Treatment with IQ resulted in the decrease in the levels of procaspase-8 and -9, and Bcl-2 protein, and an increase in the expression of cleaved PARP and Bax. Moreover, AIF and Endo G protein expression increased, indicating a caspase-independent mitochondrial-mediated apoptosis. The anti-proliferative activity of IQ against SK-MEL-2 can also be attributed to the downregulation of the PI3K/AktmTOR signaling pathway. These findings showed that IQ can be developed into a chemopreventive therapeutic agent against the melanoma cells.Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials.  https://www.selleckchem.com/products/motolimod-vtx-2337.html  Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis. We evaluated the correlation of Tn antigen expression by immunohistochemistry with mismatch-repair (MMR) status, tumor-infiltrating lymphocytes, tumor cell PD-L1 expression, and clinicopathological characteristics in 507 CRC patients. Although 91.9% of CRCs showed negative or weak Tn antigen staining (Tn-negative/weak), we identified a small subset of CRCs (8.1%) that displayed particularly intense and diffuse distribution of Tn antigen immunoreactivity (Tn-strong) that closely related to deficient MMR (dMMR). Moreover, 40 dMMR CRCs were stratified into 24 Tn-negative/weak dMMR tumors (60.0%) exhibiting dense CD8+ lymphocyte infiltrate concomitant with a high rate of PD-L1 positivity, and 16 Tn-strong dMMR tumors (40.0%) that demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression, which was comparable to those of proficient MMR. Our finding suggests that the immune cold subset of patients with Tn-strong dMMR CRC may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigen.The migrant population has increased in recent years and, as a result, so has cultural diversity. Universities are incorporating specific modules addressing cultural diversity. However, the native population has negative attitudes towards immigrants, as they believe that immigrants receive more social benefits and abuse healthcare services. Nurses may have these attitudes too, which may affect the way they treat patients. The objective of this study was to determine nursing students' attitudes towards the rights of the migrant population. This is a descriptive ex post facto study using a cross-sectional design, with 821 nursing students in Melilla, Ceuta, and Almeria, Spain. An anonymous questionnaire was used for data collection. Students recognize the same rights for both the immigrant and native populations. More than 80% of the sample upholds the right of undocumented immigrants and their families to access publicly funded healthcare. Attitudes were more positive among students with a Berber background and first-year students. Students approved of the right of immigrants and their families to healthcare and education. The students' negative attitudes towards the social rights of immigrants need to be addressed with intercultural training to reduce their prejudices as future professionals in a multicultural society.Social engagement and networking deter depression among older adults. During the COVID-19 pandemic, older adults are especially at risk of isolation from face-to-face and non-face-to-face interactions. We developed the National Center for Geriatrics and Gerontology Social Network Scale (NCGG-SNS) to assess frequency of, and satisfaction with, social interactions. The NCGG-SNS consists of four domains face-to-face/non-face-to-face interactions with family/friends. Each domain score is obtained by multiplying frequency ratings by satisfaction ratings for each item; all scores were summed to obtain a total NCGG-SNS score (range 0-64). Additionally, face-to-face and non-face-to-face subscores were calculated. Higher scores indicated satisfactory social networking. A cohort of 2445 older Japanese adults completed the NCGG-SNS and the Geriatrics Depression Scale-Short form. Receiver Operating Characteristic (ROC) analysis and logistic regression determined predictive validity for depressive symptoms. Depressive symptoms were reported by 284 participants (11.6%). The optimal NCGG-SNS cut-off value to identify depressive symptoms was 26.5 points. In logistic regression analysis adjusted for potential confounders, lower NCGG-SNS values were significantly associated with greater prevalence of depressive symptoms. Face-to-face and non-face-to-face subscores were associated with depressive symptoms. The NCGG-SNS is a valid and useful indicator of multidimensional social networking enabling identification of depressive symptoms in older adults.Prevotella bivia is an anaerobic, gram-negative bacillus which naturally thrives in the human vagina, and is usually related to vaginal tract infections. However, this microorganism can also cause infections in other body locations. Infections with Prevotella bivia are frequently severe due to the risk of osteomyelitis and the lack of good protocols for adequate therapeutic management. Staphylococcus haemolyticus infection is one of the most frequent etiological factors of nosocomial infections, which hasthe ability to acquire multiple resistance against antimicrobial agents. We report a rare case of foot and hand paronychia with superinfection of Prevotella bivia and Staphylococcus haemolyticus. We highlight the importance of early microbiological diagnosis, and proper therapeutic management to avoid the risk of complications and the development of bacterial resistance to antibiotics.Transactive response DNA and RNA binding protein 43 kDa (TDP-43) is a highly conserved heterogeneous nuclear ribonucleoprotein (hnRNP), which is involved in several steps of protein production including transcription and splicing. Its aggregates are frequently observed in motor neurons from amyotrophic lateral sclerosis patients and in the most common variant of frontotemporal lobar degeneration. Recently it was shown that TDP-43 is able to bind Zn2+ by its RRM domain. In this work, we have investigated Zn2+ binding to a short peptide 256-264 from C-terminus of RRM2 domain using isothermal titration calorimetry, electrospray ionization mass spectrometry, QM/MM simulations, and NMR spectroscopy. We have found that this peptide is able to bind zinc ions with a Ka equal to 1.6 × 105 M-1. Our findings suggest the existence of a zinc binding site in the C-terminal region of RRM2 domain. Together with the existing structure of the RRM2 domain of TDP-43 we propose a model of its complex with Zn2+ which illustrates how zinc might regulate DNA/RNA binding.