Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.
Formulations for Bacteriophage Therapy and the Potential Uses of Immobilization

The emergence of antibiotic-resistant pathogens is becoming increasingly problematic in the treatment of bacterial diseases. This has led to bacteriophages receiving increased attention as an alternative form of treatment. Phages are effective at targeting and killing bacterial strains of interest and have yielded encouraging results when administered as part of a tailored treatment to severely ill patients as a last resort. Despite this, success in clinical trials has not always been as forthcoming, with several high-profile trials failing to demonstrate the efficacy of phage preparations in curing diseases of interest. Whilst this may be in part due to reasons surrounding poor phage selection and a lack of understanding of the underlying disease, there is growing consensus that future success in clinical trials will depend on effective delivery of phage therapeutics to the area of infection. This can be achieved using bacteriophage formulations instead of purely liquid preparations. Several encapsulation-based strategies can be applied to produce phage formulations and encouraging results have been observed with respect to efficacy as well as long term phage stability. Immobilization-based approaches have generally been neglected for the production of phage therapeutics but could also offer a viable alternative.
Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

Recent advances in prostate cancer (PC) research unveiled real androgen receptor (AR) functions in castration-resistant PC (CRPC). Moreover, AR still accelerates PC cell proliferation via the activation of several mechanisms (e.g., mutation, variants, and amplifications in CRPC). New-generation AR signaling-targeted agents, inhibiting extremely the activity of AR, were developed based on these incontrovertible mechanisms of AR-induced CRPC progression. However, long-term administration of AR signaling-targeted agents subsequently induces the major problem that AR (complete)-independent CRPC cells present neither AR nor prostate-specific antigen, including neuroendocrine differentiation as a subtype of AR-independent CRPC. Moreover, there are few treatments effective for AR-independent CRPC with solid evidence. This study focuses on the transformation mechanisms of AR-independent from AR-dependent CRPC cells and potential treatment strategy for AR-independent CRPC and discusses them based on a review of basic and clinical literature.
3D Bioprinted Scaffolds Containing Mesenchymal Stem/Stromal Lyosecretome: Next Generation Controlled Release Device for Bone Regenerative Medicine

Three-dimensional printing of poly(ε-caprolactone) (PCL) is a consolidated scaffold manufacturing technique for bone regenerative medicine. Simultaneously, the mesenchymal stem/stromal cell (MSC) secretome is osteoinductive, promoting scaffold colonization by cells, proliferation, and differentiation. The present paper combines 3D-printed PCL scaffolds with lyosecretome, a freeze-dried formulation of MSC secretome, containing proteins and extracellular vesicles (EVs). We designed a lyosecretome 3D-printed scaffold by two loading strategies: (i) MSC secretome adsorption on 3D-printed scaffold and (ii) coprinting of PCL with an alginate-based hydrogel containing MSC secretome (at two alginate concentrations, i.e., 6% or 10% w/v). A fast release of proteins and EVs (a burst of 75% after 30 min) was observed from scaffolds obtained by absorption loading, while coprinting of PCL and hydrogel, encapsulating lyosecretome, allowed a homogeneous loading of protein and EVs and a controlled slow release. For both loading modes, protein and EV release was governed by diffusion as revealed by the kinetic release study. The secretome’s diffusion is influenced by alginate, its concentration, or its cross-linking modes with protamine due to the higher steric hindrance of the polymer chains. Moreover, it is possible to further slow down protein and EV release by changing the scaffold shape from parallelepiped to cylindrical. In conclusion, it is possible to control the release kinetics of proteins and EVs by changing the composition of the alginate hydrogel, the scaffold’s shape, and hydrogel cross-linking. Such scaffold prototypes for bone regenerative medicine are now available for further testing of safety and efficacy.
A Deep Learning Method for 3D Object Classification and Retrieval Using the Global Point Signature Plus and Deep Wide Residual Network

A vital and challenging task in computer vision is 3D Object Classification and Retrieval, with many practical applications such as an intelligent robot, autonomous driving, multimedia contents processing and retrieval, and augmented/mixed reality. Various deep learning methods were introduced for solving classification and retrieval problems of 3D objects. Almost all view-based methods use many views to handle spatial loss, although they perform the best among current techniques such as View-based, Voxelization, and Point Cloud methods. Many views make network structure more complicated due to the parallel Convolutional Neural Network (CNN). We propose a novel method that combines a Global Point Signature Plus with a Deep Wide Residual Network, namely GPSP-DWRN, in this paper. Global Point Signature Plus (GPSPlus) is a novel descriptor because it can capture more shape information of the 3D object for a single view. First, an original 3D model was converted into a colored one by applying GPSPlus. Then, a 32 × 32 × 3 matrix stored the obtained 2D projection of this color 3D model. This matrix was the input data of a Deep Residual Network, which used a single CNN structure. We evaluated the GPSP-DWRN for a retrieval task using the Shapnetcore55 dataset, while using two well-known datasets—ModelNet10 and ModelNet40 for a classification task. Based on our experimental results, our framework performed better than the state-of-the-art methods.
Challenges in the Fabrication of Biodegradable and Implantable Optical Fibers for Biomedical Applications

The limited penetration depth of visible light in biological tissues has encouraged researchers to develop novel implantable light-guiding devices. Optical fibers and waveguides that are made from biocompatible and biodegradable materials offer a straightforward but effective approach to overcome this issue. In the last decade, various optically transparent biomaterials, as well as different fabrication techniques, have been investigated for this purpose, and in view of obtaining fully fledged optical fibers. This article reviews the state-of-the-art in the development of biocompatible and biodegradable optical fibers. Whilst several reviews that focus on the chemical properties of the biomaterials from which these optical waveguides can be made have been published, a systematic review about the actual optical fibers made from these materials and the different fabrication processes is not available yet. This prompted us to investigate the essential properties of these biomaterials, in view of fabricating optical fibers, and in particular to look into the issues related to fabrication techniques, and also to discuss the challenges in the use and operation of these optical fibers. We close our review with a summary and an outline of the applications that may benefit from these novel optical waveguides.
AKT Inhibitors: The Road Ahead to Computational Modeling-Guided Discovery

AKT, is a serine/threonine protein kinase comprising three isoforms—namely: AKT1, AKT2 and AKT3, whose inhibitors have been recognized as promising therapeutic targets for various human disorders, especially cancer. In this work, we report a systematic evaluation of multi-target Quantitative Structure-Activity Relationship (mt-QSAR) models to probe AKT’ inhibitory activity, based on different feature selection algorithms and machine learning tools. The best predictive linear and non-linear mt-QSAR models were found by the genetic algorithm-based linear discriminant analysis (GA-LDA) and gradient boosting (Xgboost) techniques, respectively, using a dataset containing 5523 inhibitors of the AKT isoforms assayed under various experimental conditions. The linear model highlighted the key structural attributes responsible for higher inhibitory activity whereas the non-linear model displayed an overall accuracy higher than 90%. Both these predictive models, generated through internal and external validation methods, were then used for screening the Asinex kinase inhibitor library to identify the most potential virtual hits as pan-AKT inhibitors. The virtual hits identified were then filtered by stepwise analyses based on reverse pharmacophore-mapping based prediction. Finally, results of molecular dynamics simulations were used to estimate the theoretical binding affinity of the selected virtual hits towards the three isoforms of enzyme AKT. Our computational findings thus provide important guidelines to facilitate the discovery of novel AKT inhibitors.
Genetically Encoded Fluorescent Indicators for Imaging Brain Chemistry

Genetically encoded fluorescent indicators, combined with optical imaging, enable the detection of physiologically or behaviorally relevant neural activity with high spatiotemporal resolution. Recent developments in protein engineering and screening strategies have improved the dynamic range, kinetics, and spectral properties of genetically encoded fluorescence indicators of brain chemistry. Such indicators have detected neurotransmitter and calcium dynamics with high signal-to-noise ratio at multiple temporal and spatial scales in vitro and in vivo. This review summarizes the current trends in these genetically encoded fluorescent indicators of neurotransmitters and calcium, focusing on their key metrics and in vivo applications.
Letermovir Primary Prophylaxis in High-Risk Hematopoietic Cell Transplant Recipients: A Matched Cohort Study

Background: Real-life data on the administration of letermovir as cytomegalovirus (CMV) primary prophylaxis after allogeneic hematopoietic cell transplantation (HCT) remain limited. Methods: We conducted a retrospective single-center matched cohort study, comparing consecutive high-risk allogeneic HCT recipients (cases) receiving primary prophylaxis with letermovir and untreated matched historical controls, during a study period of 180 days. The primary outcome was the incidence of clinically significant (cs) CMV infection. Secondary outcomes included duration and costs of CMV-antiviral treatments, hospital resource utilization, hematology and laboratory parameters. Results: Letermovir prophylaxis decreased csCMV infection incidence from 82.7% (controls) to 34.5% (cases; p-value < 0.0001). Controls were more likely to have >1 episode of csCMV infection (59.6%) compared to cases (11.5%; p-value < 0.0001). Letermovir was associated with: shorter overall CMV-associated treatment duration (49 days vs. 77.8 days; p-value: 0.02) and a trend for lower costs of CMV-associated treatments ($4096 vs. $9736; p-value: 0.07) and reduced length of stay (44.8 days vs. 59.8 days; p-value: 0.16). Letermovir administration was associated with significantly shorter duration (27.3 days vs. 57.1 days; p-value: 0.008) and lower costs ($1089 vs. $2281; p-value: 0.008) of valganciclovir treatment. Compared to controls, higher platelet counts were observed in cases (138 G/L vs. 92 G/L; p-value: 0.03) and renal function was improved (94 mL/min/1.73 m2 vs. 74 mL/min/1.73 m2; p-value: 0.006). Conclusions: Primary anti-CMV letermovir prophylaxis decreased the incidence of csCMV infection and the administration of CMV-associated treatments and costs, particularly those associated with valganciclovir. An effect of letermovir on platelet reconstitution and renal function of csCMV post-HCT was observed and needs further investigation.
Divergence Entropy-Based Evaluation of Hydrophobic Core in Aggressive and Resistant Forms of Transthyretin

The two forms of transthyretin differing slightly in the tertiary structure, despite the presence of five mutations, show radically different properties in terms of susceptibility to the amyloid transformation process. These two forms of transthyretin are the object of analysis. The search for the sources of these differences was carried out by means of a comparative analysis of the structure of these molecules in their native and early intermediate stage forms in the folding process. The criterion for assessing the degree of similarity and differences is the status of the hydrophobic core. The comparison of the level of arrangement of the hydrophobic core and its initial stages is possible thanks to the application of divergence entropy for the early intermediate stage and for the final forms. It was shown that the minimal differences observed in the structure of the hydrophobic core of the forms available in PDB, turned out to be significantly different in the early stage (ES) structure in folding process. The determined values of divergence entropy for both ES forms indicate the presence of the seed of hydrophobic core only in the form resistant to amyloid transformation. In the form of aggressively undergoing amyloid transformation, the structure lacking such a seed is revealed, being a stretched one with a high content of β-type structure. In the discussed case, the active presence of water in the structural transformation of proteins expressed in the fuzzy oil drop model (FOD) is of decisive importance for the generation of the final protein structure. It has been shown that the resistant form tends to generate a centric hydrophobic core with the possibility of creating a globular structure, i.e., a spherical micelle-like form. The aggressively transforming form reveals in the structure of its early intermediate, a tendency to form the ribbon-like micelle as observed in amyloid.
RNA Proximity Labeling: A New Detection Tool for RNA–Protein Interactions

Multiple cellular functions are controlled by the interaction of RNAs and proteins. Together with the RNAs they control, RNA interacting proteins form RNA protein complexes, which are considered to serve as the true regulatory units for post-transcriptional gene expression. To understand how RNAs are modified, transported, and regulated therefore requires specific knowledge of their interaction partners. To this end, multiple techniques have been developed to characterize the interaction between RNAs and proteins. In this review, we briefly summarize the common methods to study RNA–protein interaction including crosslinking and immunoprecipitation (CLIP), and aptamer- or antisense oligonucleotide-based RNA affinity purification. Following this, we focus on in vivo proximity labeling to study RNA–protein interactions. In proximity labeling, a labeling enzyme like ascorbate peroxidase or biotin ligase is targeted to specific RNAs, RNA-binding proteins, or even cellular compartments and uses biotin to label the proteins and RNAs in its vicinity. The tagged molecules are then enriched and analyzed by mass spectrometry or RNA-Seq. We highlight the latest studies that exemplify the strength of this approach for the characterization of RNA protein complexes and distribution of RNAs in vivo.
The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”.
Combined experimental and quantum chemical study on the adsorption mechanism of phosphorous anions on the hydrotalcite surfaces

In the present work, the hydrotalcite-like compound [Mg6Al2(OH)16]CO3⋅ nH2O (shorted as MgAl–CO3) is synthesized and the adsorption of phosphorous anions, their adsorption performance on the surface of hydrotalcites, and its mechanism are analyzed. To theoretically clarify the adsorption mechanism and adsorption structures, we perform quantum chemistry calculations of reactants, locally stable states, transition states, and products among phosphorous anion, water, and hydrotalcite in a variety of pH ranges. The experimental result shows that the efficiency of phosphate removal does not depend on pH of the solution, with which the numerical results are consistent. In particular, we identify the factors of influencing the adsorption ratio in different pH ranges from the quantum chemistry calculations: the stability of locally stable states, and the energies and locations of potential barriers along the reaction pathway relative to those of the locally stable states. The results suggest that hydrotalcites synthesized in this work are suitable as sorbent materials for the adsorption and removal of phosphorous anions from aqueous solutions.
Condition Assessment of Industrial Gas Turbine Compressor Using a Drift Soft Sensor Based in Autoencoder

Maintenance is the process of preserving the good condition of a system to ensure its reliability and availability to perform specific operations. The way maintenance is nowadays performed in industry is changing thanks to the increasing availability of data and condition assessment methods. Soft sensors have been widely used over last years to monitor industrial processes and to predict process variables that are difficult to measured. The main objective of this study is to monitor and evaluate the condition of the compressor in a particular industrial gas turbine by developing a soft sensor following an autoencoder architecture. The data used to monitor and analyze its condition were captured by several sensors located along the compressor for around five years. The condition assessment of an industrial gas turbine compressor reveals significant changes over time, as well as a drift in its performance. These results lead to a qualitative indicator of the compressor behavior in long-term performance.
Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.