Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model

ABSTRACT Purpose To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. Materials and Methods An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated. Results Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group. Conclusions The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis.
Oncological Outcomes after Liver Venous Deprivation for Colorectal Liver Metastases: A Single Center Experience

Simple Summary In the original retrospective study entitled “Oncological outcomes after Liver Venous Deprivation for Colorectal Liver Metastases: a single center experience” the authors report for the first time the oncological outcomes of Liver Venous Deprivation (LVD) for Colorectal Liver Metastases. LVD is an interventional radiologic technique recently employed before major liver resections and has already showed its safety and effectiveness in inducing contralateral liver hypertrophy. Seventeen consecutive patients undergoing LVD between July 2015 and May 2020 before a right (or extended right) hepatectomy were retrospectively analyzed from an institutional database. The 1-year and 3-year overall survival (OS), as well as hepatic recurrence and Disease Free Survival (DFS), were comparable to literature reports of portal vein embolization (PVE) oncological outcomes. Abstract Colorectal liver metastases (CRLM) are the major cause of death in patients with colorectal cancer (CRC). The cornerstone treatment of CRLM is surgical resection. Post-operative morbidity and mortality are mainly linked to an inadequate future liver remnant (FLR). Nowadays preoperative portal vein embolization (PVE) is the most widely performed technique to increase the size of the future liver remnant (FLR) before major hepatectomies. One method recently proposed to increase the FLR is liver venous deprivation (LVD), but its oncological impact is still unknown. The aim of this study is to report first short- and long-term oncological outcomes after LVD in patients undergoing right (or extended right) hepatectomy for CRLM. Seventeen consecutive patients undergoing LVD between July 2015 and May 2020 before an (extended) right hepatectomy were retrospectively analyzed from an institutional database. Post-operative and follow-up data were analyzed and reported. Primary outcomes were 1-year and 3-year overall survival (OS) and hepatic recurrence (HR). Postoperative complications occurred in 8 patients (47%). No deaths occurred after surgery. HR occurred in 9 patients (52.9%). 1-year and 3-year OS were 87% (95% confidence interval [CI]: ±16%) and 60.3%, respectively (95% CI: ±23%). Median Disease-Free Survival (DFS) was 6 months (CI 95%: 4.7–7.2). With all the limitations of a retrospective study with a small sample size, LVD showed similar oncological outcomes compared to literature reports for Portal Vein Embolization (PVE).
Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.
Effects of family history of diabetes on pancreatic β-cell function and diabetic ketoacidosis in newly diagnosed patients with type 2 diabetes: a cross-sectional study in China

Objective To investigate the association between a parental and/or sibling history of diabetes and clinical characteristics. Design A cross-sectional study. Setting The data were collected from the endocrinology department of The Second Xiangya Hospital of Central South University from June 2017 to October 2019. Participants A total of 894 newly diagnosed patients with type 2 diabetes were recruited. Data on clinical characteristics were collected from patient medical records. Pancreatic β-cell function and insulin resistance were calculated with the homeostatic model assessment. SPSS V.25. 0 was used to perform the analysis. Results The percentages of patients with parental and sibling histories of diabetes were 14.8% and 9.8%, respectively. The prevalence of diabetic ketoacidosis (DKA) was 3.9%. Compared with those with no parental history of diabetes, patients with a parental history of diabetes were characterised by early-onset disease (41.70±10.88 vs 51.17±14.09 years), poor glycaemic control of fasting blood glucose (10.84±5.21 vs 8.91±4.38 mmol/L) and a high prevalence of DKA (7.6% vs 3.3%). The patients with a sibling history of diabetes had later disease onset (56.05±9.86 vs 49.09±14.29 years) and lower BMI (24.49±3.48 vs 25.69±3.86 kg/m2) than those with no sibling history of diabetes. Univariate regression suggested that both parental history (p=0.037) and sibling history (p=0.011) of diabetes were associated with β-cell function; however, multiple regression analysis showed that only a sibling history of diabetes was associated with β-cell function (p=0.038). Univariate regression revealed a positive correlation between parental history of diabetes (p=0.023, OR=2.416, 95% CI 1.132 to 5.156) and DKA. Unfortunately, this correlation was not statistically significant for either patients with a parental history (p=0.234, OR=1.646, 95% CI 0.724 to 3.743) or those with a sibling history (p=0.104, OR=2.319, 95% CI 0.841 to 6.389) after adjustments for confounders. Conclusion A sibling history of diabetes was associated with poor β-cell function, and a parental history of diabetes was associated with poor glycaemic control and a high prevalence of DKA.
Multiple signaling pathways are essential for synapse formation induced by synaptic adhesion molecules

Significance Formation of synapses is thought to be mediated by transsynaptic adhesion molecules, but the intracellular signaling pathways involved are largely unknown. Here we studied synapse formation using as an approach heterologous synapse formation assays, in which synaptic adhesion molecules expressed in a nonneuronal cell induce formation of pre- or postsynaptic specializations in cocultured neurons. Aided by pharmacological inhibitors and genetic tools, we found that c-jun N-terminal kinases (JNK) and protein kinase-A signaling contributes to the formation of both pre- and postsynaptic specializations during heterologous synapse formation, whereas the PI3 kinase/AKT signaling pathway is required only for formation of post- but not of presynaptic specializations. Our results suggest that a multistage kinase network is essential for heterologous synapse formation. Little is known about the cellular signals that organize synapse formation. To explore what signaling pathways may be involved, we employed heterologous synapse formation assays in which a synaptic adhesion molecule expressed in a nonneuronal cell induces pre- or postsynaptic specializations in cocultured neurons. We found that interfering pharmacologically with microtubules or actin filaments impaired heterologous synapse formation, whereas blocking protein synthesis had no effect. Unexpectedly, pharmacological inhibition of c-jun N-terminal kinases (JNKs), protein kinase-A (PKA), or AKT kinases also suppressed heterologous synapse formation, while inhibition of other tested signaling pathways—such as MAP kinases or protein kinase C—did not alter heterologous synapse formation. JNK and PKA inhibitors suppressed formation of both pre- and postsynaptic specializations, whereas AKT inhibitors impaired formation of post- but not presynaptic specializations. To independently test whether heterologous synapse formation depends on AKT signaling, we targeted PTEN, an enzyme that hydrolyzes phosphatidylinositol 3-phosphate and thereby prevents AKT kinase activation, to postsynaptic sites by fusing PTEN to Homer1. Targeting PTEN to postsynaptic specializations impaired heterologous postsynaptic synapse formation induced by presynaptic adhesion molecules, such as neurexins and additionally decreased excitatory synapse function in cultured neurons. Taken together, our results suggest that heterologous synapse formation is driven via a multifaceted and multistage kinase network, with diverse signals organizing pre- and postsynaptic specializations.
Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.
Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn’s disease

ABSTRACT Gut microbial dysbiosis and altered metabonomics have been implicated in the pathogenesis of Crohn’s disease (CD). The aim of our study was to characterize the gut microbiome structure and metabolic activities in pediatric CD patients with different clinical outcomes after infliximab (IFX) therapy. Fecal samples were collected from 20 healthy children and 29 newly diagnosed pediatric CD patients. 16S rRNA/ITS2 gene sequencing and targeted metabolomics analysis were applied to profile the gut bacterial microbiome, mycobiome, and metabolome, respectively. Pediatric CD patients exhibited lower relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Faecalibacterium, Clostridium clusters IV and XIVb, Roseburia, and Ruminococcus, which were correlated with reduced fecal levels of SCFAs. Decreased unconjugated bile acids (BAs) pool size and a lower unconjugated/conjugated BAs ratio were associated with reduced relative abundances of Bifidobacterium and Clostridium clusters IV and XIVb which contain bile salt hydrolases (BSH) genes. IFX treatment enriched the BSH-producing bacteria in CD subjects, which may explain a decreased level of conjugated BAs and an increase in unconjugated BAs as well as the unconjugated/conjugated BAs ratio. Furthermore, a sustained response (SR) of IFX therapy was associated with higher abundances of Methylobacterium, Sphingomonas, Staphylococcus, and Streptococcus, and higher fecal concentrations of amino acids, including L-aspartic acid, linoleic acid, and L-lactic acid at baseline. Our study suggests that the effects of IFX might be partially mediated by enriching bacteria taxa that producing SCFAs and BSH thereby inhibiting inflammation and restoring the BA metabolism. Some fecal bacteria and metabolites may be predictive of outcomes of IFX therapy for pediatric CD patients.
Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing

Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myeloid cells and 3 types in endometrial epithelial cells were identified. Distinct CD8+ T cell states and different monocyte-macrophage populations were discovered, among which exhausted CD8+ T cells and macrophages were preferentially enriched in tumor. Both CD8+ T cells and macrophages comport with continuous activation model. Gene expression patterns examination and gene ontology enrichment analysis of endometrial epithelial cells revealed 3 subtypes: stem-like cells, secretory glandular cells and ciliated cells. Overall, our study presents a view of endometrial carcinoma at single-cell resolution that reveals the characteristics of endometrial epithelial cells in the endometrium, and provides a cellular landscape of the tumor immune microenvironment.
Loss of ARID1B and SMARCB1 expression are specific for the diagnosis of dedifferentiated/undifferentiated carcinoma in tumours of the upper gynaecological tract and cervix

Genomic inactivation of ARID1B in ARID1A‐inactivated tumour and genomic inactivation of SMARCB1 represent two recurrent mechanisms, core SWItch/sucrose non‐fermentable (SWI/SNF) complex inactivation, that are associated with de‐differentiation in endometrial carcinoma. Approximately one‐third of dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) show loss of ARID1B expression with a minor subset showing loss of SMARCB1 expression, but little is known regarding the specificity of ARID1B or SMARCB1 loss in gynaecological tract tumours in general. The aim of this study was to examine the frequency of ARID1B and SMARCB1 loss by immunohistochemistry in a series of gynaecological tract epithelial/mesenchymal neoplasms.
The relationship between respiratory health and hard metal dust exposure: A cross-sectional study

Abstract The frequency and severity of respiratory disorders among workers exposed to hard metal dust is not well known.The objective of this cross-sectional study is to report the prevalence of respiratory symptoms, functional status, and radiological findings in hard metal-exposed workers in Türkiye. Among 139 workers, 96 were machining workers, and 43 were industrial tool sharpening workers. Radiographic abnormalities compatible with pneumoconiosis were found 39% of the workers and were more in machining workers statistically significant.Also, in machining workers group, percentage of expected values of FVC was lower than industrial tool sharpening workers group. The prevalence of respiratory symptoms was 14.3%, and there was not a statistically significant difference in working groups. The study reveals that pulmonary symptoms, functional abnormalities, and radiological findings are mild. Assuming that reversibility may develop with avoidance from exposure when detected at this stage, early diagnosis of lung damage is essential.
Sculpting crystals one Burgers vector at a time: Toward colloidal lattice robot swarms

Significance Colloidal nanoparticles that exert local forces suggest a future class of swarm metamaterials. These swarms must coordinate their actions to accomplish useful tasks, such as changing the shape of the swarm or engulfing an object. We use computer simulation to show how the coordination of active colloidal nanoparticle swarms can be simplified by harnessing crystalline defects. We demonstrate that with only a single degree of freedom (the diameter of a small fraction of particles) repeatable shape changes can be achieved in a 2D collection of particles with crystalline ordering and isotropic attraction. This work also relates to macroscopic robotic swarms, illuminating a mechanism for emergent control. Plastic deformation of crystalline materials with isotropic particle attractions proceeds by the creation and migration of dislocations under the influence of external forces. If dislocations are produced and migrated under the action of local forces, then material shape change can occur without the application of surface forces. We investigate how particles with variable diameters can be embedded in colloidal monolayers to produce dislocations on demand. We find in simulation that when embedded clusters of variable diameter particles are taken through multiple cycles of swelling and shrinking, large cumulative plastic slip is produced by the creation and biased motion of dislocation pairs in the solid for embedded clusters of particular geometries. In this way, dislocations emitted by these clusters (biased “dislocation emitters”) can be used to reshape colloidal matter. Our results are also applicable to larger-scale swarms of robotic particles that organize into dense ordered two-dimensional (2D) arrangements. We conclude with a discussion of how dislocations fulfill for colloids the role sought by “metamodules” in lattice robotics research and show how successive applications of shear as a unit operation can produce shape change through slicing and swirling.
Route to High-Performance Micro-solid Oxide Fuel Cells on Metallic Substrates

Micro-solid oxide fuel cells based on thin films have strong potential for use in portable power devices. However, devices based on silicon substrates typically involve thin-film metallic electrodes which are unstable at high temperatures. Devices based on bulk metal substrates overcome these limitations, though performance is hindered by the challenge of growing state-of-the-art epitaxial materials on metals. Here, we demonstrate for the first time the growth of epitaxial cathode materials on metal substrates (stainless steel) commercially supplied with epitaxial electrolyte layers (1.5 μm (Y2O3)0.15(ZrO2)0.85 (YSZ) + 50 nm CeO2). We create epitaxial mesoporous cathodes of (La0.60Sr0.40)0.95Co0. 20Fe0.80O3 (LSCF) on the substrate by growing LSCF/MgO vertically aligned nanocomposite films by pulsed laser deposition, followed by selectively etching out the MgO. To enable valid comparison with the literature, the cathodes are also grown on single-crystal substrates, confirming state-of-the-art performance with an area specific resistance of 100 Ω cm2 at 500 °C and activation energy down to 0.97 eV. The work marks an important step toward the commercialization of high-performance micro-solid oxide fuel cells for portable power applications.
DSP Toxin Distribution across Organs in Mice after Acute Oral Administration

Okadaic acid (OA) and its main structural analogs dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine lipophilic phycotoxins distributed worldwide that can be accumulated by edible shellfish and can cause diarrheic shellfish poisoning (DSP). In order to study their toxicokinetics, mice were treated with different doses of OA, DTX1, or DTX2 and signs of toxicity were recorded up to 24 h. Toxin distribution in the main organs from the gastrointestinal tract was assessed by liquid chromatography-mass spectrometry (LC/MS/MS) analysis. Our results indicate a dose-dependency in gastrointestinal absorption of these toxins. Twenty-four hours post-administration, the highest concentration of toxin was detected in the stomach and, in descending order, in the large intestine, small intestine, and liver. There was also a different toxicokinetic pathway between OA, DTX1, and DTX2. When the same toxin doses are compared, more OA than DTX1 is detected in the small intestine. OA and DTX1 showed similar concentrations in the stomach, liver, and large intestine tissues, but the amount of DTX2 is much lower in all these organs, providing information on DSP toxicokinetics for human safety assessment.
Crescimento e produtividade do girassol cultivado na entressafra com diferentes lâminas de água

In this study the experimental data obtained in the period from March to July of 2004 in the Federal University of Lavras (UFLA) were used, with the objective of evaluating the productivity of grains and of oil and other agronomic characteristics of two sunflower genotypes (Helianthus annuus L.) (H250 and H251), irrigated in the late summer growth period. The experiment was carried out with four treatments of drip irrigation water depths of 0 (L0), 75 (L1), 100 (L2) and 130% (L3) of the evapotranspiration estimated for the crop, corresponding, respectively, to the water depths of 117.20, 350.84, 428.70 and 522.14 mm. The productivity of grains and of oil, the height of sunflower plants and the capitulum diameter increased with water depth. The used cultivars presented differences of oil productivity, weight of 1000 achene's and plants height. There was an technical efficiency in production, even without irrigation, with average productivity of 1924.27 kg ha-1 and, in irrigated condition, there was increase of this productivity reaching the 2863.12 kg ha-1 for water depth of 522.14 mm (130% ETc) applied in the crop cycle. The analyzed genotypes can be used during the summer cycle, in Lavras, as an option in the crop rotation.