and ripening. A total of 1,675 and 4,102 differentially expressed genes (DEGs) were identified between PG and SG. Further functional enrichment analysis revealed that these DEGs were associated with carbohydrate biosynthesis, phytohormone signaling transmission, and cell wall metabolism categories. ABA centric phytohormone signaling and fruit quality-related genes including ABA receptor, PP2C proteins, AP2-EREBP transcription factors, sucrose transporter, and carotenoid isomerase were co-expressed with fruit ripening. These results provide the valuable resource for understanding the mechanism of pumpkin grafting effect on watermelon fruit ripening and quality development.
Comparison of Longitudinal Changes of Cerebral Small Vessel Disease Markers and Cognitive Function Between Subcortical Vascular Mild Cognitive Impairment With and Without NOTCH3 Variant: A 5-Year Follow-Up Study

No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without NOTCH3 variant [NOTCH3(+) svMCI vs. NOTCH3(–) svMCI]. We prospectively recruited patients with svMCI and screened for NOTCH3 variants by sequence analysis for mutational hotspots in the NOTCH3 gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the NOTCH3(+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the NOTCH3(–) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.
Can Mindfulness Help to Alleviate Loneliness? A Systematic Review and Meta-Analysis

Objective: Mindfulness-based intervention (MBI) has been proposed to alleviate loneliness and improve social connectedness. Several randomized controlled trials (RCTs) have been conducted to evaluate the effectiveness of MBI. This study aimed to critically evaluate and determine the effectiveness and safety of MBI in alleviating the feeling of loneliness. Methods: We searched Medline, Embase, PsycInfo, Cochrane CENTRAL, and AMED for publications from inception to May 2020. We included RCTs with human subjects who were enrolled in MBI with loneliness as an outcome. The quality of evidence was assessed using Cochrane's Risk of Bias (ROB) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A random-effects model was used for meta-analysis. Results: Out of 92 articles identified, eight studies involving 815 participants were included in this study. Most (7/8) trials conducted a minimum of 8 weeks of MBI. Most of the trials (5/8) used UCLA-Loneliness Scale. A pooled analysis combining three trials and compared with wait-list showed significant improvement in loneliness score reduction using the UCLA-R scale with MD of −6.33 [95% confidence interval (CI): −9.39, −3.26]. Subgroup analysis with only two Cognitively-Based Compassion Training (CBCT) trials also showed similar MD of −6.05 (95% CI: −9.53, 2.58). The overall quality of evidence (GRADE) was low. Conclusions: Mindfulness intervention with an average length of 8-week duration significantly improved the population's loneliness level with no mental health issue. However, this evidence had a low GRADE level.
A Simplified Amino Acidic Alphabet to Unveil the T-Cells Receptors Antigens: A Computational Perspective

The exposure to pathogens triggers the activation of adaptive immune responses through antigens bound to surface receptors of antigen presenting cells (APCs). T cell receptors (TCR) are responsible for initiating the immune response through their physical direct interaction with antigen-bound receptors on the APCs surface. The study of T cell interactions with antigens is considered of crucial importance for the comprehension of the role of immune responses in cancer growth and for the subsequent design of immunomodulating anticancer drugs. RNA sequencing experiments performed on T cells represented a major breakthrough for this branch of experimental molecular biology. Apart from the gene expression levels, the hypervariable CDR3α/β sequences of the TCR loops can now be easily determined and modelled in the three dimensions, being the portions of TCR mainly responsible for the interaction with APC receptors. The most direct experimental method for the investigation of antigens would be based on peptide libraries, but their huge combinatorial nature, size, cost, and the difficulty of experimental fine tuning makes this approach complicated time consuming, and costly. We have implemented in silico methodology with the aim of moving from CDR3α/β sequences to a library of potentially antigenic peptides that can be used in immunologically oriented experiments to study T cells’ reactivity. To reduce the size of the library, we have verified the reproducibility of experimental benchmarks using the permutation of only six residues that can be considered representative of all ensembles of 20 natural amino acids. Such a simplified alphabet is able to correctly find the poses and chemical nature of original antigens within a small subset of ligands of potential interest. The newly generated library would have the advantage of leading to potentially antigenic ligands that would contribute to a better understanding of the chemical nature of TCR-antigen interactions. This step is crucial in the design of immunomodulators targeted towards T-cells response as well as in understanding the first principles of an immune response in several diseases, from cancer to autoimmune disorders.