Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a Cationic Amphiphilic Helical Peptidomimetic (B18L) As A Novel Anti-Cancer Drug Lead

Simple Summary We have previously shown that overexpression of BST-2 in breast cancer cells promotes cancer cell adhesion and aggressiveness. Although the level of BST-2 in breast tumors is higher than those of established cancer markers, there is no therapy targeting BST-2 in cancer cells. Thus, we developed the first-generation BST-2-based peptide series―B49/B49Mod1 that impairs adhesion-dependent biological events in breast cancer cells and inhibits tumor growth. Using sequence/structure modification and bioactivity guided separation, we identified B18 as the minimal sequence required for the anti-adhesion activity of B49Mod1. The current study demonstrates that a derivative of B18, a cationic amphiphilic α-helical peptidomimetic B18L, kills drug-resistant and drug-sensitive breast cancer cells. B18L impairs cancer cell membrane and dysregulates mitochondrial and signaling events necessary for the survival of cancer cells. This study provides the first evidence that a BST-2-based peptide (B18L) is a promising therapeutic agent for treatment of breast cancers, thus supporting further development. Abstract BST-2 is a novel driver of cancer progression whose expression confers oncogenic properties to breast cancer cells. As such, targeting BST-2 in tumors may be an effective therapeutic approach against breast cancer. Here, we sought to develop potent cytotoxic anti-cancer agent using the second-generation BST-2-based anti-adhesion peptide, B18, as backbone. To this end, we designed a series of five B18-derived peptidomimetics. Among these, B18L, a cationic amphiphilic α-helical peptidomimetic, was selected as the drug lead because it displayed superior anti-cancer activity against both drug-resistant and drug-sensitive cancer cells, with minimal toxicity on normal cells. Probing mechanism of action using molecular dynamics simulations, biochemical and membrane biophysics studies, we observed that B18L binds BST-2 and possesses membranolytic characteristics. Furthermore, molecular biology studies show that B18L dysregulates cancer signaling pathways resulting in decreased Src and Erk1/2 phosphorylation, increased expression of pro-apoptotic Bcl2 proteins, caspase 3 cleavage products, as well as processing of the caspase substrate, poly (ADP-ribose) polymerase-1 (PARP-1), to the characteristic apoptotic fragment. These data indicate that through the coordinated regulation of membrane, mitochondrial and signaling events, B18L executes cancer cell death and thus has the potential to be developed into a potent and selective anti-cancer compound.
Structure and Sequence of the Sex Determining Locus in Two Wild Populations of Nile Tilapia

In domesticated strains of the Nile tilapia, phenotypic sex has been linked to genetic variants on linkage groups 1, 20 and 23. This diversity of sex-loci might reflect a naturally polymorphic sex determination system in Nile tilapia, or it might be an artefact arising from the process of domestication. Here, we searched for sex-determiners in wild populations from Kpandu, Lake Volta (Ghana-West Africa), and from Lake Koka (Ethiopia-East Africa) that have not been subjected to any genetic manipulation. We analysed lab-reared families using double-digest Restriction Associated DNA sequencing (ddRAD) and analysed wild-caught males and females with pooled whole-genome sequencing (WGS). Strong sex-linked signals were found on LG23 in both populations, and sex-linked signals with LG3 were observed in Kpandu samples. WGS uncovered blocks of high sequence coverage, suggesting the presence of B chromosomes. We confirmed the existence of a tandem amh duplication in LG23 in both populations and determined its breakpoints between the oaz1 and dot1l genes. We found two common deletions of ~5 kb in males and confirmed the presence of both amhY and amh∆Y genes. Males from Lake Koka lack both the previously reported 234 bp deletion and the 5 bp frameshift-insertion that creates a premature stop codon in amh∆Y.
The Fault Tolerant Control Design of an Intensified Heat-Exchanger/Reactor Using a Two-Layer, Multiple-Model Structure †

The heat-exchanger/reactor (HEX reactor) is a kind of plug-flow chemical reactor which combines high heat transfer ability with good chemical performances. It was designed under the popular trend of process intensification in chemical engineering. Previous studies have investigated its characteristics and developed its nominal model. This paper is concerned with its fault tolerant control (FTC) applications. To avoid the difficulties and nonlinearities of this HEX reactor under chemical reactions, a two-layer, multiple-model structure is proposed for designing the FTC scheme. The first layer focuses on representing the nonlinear system with a bank of local linear models while the second layer uses model banks for approaching faulty situations. Model banks are achieved by system identification, and the corresponding controller banks are designed using model predictive control (MPC). The unscented Kalman filter (UKF) is introduced to estimate the states and form the fault detection and isolation (FDI) section. Finally, the FTC simulation and validation results are presented. The idea of a two-layer, multiple-model structure presents a general framework for FTC design of complex and highly nonlinear systems, such as the HEX reactor, whose mathematical model has been created. It implements the design process in an unusual way and is also worth trying on other cases.
Beneficial effect on serum cholesterol levels, but not glycaemic regulation, after replacing SFA with PUFA for 3 d: a randomised crossover trial

Abstract Replacing intake of SFA with PUFA reduces serum cholesterol levels and CVD risk. The effect on glycaemic regulation is, however, less clear. The main objective of the present study was to investigate the short-term effect of replacing dietary SFA with PUFA on glycaemic regulation. Seventeen healthy, normal-weight participants completed a 25-d double-blind, randomised and controlled two-period crossover study. Participants were allocated to either interventions with PUFA products or SFA products (control) in a random order for three consecutive days, separated by a 1·5-week washout period between the intervention periods. Glucose, insulin and TAG were measured before and after an oral glucose tolerance test. In addition, fasting total cholesterol, NEFA and plasma total fatty acid profile were measured before and after the 3-d interventions. Fasting and postprandial glucose, insulin, and TAG levels and fasting levels of NEFA and plasma fatty acid profile did not differ between the groups. However, replacing dietary SFA with PUFA significantly reduced total cholesterol levels by 8 % after 3 d (P = 0·002). Replacing dietary SFA with PUFA for only 3 d has beneficial cardio-metabolic effects by reducing cholesterol levels in healthy individuals.
Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment

Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. APOE, Amyloid Beta Precursor Protein (APP), and Presenilin-1 (PSEN1) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with limma package on ADNI Cohort data highlighted eight differential expressed (DE) genes (AGER, LINC00483, MMP19, CATSPER1, ARFGAP1, GPER1, PHLPP2, TRPM2) (false discovery rate (FDR) p-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and edgeR (FDR p-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA–gene interactions that may be involved in cognitive and neurodegeneration processes.
Genome Wide Analysis Reveals the Role of VadA in Stress Response, Germination, and Sterigmatocystin Production in Aspergillus nidulans Conidia

In the Aspergillus species, conidia are asexual spores that are infectious particles responsible for propagation. Conidia contain various mycotoxins that can have detrimental effects in humans. Previous study demonstrated that VadA is required for fungal development and spore viability in the model fungus Aspergillus nidulans. In the present study, vadA transcriptomic analysis revealed that VadA affects the mRNA expression of a variety of genes in A. nidulans conidia. The genes that were primarily affected in conidia were associated with trehalose biosynthesis, cell-wall integrity, stress response, and secondary metabolism. Genetic changes caused by deletion of vadA were related to phenotypes of the vadA deletion mutant conidia. The deletion of vadA resulted in increased conidial sensitivity against ultraviolet stress and induced germ tube formation in the presence and absence of glucose. In addition, most genes in the secondary metabolism gene clusters of sterigmatocystin, asperfuranone, monodictyphenone, and asperthecin were upregulated in the mutant conidia with vadA deletion. The deletion of vadA led to an increase in the amount of sterigmatocystin in the conidia, suggesting that VadA is essential for the repression of sterigmatocystin production in conidia. These results suggest that VadA coordinates conidia maturation, stress response, and secondary metabolism in A. nidulans conidia.
Control Methods for Transradial Prostheses Based on Remnant Muscle Activity and Its Relationship with Proprioceptive Feedback

The loss of a hand can significantly affect one’s work and social life. For many patients, an artificial limb can improve their mobility and ability to manage everyday activities, as well as provide the means to remain independent. This paper provides an extensive review of available biosensing methods to implement the control system for transradial prostheses based on the measured activity in remnant muscles. Covered techniques include electromyography, magnetomyography, electrical impedance tomography, capacitance sensing, near-infrared spectroscopy, sonomyography, optical myography, force myography, phonomyography, myokinetic control, and modern approaches to cineplasty. The paper also covers combinations of these approaches, which, in many cases, achieve better accuracy while mitigating the weaknesses of individual methods. The work is focused on the practical applicability of the approaches, and analyses present challenges associated with each technique along with their relationship with proprioceptive feedback, which is an important factor for intuitive control over the prosthetic device, especially for high dexterity prosthetic hands.
Multi-Camera-Based Product Recognition for Inventory Management

Recently developed deep learning research has made remarkable advances in object detection. However, the difficulty of object recognition in complex occlusion environments remains to be overcome. For instance, recognizing densely displayed products on checkout-free store shelves is challenging for state-of-the-art deep-learning object detectors. We propose a deep learning-based inventory management system using a changed inventory tracking method for a multi-camera checkout-free store. The proposed method utilizes the image difference before and after the event as a region of interest (ROI) to detect occluded objects. The proposed method archive a 25.93% and 19.61% higher detection rate compared to the single camera detection rate and the non-ROI detection rate, respectively.
Wearable Physiological Monitoring System Based on Electrocardiography and Electromyography for Upper Limb Rehabilitation Training

Secondary injuries are common during upper limb rehabilitation training because of uncontrollable physical force and overexciting activities, and long-time training may cause fatigue and reduce the training effect. This study proposes a wearable monitoring device for upper limb rehabilitation by integrating electrocardiogram and electromyogram (ECG/EMG) sensors and using data acquisition boards to obtain accurate signals during robotic glove assisting training. The collected ECG/EMG signals were filtered, amplified, digitized, and then transmitted to a remote receiver (smart phone or laptop) via a low-energy Bluetooth module. A software platform was developed for data analysis to visualize ECG/EMG information, and integrated into the robotic glove control module. In the training progress, various hand activities (i.e., hand closing, forearm pronation, finger flexion, and wrist extension) were monitored by the EMG sensor, and the changes in the physiological status of people (from excited to fatigue) were monitored by the ECG sensor. The functionality and feasibility of the developed physiological monitoring system was demonstrated by the assisting robotic glove with an adaptive strategy for upper limb rehabilitation training improvement. The feasible results provided a novel technique to monitor individual ECG and EMG information holistically and practically, and a technical reference to improve upper limb rehabilitation according to specific treatment conditions and the users’ demands. On the basis of this wearable monitoring system prototype for upper limb rehabilitation, many ECG-/EMG-based mobile healthcare applications could be built avoiding some complicated implementation issues such as sensors management and feature extraction.
Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control

ABSTRACT Objective: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. Subjects and methods: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. Results: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. Conclusion: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.
Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatic Cytochrome P450 (CYP) Enzymes

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat in the liver. An international consensus panel has recently proposed to rename the disease to metabolic dysfunction associated with fatty liver disease (MAFLD). The disease can range from simple steatosis (fat accumulation) to nonalcoholic steatohepatitis (NASH) which represents a severe form of NAFLD and is accompanied by inflammation, fibrosis, and hepatocyte damage in addition to significant steatosis. This review collates current knowledge of changes in human hepatic cytochrome P450 enzymes in NAFLD. While the expression of these enzymes is well studied in healthy volunteers, our understanding of the alterations of these proteins in NAFLD is limited. Much of the existing knowledge on the subject is derived from preclinical studies, and clinical translation of these findings is poor. Wherever available, the effect of NAFLD on these proteins in humans is debatable and currently lacks a consensus among different reports. Protein expression is an important in vitro physiological parameter controlling the pharmacokinetics of drugs and the last decade has seen a rise in the accurate estimation of these proteins for use with physiologically based pharmacokinetic (PBPK) modeling to predict drug pharmacokinetics in special populations. The application of label-free, mass spectrometry-based quantitative proteomics as a promising tool to study NAFLD-associated changes has also been discussed.
Stochastic Recursive Gradient Support Pursuit and Its Sparse Representation Applications

In recent years, a series of matching pursuit and hard thresholding algorithms have been proposed to solve the sparse representation problem with ℓ0-norm constraint. In addition, some stochastic hard thresholding methods were also proposed, such as stochastic gradient hard thresholding (SG-HT) and stochastic variance reduced gradient hard thresholding (SVRGHT). However, each iteration of all the algorithms requires one hard thresholding operation, which leads to a high per-iteration complexity and slow convergence, especially for high-dimensional problems. To address this issue, we propose a new stochastic recursive gradient support pursuit (SRGSP) algorithm, in which only one hard thresholding operation is required in each outer-iteration. Thus, SRGSP has a significantly lower computational complexity than existing methods such as SG-HT and SVRGHT. Moreover, we also provide the convergence analysis of SRGSP, which shows that SRGSP attains a linear convergence rate. Our experimental results on large-scale synthetic and real-world datasets verify that SRGSP outperforms state-of-the-art related methods for tackling various sparse representation problems. Moreover, we conduct many experiments on two real-world sparse representation applications such as image denoising and face recognition, and all the results also validate that our SRGSP algorithm obtains much better performance than other sparse representation learning optimization methods in terms of PSNR and recognition rates.
Novel Protein Sequence Comparison Method Based on Transition Probability Graph and Information Entropy.

AIM AND OBJECTIVE Sequence analysis is one of the foundations in bioinformatics. It is widely used to find out the feature metric hidden in the sequence. Otherwise, the graphical representation of biologic sequence is an important tool for sequencing analysis. This study is undertaken to find out a new graphical representation of biosequences. MATERIALS AND METHODS The transition probability is used to describe amino acid combinations of protein sequences. The combinations are composed of amino acids directly adjacent to each other or separated by multiple amino acids. The transition probability graph is built up by the transition probabilities of amino acid combinations. Next, a map is defined as a representation from transition probability graph to transition probability vector by k-order transition probability graph. Transition entropy vectors are developed by the transition probability vector and information entropy. Finally, the proposed method is applied to two separate applications, 499 HA genes of H1N1, and 95 coronaviruses. RESULTS By constructing a phylogenetic tree, we find that the results of each application are consistent with other studies. CONCLUSION the graphical representation proposed in this article is a practical and correct method.
Identifying bifurcated paths with differential function impact in glioblastomas evolution

The evolutionary dynamics of human cancers has been investigated popularly and several bifurcated paths in cancer evolutionary trajectories are revealed to be with differential outcomes and phenotypes. However, whether such bifurcated paths exist in glioblastoma (GBM) remains unclear. In 385 GBM samples, through determining the clonal status of cancer driver events and inferring their temporal order, we constructed a temporal map of evolutionary trajectories at the patient population level. By investigating the differential impact on clinical outcome, we identified four key bifurcated paths, namely, “chromosome 10 copy number loss (ie, 10 loss) → chromosome 19 copy number gain (ie, 19 gain): 10 loss → 13q loss”; “10 loss → 19 gain: 10 loss → 15q loss”; “10 loss → 19 gain: 10 loss → 6q loss” and “10 loss → 19 gain: 10 loss → 16q loss”. They formed a core multibranches path, with 10 loss being regarded as the common earliest event followed by 19 gain and four other departure events (13q loss, 15q loss, 6q loss and 16q loss), which may account for their difference in genome instability and patient survival time. Compared to “10 loss → 19 gain”, the patients with “10 loss → 13q loss” had higher telomerase activity. Notably, there were obvious discrepancies in immune activity and immune cell infiltration level between patients with “10 loss → 13q/16q loss” and “10 loss → 19 gain”, highlighting the bifurcated paths' effect on tumor immune microenvironment. In summary, our study identifies four key bifurcated paths in GBM for the first time, suggesting the feasibility of patient stratification and prognosis prediction based on key bifurcated paths.
Association of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 polymorphisms with systemic lupus erythematosus disease activity and biomarker levels

Supplemental Digital Content is available in the text Abstract Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with considerable genetic predisposition. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) is crucial for the innate immunity and implicated in SLE pathogenesis. Accordingly, we conducted a case-control study to find the association of NLRP3 variations with SLE susceptibility and disease activity. Three single nucleotide polymorphisms of NLRP3 (rs3806268, rs4612666, and rs10754558) were genotyped in 400 SLE patients and 400 healthy controls; the patients were further divided into mild-to-moderate or high disease activity subgroup. Serum cytokines, complements, and autoantibodies were also detected. We found that rs4612666 TT genotype conferred a higher risk of severe disease activity with adjusted odds ratio = 2.08, P = . 02 and adjusted odds ratio = 2.34, P = . 01 in the codominant and recessive model, respectively. Nevertheless, there was no association between the 3 single nucleotide polymorphisms of NLRP3 gene and SLE susceptibility. In addition, C4 decreased significantly in rs3806268 GG (P < .001) and rs4612666 TT genotype carriers (P = .03). A higher trend of interleukin-1β and interleukin-γ release were identified in rs3806268 AA and rs10754558 CC genotype carriers, respectively. NLRP3 polymorphisms are associated with SLE disease activity and hypocomplementemia. Interleukin-1β and interleukin-γ levels in SLE patients are correlated with NLRP3 variants as well.