Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association ...between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.
The pseudocubic structure of a (Na0.5K0.5)NbO3 (NKN) film grown on a Pt/Ti/SiO2/Si substrate changed to an orthorhombic structure when the film was transferred onto a polyimide substrate. ...Piezoelectric constant for the transferred NKN film increased considerably from 74 ± 11 to 120 ± 18 pm/V because the crystal structure of the film had changed from pseudocubic to orthorhombic. A gold interdigitated electrode was deposited onto the transferred NKN film to synthesize a NKN piezoelectric energy harvester. The NKN piezoelectric energy harvester was poled before bending under a 100 kV/cm DC electric field across the electrodes. When a strain of 0.85% and a strain rate of 4.05%/s were applied to the NKN piezoelectric energy harvester, it produced a maximum output voltage of 1.9 V and a current of 38 nA, corresponding to a power density of 2.89 μW/cm3.
A series of three thiophene–naphthalene‐based asymmetric oligomers—5‐decyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (DtT), 5‐decyl‐5′′‐(naphthalen‐2‐yl)‐2,2′:5′,2′′‐terthiophene (D3TN), and ...5‐(4‐decylphenyl)‐5′‐(naphthalen‐2‐yl)‐2,2′‐bithiophene (DP2TN)—was synthesized by Suzuki cross‐coupling reactions. The long alkyl side chains improved both the solubility of the oligomers in solvents and their tendency to self‐assemble. UV/Vis absorption measurements suggested that DtT, D3TN, and DP2TN form H‐type aggregates with a face‐to‐face packing structure. In addition, the three oligomers were found to adopt vertically aligned crystalline structures in films deposited on substrates, as revealed by grazing‐incidence wide‐angle X‐ray scattering. These oligomers were used as the active layers of p‐type organic field‐effect transistors, and the resulting devices showed field‐effect mobilities of 3.3×10−3 cm2 V−1 s−1 for DtT, 1.6×10−2 cm2 V−1 s−1 for D3TN, and 3.7×10−2 cm2 V−1 s−1 for DP2TN. The differences in transistor performances were attributed to the degree of π overlap and the morphological differences determined by the molecular structures.
Asymmetric organic semiconductors based on thiophene–naphthalene oligomers were prepared: 5‐decyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (DtT), 5‐decyl‐5′′‐(naphthalen‐2‐yl)‐2,2′:5′,2′′‐terthiophene (D3TN), and 5‐(4‐decylphenyl)‐5′‐(naphthalen‐2‐yl)‐2,2′‐bithiophene (DP2TN). UV/Vis absorption measurements suggested that DtT, D3TN, and DP2TN form H‐type aggregates. These oligomers were used as the active layers of organic field‐effect transistors (see figure), and the resulting devices showed field‐effect mobilities of 3.3×10−3, 1.6×10, and 3.7×10−2 cm2 V−1 s−1 for DtT, D3TN, and DP2TN, respectively.
Metastasis relies on angiogenesis for tumor expansion. Tumor angiogenesis is restrained by a variety of endogenous inhibitors, including thrombospondin 1 (TSP1). The principal antiangiogenic activity ...of TSP1 resides in a domain containing three TSP1 repeats (3TSR), and TSP1 cleavage is regulated, in part, by the metalloproteinase ADAMTS1. In this study, we examined the role of TSP1 and ADAMTS1 in controlling metastatic disease in the liver and lung. TSP1 overexpression inhibited metastatic growth of colon or renal carcinoma cells in liver but not lung. Metastatic melanoma in liver grew more rapidly in Tsp1-null mice compared with controls, whereas in lung grew similarly in Tsp1-null mice or controls. Recombinant TSP1 was cleaved more efficiently in lysates from liver than lung. ADAMTS1 inhibition by neutralizing antibody, small interfering RNA, or genetic deletion abrogated cleavage activity. To confirm that lack of cleavage of TSP1 ablated its antiangiogenic function in the lung, we generated colon cancer cells stably secreting only the 3TSR domain and found that they inhibited formation of both liver and lung metastases. Collectively, our results indicate that the antiangiogenic activity of TSP1 is differentially regulated by ADAMTS1 in the liver and lung, emphasizing the concept that regulation of angiogenesis is varied in different tissue environments.
Objective
This study examined clinical and gender‐specific risk factors for low bone mineral density (BMD) in adult patients with psychotic disorders.
Methods
The study included 285 ...community‐dwelling patients with psychotic disorders. Dual‐energy X‐ray absorptiometry was used to measure BMD. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender.
Results
Fifty‐eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use.
Conclusion
Managing the risk factors associated with low BMD among patients with psychotic disorder should be done gender‐specifically. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders.
Identification of loss of SMARCB1/INI1 expression in poorly differentiated (PD) chordoma in pediatric patients suggests that PD chordoma is an entity molecularly distinct from conventional chordoma ...or atypical teratoid/rhabdoid tumor, which is also characterized by loss of SMARCB1/INI1 expression by inactivating mutation of the SMARCB1/INI gene. So far, around 20 cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression have been reported. Here, we report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break‐apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma.
In this study, the dynamic characteristics of three different bogie configurations, a conventional Steel bogie (SB), a composite bogie without primary suspension (CB1), and a composite bogie with ...primary suspensions of conical rubber type (CB2), were compared. The CB1 shows the highest critical speed while the CB2 shows the lowest. The SB configuration showed the highest ride index value while the CB2 showed the lowest. Both of the composite configurations showed better ride comfort index than that of the steel configuration. The trend of the derailment index was opposite to that of the critical speed. In the derailment index measuring test, the CB1 bogie configuration had a 12.3 % higher derailment index than that of the SB. These results show good agreement in overall trends with the simulation results.
Background: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in ...patients with hormone-receptor-positive, HER2-negative (HR+HER2−) breast cancer. Methods: We retrospectively analyzed 401 HR+HER2− breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014–April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes. Results: YAP1 expression negatively correlated with ODX RS (OR 0.373, p = 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets (p < 0.0001 OS in METABRIC, p = 0.00085 RFS in METABRIC, p = 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed. Conclusion: YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2− breast cancer patients.
Yes-associated protein 1 (YAP1) is a transcription factor regulated by the Hippo pathway and functions as an oncogene in various solid tumors under dysregulated Hippo pathway. However, the role of ...YAP1 in breast cancer remains controversial. Here, we investigated the impact of different levels of nuclear YAP1 expression on the clinical characteristics and survival outcome in patients with breast cancer.
Retrospectively obtained 455 breast tumor samples at Gangnam Severance Hospital were examined for YAP1 expression by immunohistochemistry, and the clinical data were analyzed. External validation was performed using a retrospective cohort and tissues in 482 patients from Severance Hospital.
High nuclear YAP1 expression was associated with hormone receptor negativity and aggressive tumor behavior, including lymph node metastasis, high Ki67 labeling index and inferior distant metastasis-free survival (DMFS, hazard ratio HR 2.271, 95% confidence intervals CIs 1.109-4.650,
= 0.0249), and also confirmed inferior disease free survival (HR 3.208, 95% CIs 1.313-7.833,
= 0.0105) in external validation cohort. In patients with triple-negative breast cancer (TNBC), high nuclear YAP1 expression was an independent significant determinant of poor DMFS (HR 2.384, 95% CIs 1.055-5.386,
= 0.0367).
Our findings suggest that nuclear YAP1 expression is a biomarker of adverse prognosis and a potential therapeutic target in patients with breast cancer, especially in TNBC.
C-terminal binding protein 1 (CtBP1) is a critical transcriptional corepressor of many tumor suppressor genes and plays diverse roles in the progression of cancers. The transcriptional repression ...function of CtBP1 is mediated by recruiting histone-modifying enzymes, such as histone deacetylases and histone methyltransferases, to target genes by binding with DNA-interacting factors. Several post-translational modifications of CtBP1 have been identified, including ubiquitination, phosphorylation, and SUMOylation. This paper reports that CtBP1 is conjugated by ISG15. Endogenous CtBP1 was modified by ISG15 after interferon-α treatment in HeLa cells. The ISGylation process of CtBP1 was regulated by deISGylation enzyme USP18 and ISG15 E3 ligase EFP. Interestingly, CtBP1 ISGylation affected the binding affinity between CtBP1 and some components of CtBP1-associated transcriptional complexes. HDAC1 and LSD1 bound more efficiently to ISG15-conjugated CtBP1 than non-conjugated CtBP1. On the other hand, binding between CtBP1 and HDAC4 was unaffected by ISG15 modification. Furthermore, ISG15 modification enhanced the transcriptional repression activity of CtBP1 on several target genes related to EMT and apoptosis. These findings suggest that the ISG15 modification of CtBP1 modulates the function and activity of CtBP1 and that CtBP1 ISGylation may provide a new insight for CtBP1-mediated cancers.
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