Iron deficiency and cobalamin deficiency, as sequelae to chronic gastrointestinal (GI) disease, could result in anemia and increased morbidity in cats with chronic enteropathies.

To evaluate iron deficiency in cats with chronic GI disease and its relationship with hypocobalaminemia, anemia, and disease severity.

Twenty client-owned cats with primary GI disease.

Prospective, cross-sectional study. Cats were enrolled at the time of evaluation for chronic GI disease, after exclusion of comorbidities. CBC with reticulocyte indices, iron metabolism (serum iron and ferritin concentrations, total iron binding capacity [TIBC]), serum methylmalonic acid (MMA), cobalamin, and folate concentrations, pancreatic lipase and trypsin-like immunoreactivity, and disease severity were evaluated.

Anemia (hematocrit <30%), iron deficiency, and cobalamin deficiency were diagnosed in 4/20, 7/20, and 8/20 cats, respectively. Hematocrit (r

= -.45; P < .05) and body condition score (r

= -.60; P < .01) negatively correlated with MMA. Median TIBC was lower in cats with increased vs normal MMA (218 μg/mL; range, 120-466 μg/mL vs 288 μg/mL; range, 195-369 μg/mL; P = .02). Hematocrit (r

= .51; P = .02), reticulocyte MCV (r

= .52; P = .02), reticulocyte hemoglobin content (r

= .71; P < .001), and percent transferrin saturation (r

= .79; P < .0001) positively correlated with serum iron concentration.

Functional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.

Functional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.A new series of 1,2,4-triazolo[4,3-c]quinazoline derivatives was designed and synthesized as Topo II inhibitors and DNA intercalators. The cytotoxic effect of the new members was evaluated in vitro against a group of cancer cell lines including HCT-116, HepG-2, and MCF-7. Compounds 14c , 14d , 14e , 14e , 15b , 18b , 18c , and 19b exhibited the highest activities with IC50 values ranging from 5.22 to 24.24 µM. Furthermore, Topo II inhibitory activities and DNA intercalating affinities of the most promising candidates were evaluated as a possible mechanism for the antiproliferative effect. The results of the Topo II inhibition and DNA binding tests were coherent with that of in vitro cytotoxicity. Additionally, the most promising compound 18c was analyzed in HepG-2 cells for its apoptotic effect and cell cycle arrest. It was found that 18c can induce apoptosis and arrest the cell cycle at the G2-M phase. Finally, molecular docking studies were carried out for the designed compounds against the crystal structure of the DNA-Topo II complex as a potential target to explore their binding modes. On the basis of these studies, it was hypothesized that the DNA binding and/or Topo II inhibition would participate in the noted cytotoxicity of the synthesized compounds.Some tardigrades can survive extremely desiccated conditions through transition into a state called anhydrobiosis. Anhydrobiotic tardigrades have proteins unique to them and they are thought to be keys to the understanding of unusual desiccation resistance. In fact, previous transcriptome data show that several tardigrade-specific proteins are significantly upregulated under desiccated conditions. However, their physiological roles and chemical properties have been ambiguous because they show low or no similarity of amino acid sequences to proteins found in other organisms. Here, we report a crystal structure of one of such proteins. This protein shows a β-sandwich structure composed of 8 β-strands, three Ca2+ -binding sites, and hydrophobic residues on Ca2+ -binding (CBD) loops, which resemble characteristics of C2 domain proteins. We therefore conveniently describe this protein as tardigrade C2 domain protein (TC2P). Because the C2 domain functions as a Ca2+ -mediated membrane docking module, which is related to signal transduction or membrane trafficking, TC2Ps may play a role in Ca2+ -triggered phenomenon under desiccated situations. Our finding provides not only structural insights into a newly discovered desiccation-related protein family but also insights into the evolution and diversity of C2 domain proteins.Advancements in the risk literature and recent events have highlighted the need for recognizing and managing system vulnerabilities. However, established definitions of vulnerability typically involve only static concepts that are limited to measurement of system characteristics. Advancements in risk modeling, combined with the dynamic nature of data availability, and processing call for the need to understand the various dimensions and time-dependent properties of vulnerability within risk-informed decision making. There is need to (1) Understand and classify aspects of vulnerability that exist in various systems, such as related to engineering, business, and healthcare, while recognizing both properties of the system and associated knowledge, (2) reconcile these definitions of vulnerabilities with existing concepts, such as sensitivity analysis and fragility, and (3) explore the implications of various types of vulnerability on risk management decisions. The main contributions of this work include classifying dynamic characteristics of system vulnerability and leveraging information about the multidimensional properties of vulnerability within risk management decisions that apply to a collection of risk events. As a proof of concept, we illustrate the vulnerability classification on the COVID-19 pandemic. This article will be of interest to both risk researchers and practitioners.Neuroticism is a robust personality trait associated with multiple mental disorders. Heretofore, research on the relationship among genes, brain, and behavior to explore individual differences in neuroticism is scarce. Hence, in this study (N = 630), genetic data, self-reported neuroticism, and brain structural data were combined to explore whether the cortical thickness (CT) of brain regions mediated the relationship between the polygenic risk score (PRS) of neuroticism and NEO neuroticism (NEO-N), and the enrichment analysis was performed to reveal the underlying mechanism of their relationship. Results showed that the PRSs were significantly associated with NEO-N scores (p less then .05). Namodenoson clinical trial The CT of left rostral middle frontal gyrus was negatively related to the best PRS in PRSice (PRSbest ) or the PRS at 0.05 threshold (PRS0.05 ) (corrected p less then .05), which was also found to mediate the association between the PRS and NEO-N (PRSbest ab = .012, p less then .05; PRS0.05 ab = .012, p less then .