Miracle-dz/UniFAR-FTUs huggingface dataset:
Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT.
Deletion of the Bcnrps1 Gene Increases the Pathogenicity of Botrytis cinerea and Reduces Its Tolerance to the Exogenous Toxic Substances Spermidine and Pyrimethanil

During the infection of grapevine (Vitis vinifera) by the fungus Botrytis cinerea, the concentration of polyamines, which are toxic substances for the phytopathogen, increases in the grape. Nine NRPS genes have been identified in the genome of B. cinerea, yet the function of five of them remains unknown. For this reason, we have studied the expression of the 9 NRPS genes by RT-qPCR in a medium supplemented with sublethal concentrations of three polyamines (1,3-diaminopropane (1,3-DAP), spermidine (SPD), and spermine (SPM)). Our results show that the presence of polyamines in the culture medium triggered the overexpression of the Bcnrps1 gene in the pathogen. Deleting Bcnrps1 did not affect mycelial growth or adaptation to osmotic stress, and we show that its expression is not essential for the cycle of infection of the B. cinerea. However, mutating the Bcnrps1 gene resulted in overexpression of the Bcnrps6 gene, which encodes for the excretion of siderophores of the coprogen family. Moreover, gene deletion has reduced the tolerance of B. cinerea B05.10 to toxic substances such as the polyamine SPD and the fungicide pyrimethanil, and its virulence has increased. Our findings provide new insights into the function of the Bcnrps1 gene and its involvement in the tolerance of B. cinerea against exogenous toxic compounds.
QRISK3 Performance in the Assessment of Cardiovascular Risk in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare the predictive ability of QRISK3 with that of a well-established European CV risk calculator, the Systematic Coronary Risk Assessment (SCORE), to identify the presence of subclinical carotid atherosclerosis in patients with IBD. In all, 186 patients with IBD and 178 controls were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied in patients and controls. SCORE (0.2 (interquartile range 0.1–0.9) vs. 0.4 (0.1–1.4), p = 0.55) and QRISK3 1.7 ((0.6–4.6) vs. 3.0 (1.0–7.8), p = 0.16) absolute values did not differ between patients and controls. QRISK3 and SCORE correlated equally with cIMT within both populations. However, SCORE correlation with cIMT was found to be significantly lower in patients with IBD when compared to controls (Spearman’s Rho 0.715 vs. 0.587, p = 0.034). Discrimination analysis of both calculators with carotid plaque was similar within both populations. Nevertheless, in patients with IBD, QRISK3 showed a trend toward a higher discrimination (QRISK3 area under the curve 0.812 (95%CI 0.748–0.875) vs. SCORE 0.790 (95%CI 0.723–0.856), p = 0.051). In conclusion, QRISK3 discrimination for subclinical atherosclerosis is optimal and equivalent to that of SCORE in IBD patients. However, our findings highlight the role of QRISK3 as an appropriate tool for the assessment of CV risk in patients with IBD.
The Effects of Green Tea on Diabetes and Gut Microbiome in db/db Mice: Studies with Tea Extracts vs. Tea Powder

Green tea extracts and tea catechins have been shown to prevent or alleviate diabetes. The present study tests the hypothesis that green tea leaves in powder form (GTP), which also contain fiber and other water non-extractable materials, are more effective than the corresponding green tea extracts (GTE) in impeding the development of diabetes in db/db mice. Female db/db mice were treated with a diet containing 1% of GTE, 2% of GTE, 2% of GTP (with the same catechin content as 1% GTE) or 1% GTP. The 1% GTE group had lower food intake, water consumption, body weight and fasting blood glucose levels than the control group, while 2% GTP did not have any significant effect. Dietary 1% GTE also preserved β-cell insulin secretion. However, 1% GTP increased food intake, water consumption and blood glucose levels. Microbiome analysis with 16S rRNA gene V4 sequencing showed that the gut microbiota was modified by GTE and GTP, and a few bacterial guilds were associated with blood glucose levels. In the Random Forest regression model, the leading predictor of metabolic outcome was food consumption, followed by changes in some bacterial guilds. The results illustrate the importance of food consumption and gut microbiota in affecting the progression of diabetes.
Novel Insights into Epigenetic Regulation of IL6 Pathway: In Silico Perspective on Inflammation and Cancer Relationship

IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients.
Determination Ethanol In Arak With Gas Chromatography

Ethanol is a type of alcohol that can be consumed. One of drinks containing ethanol is Arak. Due to ethanol drink containing in excessive levels, has many causes and event such as accidents caused by drunken brawl. The purpose of this research was to determine the levels of ethanol in Arak is sold in the Merita village of Karangasem regency. Determination levels of ethanol done by gas chromatography. Results of the determination of levels ethanol of 5 samples taken at random to meet the standard required by Menkes RI number 86/Menkes/Per/IV/77, alcohol group B at the rate of 5-20% is sampel ‘a’ that is at the rate of 18.47%, sample ‘c’ with the rate of 16.11% and sampel ‘d’ with the rate 11.68%. Alcohol group C with 20-55% rate that is in the sample ‘b’ with a sample rate of 25.28% and sampel ‘e’ with the rate 25.94%.
Seven Years at High Salinity—Experimental Evolution of the Extremely Halotolerant Black Yeast Hortaea werneckii

The experimental evolution of microorganisms exposed to extreme conditions can provide insight into cellular adaptation to stress. Typically, stress-sensitive species are exposed to stress over many generations and then examined for improvements in their stress tolerance. In contrast, when starting with an already stress-tolerant progenitor there may be less room for further improvement, it may still be able to tweak its cellular machinery to increase extremotolerance, perhaps at the cost of poorer performance under non-extreme conditions. To investigate these possibilities, a strain of extremely halotolerant black yeast Hortaea werneckii was grown for over seven years through at least 800 generations in a medium containing 4.3 M NaCl. Although this salinity is well above the optimum (0.8–1.7 M) for the species, the growth rate of the evolved H. werneckii did not change in the absence of salt or at high concentrations of NaCl, KCl, sorbitol, or glycerol. Other phenotypic traits did change during the course of the experimental evolution, including fewer multicellular chains in the evolved strains, significantly narrower cells, increased resistance to caspofungin, and altered melanisation. Whole-genome sequencing revealed the occurrence of multiple aneuploidies during the experimental evolution of the otherwise diploid H. werneckii. A significant overrepresentation of several gene groups was observed in aneuploid regions. Taken together, these changes suggest that long-term growth at extreme salinity led to alterations in cell wall and morphology, signalling pathways, and the pentose phosphate cycle. Although there is currently limited evidence for the adaptive value of these changes, they offer promising starting points for future studies of fungal halotolerance.
Two Antibody-Guided Lactic-co-Glycolic Acid-Polyethylenimine (LGA-PEI) Nanoparticle Delivery Systems for Therapeutic Nucleic Acids

We previously reported a new polymer, lactic-co-glycolic acid-polyethylenimine (LGA-PEI), as an improved nanoparticle (NP) delivery for therapeutic nucleic acids (TNAs). Here, we further developed two antibody (Ab)-conjugated LGA-PEI NP technologies for active-targeting delivery of TNAs. LGA-PEI was covalently conjugated with a single-chain variable fragment antibody (scFv) against mesothelin (MSLN), a biomarker for pancreatic cancer (PC), or a special Ab fragment crystallizable region-binding peptide (FcBP), which binds to any full Ab (IgG). TNAs used in the current study included tumor suppressor microRNA mimics (miR-198 and miR-520h) and non-coding RNA X-inactive specific transcript (XIST) fragments; green fluorescence protein gene (GFP plasmid DNA) was also used as an example of plasmid DNA. MSLN scFv-LGA-PEI NPs with TNAs significantly improved their binding and internalization in PC cells with high expression of MSLN in vitro and in vivo. Anti-epidermal growth factor receptor (EGFR) monoclonal Ab (Cetuximab) binding to FcBP-LGA-PEI showed active-targeting delivery of TNAs to EGFR-expressing PC cells.
RSK1 vs. RSK2 Inhibitory Activity of the Marine β-Carboline Alkaloid Manzamine A: A Biochemical, Cervical Cancer Protein Expression, and Computational Study

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia, and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, SIX1, and vacuolar ATPases. We hypothesized that additional, yet undiscovered molecular targets might be associated with Manzamine A’s (MZA) reported pharmacological properties. We report here, for the first time, that MZA selectively inhibited a 90 kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases, while in vitro RSK kinase assays demonstrated a 10-fold selectivity in the potency of MZA against RSK1 versus RSK2. The effect of MZA on inhibiting cellular RSK1 and RSK2 protein expression was validated in SiHa and CaSki human cervical carcinoma cell lines. MZA’s differential binding and selectivity toward the two isoforms was also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2–MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes, including growth, survival, and proliferation. Consequently, our findings have led us to hypothesize that MZA and the currently known manzamine-type alkaloids isolated from several sponge genera may have novel pharmacological properties with unique molecular targets, and MZA provides a new tool for chemical-biology studies involving RSK1.
Temperate Air Breathing Increases Cycling Performance in Hot and Humid Climate Environment

Practicing physical activity in a hot and humid climate (HHC) is becoming increasingly common due to anthropogenic climate change and the growing number of international sports events held in warm countries. The aim of this study was to understand the physiological and psychological effects of breathing two air temperatures during cycling exercise in HHC. Ten male athletes performed two sessions of exercise in HHC (T°: 32.0 ± 0.5 °C, relative humidity: 78.6 ± 0.7%) during which they breathed hot air (HA, 33.2 ± 0.06 °C) or temperate air (TA, 22.6 ± 0.1 °C). Each session was composed of 30 min of pre-fatigue cycling at constant intensity, followed by a 10 min self-regulated performance. During pre-fatigue, TA induced a better feeling score and a lower rating of perceived effort (respectively, +0.9 ± 0.2, p < 0.05; 1.13 ± 0.21; p < 0.05) with no changes in physiological parameters. During performance, oxygen consumption and mechanical workload were increased by TA (respectively, +0.23 ± 0.1 L min−1, p < 0.05 and +19.2 ± 6.1 W, p < 0.01), whereas no significant differences were observed for psychological parameters. Reducing the breathed air temperature decreased the discomfort induced by HHC during exercise and increased the performance capacity during self-regulated exercise. Thus, breathed air temperature perception is linked to the hardship of training sessions and directly contributes to the performance decrease in HHC.
Job Satisfaction and Chronic Stress of General Practitioners and Their Teams: Baseline Data of a Cluster-Randomised Trial (IMPROVEjob)

Background: A high prevalence of poor job satisfaction and high chronic stress is documented for general practitioners (GPs) and non-physician practice staff from various countries. The reasons are multifactorial and include deficits in leadership, communication and workflows. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVEjob intervention on improving job satisfaction among GPs and practice personnel. Here, we report the baseline characteristics of the participating GPs and practice assistants, focusing on job satisfaction and perceived chronic stress. Methods: The IMPROVEjob study was performed as a cluster-randomised, controlled trial (cRCT) with German GP practices in the North Rhine Region. The IMPROVEjob intervention comprised two leadership workshops (one for practice leaders only; a second for leaders and practice assistants), a toolbox with supplemental printed and online material, and a nine-month implementation phase supported by IMPROVEjob facilitators. The intervention addressed issues of leadership, communication, and work processes. During study nurse visits, participants completed questionnaires at baseline and after nine months follow up. The primary outcome was the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (German COPSOQ, version 2018). Perceived chronic stress was measured using the Trier Inventory of Chronic Stress (TICS- SSCS). Results: Recruitment of 60 practices was successful: 21 were solo, 39 were group practices. At baseline, n = 84 practice owners, n = 28 employed physicians and n = 254 practice assistants were included. The mean age of all participants was 44.4 (SD = 12.8). At baseline, the job satisfaction score in the total sample was 74.19 of 100 (±14.45) and the perceived chronic stress score was 19.04 of 48 (±8.78). Practice assistants had a significantly lower job satisfaction than practice owners (p < 0.05) and employed physicians (p < 0.05). In the regression analysis, perceived chronic stress was negatively associated with job satisfaction (b= −0.606, SE b = 0.082, p < 0.001, ICC = 0.10). Discussion: The degree of job satisfaction was similar to those in other medical professionals published in studies, while perceived chronic stress was markedly higher compared to the general German population. These findings confirm the need for interventions to improve psychological wellbeing in GP practice personnel.
Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.
Trait Plasticity among Invasive Populations of the Ant Technomyrmex brunneus in Japan

Simple Summary Invasive ants are a global economic and ecological problem. Understanding what makes them tick is thus an active area of scientific research. Many invasive ant species form large networks of inter-connected colonies (‘supercolonies’) which can span many hundreds of kilometres. Supercolonies are typically a characteristic of invasive populations, and studies have also identified shifts in other traits including diet in invasive populations compared to populations in the native range. This suggests that the ability to plastically change behaviour in this way may facilitate invasiveness. In this study, we assess trait plasticity in the invasive range of the ant Technomyrmex brunneus. This species is native to southern Asia and has invaded many islands of the southern Japanese archipelago, allowing us to compare traits among different invasive populations. We find a supercolony in one of the three invasive populations studied, though interestingly, this population did not show the expected pattern of lower genetic diversity. The supercolony population did differ in diet compared to other populations. While it is unclear if variation in these traits is linked, our findings add weight to arguments that plasticity is important in facilitating invasiveness. Abstract Characters in invasive populations often differ from those in the native range, and the ability to express different characters may enhance invasive potential. Ants are among the most pervasive and damaging invasive species, by virtue of their transportability and broad-ranging ecological interactions. Their success is often attributed to the ability to exhibit different characteristics in invasive populations, including the formation of large, unicolonial associations (‘supercolonies’). It remains unclear, however, if such characteristics are a product or cause of the ecological dominance of invasive ants, and the advancement of our understanding has likely been restrained by the fact that studies to date have focused on a few globally important species with well-established invasions. In this study, we take advantage of an ongoing invasion of the tramp ant Technomyrmex brunneus in Japan to assess trait plasticity in the invasive range of this species. We find evidence for plasticity in social structure among island populations, with a supercolony evident on one of the three islands studied. Interestingly, we found no evidence of lower genetic diversity in this population, though natural isotope data indicate it was operating at a lower trophic level than other populations. These findings add weight to arguments that invasive species may benefit from the capacity to adaptively mould themselves to new ecological contexts.
WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Insulin and Insulin Resistance in Breast Cancer Survivors

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0–5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.