Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of Chalcone Isomerase Genes Involved in Flavonoid Production in Dracaena cambodiana

Dragon’s blood is a traditional medicine in which flavonoids are the main bioactive compounds; however, the underlying formation mechanism of dragon’s blood remains largely poorly understood. Chalcone isomerase (CHI) is the key enzyme in the flavonoid biosynthesis pathway. However, CHI family genes are not well understood in Dracaena cambodiana Pierre ex Gagnep, an important source plant of dragon’s blood. In this study, 11 CHI family genes were identified from D. cambodiana, and they were classified into three types. Evolutionary and transcriptional profiling analysis revealed that DcCHI1 and DcCHI4 might be involved in flavonoid production. Both DcCHI1 and DcCHI4 displayed low expression levels in stem under normal growth conditions and were induced by methyl jasmonate (MeJA), 6-benzyl aminopurine (6-BA, synthetic cytokinin), ultraviolet-B (UV-B), and wounding. The recombinant proteins DcCHI1 and DcCHI4 were expressed in Escherichia coli and purified by His-Bind resin chromatography. Enzyme activity assay indicated that DcCHI1 catalyzed the formation of naringenin from naringenin chalcone, while DcCHI4 lacked this catalytic activity. Overexpression of DcCHI1 or DcCHI4 enhanced the flavonoid production in D. cambodiana and tobacco. These findings implied that DcCHI1 and DcCHI4 play important roles in flavonoid production. Thus, our study will not only contribute to better understand the function and expression regulation of CHI family genes involved in flavonoid production in D. cambodiana but also lay the foundation for developing the effective inducer of dragon’s blood.
Biological calorimetry and the thermodynamics of the origination and evolution of life

Abstract Calorimetric measurements on biological systems from small molecules to whole organisms lead to a new conception of the nature of live matter that has profound consequences for our understanding of biology. The data show that the differences in Gibbs energy (ΔG) and enthalpy (ΔH) are near zero or negative and the difference in entropy (ΔS) is near zero between a random mixture of molecules and live matter of the same composition. A constant input of energy is required to maintain ion gradients, ATP production, and the other functions of living matter, but because cells are organized in a spontaneous process, no energy input is required to maintain the structure or organization of cells. Thus, the origin of life and evolution of complex life forms occurs by thermodynamically spontaneous processes, carbon-based life should be common throughout the universe, and because there is no energy cost, evolution can occur relatively rapidly.
Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

As a CRISPR-Cas9-based tool to help scientists to investigate gene functions, Cancer Dependency Map genes (CDMs) include an enormous series of loss-of-function screens based on genome-scale RNAi. These genes participate in regulating survival and growth of tumor cells, which suggests their potential as novel therapeutic targets for malignant tumors. By far, studies on the roles of CDMs in gastric adenocarcinoma (GA) are scarce and only a small fraction of CDMs have been investigated. In the present study, datasets of the differentially expressed genes (DEGs) were extracted from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which differentially expressed CDMs were determined. Functions and prognostic significance of these verified CDMs were evaluated using a series of bioinformatics methods. In all, 246 differentially expressed CDMs were determined, with 147 upregulated and 99 downregulated. Ten CDMs (ALG8, ATRIP, CCT6A, CFDP1, CINP, MED18, METTL1, ORC1, TANGO6, and PWP2) were identified to be prognosis-related and subsequently a prognosis model based on these ten CDMs was constructed. In comparison with that of patients with low risk in TCGA training, testing and GSE84437 cohort, overall survival (OS) of patients with high risk was significantly worse. It was then subsequently demonstrated that for this prognostic model, area under the ROC (receiver operating characteristic) curve was 0.771 and 0.697 for TCGA training and testing cohort respectively, justifying its reliability in predicting survival of GA patients. With the ten identified CDMs, we then constructed a nomogram to generate a clinically practical model. The regulatory networks and functions of the ten CDMs were then explored, the results of which demonstrated that as the gene significantly associated with survival of GA patients and Hazard ratio (HR), PWP2 promoted in-vitro invasion and migration of GA cell lines through the EMT signaling pathway. Therefore, in conclusion, the present study might help understand the prognostic significance and molecular functions of CDMs in GA.
Traditional Versus Velocity-Based Resistance Training in Competitive Female Cyclists: A Randomized Controlled Trial

We assessed the effects of a short-term velocity-based resistance training (VBRT, where exercise intensity is individualized based on the loads and repetitions that maximize power output) program compared with traditional resistance training (TRT, where the same number of repetitions and relative load are used for every individual) on body composition, muscle strength/power, and endurance performance in competitive female cyclists. Seventeen participants were randomly assigned to 6 weeks (two sessions/week) of TRT (n = 8) or VBRT (n = 9), during which they maintained their usual endurance program. Both interventions included squat, hip thrust, and split squat exercises. Training loads were continuously registered, and outcomes were measures of muscle strength/power, body composition, and endurance performance (incremental test and 8-min time trial). No differences between TRT and VBRT groups were found for overall internal training loads during resistance training or cycling sessions (p > 0.05). Both interventions led to significant improvements in all strength/power-related outcomes, but VBRT induced greater improvements than TRT in maximum muscle strength and power as assessed with the hip thrust exercise (p < 0.05 for the group by time interaction effect). However, no significant group by time interaction effect was found for body composition or endurance performance-related outcomes. In conclusion, the addition of a short-term intervention of VBRT or TRT to the usual training regimen of competitive female cyclists improves muscle strength/power, albeit VBRT might induce superior gains on maximum strength/power for the hip thrust exercise.
Footprints of Immune Cells in the Pancreas in Type 1 Diabetes; to “B” or Not to “B”: Is That Still the Question?

Significant progress has been made in understanding the phenotypes of circulating immune cell sub-populations in human type 1 diabetes but much less is known about the equivalent populations that infiltrate the islets to cause beta-cell loss. In particular, considerable uncertainties remain about the phenotype and role of B-lymphocytes in the pancreas. This gap in understanding reflects both the difficulty in accessing the gland to study islet inflammation during disease progression and the fact that the number and proportion of islet-associated B-lymphocytes varies significantly according to the disease endotype. In very young children (especially those <7 years at onset) pancreatic islets are infiltrated by both CD8+ T- and CD20+ B-lymphocytes in roughly equal proportions but it is widely held that the CD8+ T-lymphocytes are responsible for driving beta-cell toxicity. By contrast, the role played by B-lymphocytes remains enigmatic. This is compounded by the fact that, in older children and teenagers (those ≥13 years at diagnosis) the proportion of B-lymphocytes found in association with inflamed islets is much reduced by comparison with those who are younger at diagnosis (reflecting two endotypes of disease) whereas CD8+ T-lymphocytes form the predominant population in both groups. In the present paper, we review the current state of understanding and develop a proposal to stimulate further discussion of the roles played by islet-associated B-lymphocytes in human type 1 diabetes. We cite evidence indicating that sites of direct contact can be found between CD8+ and CD20+-lymphocytes in and around inflamed islets and propose that such interactions may be important in determining the efficiency of beta cell killing.
Non-Epithelial Stromal Cells in Thymus Development and Function

The thymus supports T-cell development via specialized microenvironments that ensure a diverse, functional and self-tolerant T-cell population. These microenvironments are classically defined as distinct cortex and medulla regions that each contain specialized subsets of stromal cells. Extensive research on thymic epithelial cells (TEC) within the cortex and medulla has defined their essential roles during T-cell development. Significantly, there are additional non-epithelial stromal cells (NES) that exist alongside TEC within thymic microenvironments, including multiple subsets of mesenchymal and endothelial cells. In contrast to our current understanding of TEC biology, the developmental origins, lineage relationships, and functional properties, of NES remain poorly understood. However, experimental evidence suggests these cells are important for thymus function by either directly influencing T-cell development, or by indirectly regulating TEC development and/or function. Here, we focus attention on the contribution of NES to thymic microenvironments, including their phenotypic identification and functional classification, and explore their impact on thymus function.
Differential Effect of Metabolic Health and Obesity on Incident Heart Failure: A Nationwide Population-Based Cohort Study

Background Metabolically healthy obese (MHO) individuals and their association with cardiometabolic diseases have remained controversial. We aimed to explore the risk of incident heart failure (HF) based on the baseline metabolic health and obesity status as well as their transition over 2 years. Methods The Korean National Health Insurance Service-National Health Screening Cohort data of 514,886 participants were analyzed. Obesity was defined as BMI ≥25 kg/m2 according to the Korean Centers for Disease Control and Prevention. The metabolic health and obesity status were evaluated at baseline and after two years. Study participants were followed to either the date of newly diagnosed HF or the last follow-up visit, whichever occurred first. Results The MHO group comprised 9.1% of the entire population and presented a better baseline metabolic profile than the metabolically unhealthy non-obese (MUNO) and metabolicavlly unhealthy obese (MUO) groups. During the median 71.3 months of follow-up, HF developed in 5,406 (1.5%) participants. The adjusted hazard ratios [HRs (95% CI)] of HF at baseline compared with the metabolically healthy non-obese (MHNO) group were 1.29 [1.20–1.39], 1.37 [1.22–1.53], and 1.63 [1.50–1.76] for MUNO, MHO, and MUO groups, respectively. With the stable MHNO group as reference, transition into metabolically unhealthy status (MUNO and MUO) increased the risk of HF, regardless of the baseline status. Subjects who were obese at both baseline and follow-up showed an increased risk of HF, regardless of their metabolic health status. Conclusions Metabolic health and obesity status and their transition can predict the risk of incident HF. Losing metabolic health in baseline non-obese and obese individuals and remaining obese in baseline obese individuals showed a significantly increased risk of incident HF. Maintaining good metabolic health and a lean body may prevent the development of HF.
Detection of DENV-2 and Insect-Specific Flaviviruses in Mosquitoes Collected From Jeddah, Saudi Arabia

Background Mosquito-borne diseases are rapidly spreading due to increasing international travel and trade. Routine mosquito surveillance and screening for mosquito-borne pathogens can be early indicators for local disease transmission and outbreaks. However, arbovirus detection in mosquito vectors has rarely been reported in Saudi Arabia. Methods A total of 769,541 Aedes and Culex mosquitoes were collected by Black Hole traps during routine mosquito surveillance in the first half of 2016. Culex. quinquefasciatus and Ae. aegypti were the most prevalent species observed. Twenty-five and 24 randomly selected pools of Ae. aegypti and Cx. quinquefasciatus, respectively, were screened for arboviruses by RT-PCR. Results Dengue 2 (DENV-2) and four strains of insect-specific flaviviruses, including one of cell-fusing agent virus (CFAV) and three of Phlebotomus-associated flavivirus (PAFV) were detected in pools of Ae. aegypti. We also detected 10 strains of Culex flavivirus (CxFV) in pools of Cx. quinquefasciatus. Phylogenetic analysis using whole genome sequences placed the DENV strain into the cosmopolitan 1 sub-DENV-2 genotype, and the CxFVs into the African/Caribbean/Latin American genotype. These analyses also showed that the DENV-2 strain detected in the present study was closely related to strains detected in China in 2014 and in Japan in 2018, which suggests frequent movement of DENV-2 strains among these countries. Furthermore, the phylogenetic analysis suggested at least five introductions of DENV-2 into Saudi Arabia from 2014 through 2018, most probably from India. Conclusions To our knowledge, this study reports the first detection of four arboviruses DENV, CFAV, PAFV, and CxFV in mosquitoes in Saudi Arabia, which shows that they are co-circulating in Jeddah. Our findings show a need for widespread mosquito-based arbovirus surveillance programs in Saudi Arabia, which will improve our understanding of the transmission dynamics of the mosquito-borne arboviruses within the country and help early predict and mitigate the risk of human infections and outbreaks.
Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using 68Ga-FAPI PET/CT

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)]. Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.
Inflammation Spreading: Negative Spiral Linking Systemic Inflammatory Disorders and Alzheimer’s Disease

As a physiological response to injury in the internal body organs, inflammation is responsible for removing dangerous stimuli and initiating healing. However, persistent and exaggerative chronic inflammation causes undesirable negative effects in the organs. Inflammation occurring in the brain and spinal cord is known as neuroinflammation, with microglia acting as the central cellular player. There is increasing evidence suggesting that chronic neuroinflammation is the most relevant pathological feature of Alzheimer’s disease (AD), regulating other pathological features, such as the accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau. Systemic inflammatory signals caused by systemic disorders are known to strongly influence neuroinflammation as a consequence of microglial activation, inflammatory mediator production, and the recruitment of peripheral immune cells to the brain, resulting in neuronal dysfunction. However, the neuroinflammation-accelerated neuronal dysfunction in AD also influences the functions of peripheral organs. In the present review, we highlight the link between systemic inflammatory disorders and AD, with inflammation serving as the common explosion. We discuss the molecular mechanisms that govern the crosstalk between systemic inflammation and neuroinflammation. In our view, inflammation spreading indicates a negative spiral between systemic diseases and AD. Therefore, “dampening inflammation” through the inhibition of cathepsin (Cat)B or CatS may be a novel therapeutic approach for delaying the onset of and enacting early intervention for AD.
Virulence Plasmids of Rhodococcus equi Isolates From Cuban Patients With AIDS

Rhodococcus equi is an animal pathogen and zoonotic human opportunistic pathogen associated with immunosuppressive conditions. The pathogenicity of R. equi is linked to three animal host-associated virulence plasmids encoding a family of “Virulence Associated Proteins” (VAPs). Here, the PCR-based TRAVAP molecular typing system for the R. equi virulence plasmids was applied to 26 R. equi strains isolated between 2010 and 2016 at the Institute of Tropical Medicine “Pedro Kourí,” Cuba, from individuals living with HIV/AIDS. TRAVAP detects 4 gene markers, traA common to the three virulence plasmids, and vapA, vapB, and vapN specific to each of the host-associated plasmid types (equine pVAPA, porcine pVAPB, and ruminant pVAPN). Of the 26 isolates, six were positive to the vapB (porcine-type) marker, 4 (15.4%) to the vapA (equine-type) marker, and 1 (3.8%) to the vapN (ruminant-type) marker. Most of the isolates 14 (53.8%) were negative to all TRAVAP markers, suggesting they lacked a virulence plasmid. To our knowledge, this work is the first to report the molecular characterization of R. equi isolates from Cuba. Our findings provide insight into the zoonotic origin of R. equi infections in people and the potential dispensability of the virulence plasmid in immunosuppressed patients.
Burden of HIV-Related Stigma and Post-Partum Depression: A Cross-Sectional Study of Patients Attending Prevention of Mother-to-Child Transmission Clinic at Kenyatta National Hospital in Nairobi

Background: We look at how various HIV-related stigma subtypes, especially internalizing types, interact with postpartum depression (PPD) among women living with HIV. Additionally, we identify key psychosocial risk factors that influence stigma and PPD among women attending Prevention of Mother-to-Child Transmission (PMTCT) clinics. Methods: In this cross-sectional design, 123 women living with HIV were recruited. Participants ages between 18 and 50, who were at least 8 weeks postpartum seeking PMTCT services at Kenyatta National Hospital (KNH), between June and September 2014 participated in the study. HIV/AIDS Stigma Instrument—PLWHA (HASI–P) was used to assesses stigma and Postpartum depression was assessed by Edinburgh Postnatal Depression Scale (EPDS). Bivariate and multivariate regression models were used to determine the individual characteristics associated with the HIV-related stigma Scale. Post survey a few in-depth-interviews were conducted to explore individuals' stigma and depression experiences. Results: The mean age was 31.2 years (SD = 5.2). Fifty-nine (48%) women screened positive for significant depressive symptoms. Post-partum depression was a significant predictor of internalized stigma, enacted, and total stigma (P < 0.05). Older age was associated with less internalized stigma. Living with a partner was associated with more internalized stigma. Having an income above 100 USD per month was protective against stigma. Having good family social support was protective against internalized stigma. A higher educational level was protective against enacted stigma. Being treated for STIs was a risk factor for both enacted and overall stigma. Conclusions: HIV-related stigma needs to be addressed through integrated mental health care programs in PMTCT. Postpartum depression requires comprehensive management to improve short- and long-term outcomes of women living with HIV.
The Training Characteristics of World-Class Male Long-Distance Cross-Country Skiers

Purpose: To investigate the training characteristics of world-class long-distance cross-country skiers. Methods: Twelve world-class male long-distance cross-country skiing specialists reported training from their best season, through a questionnaire and follow-up interviews. Training data were systemized by training form (endurance, strength, and speed), intensity [low- (LIT), moderate- (MIT), and high-intensity training (HIT)], and exercise mode, followed by a division into different periodization phases. Specific sessions utilized in the various periodization phases were also analyzed. Results: The annual training volume was 861 ± 90 h, consisting of 795 ± 88 h (92%) of endurance training, 53 ± 17 h (6%) of strength training, and 13 ± 14 h (2%) of speed training. A pyramidal (asymptotic) endurance training distribution was employed (i.e., 88.7% LIT, 6.4% MIT, and 4.8% HIT). Out of this, 50–60% of the endurance training was performed with double poling (DP), typically in the form of a daily 3- to 5-h session. A relatively evenly distributed week-to-week periodization of training load was commonly used in the general preparation period, whereas skiers varied between high-load training weeks and competition weeks, with half the training volume and a reduced amount of DP during the competition period. Conclusions: To match the specific demands of long-distance cross-country skiing, specialized long-distance skiers perform relatively long but few training sessions and use a pyramidal intensity distribution pattern and a large amount of training spent using the DP technique.
Influenza B Virus Infection Is Enhanced Upon Heterotypic Co-infection With Influenza A Virus

Homotypic co-infections with influenza viruses are described to increase genetic population diversity, to drive viral evolution and to allow genetic complementation. Less is known about heterotypic co-infections between influenza A (IAV) and influenza B (IBV) viruses. Previous publications showed that IAV replication was suppressed upon co-infection with IBV. However, the effect of heterotypic co-infections on IBV replication was not investigated. To do so, we produced by reverse genetics a pair of replication-competent recombinant IAV (A/WSN/33) and IBV (B/Brisbane/60/2008) expressing a GFP and mCherry fluorescent reporter, respectively. A549 cells were infected simultaneously or 1 h apart at a high MOI with IAV-GFP or IBV-mCherry and the fluorescence was measured at 6 h post-infection by flow cytometry. Unexpectedly, we observed that IBV-mCherry infection was enhanced upon co-infection with IAV-GFP, and more strongly so when IAV was added 1 h prior to IBV. The same effect was observed with wild-type viruses and with various strains of IAV. Using UV-inactivated IAV or type-specific antiviral compounds, we showed that the enhancing effect of IAV infection on IBV infection was dependent on transcription/replication of the IAV genome. Our results, taken with available data in the literature, support the hypothesis that the presence of IAV proteins can enhance IBV genome expression and/or complement IBV defective particles.