Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein-Bound Polysaccharides from Coriolus Versicolor Induce RIPK1/RIPK3/MLKL-Mediated Necroptosis in ER-Positive Breast Cancer and Amelanotic Melanoma Cells.

BACKGROUND/AIMS The induction of necroptosis, a form of caspase-independent cell death, represents one of the most promising anticancer therapeutic modalities, as necroptosis serves as an alternative way to eliminate apoptosis-resistant tumor cells. Here, we investigated whether protein-bound polysaccharides (PBPs) derived from the fungus Coriolus versicolor (CV) induce the necroptotic death pathway in breast cancer and melanoma cells. METHODS MCF-7 and SKMel-188 cells were exposed to PBPs either alone or in combination with necrostatin-1 (Nec-1), GSK'872 or necrosulfonamide (NSA), pharmacological inhibitors of the kinases receptor-interacting protein 1 kinase (RIPK1), receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL), respectively, which are involved in necroptotic processes. The effects of cellular treatment with these inhibitors were quantified by measuring cell viability and reactive oxygen species (ROS) generation via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and 2',7'-dichlorofluorescein diacetate (DCF-DA) assays, respectively. The morphological changes induced in these cells were detected using holotomographic (HT) microscopy. Activation of the TNF-α/TNFR1 pathway in the PBP-stimulated cells was evaluated using TNF-α-neutralizing antibody, qRT-PCR and immunofluorescence-based assays. RESULTS PBPs showed effective antitumor activity against MCF-7 and SKMel-188 cells. Cotreatment of the cells with Nec-1, GSK'872 or NSA abrogated PBP-induced cell death, and the cells were protected against membrane rupture. Moreover, breast cancer cell death caused by PBPs was mediated by induced activation of the TNF-α/TNFR1 pathway. Interestingly, the melanoma cells did not express TNF-α or TNFR1 after PBP stimulation; instead, PBPs triggered intracellular ROS generation, which was partially diminished by the inhibitors Nec-1, GSK'872 and NSA. CONCLUSION These results suggest that PBPs from the fungus CV induce RIPK1/RIPK3/MLKL-mediated necroptosis in breast cancer and melanoma cells, providing novel insights into the molecular effects of PBPs on cancer cells.
Controlling for openness in the male-dominated collaborative networks of the global film industry

Studies of gender inequality in film industries have noted the persistence of male domination in creative roles (usually defined as director, producer, writer) and the slow pace of reform. Typical policy remedies are premised on aggregate counts of women as a proportion of overall industry participation. Network science offers an alternative way of identifying and proposing change mechanisms, as it puts emphasis on relationships instead of individuals. Preliminary work on applying network analysis to understand inequality in the film industry has been undertaken. However, in this study we offer a comprehensive approach that enables us to not only understand what inequality in the film industry looks like through the lens of network science but also how we can attempt to address this issue. We offer a data-driven simulation framework that investigates various what-if scenarios when it comes to network evolution. We then assess each of these scenarios with respect to its potential to address gender inequality in the film industry. As suggested by previous studies, inequality is exacerbated when industry networks are most closed. We review evidence from three different national film industries on network relationships in creative teams and identify a high proportion of men who only work with other men. In response to this observation, we test several mechanisms through which industry structures may generate higher levels of openness. Our results reveal that the most critical factor for improving network openness is not simply the statistical improvement of the number of women in a network, nor the removal of men who do not work with women. The most likely behavioural changes to a network will involve the production of connections between women and powerful men.
Epicuticular hydrocarbons of the sugarcane borer Diatraea saccharalis (Lepidoptera: Crambidae)

The epicuticular hydrocarbons of the larval, pupal and adult stages of the sugarcane borer Diatraea saccharalis Fabricius (Lepidoptera: Crambidae) are analysed. Dramatic changes are observed between the stages studied. Adult hydrocarbons are mostly saturated, with a predominance of 1–4 methyl‐branched straight carbon skeletons of 37–47 atoms; the major components are isomeric mixtures of internally branched trimethylderivatives of C39, C37 and C41 carbon backbones. By contrast, very small amounts of methyl‐branched components are detected in the pupae, although straight chain hydrocarbons of 23–35 carbons are the prevailing structures (70.7 ± 3.4%) with n‐C29 and n‐C27 as the major components. Unsaturated hydrocarbons (29.0 ± 3.5%) of similar chain lengths elute by gas chromatography of epicuticular extracts as complex mixtures of mono‐, di‐ and trienes; with the degree of unsaturation increasing with chain length. This is the first report of very long chain unsaturated hydrocarbons in cuticular extracts of a larval lepidopteran (93.3 ± 0.6% of the lipid components), with chain lengths in the range 37–53 carbons and up to four double bonds; the major component being C49:3, which co‐elutes with C49:4 and C49:2.
Preparation and Characterization of pH Sensitive Chitosan/3-Glycidyloxypropyl Trimethoxysilane (GPTMS) Hydrogels by Sol-Gel Method

pH responsive chitosan and 3-Glycidyloxypropyl trimethoxysilane (GPTMS) hydrogels were synthesized by the sol-gel crosslinking reaction. GPTMS was introduced to influence several behaviors of the chitosan hydrogels, such as the swelling ratio, mechanical properties, swelling thermodynamics, kinetics, and expansion mechanism. The functional groups of Chitosan/GPTMS hybrid hydrogels were verified by FT-IR spectrometer. Differential scanning calorimetry (DSC) and the thermogravimetric analysis (TGA) were used to analyzed the thermal behavior of water molecules, the expansion of thermodynamics, and the content of water molecules in the hydrogel. The results show that hydrogel consists of 50 wt. % GPTMS (CG50) and has good mechanical properties and sensitivity to pH response characteristics in the acidic/alkaline buffer solution. The increase of GPTMS content leads to the increase of hydrophobic groups in the hydrogel and causes the decrease of the overall water content and the freezing bond water content. When the hydrogels were immersed in acid solution, the interaction force parameter was smaller than that of DI-water and alkaline. It means that the interaction forces between hydrogel and water molecules are relatively strong. The swelling kinetics of hybrid hydrogels were investigated to inspect the swelling mechanism. The result is consistent with the Fisk’s diffusion mechanism, meaning that the rate of water penetration is adjustable. The biodegradable hydrogel (CG50) in this study has good environmental sensitivity and mechanical properties. It is suitable to be applied in the fields of drug release or biomedical technology.
Modulation of Macrophage Polarization by Phospholipids on the Surface of Titanium

Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the discs. The coated discs were hydrated before cell culture was added. The shape of the hydrated phospholipids varied with the concentration of loaded phospholipids: a perforated layer (0.1 mM), tubules and spheres (1 mM), and spheres (10 mM). RAW 264.7 cells exhibited different morphologies, depending on the concentration of phospholipids. On the coated discs, the gene expression and protein release of TGF-β1, VEGF, Arg-1, and TNF-α were downregulated, especially with 10 mM phospholipids. The stimulation of mRNA expression and the protein release of those genes by IL-4 and LPS were also disturbed on the phospholipid-coated discs. In conclusion, the polarization of RAW 264.7 cells was prevented by hydrated phospholipids on Ti discs.
Low Volume Acute Multi-Joint Resistance Exercise Elicits a Circulating Brain-Derived Neurotrophic Factor Response but Not a Cathepsin B Response in Well-Trained Men.

This study examined if acute multi-joint resistance exercises (RE - back squat, bench press, and deadlift) to volitional failure elicited a post-exercise increase in the circulating response of biomarkers associated with neuroprotection. Thirteen males (age: 24.5±3.8yrs, body mass: 84.01±15.44kg, height: 173.43±8.57cm, training age: 7.1±4.2yrs) performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the squat, bench press, and deadlift in successive weeks. The measured biomarkers were brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). Biomarkers were assessed immediately pre- and 10-minutes post-exercise. There was a main time effect (pre-exercise: 24.00±0.61 to post-exercise: 27.38±0.48ng/mL; p<0.01) for BDNF with increases in the deadlift (p=0.01) and bench press (p=0.01) conditions, but not in the squat condition (p=0.21). There was a main time effect (pre-exercise: 0.87±0.16 to post-exercise: 2.03±0.32pg/mL; p<0.01) for IL-6 with a significant increase in the squat (p<0.01), but not the bench press (p=0.88) and deadlift conditions (p=0.24). No main time effect was observed for either CatB (p=0.62) or IGF-1 (p=0.56). In summary, acute multi-joint RE increases circulating BDNF. Further, this investigation is the first to report the lack of a transient change of CatB to an acute RE protocol. Novelty • Low-volume resistance exercise to failure can increase BDNF • Resistance training does not confer an acute Cat B response.
Abnormal Liver Function Tests of Patients with Coronavirus Disease 2019 in Mainland China: A Systematic Review and Meta- Analysis.

AIMS Comparing the risk of abnormal liver function tests between severe and non-severe patients with coronavirus disease 2019 (COVID-19) by meta-analysis. METHODS A literature search was conducted using the databases PubMed, Embase, and Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Publication bias was detected by the Harbord test. RESULTS We included 8 articles comprising 7,467 COVID-19 patients. When compared between severe and non-severe COVID-19 patients, the pooled ORs of elevated alanine aminotransferase, aspartate aminotransferase, total bilirubin, and lactate dehydrogenase levels were 2.35 (95% CI 1.38-3.98), 3.21 (95% CI 2.59-3.98), 1.87 (95% CI 1.32-2.65), and 4.83 (95% CI 2.90-8.05), respectively. CONCLUSIONS The severity of COVID-19 is associated with liver damage, and can be a risk factor for abnormal liver function tests.
Seasonal Population Dynamics of Potato Psyllid (Hemiptera: Triozidae) in the Columbia River Basin

Abstract Understanding factors that affect the population dynamics of insect pest species is key for developing integrated pest management strategies in agroecosystems. Most insect pest populations are strongly regulated by abiotic factors such as temperature and precipitation, and assessing relationships between abiotic conditions and pest dynamics can aid decision-making. However, many pests are also managed with insecticides, which can confound relationships between abiotic factors and pest dynamics. Here we used data from a regional monitoring network in the Pacific Northwest United States to explore effects of abiotic factors on populations of an intensively managed potato pest, the potato psyllid (Bactericera cockerelli Šulc), which can vector Candidatus Liberibacter psyllaurus, a bacterial pathogen of potatoes. We assessed effects of temperature on psyllid populations, and show psyllid population growth followed predictable patterns within each year, but there was considerable variation across years in psyllid abundance. Examination of seasonal weather patterns suggested that in 2017, when psyllid populations were less abundant by several orders of magnitude than other years, a particularly long and cold period of winter weather may have harmed overwintering populations and limited population growth. The rate of degree-day accumulation over time, as well as total degree-day accumulation also affected trap catch abundance, likely by mediating the number of psyllid generations per season. Our findings indicate that growers can reliably infer the potential magnitude of risk from potato psyllids using monitoring data, date of first detection, seasonal weather patterns, and population size early in the growing season.
Clinical outcome of endoscopic treatment for symptomatic sterile walled-off necrosis

Abstract Background The majority of patients with symptomatic sterile walled-off necrosis (WON) can be treated conservatively. Although endoscopic transluminal drainage (ETD) is often performed in cases of persistent symptoms, post-procedural iatrogenic infection may occur. This study aimed to evaluate clinical outcomes after ETD of symptomatic sterile WON. Methods This was a retrospective, multicenter, open-label case series of 56 patients with necrotizing pancreatitis who underwent ETD for symptomatic sterile WON between July 2001 and August 2018 at two tertiary referral hospitals. Primary end point was clinically relevant post-procedural iatrogenic infection, defined as need for endoscopic transluminal necrosectomy. Secondary end points included mortality, total number of interventions, hospital stay, and resolution of symptoms at 1-year follow-up. Results ETD of sterile WON was performed in 56 patients (median age 55 years, 57 % male), who presented with abdominal pain (71 %), gastric outlet obstruction (45 %), jaundice (20 %), and failure to thrive (27 %). A total of 41 patients (73 %) developed clinically relevant post-procedural iatrogenic infection, resulting in a median of 3 (interquartile range [IQR] 2 – 4) endoscopic, radiological, and/or surgical interventions. Mortality rate was 2 %. Median total hospital stay was 12 days (IQR 6 – 17). Resolution of symptoms was reported in 40 of 46 patients (87 %) for whom long-term follow-up data were available (median follow-up 13 months, IQR 6 – 29). Conclusions ETD of symptomatic sterile WON resulted in high clinical success. Nonetheless, the majority of patients required additional reinterventions for clinically relevant post-procedural iatrogenic infection.
A Doxorubicin-Glucuronide Prodrug Released from Nanogels Activated by High-Intensity Focused Ultrasound Liberated β-Glucuronidase

The poor pharmacokinetics and selectivity of low-molecular-weight anticancer drugs contribute to the relatively low effectiveness of chemotherapy treatments. To improve the pharmacokinetics and selectivity of these treatments, the combination of a doxorubicin-glucuronide prodrug (DOX-propGA3) nanogel formulation and the liberation of endogenous β-glucuronidase from cells exposed to high-intensity focused ultrasound (HIFU) were investigated in vitro. First, a DOX-propGA3-polymer was synthesized. Subsequently, DOX-propGA3-nanogels were formed from this polymer dissolved in water using inverse mini-emulsion photopolymerization. In the presence of bovine β-glucuronidase, the DOX-propGA3 in the nanogels was quantitatively converted into the chemotherapeutic drug doxorubicin. Exposure of cells to HIFU efficiently induced liberation of endogenous β-glucuronidase, which in turn converted the prodrug released from the DOX-propGA3-nanogels into doxorubicin. β-glucuronidase liberated from cells exposed to HIFU increased the cytotoxicity of DOX-propGA3-nanogels to a similar extend as bovine β-glucuronidase, whereas in the absence of either bovine β-glucuronidase or β-glucuronidase liberated from cells exposed to HIFU, the DOX-propGA3-nanogels hardly showed cytotoxicity. Overall, DOX-propGA3-nanogels systems might help to further improve the outcome of HIFU-related anticancer therapy.
Another Breaker of the Wall: the Biological Function of the Usp45 Protein of Lactococcus lactis

The cell wall, composed mainly of peptidoglycan, is key to maintaining the cell shape and protecting the cell from bursting. Peptidoglycan degradation by peptidoglycan hydrolysis and autolysins occurs during growth and cell division. Since peptidoglycan hydrolases are important for virulence, envelope integrity, and regulation of cell division, it is valuable to investigate their function and regulation. Notably, PcsB-like proteins such as Usp45 have been proposed as new targets for antimicrobial drugs and could also be target for the development of food-grade suicide systems. In addition, although various other expression and secretion systems have been developed for use in Lactococcus lactis, the most-used signal peptide for protein secretion in this bacterium is that of the Usp45 protein. Thus, elucidating the biological function of Usp45 and determining the factors affecting its expression would contribute to optimize several applications. ABSTRACT Lactococcus lactis is a Gram-positive bacterium that is widely used as a cell factory for the expression of heterologous proteins that are relevant in the pharmaceutical and nutraceutical fields. The signal peptide of the major secreted protein of L. lactis, Usp45, has been employed extensively in engineering strategies to secrete proteins of interest. However, the biological function of Usp45 has remained obscure despite more than 25 years of research. Studies on Usp45 homologs in other Gram-positive bacteria suggest that Usp45 may play a role in cell wall turnover processes. Here, we show the effect of inactivation and overexpression of the usp45 gene on L. lactis growth, phenotype, and cell division. Our results are in agreement with those obtained in streptococci and demonstrate that the L. lactis Usp45 protein is essential for proper cell division. We also show that the usp45 promoter is highly activated by galactose. Overall, our results indicate that Usp45 mediates cell separation, probably by acting as a peptidoglycan hydrolase. IMPORTANCE The cell wall, composed mainly of peptidoglycan, is key to maintaining the cell shape and protecting the cell from bursting. Peptidoglycan degradation by peptidoglycan hydrolysis and autolysins occurs during growth and cell division. Since peptidoglycan hydrolases are important for virulence, envelope integrity, and regulation of cell division, it is valuable to investigate their function and regulation. Notably, PcsB-like proteins such as Usp45 have been proposed as new targets for antimicrobial drugs and could also be target for the development of food-grade suicide systems. In addition, although various other expression and secretion systems have been developed for use in Lactococcus lactis, the most-used signal peptide for protein secretion in this bacterium is that of the Usp45 protein. Thus, elucidating the biological function of Usp45 and determining the factors affecting its expression would contribute to optimize several applications.
Plasma IL8 Is a Biomarker for TAK1 Activation and Predicts Resistance to Nanoliposomal Irinotecan in Patients with Gemcitabine-Refractory Pancreatic Cancer

Purpose: Pancreatic cancer is one of the most lethal solid tumors, mainly because of its intrinsic chemoresistance. We identified TAK1 as a central hub sustaining this resistance. Nanoliposomal irinotecan (nal-IRI) is a novel treatment for metastatic gemcitabine-refractory pancreatic cancer. We endeavored to identify circulating markers for TAK1 activation predicting chemoresistance in this setting. Experimental Design: In vivo activity of nal-IRI was validated in an orthotopic nude murine model expressing TAK1-specific shRNA. Plasma concentration of 20 different cytokines were measured by a multiplex xMAP/Luminex technology in patients prospectively enrolled to receive nal-IRI plus 5-fluorouracil/leucovorin (5-FU/LV). The optimal cutoff thresholds able to significantly predict patients' outcome were obtained on the basis of the maximization of the Youden's statistics. Results: Differential expression profiling revealed the gene coding for IL8 as the most significantly downregulated in shTAK1 pancreatic cancer cell lines. Mice bearing shTAK1 tumors had significantly lower plasma levels of IL8 and experienced a significant reduction in tumor growth if treated with nal-IRI, whereas those bearing TAK1-proficient tumors were resistant to this agent. In a discovery cohort of 77 patients, IL8 was the circulating factor most significantly correlated with survival (plasma levels lower vs higher than cutoff: mPFS 3.4 months vs 2.8 months; hazard ratio [HR], 2.55; 95% CI, 1.39–4.67; P = 0.0017; median overall survival 8.9 months vs 5.3 months; HR, 3.51; 95% CI, 0.84–6.68; P = 4.9e−05). These results were confirmed in a validation cohort of 50 patients. Conclusions: Our study identified IL8 as the most significant circulating factor for TAK1 pathway activation and candidates IL8 as a potential predictive biomarker of resistance to nal-IRI in gemcitabine-refractory patients with pancreatic cancer.
The strength of trophic cascades across ecosystems: predictions from allometry and energetics

Summary 1 Top-down control of trophic structure is often highly variable both within and among ecosystems. We explored the roles of relative body sizes of predators and prey, their metabolic types, the production-to-biomass ratio (P : B) of plants, and system productivity in determining the strength of the indirect effects of predators on plants. 2 We used a well-studied food chain model with three trophic levels that is parameterized based on allometric relationships for rates of ingestion and metabolic efficiency. The model predicts that invertebrate and ectotherm predators and herbivores should propagate cascades to a greater degree than vertebrates and endotherms because of their higher metabolic efficiency. 3 Increasing the herbivore-to-plant body-size ratio strengthened the effects of cascades, while predator body-size was predicted to have no effect. Increasing system productivity or plant P : B magnified cascades. Because herbivore : plant body size ratios and plant P : B are both generally greater in aquatic than terrestrial systems (especially those with unicellular producers), the model predicts stronger cascades in water than on land. This prediction is supported by a recent cross-system comparison of trophic cascade experiments. 4 We discuss features of natural systems that are not incorporated into the model and their implications for the intensity of trophic cascades across ecosystems.