Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptome Analysis Reveals HgCl2 Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl2 on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl2 treatment causes inhibition of cell growth via cell cycle arrest at G0/G1- and S-phase. In addition, HgCl2 induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl2 treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl2 treatment. Altogether, these data show that HgCl2 induces apoptotic cell death through the dysfunction of mitochondria.
Visual Cortex Transcranial Direct Current Stimulation for Proliferative Diabetic Retinopathy Patients: A Double-Blinded Randomized Exploratory Trial

Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes. PDR-related retinal hemorrhages often lead to severe vision loss. The main goals of management are to prevent visual impairment progression and improve residual vision. We explored the potential of transcranial direct current stimulation (tDCS) to enhance residual vision. tDCS applied to the primary visual cortex (V1) may improve visual input processing from PDR patients’ retinas. Eleven PDR patients received cathodal tDCS stimulation of V1 (1 mA for 10 min), and another eleven patients received sham stimulation (1 mA for 30 s). Visual acuity (logarithm of the minimum angle of resolution (LogMAR) scores) and number acuity (reaction times (RTs) and accuracy rates (ARs)) were measured before and immediately after stimulation. The LogMAR scores and the RTs of patients who received cathodal tDCS decreased significantly after stimulation. Cathodal tDCS has no significant effect on ARs. There were no significant changes in the LogMAR scores, RTs, and ARs of PDR patients who received sham stimulation. The results are compatible with our proposal that neuronal noise aggravates impaired visual function in PDR. The therapeutic effect indicates the potential of tDCS as a safe and effective vision rehabilitation tool for PDR patients.
Association between disease-related malnutrition and innate immunity gene expression in critically ill patients at intensive care unit admission

The aim of the study was to analyse the relationship between nutritional disorders and the expression of innate antibacterial response genes in patients admitted to the intensive care unit (ICU). In 46 patients with severe malnutrition and life-threatening surgical complications, nutritional status tests were performed on the basis of the NRS 2002 (Nutritional Risk Screening) scale, cytokine, albumin, C-reactive protein concentrations, anthropometric tests, and body composition analysis. Concurrently, the expression of Toll-like receptor 2, NOD1, TRAF6, and HMGB1 genes was determined in peripheral blood leukocytes at the mRNA level using real-time polymerase chain reaction. It was found that both the nutritional status and the gene expression changed depending on the group of patients studied (including the group of survivors vs. non-survivors). Significant correlations were found between the results of routine tests used in the diagnostics of malnutrition (including NRS 2002, resistance, reactance, phase angle, excess of extracellular water) and the expression of the studied genes. Moreover, the expression of TRAF6 and HMGB1 genes correlated with the Acute Physiology and Chronic Health Evaluation II scale and the age of the patients. The results of the research suggest that the expression of innate antibacterial response genes may be a new diagnostic tool complementing the assessment of nutritional disorders in surgical patients admitted to the ICU. These tests may be helpful in providing more accurate diagnostics of the genetic effects of malnutrition and in the monitoring of patients for whom nutritional treatment is planned to support the functions of the immune system, thereby increasing the effectiveness of this type of treatment in the ICU.
Reorganizing the Multidisciplinary Team Meetings in a Tertiary Centre for Gastro-Intestinal Oncology Adds Value to the Internal and Regional Care Pathways. A Mixed Method Evaluation

Introduction: The reorganisation of the structure of a Gastro-Intestinal Oncology Multidisciplinary Team Meeting (GIO-MDTM) in a tertiary centre with three care pathways is evaluated on added value. Methods: In a mixed method investigation, process indicators such as throughput times were analysed and stakeholders were interviewed regarding benefits and drawbacks of the reorganisation and current MDTM functioning. Results: For the hepatobiliary care pathway, the time to treatment plan increased, but the time to start treatment reduced significantly. The percentage of patients treated within the Dutch standard of 63 days increased for the three care pathways. From the interviews, three themes emerged: added value of MDTMs, focus on planning integrated care and awareness of possible improvements. Discussion: The importance of evaluating interventions in oncology care pathways is shown, including detecting unexpected drawbacks. The evaluation provides insight into complex dynamics of the care pathways and contributes with recommendations on functioning of an MDTM. Conclusions: Throughput times are only partly determined by oncology care pathway management, but have influence on the functioning of MDTMs. Process indicator information can help to reflect on integration of care in the region, resulting in an increase of patients treated within the Dutch standard.
Membrane Association and Topology of Citrus Leprosis Virus C2 Movement and Capsid Proteins

Although citrus leprosis disease has been known for more than a hundred years, one of its causal agents, citrus leprosis virus C2 (CiLV-C2), is poorly characterized. This study described the association of CiLV-C2 movement protein (MP) and capsid protein (p29) with biological membranes. Our findings obtained by computer predictions, chemical treatments after membrane fractionation, and biomolecular fluorescence complementation assays revealed that p29 is peripherally associated, while the MP is integrally bound to the cell membranes. Topological analyses revealed that both the p29 and MP expose their N- and C-termini to the cell cytoplasmic compartment. The implications of these results in the intracellular movement of the virus were discussed.
Spatial and Temporal Characteristics of Hand-Foot-and-Mouth Disease and Its Response to Climate Factors in the Ili River Valley Region of China

Background: As the global climate changes, the number of cases of hand-foot-and-mouth disease (HFMD) is increasing year by year. This study comprehensively considers the association of time and space by analyzing the temporal and spatial distribution changes of HFMD in the Ili River Valley in terms of what climate factors could affect HFMD and in what way. Methods: HFMD cases were obtained from the National Public Health Science Data Center from 2013 to 2018. Monthly climate data, including average temperature (MAT), average relative humidity (MARH), average wind speed (MAWS), cumulative precipitation (MCP), and average air pressure (MAAP), were obtained from the National Meteorological Information Center. The temporal and spatial distribution characteristics of HFMD from 2013 to 2018 were obtained using kernel density estimation (KDE) and spatiotemporal scan statistics. A regression model of the incidence of HFMD and climate factors was established based on a geographically and temporally weighted regression (GTWR) model and a generalized additive model (GAM). Results: The KDE results show that the highest density was from north to south of the central region, gradually spreading to the whole region throughout the study period. Spatiotemporal cluster analysis revealed that clusters were distributed along the Ili and Gongnaisi river basins. The fitted curves of MAT and MARH were an inverted V-shape from February to August, and the fitted curves of MAAP and MAWS showed a U-shaped change and negative correlation from February to May. Among the individual climate factors, MCP coefficient values varied the most while MAWS values varied less from place to place. There was a partial similarity in the spatial distribution of coefficients for MARH and MAT, as evidenced by a significant degree of fit performance in the whole region. MCP showed a significant positive correlation in the range of 15–35 mm, and MAAP showed a positive correlation in the range of 925–945 hPa. HFMD incidence increased with MAT in the range of 15–23 °C, and the effective value of MAWS was in the range of 1.3–1.7 m/s, which was positively correlated with incidences of HFMD. Conclusions: HFMD incidence and climate factors were found to be spatiotemporally associated, and climate factors are mostly non-linearly associated with HFMD incidence.
The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone

Background Cholesterol gallstone (CG) is the most common gallstone disease, which is induced by biliary cholesterol supersaturation. The purpose of this study is to investigate the pathogenesis of CG. Methods Sixteen mice were equally and randomly divided into model group and normal control group. The model group was fed with lithogenic diets to induce CG, and then gallbladder bile lipid analysis was performed. After RNA-seq library was constructed, differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) between model group and normal control group were analyzed by DESeq2 package. Using the cluster Profiler package, enrichment analysis for the DE-mRNAs was carried out. Based on Cytoscape software, the protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were built. Using quantitative real-time reverse transcription-PCR (qRT-PCR) analysis, the key RNAs were validated. Results The mouse model of CG was suc cessfully established, and then 181 DE-mRNAs and 33 DE-lncRNAs between model and normal groups were obtained. Moreover, KDM4A was selected as a hub node in the PPI network, and lncRNA MEG3 was considered as a key lncRNA in the regulatory network. Additionally, the miR-107-5p/miR-149-3p/miR-346-3-MEG3 regulatory pairs and MEG3-PABPC4/CEP131/NUMB1 co-expression pairs existed in the regulatory network. The qRT-PCR analysis showed that KDM4A expression was increased, and the expressions of MEG3, PABPC4, CEP131, and NUMB1 were downregulated. Conclusion These RNAs might be related to the pathogenesis of CG.
Characterization of the GRAS gene family reveals their contribution to the high adaptability of wheat

GRAS transcription factors play important roles in many processes of plant development as well as abiotic and biotic stress responses. However, little is known about this gene family in bread wheat (Triticum aestivum), one of the most important crops worldwide. The completion of a quality draft genome allows genome-wide detection and evolutionary analysis of the GRAS gene family in wheat. In this study, 188 TaGRAS genes were detected and divided into 12 subfamilies based on phylogenetic analyses: DELLA, DLT, HAM, LISCL, SCL3, SCL4/7, SCR, SHR, PAT1, Os19, Os4 and LAS. Tandem and segmental duplications are the main contributors to the expansion of TaGRAS, which may contribute to the adaptation of wheat to various environmental conditions. A high rate of homoeolog retention during hexaploidization was detected, suggesting the nonredundancy and biological importance of TaGRAS homoeologs. Systematic analyses of TaGRAS indicated the conserved expression pattern and function of the same subfamily during evolution. In addition, we detected five genes belonging to the LISCL subfamily induced by both biotic and abiotic stresses and they may be potential targets for further research through gene editing. Using degradome and ChIP-seq data, we identified the targets of miR171 and histone modifications and further analyzed the contribution of epigenetic modification to the subfunctionalization of TaGRAS. This study laid a foundation for further functional elucidation of TaGRAS genes.
Caftaric Acid Isolation from Unripe Grape: A “Green” Alternative for Hydroxycinnamic Acids Recovery

Phenolic acids represent about one-third of the dietary phenols and are widespread in vegetable and fruits. Several plants belonging to both vegetables and medical herbs have been studied for their hydroxycinnamic acid content. Among them, Echinacea purpurea is preferentially used for caffeic acid-derivatives extraction. The wine industry is a source of by-products that are rich in phenolic compounds. This work demonstrates that unripe grape juice (verjuice) presents a simple high-pressure liquid chromatography (HPLC) profile for hydroxycinnamic acids (HCAs), with a great separation of the caffeic-derived acids and a low content of other phenolic compounds when compared to E. purpurea and other grape by-products. Here it is shown how this allows the recovery of pure hydroxycinnamic acids by a simple and fast method, fast protein liquid chromatography (FPLC). In addition, verjuice can be easily obtained by pressing grape berries and filtering, thus avoiding any extraction step as required for other vegetable sources. Overall, the proposed protocol could strongly reduce the engagement of solvent in industrial phenolic extraction.
The Effect of Ventilation with Individualized Positive End-Expiratory Pressure on Postoperative Atelectasis in Patients Undergoing Robot-Assisted Radical Prostatectomy: A Randomized Controlled Trial

For patients undergoing robot-assisted radical prostatectomy, the pneumoperitoneum with a steep Trendelenburg position could worsen intraoperative respiratory mechanics and result in postoperative atelectasis. We investigated the effects of individualized positive end-expiratory pressure (PEEP) on postoperative atelectasis, evaluated using lung ultrasonography. Sixty patients undergoing robot-assisted radical prostatectomy were randomly allocated into two groups. Individualized groups (n = 30) received individualized PEEP determined by a decremental PEEP trial using 20 to 7 cm H2O, aiming at maximizing respiratory compliance, whereas standardized groups (n = 30) received a standardized PEEP of 7 cm H2O during the pneumoperitoneum. Ultrasound examination was performed on 12 sections of thorax, and the lung ultrasound score was measured as 0–3 by considering the number of B lines and the degree of subpleural consolidation. The primary outcome was the difference between the lung ultrasound scores measured before anesthesia induction and just after extubation in the operating room. An increase in the difference means the development of atelectasis. The optimal PEEP in the individualized group was determined as the median (interquartile range) 14 (12–18) cm H2O. Compared with the standardized group, the difference in the lung ultrasound scores was significantly smaller in the individualized group (−0.5 ± 2.7 vs. 6.0 ± 2.9, mean difference −6.53, 95% confidence interval (−8.00 to −5.07), p < 0.001), which means that individualized PEEP was effective to reduce atelectasis. The lung ultrasound score measured after surgery was significantly lower in the individualized group than the standardized group (8.1 ± 5.7 vs. 12.2 ± 4.2, mean difference −4.13, 95% confidence interval (−6.74 to −1.53), p = 0.002). However, the arterial partial pressure of the oxygen/fraction of inspired oxygen levels during the surgery showed no significant time-group interaction between the two groups in repeated-measures analysis of variance (p = 0.145). The incidence of a composite of postoperative respiratory complications was comparable between the two groups. Individualized PEEP determined by maximal respiratory compliance during the pneumoperitoneum and steep Trendelenburg position significantly reduced postoperative atelectasis, as evaluated using lung ultrasonography. However, the clinical significance of this finding should be evaluated by a larger clinical trial.
The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy

The immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8+ cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I) molecules. Cancer cells circumvent immune surveillance using diverse strategies. A key mechanism of cancer immune evasion is downregulation of MHC-I and key proteins of the antigen processing and presentation machinery (APM). Even though impaired MHC-I expression in cancers is well-known, reversing the MHC-I defects remains the least advanced area of tumor immunology. The discoveries that NLRC5 is the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are the most common cause of MHC-I defects in cancers, have raised the hopes for restoring MHC-I expression. Here, we provide an overview of cancer immunity mediated by CD8+ T cells and the functions of NLRC5 in MHC-I antigen presentation pathways. We describe the impressive advances made in understanding the regulation of NLRC5 expression, the data supporting the antitumor functions of NLRC5 and a few reports that argue for a pro-tumorigenic role. Finally, we explore the possible avenues of exploiting NLRC5 for cancer immunotherapy.
Bullying Victimization and Problem Video Gaming: The Mediating Role of Externalizing and Internalizing Problems

Background: Adolescent victims of bullying are more likely to experience a range of mental health problems. Although research has investigated the relationship between bullying victimization and various addictive behaviors, the impact of bullying on problem video gaming (PVG) remains largely unexplored. The purpose of this study is to investigate the relationship between bullying victimization and PVG as mediated by the presence of internalizing and externalizing problems. Methods: Survey responses were collected from 6353 high-school students aged 12 to 18. Measures include bullying victimization (physical, verbal, cyber and indirect), internalizing (e.g., anxious and depressive symptoms) and externalizing (e.g., aggressive and delinquent problems) problems, and PVG (measured by the Internet Gaming Disorder Scale–Short Form). Results: Mediation analyses indicated that the relationship between verbal bullying and PVG was completely mediated by the presence of internalizing and externalizing problems. The relationship between physical bullying and PVG was completely mediated by externalizing problems and the relationship between cyberbullying and PVG was completely mediated by internalizing problems. Lastly, the relationship between indirect bullying and PVG was partially mediated by externalizing and internalizing problems. Conclusions: Results suggest that different types of bullying victimization are differentially associated with PVG, with mental health symptoms significantly mediating this relationship.
The complete chloroplast genome of a distylous-homostylous species, Primula homogama (Primulaceae)

Abstract Primula homogama F. H. Chen & C. M. Hu (Primulaceae) is endemic to the Emei Mountain of China. In this study, we characterized the complete chloroplast genome of P. homogama based on next-generation sequencing (NGS). The complete chloroplast genome of P. homogama was 154,677 bp in size with a typical quadripartite structure, containing a large single-copy (LSC) region of 85,299 bp and a small single-copy (SSC) region of 17,816 bp. These two regions were separated by a pair of inverted repeat regions (IRs), each of 25,781 bp. A total of 130 functional genes were encoded, consisted of 86 protein-coding genes (PCG), 36 tRNA genes, and eight ribosomal RNA (rRNA) genes.
Human TRIM5α: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning

Human immunodeficiency virus-1 (HIV-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. Combination antiretroviral treatment is highly effective, but HIV-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. It is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for HIV-1. It has been long accepted that the restriction factor tripartite motif protein 5 isoform alpha (TRIM5α) restricts HIV-1 infection in a species-specific manner, with rhesus macaque TRIM5α strongly restricting HIV-1, and human TRIM5α having a minimal restriction capacity. However, several recent studies underscore human TRIM5α as a cell-dependent HIV-1 restriction factor. Here, we present an overview of the latest research on human TRIM5α and propose a novel conceptualization of TRIM5α as a restriction factor with a varied portfolio of antiviral functions, including mediating HIV-1 degradation through autophagy- and proteasome-mediated mechanisms, and acting as a viral sensor and effector of antiviral signaling. We have also expanded on the protective antiviral roles of autophagy and outline the therapeutic potential of autophagy modulation to intervene in chronic HIV-1 infection.