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However, because of frequent (common) cross-reactivity to non-hematopoietic cells with optimized TCR DP T cells, safety mechanisms are mandatory.The Mandarin vole (Lasiopodomys mandarinus), a typical subterranean rodent, has undergone hematological adaptations to tolerate the hypoxic/hypercapnic underground environment. Hemoglobin (Hb) genes encode respiratory proteins functioning principally in oxygen binding and transport to various tissues and organs. To investigate the evolution of α- and β-hemoglobin (Hb) in subterranean rodent species, we sequenced Hb genes of the Mandarin vole and the related aboveground Brandt’s vole (L. brandtii). Sequencing showed that in both voles, α-globin was encoded by a cluster of five functional genes in the following linkage order HBZ, HBA-T1, HBQ-T1, HBA-T2, and HBQ-T2; among these, HBQ-T2 is a pseudogene in both voles. Apitolisib The β-globin gene cluster in both voles also included five functional genes in the following linkage order HBE, HBE/HBG, HBG, HBB-T1, and HBB-T2. Phylogenetic analysis revealed that the Mandarin vole underwent convergent evolution with its related aboveground species (Brandt’s vole) but not with other subterranean rodent species. Selection pressure analyses revealed that α- and β-globin genes are under strong purifying selection (ω less then 1), and branch-site analyses identified positive selection sites on HBAT-T1 and HBB-T1 in different subterranean rodent species. This suggests that the adaptive evolution of these genes enhanced the ability of Hb to store and transport oxygen in subterranean rodent species. Our findings highlight the critical roles of Hb genes in the evolution of hypoxia tolerance in subterranean rodent species.Background Physical diseases, such as infection, and emotional distress are associated with herpes zoster (HZ). However, the relationship between adhesive capsulitis of the shoulder (ACoS) and HZ remains unknown. Objective This study investigated the risk of HZ development in patients with ACoS. Methods We analyzed the Longitudinal Health Insurance Database, a subset of 1 million beneficiaries from the National Health Insurance Research Database. Patients newly diagnosed with ACoS during the 2000-2012 period were the case group. Each patient with ACoS was matched to a control, according to age and index year, through frequency matching. HZ was the primary event in this study. Results A total of 60,478 patients were included and each group contained 30,239 patients. The risk of HZ infection in the case cohort was 1.28 times that of the control cohort. ACoS increased the risk of HZ infection in each age group, particularly among patients aged younger than 50 [adjusted hazard ratio (aHR) = 1.52, 95% confidence interval (CI) 1.31-1.75]. Relative to the control group, the hazard ratio of HZ for male patients (aHR = 1.40, 95% CI 1.26-1.55) in the case group was higher than that for female patients (aHR = 1.22, 95% CI 1.13-1.32). Conclusion Patients with ACoS have a higher risk of HZ development, particularly among those aged younger than 50 years. The effect of ACoS on HZ development among young adults requires attention.Liposomes containing copper and the copper ionophore neocuproine were prepared and characterized for in vitro and in vivo anticancer activity. Thermosensitive PEGylated liposomes were prepared with different molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) in the presence of copper(II) ions. Optimal, temperature dependent drug release was obtained at 7030 DPPC to HSPC weight ratio. Neocuproine (applied at 0.2 mol to 1 mol phospholipid) was encapsulated through a pH gradient while using unbuffered solution at pH 4.5 inside the liposomes, and 100 mM HEPES buffer pH 7.8 outside the liposomes. Copper ions were present in excess, yielding 0.5 mM copper-(neocuproine)2 complex and 0.5 mM free copper. Pre-heating to 45 °C increased the toxicity of the heat-sensitive liposomes in short-term in vitro experiments, whereas at 72 h all investigated liposomes exhibited similar in vitro toxicity to the copper(II)-neocuproine complex (11 ratio). Thermosensitive liposomes were found to be more effective in reducing tumor growth in BALB/c mice engrafted with C26 cancer cells, regardless of the mild hyperthermic treatment. Copper uptake of the tumor was verified by PET/CT imaging following treatment with [64Cu]Cu-neocuproine liposomes. Taken together, our results demonstrate the feasibility of targeting a copper nanotoxin that was encapsulated in thermosensitive liposomes containing an excess of copper.Despite a multitude of nutritional risk factors among older adults, there is a lack of community-based programs and activities that screen for malnutrition and address modifiable risk among this vulnerable population. Given the known association of protein and fluid consumption with fall-related risk among older adults and the high prevalence of falls among Americans age 65 years and older each year, a brief intervention was created. Stepping Up Your Nutrition (SUYN) is a 2.5 h workshop developed through a public/private partnership to motivate older adults to reduce their malnutrition risk. The purposes of this naturalistic workshop dissemination were to (1) describe the SUYN brief intervention; (2) identify participant characteristics associated with malnutrition risk; and (3) identify participant characteristics associated with subsequent participation in Stepping On (SO), an evidence-based fall prevention program. Data were analyzed from 429 SUYN participants, of which 38% (n = 163) subsequently attended SO. As measured by the SCREEN II®, high and moderate malnutrition risk scores were reported among approximately 71% and 20% of SUYN participants, respectively. Of the SUYN participants with high malnutrition risk, a significantly larger proportion attended a subsequent SO workshop (79.1%) compared to SUYN participants who did not proceed to SO (65.8%) (χ2 = 8.73, p = 0.013). Findings suggest SUYN may help to identify malnutrition risk among community-dwelling older adults and link them to needed services like evidence-based programs. Efforts are needed to expand the delivery infrastructure of SUYN to reach more at-risk older adults.