Miracle-dz/UniFAR-FTUs huggingface dataset:
Drosophila Relish Activating lncRNA-CR33942 Transcription Facilitates Antimicrobial Peptide Expression in Imd Innate Immune Response

Long noncoding RNAs (lncRNAs) are an emerging class of regulators that play crucial roles in regulating the strength and duration of innate immunity. However, little is known about the regulation of Drosophila innate immunity-related lncRNAs. In this study, we first revealed that overexpression of lncRNA-CR33942 could strengthen the expression of the Imd pathway antimicrobial peptide (AMP) genes Diptericin (Dpt) and Attacin-A (AttA) after infection, and vice versa. Secondly, RNA-seq analysis of lncRNA-CR33942-overexpressing flies post Gram-negative bacteria infection confirmed that lncRNA-CR33942 positively regulated the Drosophila immune deficiency (Imd) pathway. Mechanistically, we found that lncRNA-CR33942 interacts and enhances the binding of NF-κB transcription factor Relish to Dpt and AttA promoters, thereby facilitating Dpt and AttA expression. Relish could also directly promote lncRNA-CR33942 transcription by binding to its promoter. Finally, rescue experiments and dynamic expression profiling post-infection demonstrated the vital role of the Relish/lncRNA-CR33942/AMP regulatory axis in enhancing Imd pathway and maintaining immune homeostasis. Our study elucidates novel mechanistic insights into the role of lncRNA-CR33942 in activating Drosophila Imd pathway and the complex regulatory interaction during the innate immune response of animals.
Robust Control for a Gas Turbine in Biomass-Based Electric Power Plants

A power plant can generate electric power using biomass from olive trees in Spain. The gasifier is capable of converting tons of wood chips per day into a gaseous fuel that is fed into a gas turbine. While there are significant systems whose models may be exactly obtained from physical laws and whose states are measured, it is much less realistic to assume that all the parameters, such as biogas pressure or specific heat ratio in gas turbines, are exactly known. It is then natural to investigate what happens to control systems involving unknown, or not precisely known, parameters. In this paper, the derived model of gas turbine is quite valid for robust control studies in biomass-based electric power plants.
Insight Into Novel Anti-tuberculosis Vaccines by Using Immunoinformatics Approaches

Tuberculosis (TB), an infectious disease, has been a leading cause of morbidity and mortality for decades. The causative agent of TB is the Mycobacterium tuberculosis (Mtb) which can infects various parts of the body, mainly the lungs in pulmonary TB cases. Mycobacterium bovis Bacillus Calmette–Guerin (BCG) is the only approved vaccine for TB, but its efficiency to combat pulmonary TB is limited. Multidrug-resistant (MDR) TB and extensive drug-resistant (XDR) TB requires the evolution of more potent vaccines. Therefore, this research aims to generate a universal TB subunit vaccine using advanced immunoinformatics techniques. In generating a novel multiepitope subunit vaccine, we selected the conserved and experimentally confirmed antigens Rv0058, Rv0101, and Rv3343. After a rigorous evaluation, the top candidates from predicted Helper T-lymphocytes (HTL), Cytotoxic T-lymphocytes (CTL), and B-cell epitopes were considered potential vaccine candidates. Immunogenicity was enhanced by the addition of an adjuvant to the ultimate construct of the vaccine. B-cell epitopes predictions guaranteed the eventual induction of a humoral response. Thereafter, dynamics simulations and molecular docking validated the vaccine-receptor complex’s stability and high affinity for the immune receptor TLR-3. Also, immune simulations revealed the significantly elevated levels of immunoglobulins such as IgM, cytokines such as interleukin-2, helper T (Th) cells, and cytotoxic T-cell populations. These results agreed with the actual inflammatory response and showed rapid antigen clearance after manifold exposure. Finally, the E. coli K12 strain was confirmed via in-silico cloning for quality expression. Nevertheless, in vivo experiments should be performed to validate the safety of the proposed vaccine and its inherent ability to prevent TB infection.
Case Report: Notoedric Mange and Aelurostrongylidosis in Two Domestic Cats From Rural Environment in Romania

This article describes two cases of notoedric mange concurrent with aelurostrongylidosis in two domestic-owned cats from a rural environment in Romania. Two European shorthair cats originating from the same litter were referred to our clinic, at 2 months apart, with a history of skin lesions, pruritus, weight loss, and respiratory signs. Cats lived mainly outdoor together with the queen and a third littermate. The latter two expressed the same clinical signs and had died before the presentation of the first cat. None of the four cats was vaccinated, dewormed, or treated for external parasites. Coat brushing, skin scrapings, skin cytology, earwax direct microscopic examination, and coproparasitological techniques (flotation and Baermann methods) were used as laboratory procedures. A blood sample was also collected for hematology, blood biochemistry, and feline immunodeficiency virus/feline leukemia virus (FIV/FeLV) test. Notoedres cati mites in high numbers were identified by all complementary tests, alongside fleas and Aelurostrongylus abstrusus first-stage larvae. The blood analysis revealed neutrophilia, and the FIV/FeLV fast test was negative. The cats were successfully treated off-label with selamectin spot-on formulation (Stronghold®, Zoetis) three times at 1- or 4-week intervals. Furthermore, they were treated with amoxicillin trihydrate/clavulanic acid, housed indoor, and fed with a commercial diet. Before presentation to the clinic, the female cat was unsuccessfully treated with a combination of fipronil, S-methoprene, eprinomectin, and praziquantel. During this period, the female cat remained outdoor and fed with home wastes. The cats become negative for A. abstrusus L1 larvae after 2–4 months of treatment. The owners developed pruritic skin lesions 1 month after introducing the first cat in the house. In conclusion, notoedric mange and aelurostrongylidosis can be treated successfully with selamectin as a spot-on formulation and the treatment must be continued until no parasite will be detected through specific techniques. The success of treatment depends on improving the quality of animal life (nutrition and hygiene) and treatment of secondary complications.
Pan-Cancer Methylated Dysregulation of Long Non-coding RNAs Reveals Epigenetic Biomarkers

Different cancer types not only have common characteristics but also have their own characteristics respectively. The mechanism of these specific and common characteristics is still unclear. Pan-cancer analysis can help understand the similarities and differences among cancer types by systematically describing different patterns in cancers and identifying cancer-specific and cancer-common molecular biomarkers. While long non-coding RNAs (lncRNAs) are key cancer modulators, there is still a lack of pan-cancer analysis for lncRNA methylation dysregulation. In this study, we integrated lncRNA methylation, lncRNA expression and mRNA expression data to illuminate specific and common lncRNA methylation patterns in 23 cancer types. Then, we screened aberrantly methylated lncRNAs that negatively regulated lncRNA expression and mapped them to the ceRNA relationship for further validation. 29 lncRNAs were identified as diagnostic biomarkers for their corresponding cancer types, with lncRNA AC027601 was identified as a new KIRC-associated biomarker, and lncRNA ACTA2-AS1 was regarded as a carcinogenic factor of KIRP. Two lncRNAs HOXA-AS2 and AC007228 were identified as pan-cancer biomarkers. In general, the cancer-specific and cancer-common lncRNA biomarkers identified in this study may aid in cancer diagnosis and treatment.
The Stress Barometer: Validation of a Bio–Psycho–Social Brief Screening Instrument of Pandemic Stress Reaction

Background To capture the psychosocial impact of the SARS-CoV-2 pandemic, a model based on the International Classification of Functioning, Disability, and Health (ICF) was developed during the first lockdown in Germany in April 2020. FACT-19, the questionnaire for the assessment of pandemic stress load, measures (1) pre-pandemic stress, (2) pandemic stress, and (3) contextual factors (functioning as facilitators or barriers). Derived from this model, the stress barometer as a brief screening instrument captures these factors. The purpose of this study is a preliminary validation of the instrument. Method The stress barometer was applied in conjunction with the Symptom-Checklist SCL-90-S at the beginning of the first lockdown in psychosomatic and psychotraumatological care in two federal states in Germany. The sample consists of n = 341 (68.6% female) from 18–73 years of age (M = 49.36, SD = 11.4). Results The structure of the short screening was examined in the overall sample using an exploratory factor analysis [Chi2 (78) = 875.720, KMO = 0.688]. The results indicate a four-factor-structure that explains 59.5% of the total cumulative variance. The factors of the stress barometer correlate with the Global Severity Index (GSI, measured by SCL-90-S) with moderate to weak effects: pre-pandemic stress (rs = 0.431, p < 0.001, n = 295), pandemic stress (rs = 0.310, p < 0.001, n = 298), distal facilitator (rs = −0.155, p < 0.001, n = 312), and proximal barriers (rs = 0.232, p < 0.001, n = 312). Discussion The results indicate the suitability of the stress barometer to complement the measurement of the impact of pandemics with an ICF-oriented approach, taking into consideration pre-pandemic stress as well as interactions with facilitators and barriers. Further analysis will be necessary for a revision of the items of the scale.
Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants

SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a KD of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 μg mL−1. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC50 values ranging from 0.35 to 1.66 μg mL−1 for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 μg mL−1 for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a “conformation competition” mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.
A Genetic Association Test Accounting for Skewed X-Inactivation With Application to Biotherapy Immunogenicity in Patients With Autoimmune Diseases

Despite being assayed on commercialized DNA chips, the X chromosome is commonly excluded from genome-wide association studies (GWAS). One of the reasons is the complexity to analyze the data taking into account the X-chromosome inactivation (XCI) process in women and in particular the XCI process with a potentially skewed pattern. This is the case when investigating the role of X-linked genetic variants in the occurrence of anti-drug antibodies (ADAs) in patients with autoimmune diseases treated by biotherapies. In this context, we propose a novel test statistic for selecting loci of interest harbored by the X chromosome that are associated with time-to-event data taking into account skewed X-inactivation (XCI-S). The proposed statistic relies on a semi-parametric additive hazard model and is straightforward to implement. Results from the simulation study show that the test provides higher power gains than the score tests from the Cox model (under XCI process or its escape) and the Xu et al.'s XCI-S likelihood ratio test. We applied the test to the data from the real-world observational multicohort study set-up by the IMI-funded ABIRISK consortium for identifying X chromosome susceptibility loci for drug immunogenicity in patients with autoimmune diseases treated by biotherapies. The test allowed us to select two single nucleotide polymorphisms (SNPs) with high linkage disequilibrium (rs5991366 and rs5991394) located in the cytoband Xp22.2 that would have been overlooked by the Cox score tests and the Xu et al.'s XCI-S likelihood ratio test. Both SNPs showed a similar protective effect for drug immunogenicity without any occurrence of ADA positivity for the homozygous females and hemizygous males for the alternative allele. To our knowledge, this is the first study to investigate the association between X chromosome loci and the occurrence of anti-drug antibodies. We think that more X-Chromosome GWAS should be performed and that the test is well-suited for identifying X-Chromosome SNPs, while taking into account all patterns of the skewed X-Chromosome inactivation process.
Modulation of Peripheral Immune Cell Subpopulations After RapidArc/Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: Findings and Comparison With 3D Conformal/Conventional Fractionation Treatment

Radiotherapy (RT) is an important therapeutic option in patients with localized prostate cancer (PC). Unfortunately, radiation treatment causes a decrease in peripheral lymphocytes and, consequently, influences the patients’ immune status. Our aim was to study changes in peripheral blood immune cell subpopulations after RT and during 6 months’ follow-up in 2 groups of PC patients irradiated with different techniques and dose fractions with curative intent. We also investigated the presence of correlation between immune cell modulation and genitourinary or gastrointestinal toxicity. We enrolled 44 patients treated with curative RT (RapidArc/hypofractionation regimen or 3D conformal/conventional fractionation) for localized PC. Total white blood cell (WBC), absolute lymphocyte counts (ALCs), and peripheral immune cell subpopulations were analyzed at baseline, at the end of RT, and 3 and 6 months after the end of RT. WBC and ALC greatly decreased at the end of RT with a trend to recover at 6 months’ follow-up in the hypofractionation group but not in the conventional one. Furthermore, B, total T, T CD4+, T CD8+, and NK cell values dropped significantly in both groups at the end of RT, with a minor decrease detectable in the hypofractionation group for B, total T, and T CD4+ lymphocytes with respect to the other technique/fractionation group. Double-negative T (DNT), double-positive T (DPT), and NKT cells significantly decreased at the end of RT with a slight tendency to recover values during follow-up, particularly in the hypofractionation group. No correlation with genitourinary or gastrointestinal toxicity was found. In this study, we showed, for the first time, the effects of RapidArc/moderate hypofractionation RT on immune cell subsets in patients treated for localized PC. Due to the growing interest in minority T-cell subpopulations for immunotherapy, we also reported longitudinal monitoring of the effects of RT on DNT, DPT, and NKT, which was never studied before. Our preliminary data highlight the importance of considering the effects of different RT techniques/fractionation regimens on peripheral immune cells, in the era of RT and immunotherapy combination.
Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage

The purpose of this study was to identify the biomarkers implicated in the development of intracranial hemorrhage (ICH) and potential regulatory pathways. In the transcriptomic data for patients with ICH, we identified DEmiRNAs and DEmRNAs related to hypoxia, inflammation, and their transcription factors (TFs). An ICH-based miRNA-TF-mRNA regulatory network was thus constructed, and four biomarkers (TIMP1, PLAUR, DDIT3, and CD40) were screened for their association with inflammation or hypoxia by machine learning. Following this, SP3 was found to be a transcription factor involved in hypoxia and inflammation, which regulates TIMP1 and PLAUR. From the constructed miRNA-TF-mRNA regulatory network, we identified three axes, hsa-miR-940/RUNX1/TIMP1, hsa-miR-571/SP3/TIMP1, and hsa-miR-571/SP3/PLAUR, which may be involved in the development of ICH. Upregulated TIMP1 and PLAUR were validated in an independent clinical cohort 3 days after ICH onset. According to Gene Set Enrichment Analysis (GSEA), SP3 was discovered to be important in interleukin signaling and platelet activation for hemostasis. Transcription factor SP3 associated with hypoxia or inflammation plays an important role in development of ICH. This study provides potential targets for monitoring the severity of inflammation and hypoxia in patients with ICH.
A Novel Breakthrough in Leptospira spp. Mutagenesis: Knockout by Combination of CRISPR/Cas9 and Non-homologous End-Joining Systems

Leptospirosis is of general concern as it is a widespread zoonotic disease caused by pathogenic species of the genus Leptospira, although this genus also includes free-living saprophytic strains. Understanding the pathophysiology of leptospirosis is still in its infancy even after several years of its discovery, because of the lack of effective genetic tools. The use of the Streptococcus pyogenes CRISPR/Cas9 system and its variations have pushed the leptospirosis research forward, relying on the simplicity of the technique. However, the lethality of double-strand breaks (DSB) induced by the RNA-guided Cas9 enzyme has limited the generation of knockout mutants. In this work, we demonstrated sustained cell viability after concurrent expression of CRISPR/Cas9 and Mycobacterium tuberculosis non-homologous end-joining components in a single-plasmid strategy in L. biflexa. Scarless mutations resulting in null phenotypes could be observed in most of the colonies recovered, with deletions in the junctional site ranging from 3 to almost 400 bp. After plasmid curing by in vitro passages in a medium without antibiotic, selected marker-free and targeted mutants could be recovered. Knockout mutants for LipL32 protein in the pathogen L. interrogans could be obtained using M. smegmatis NHEJ machinery, with deletions ranging from 10 to 345 bp. In conclusion, we now have a powerful genetic tool for generating scarless and markerless knockout mutants for both saprophytic and pathogenic strains of Leptospira.
Impact of Heating Temperature and Fatty Acid Type on the Formation of Lipid Oxidation Products During Thermal Processing

Thermal treatment of lipids rich in fatty acids contributes to the formation of lipid oxidation products (LOPs), which have potentially harmful effects on human health. This study included soybean oil (SO), palm oil (PO), olive oil (OO), and lard oil (LO) as the research objects, with an aim to investigate the impact of heating temperature and fatty acid type on the generation of LOPs (α-dicarbonyl compounds, malondialdehyde (MDA), α,β-unsaturated aldehydes, and 16 volatile aldehydes). Results showed that LOPs increased significantly (p < 0.05) with the increase in temperature (100 ~ 200°C). Furthermore, the amount of 2,3-butanedione (159.53 μg/g), MDA (3.15 μg/g), 4-hydroxy-hexenal (3.03 μg/g), 2-butenal (292.18%), 2-pentenal (102.26%), hexanal (898.72%), and 2,4-heptadienal (E, E) (2182.05%) were more at 200°C in SO rich in polyunsaturated fatty acids (PUFAs) than other oils. Results from heat map analysis indicated that the 2, 4-heptadienal, and glyoxal related to the myristic acid of oil. Moreover, the MDA was in close association with PUFAs. Based on the effect of temperature and fatty acid type on the generation of LOPs, this study could serve as a control method to reduce harmful LOPs.
Comparative Transcriptome Analysis Reveals the Adaptation Mechanism to High Salinity in Litopenaeus vannamei

As an euryhaline commercial species, the Pacific white shrimp Litopenaeus vannamei can be cultured under a wide range of salinities. However, different families showed various tolerance to high salinity. In order to elucidate the underlying mechanisms, a comparative transcriptome approach was used to find the differences between tolerant families and susceptible families at the transcriptional level. There were 98 and 58 differentially expressed genes (DEGs) between tolerant and susceptible families under normal and high-salinity conditions, respectively. The DEGs upregulated in tolerant families were mostly enriched in the biological process of response to a stimulus. Nine crustacyanin (CRCN)-encoding genes in this Gene Ontology (GO) term showed significantly higher expression levels in the tolerant families than those in susceptible families, suggesting that crustacyanins might play important roles in shrimp tolerance to high salinity. After high-salinity treatment, a total of 233 and 109 DEGs were identified from tolerant and susceptible families, respectively. Serine-type endopeptidase activity, serine-type peptidase activity, and serine hydrolase activity were the top three GO terms in the tolerant families after high-salinity treatment. Further analysis illustrated that these three GO terms were also the top three enriched GO terms for the DEGs specifically upregulated in the tolerant families after high-salinity stress. Meanwhile, four genes annotated in serine proteases families in these three GO terms were upregulated in the tolerant families but not changed in the susceptible families after high-salinity stress. These results indicated that serine proteases should play key roles in shrimp tolerance to high salinity. This study provides important information for understanding the mechanism of shrimp tolerance to high-salinity stress and would be useful for further molecular breeding of shrimp varieties with high-salinity tolerance.
Current Steering Using Multiple Independent Current Control Deep Brain Stimulation Technology Results in Distinct Neurophysiological Responses in Parkinson’s Disease Patients

Background Deep brain stimulation (DBS) is an effective neuromodulation therapy to treat people with medication-refractory Parkinson’s disease (PD). However, the neural networks affected by DBS are not yet fully understood. Recent studies show that stimulating on different DBS-contacts using a single current source results in distinct EEG-based evoked potentials (EPs), with a peak at 3 ms (P3) associated with dorsolateral subthalamic nucleus stimulation and a peak at 10 ms associated with substantia nigra stimulation. Multiple independent current control (MICC) technology allows the center of the electric field to be moved in between two adjacent DBS-contacts, offering a potential advantage in spatial precision. Objective Determine if MICC precision targeting results in distinct neurophysiological responses recorded via EEG. Materials and Methods We recorded cortical EPs in five hemispheres (four PD patients) using EEG whilst employing MICC to move the electric field from the most dorsal DBS-contact to the most ventral in 15 incremental steps. Results The center of the electric field location had a significant effect on both the P3 and P10 amplitude in all hemispheres where a peak was detected (P3, detected in 4 of 5 hemispheres, p < 0.0001; P10, detected in 5 of 5 hemispheres, p < 0.0001). Post hoc analysis indicated furthermore that MICC technology can significantly refine the resolution of steering. Conclusion Using MICC to incrementally move the center of the electric field to locations between adjacent DBS-contacts resulted in significantly different neurophysiological responses that may allow further precision of the programming of individual patients.