Effect of Hydrophobicity on the Self-Assembly Behavior of Urea Benzene Derivatives in Aqueous Solution

Urea benzene derivatives (UBD) with amphiphilic side chains showed self-assembly behavior in aqueous solution to form nanoparticles ~100 nm in size. Subsequent thermal treatment led to additional self-assembly of the nanoparticles due to dehydration of the amphiphilic side chains, producing microparticles. This self-assembly process was accompanied by a lower critical solution temperature (LCST) behavior, as revealed by the abrupt decrease in solution transmittance. In this study, three UBD (UBD-1–3) with different lengths of the alkyl segment in the amphiphilic side chain (namely, hexyl, heptyl, and octyl, respectively) were prepared to investigate the self-assembly behavior in aqueous solution. UBD-1–3 formed identical nanoparticles, with sizes in the 10~80 nm range but with different LCST values in the order 3 < 2 < 1. These results suggest a relationship between the hydrophobicity and the self-assembly behavior of UBD

Effect of Hydrophobicity on the Self-Assembly Behavior of Urea Benzene Derivatives in Aqueous Solution

Urea benzene derivatives (UBD) with amphiphilic side chains showed self-assembly behavior in aqueous solution to form nanoparticles ~100 nm in size. Subsequent thermal treatment led to additional self-assembly of the nanoparticles due to dehydration of the amphiphilic side chains, producing microparticles. This self-assembly process was accompanied by a lower critical solution temperature (LCST) behavior, as revealed by the abrupt decrease in solution transmittance. In this study, three UBD (UBD-1–3) with different lengths of the alkyl segment in the amphiphilic side chain (namely, hexyl, heptyl, and octyl, respectively) were prepared to investigate the self-assembly behavior in aqueous solution. UBD-1–3 formed identical nanoparticles, with sizes in the 10~80 nm range but with different LCST values in the order 3 < 2 < 1. These results suggest a relationship between the hydrophobicity and the self-assembly behavior of UBD

Water-Proton Relaxivities of Radical Nanoparticles Self-Assembled via Hydration or Dehydration Processes

Nanoparticles capable of accumulating in tumor tissues are promising materials for tumor imaging and therapy. In this study, two radical nanoparticles (RNPs), denoted as 1 and 2, composed of self-assembled ureabenzene derivatives possessing one or two amphiphilic side chains were demonstrated to be candidates for metal-free functional magnetic resonance imaging (MRI) contrast agents (CAs). Because of the self-assembly behavior of 1 and 2 in a saline solution, spherical RNPs of sizes ∼50–90 and ∼30–100 nm were detected. In a highly concentrated solution, RNP 1 showed considerably small water-proton relaxivity values (r1 and r2), whereas RNP 2 showed an r1 value that was around 5 times larger than that of RNP 1. These distinct r1 values might be caused by differences in the self-assembly behavior by a hydration or dehydration process. In vivo studies with RNP 2 demonstrated a slightly enhanced T1-weighted image in mice, suggesting that the RNPs can potentially be used as metal-free functional MRI CAs for T1-weighted imaging

Efficacy and predictor of anti-TNFα agents in patients with intestinal Behçet's disease

Abstract Background Behçet’s disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD. Methods We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents. Results A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents. Conclusions The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents.http://deepblue.lib.umich.edu/bitstream/2027.42/173563/1/12876_2022_Article_2221.pd

Water-Proton Relaxivities of Radical Nanoparticles Self-Assembled via Hydration or Dehydration Processes

Nanoparticles capable of accumulating in tumor tissues are promising materials for tumor imaging and therapy. In this study, two radical nanoparticles (RNPs), denoted as <b>1</b> and <b>2</b>, composed of self-assembled ureabenzene derivatives possessing one or two amphiphilic side chains were demonstrated to be candidates for metal-free functional magnetic resonance imaging (MRI) contrast agents (CAs). Because of the self-assembly behavior of <b>1</b> and <b>2</b> in a saline solution, spherical RNPs of sizes ∼50–90 and ∼30–100 nm were detected. In a highly concentrated solution, <b>RNP 1</b> showed considerably small water-proton relaxivity values (<i>r</i>₁ and <i>r</i>₂), whereas <b>RNP 2</b> showed an <i>r</i>₁ value that was around 5 times larger than that of <b>RNP 1</b>. These distinct <i>r</i>₁ values might be caused by differences in the self-assembly behavior by a hydration or dehydration process. In vivo studies with <b>RNP 2</b> demonstrated a slightly enhanced <i>T</i>₁-weighted image in mice, suggesting that the RNPs can potentially be used as metal-free functional MRI CAs for <i>T</i>₁-weighted imaging

Aberrant X chromosomal rearrangement through multi‐step template switching during sister chromatid formation in a patient with severe hemophilia A

Abstract Background Hemophilia A (HA) is an X‐linked recessive bleeding disorder caused by pathogenic variants of the coagulation factor VIII gene (F8). Half of the patients with severe HA have a recurrent inversion in the X chromosome, that is, F8 intron 22 or intron 1 inversion. Here, we characterized an abnormal F8 due to atypical complex X chromosome rearrangements in a Japanese patient with severe HA. Methods Recurrent F8 inversions were tested with inverse shifting‐PCR. The genomic structure was investigated using PCR‐based direct sequencing or quantitative PCR. Results The proband's X chromosome had a 119.5 kb insertion, a reverse duplex of an extragenic sequence on the F8 telomere region into the F8 intron 1 with two breakpoints. The telomeric breakpoint was a joining from the F8 intron 1 to the inverted FUNDC2 via a two‐base microhomology, and the centromeric breakpoint was a recombination between F8 intron 1 homologous sequences. The rearrangement mechanism was suggested as a multi‐step rearrangement with template switching such as fork stalling and template switching (FoSTeS)/microhomology‐mediated break‐induced replication (MMBIR) and/or homologous sequence‐associated recombination during a sister chromatid formation. Conclusion We identified the aberrant X chromosome with a split F8 due to a multi‐step rearrangement in a patient with severe HA

A Case of Takotsubo syndrome after Surgery for Papillary Thyroid Cancer

　The patient was an 82-year-old woman undergoing treatment for bronchial asthma. In December 200X, she visited her former doctor because of a left cervical mass and pain, and was referred to our hospital for detailed examination. A 19-mm mass was found in the left lobe of the thyroid gland and there were many swollen lymph nodes on both sides of her neck. Fine-needle aspiration cytology revealed malignant and papillary cancer in both the left lobe and left cervical lymph node, but no lung metastasis was found in chest CT, and it was judged to be T1bN1bM0 Stage IVa. Total thyroidectomy + bilateral cervival lymphnode dissection was performed. The left lobe mass of the thyroid gland invaded the sterno-thyroid muscle, but no infiltration to other organs, including the lymph nodes on both sides, was observed. On the night of the operation, wheezing, dyspnea, lower mandibular breathing, and impaired consciousness suddenly developed, and the oxygen saturation of peripheral artery (SpO2) decreased to 60%. No postoperative bleeding was observed. Chest CT demonstrated no signs of heart failure, but based on thickening of the bronchial wall, the cause of hypoxemia was considered to be bronchial asthma. Steroids and oxygen (high-dose, 15 L/ min) were administered, but respiratory acidosis developed and non-invasive positive pressure ventilation (NIPPV) was started. The respiratory condition gradually improved thereafter. Acute coronary syndrome (ACS) was suspected based on symptoms, increased troponin T, and ST elevation on ECG. Echocardiography revealed akinesis and left ventricular apical and basal hypercontractility. No coronary arterial stenosis was noted on coronary angiography and left ventriculography demonstrated Takotsubo-like wall movement (hypercontraction of the base and contraction failure of the apex), leading to a diagnosis of Takotsubo syndrome (TS). The subsequent course was good and she was discharged on the 10th postoperative day