Relapse of Ulcerative Colitis with Immune Thrombocytopenia and Pyoderma Gangrenosum Subsequent to Receiving COVID-19 Vaccination.

This case illustrates the complex interactions of the immune responses after vaccination and highlights their potential connections to various autoimmune conditions. A 22-year-old man with quiescent ulcerative colitis (UC) presented with abdominal pain, rectal bleeding, and thrombocytopenia 7 days after receiving the third coronavirus disease 2019 mRNA vaccination. Laboratory data confirmed the diagnosis of immune thrombocytopenia. High-dose intravenous immunoglobulin administration boosted the patient's platelet count. Simultaneously, colonoscopy revealed that his UC had relapsed. Although salazosulfapyridine briefly improved his symptoms, his stool frequency worsened one week later. The patient also developed pyoderma gangrenosum. Subsequent treatment with infliximab notably improved both pyoderma gangrenosum and UC.

Exploring indicators of genetic selection using the sniffer method to reduce methane emissions from Holstein cows.

OBJECTIVE: This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. METHODS: The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. RESULTS: The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (-0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. CONCLUSION: This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions.

Structural organization of the retriever-CCC endosomal recycling complex.

The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of vacuolar protein-sorting-associated protein (VPS)35L, VPS26C and VPS29, together with the CCC complex comprising coiled-coil domain-containing (CCDC)22, CCDC93 and copper metabolism domain-containing (COMMD) proteins, plays a crucial role in this process. The precise mechanisms underlying retriever assembly and its interaction with CCC have remained elusive. Here, we present a high-resolution structure of retriever in humans determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog retromer. By combining AlphaFold predictions and biochemical, cellular and proteomic analyses, we further elucidate the structural organization of the entire retriever-CCC complex across evolution and uncover how cancer-associated mutations in humans disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with retriever-CCC-mediated endosomal recycling.

Hemodynamic predictors of negative false lumen remodeling after frozen elephant trunk for acute aortic dissection.

OBJECTIVE: We evaluated the blood flow within the downstream aortic false lumen after frozen elephant trunk repair for acute aortic dissection and identified hemodynamic predictors of false lumen expansion and negative false lumen remodeling using four-dimensional flow magnetic resonance imaging. METHODS: Thirty-one patients (Stanford type A, n = 28; Stanford type B, n = 3) with patent false lumen who underwent frozen elephant trunk procedures for acute aortic dissection were included in this observational study. Each patient underwent computed tomography during the follow-up period and four-dimensional flow magnetic resonance imaging within 3 postoperative months. The false lumen volumetric expansion rate was calculated using computed tomography data. The direction and the rate of flow in the lower descending aortic false lumen were analyzed. Negative false lumen remodeling was defined as a volumetric increase of > 10% from the baseline volume. RESULTS: Negative false lumen remodeling had developed in 6 of the 31 patients during the observation period. Most of the false lumen flows were biphasic during systole. The range between peak and nadir flow rates was associated with the false lumen volumetric expansion rate (ß coefficient = 6.77; p < 0.01, R2 = 0.43). CONCLUSIONS: The range between peak and nadir flow rates may serve as a hemodynamic predictor of negative false lumen remodeling, enabling further treatment for patients at risk of expansion in the downstream aorta.

Structural Organization of the Retriever-CCC Endosomal Recycling Complex.

The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of VPS35L, VPS26C and VPS29, together with the CCC complex comprising CCDC22, CCDC93, and COMMD proteins, plays a crucial role in this process. The precise mechanisms underlying Retriever assembly and its interaction with CCC have remained elusive. Here, we present the first high-resolution structure of Retriever determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog, Retromer. By combining AlphaFold predictions and biochemical, cellular, and proteomic analyses, we further elucidate the structural organization of the entire Retriever-CCC complex and uncover how cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with Retriever-CCC-mediated endosomal recycling.

Structural Organization of the Retriever-CCC Endosomal Recycling Complex.

The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of VPS35L, VPS26C and VPS29, together with the CCC complex comprising CCDC22, CCDC93, and COMMD proteins, plays a crucial role in this process. The precise mechanisms underlying Retriever assembly and its interaction with CCC have remained elusive. Here, we present the first high-resolution structure of Retriever determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog, Retromer. By combining AlphaFold predictions and biochemical, cellular, and proteomic analyses, we further elucidate the structural organization of the entire Retriever-CCC complex and uncover how cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with Retriever-CCC-mediated endosomal recycling.

5­aminiolevulinic acid induces a radiodynamic effect with enhanced delayed reactive oxygen species production under hypoxic conditions in lymphoma cells: An in vitro study.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of intracranial tumor. However, PCNSL is radiosensitive; thus, whole-brain radiotherapy (WBRT) is often selected as an alternative consolidation therapy. WBRT-related delayed neurotoxicity can affect the quality of life of the elderly. 5-aminolevulinic acid (ALA) is a natural precursor of heme and has been widely used as a live molecular fluorescence marker in brain tumor surgery. Experimental studies have demonstrated that combination therapy with 5-ALA and ionizing irradiation (IR), denoted radiodynamic therapy (RDT), resulted in tumor suppression in cancer, including glioma, melanoma, colorectal cancer, prostate cancer, breast cancer and lung cancer; however, to the best of our knowledge, this method has not been investigated in lymphoma. The present study aimed to investigate the radiodynamic effect of 5-ALA on lymphoma cells in vitro. The synthesis of 5-ALA-induced protoporphyrin IX (PpIX) was assessed under normal and hypoxic conditions in lymphoma cells (Raji, HKBML and TK). Subsequently, the radiodynamic effect of 5-ALA was evaluated using a colony formation assay and reactive oxygen species (ROS) production after RDT was examined using flow cytometry. Finally, the mitochondrial density in the lymphoma cells was evaluated. Lymphoma cells exhibited a high accumulation of 5-ALA-induced PpIX in the flow cytometric analysis, and a decrease in the surviving fraction under IR in cells with 5-ALA treatment compared with cells not treated with 5-ALA in the colony formation assay under normal and hypoxic conditions. Although ROS production 12 h after IR was increased compared with that immediately after IR (0 h), pretreatment with 5-ALA enhanced the delayed ROS production in each lymphoma cell line under normoxic conditions. Raji and TK cells exhibited an increase in ROS production 12 h after IR compared with that at 0 h in the 5-ALA-untreated cells under hypoxic conditions. Raji, HKBML and TK cells exhibited an increase in ROS production 12 h after IR compared with that at 0 h in the 5-ALA-treated cells, while TK cells exhibited enhancement of ROS production 12 h after IR in 5-ALA-treated cells compared with 5-ALA-untreated cells under hypoxic conditions. Other studies have demonstrated that impaired mitochondria damaged by IR produce ROS via the metabolic process, then damage the rest of the surrounding normal mitochondria, consequently propagating oxidative stress within tumor cells and leading to cell death. Thus, we hypothesized that the propagating oxidative stress after IR was associated with mitochondrial density in tumor cells. Namely, high accumulation of 5-ALA-indcued PpIX may promote ROS production in mitochondria of tumor cells after IR, and suppress the cell surviving fraction via the propagation of oxidative stress. In the colony formation assay, Raji cell colony formation was suppressed by RDT with 5-ALA. Simultaneously, the mitochondrial density in the Raji cells was higher than that in other cell lines. Pretreatment with 5-ALA enhanced delayed ROS production after IR in lymphoma cells under normoxic conditions. Under hypoxic conditions, only TK cells exhibited enhancement of ROS production 12 h after IR in the 5-ALA-treated group compared with the 5-ALA-untreated group. Although further studies evaluating the effect of hypoxic conditions in lymphoma cells are needed, the results suggested that RDT with 5-ALA could suppress colony formation under normal and hypoxic conditions in lymphoma cells. Therefore, RDT with 5-ALA is a potential treatment option for PCNSL.

In Vitro Evaluation of the Reductase Activities of Human AKR1C3 Allelic Variants.

Aldo-keto reductase 1C3 (AKR1C3) plays a role in the detoxification and activation of clinical drugs by catalyzing reduction reactions. There are approximately 400 single-nucleotide polymorphisms (SNPs) in the AKR1C3 gene, but their impact on the enzyme activity is still unclear. This study aimed to clarify the effects of SNPs of AKR1C3 with more than 0.5% global minor allele frequency on the reductase activities for its typical substrates. Recombinant AKR1C3 wild-type and R66Q, E77G, C145Y, P180S, or R258C variants were constructed using insect Sf21 cells, and reductase activities for acetohexamide, doxorubicin, and loxoprofen by recombinant AKR1C3s were measured by liquid chromatography-tandem mass spectrometry. Among the variants tested, the C145Y variant showed remarkably low (6%-14% of wild type) intrinsic clearances of reductase activities for all three drugs. Reductase activities of these three drugs were measured using 34 individual Japanese liver cytosols, revealing that heterozygotes of the SNP g.55101G>A tended to show lower reductase activities for three drugs than homozygotes of the wild type. Furthermore, genotyping of the SNP g.55101G>A causing C145Y in 96 Caucasians, 166 African Americans, 192 Koreans, and 183 Japanese individuals was performed by polymerase chain reaction-restriction fragment length polymorphism. This allelic variant was specifically detected in Asians, with allele frequencies of 6.8% and 3.6% in Koreans and Japanese, respectively. To conclude, an AKR1C3 allele with the SNP g.55101G>A causing C145Y would be one of the causal factors for interindividual variabilities in the efficacy and toxicity of drugs reduced by AKR1C3. SIGNIFICANCE STATEMENT: This is the first study to clarify that the AKR1C3 allele with the SNP g.55101G>A causing C145Y results in a decrease in reductase activity. Since the allele was specifically observed in Asians, the allele would be a factor causing an interindividual variability in sensitivity of drug efficacy or toxicity of drugs reduced by AKR1C3 in Asians.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Expansion Culture of Hair Follicle Stem Cells through Uniform Aggregation in Microwell Array Devices.

Hair regeneration using hair follicle stem cells (HFSCs) and dermal papilla cells is a promising approach for the treatment of alopecia. One of the challenges faced in this approach is the quantitative expansion of HFSCs while maintaining their hair induction capacity. In this study, HFSC expansion was achieved through the formation of uniform-diameter cell aggregates that were subsequently encapsulated in Matrigel. We designed a microwell array device, wherein mouse HFSCs were seeded, allowed to form loosely packed aggregates for an hour, and then embedded in Matrigel. Quantitative analysis revealed a 20-fold increase in HFSC number in 2 weeks through this culture device. Gene expression of trichogenic stem cell markers in the device-grown cells showed a significant increase compared with that of typical flat substrate Matrigel suspension culture cells. These microwell array-cultured HFSCs mixed with freshly isolated embryonic mesenchymal cells indicated vigorous hair regeneration on the skin of nude mice. Furthermore, we examined the feasibility of this approach for the expansion of human HFSCs from androgenetic alopecia patients and found that the ratio of CD200+ cells was improved significantly in comparison with that of cells cultured in a typical culture dish or in a Matrigel suspension culture on a flat substrate. Therefore, the novel approach proposed in this study may be useful for HFSC expansion in hair regenerative medicine.

Primary central nervous system lymphoma of the third ventricle with intra-tumoral hemorrhage: A case report and literature review.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor that most commonly arises in the cerebral white matter, basal ganglia, peri-ventricle or corpus callosum. Confinement of PCNSL to the third ventricle is extremely rare, and seldom presents with intratumoral hemorrhage (ITH). The present study described the case of a 75-year-old woman who presented with obstructive hydrocephalus due to third-ventricle PCNSL. On magnetic resonance imaging (MRI), the tumor presented ITH on T2*-weighted images and a highly elevated regional cerebral blood volume on dynamic susceptibility contrast-enhanced MRI (DSC-MRI). Due to the high elevation of the regional cerebral blood volume, high-grade glioma was suspected as a preoperative diagnosis. The patient underwent endoscopic tumor biopsy and third ventricle PCNSL was successfully diagnosed. The patient achieved good prognosis at an early stage after the start of treatment initiation. There are many differential considerations for a third-ventricle tumor, and DSC-MRI can help the differential diagnosis of these tumors. Furthermore, the presence of ITH can lead to the inaccurate estimation of regional cerebral blood volume values. Overall, silent or microhemorrhage in PCNSL may be underestimated, and clinicians should therefore carefully evaluate tumor vascularity by MRI.

Quantitative Evaluation of the Contribution of Each Aldo-Keto Reductase and Short-Chain Dehydrogenase/Reductase Isoform to Reduction Reactions of Compounds Containing a Ketone Group in the Human Liver.

Enzymes of the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase superfamilies are involved in the reduction of compounds containing a ketone group. In most cases, multiple isoforms appear to be involved in the reduction of a compound, and the enzyme(s) that are responsible for the reaction in the human liver have not been elucidated. The purpose of this study was to quantitatively evaluate the contribution of each isoform to reduction reactions in the human liver. Recombinant cytosolic isoforms were constructed, i.e., AKR1C1, AKR1C2, AKR1C3, AKR1C4, and carbonyl reductase 1 (CBR1), and a microsomal isoform, 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1), and their contributions to the reduction of 10 compounds were examined by extrapolating the relative expression of each reductase protein in human liver preparations to recombinant systems quantified by liquid chromatography-mass spectrometry. The reductase activities for acetohexamide, doxorubicin, haloperidol, loxoprofen, naloxone, oxcarbazepine, and pentoxifylline were predominantly catalyzed by cytosolic isoforms, and the sum of the contributions of individual cytosolic reductases was almost 100%. Interestingly, AKR1C3 showed the highest contribution to acetohexamide and loxoprofen reduction, although previous studies have revealed that CBR1 mainly metabolizes them. The reductase activities of bupropion, ketoprofen, and tolperisone were catalyzed by microsomal isoform(s), and the contributions of HSD11B1 were calculated to be 41%, 32%, and 104%, respectively. To our knowledge, this is the first study to quantitatively evaluate the contribution of each reductase to the reduction of drugs in the human liver. SIGNIFICANCE STATEMENT: To our knowledge, this is the first study to determine the contribution of aldo-keto reductase (AKR)-1C1, AKR1C2, AKR1C3, AKR1C4, carbonyl reductase 1, and 11ß-hydroxysteroid dehydrogenase type 1 to drug reductions in the human liver by utilizing the relative expression factor approach. This study found that AKR1C3 contributes to the reduction of compounds at higher-than-expected rates.

Activation of Inflammation by MCF-7 Cells-Derived Small Extracellular Vesicles (sEV): Comparison of Three Different Isolation Methods of sEV.

PURPOSE: Small extracellular vesicles (sEV) containing proteins and RNAs play important roles as intercellular signal mediators. A critical issue is that there are multiple methods to prepare sEV fractions. The purpose of this study was to examine whether cancer cell-derived sEV fractions prepared by different isolation methods show similar responses for the induction of inflammatory cytokines in macrophages. METHODS: sEV fractions from the conditioned medium of MCF-7 cells were prepared by ultracentrifugation (UC), the MagCapture Exosome Isolation Kit PS (PS), or the ExoQuick-TC kit (EQ). The mRNA levels of inflammatory cytokines in differentiated THP-1 cells treated with the sEV fractions were evaluated. RESULTS: The yields of sEV fractions obtained from 1 mL conditioned medium by UC, PS, or EQ were 3.2×108 particles (0.27 µg protein), 12.8×108 particles (0.87 µg protein) and 23.5 ×108 particles (4.50 µg protein), respectively. The average particle sizes in the UC, PS, and EQ fractions were 184.8 ± 1.8 nm, 157.8 ± 1.3 nm and 165.8 ± 1.1 nm, respectively. CD9 and CD81, markers of sEV, were most highly detected in the PS fraction, followed by the EQ and UC fractions. These results suggest that PS gave sEV with relatively high purity, and many protein contaminants appear to be included in the EQ fraction. The mRNA levels of inflammatory cytokines in THP-1 macrophages were most prominently increased by treatment with the UC fraction, followed by the EQ and PS fractions, suggesting that contaminants rather than sEV may largely induce an inflammatory response. CONCLUSION: The isolation method affects the evaluation of sEV function.

Spinal cord infarction after withdrawal of veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: A case report.

BACKGROUND: Spinal cord infarction is a rare central nervous system angiopathy that impairs motor, sensory, and autonomic nerves and occurs due to various reasons. This study reports a case of spinal cord infarction in a patient following myocardial infarction that was managed by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CASE SUMMARY: A 78-year-old Japanese man visited the emergency department with a complaint of chest tightness. He had a history of hypertension, dyslipidemia, diabetes, chronic renal failure, and postoperative bladder cancer. Myocardial infarction was diagnosed after ST elevation in lead aVR was identified by electrocardiogram during the visit, and cardiopulmonary arrest occurred twice during our examination and treatment. After percutaneous coronary intervention with an intra-aortic balloon pump and VA-ECMO, the patient was admitted to the intensive care unit. His circulation stabilized, and he was withdrawn from the intra-aortic balloon pump on day 3 of illness and from VA-ECMO on day 4. However, his consciousness remained impaired. When the patient's consciousness improved on day 14, lower limb weakness was identified. Magnetic resonance imaging conducted on the following day revealed spinal cord infarction in the 5th to 12th thoracic vertebrae. CONCLUSION: Spinal cord infarction due to VA-ECMO is extremely rare but has a poor neurological prognosis upon onset. Necessary countermeasures include conducting regular neurological examinations and high blood pressure maintenance, which is very difficult in VA-ECMO patients. Therefore, patient care will benefit from the experiences reported in such cases.

Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction.

During embryonic development, reciprocal interactions between epidermal and mesenchymal layers trigger hair follicle morphogenesis. This study revealed that microenvironmental reprogramming via control over these interactions enabled hair follicle induction in vitro. A key approach is to modulate spatial distributions of epithelial and mesenchymal cells in their spontaneous organization. The de novo hair follicles with typical morphological features emerged in aggregates of the two cell types, termed hair follicloids, and hair shafts sprouted with near 100% efficiency in vitro. The hair shaft length reached ~3 mm in culture. Typical trichogenic signaling pathways were up-regulated in hair follicloids. Owing to replication of hair follicle morphogenesis in vitro, melanosome production and transportation were also monitored in the hair bulb region. This in vitro hair follicle model might be valuable for better understanding hair follicle induction, evaluating hair growth and inhibition of hair growth by drugs, and modeling gray hairs in a well-defined environment.

Sobolev-to-Lipschitz property on QCD -spaces and applications.

We prove the Sobolev-to-Lipschitz property for metric measure spaces satisfying the quasi curvature-dimension condition recently introduced in Milman (Commun Pure Appl Math, to appear). We provide several applications to properties of the corresponding heat semigroup. In particular, under the additional assumption of infinitesimal Hilbertianity, we show the Varadhan short-time asymptotics for the heat semigroup with respect to the distance, and prove the irreducibility of the heat semigroup. These results apply in particular to large classes of (ideal) sub-Riemannian manifolds.

Hemolytic anemia caused by an excessively kinked prosthetic graft after total arch replacement detected by 4-dimensional flow magnetic resonance imaging: A case report.

RATIONALE: Hemolytic anemia is a rare postoperative complication of aortic surgery, which may be caused by an excessively kinked graft that causes abnormal blood flow. It has been reported that 4-dimensional flow magnetic resonance imaging (4D flow MRI) can identify abnormal flow. Herein, we report the guidance of 4D flow MRI in performing the revision procedure for a patient with hemolytic anemia by evaluating abnormal blood flow based on this method. PATIENT CONCERNS: A 70-year-old woman presented with dizziness and fatigue. She had undergone total arch replacement with a frozen elephant trunk 5 years prior. We diagnosed hemolytic anemia caused by a kinked graft after total arch replacement. DIAGNOSIS: Although computed tomography findings revealed 3 lesions of the kinked graft at the ascending portion and cervical branches, 4D flow MRI findings showed that only the kinked graft at the ascending portion caused hemolytic anemia due to an elevated viscous energy loss around it. INTERVENTION: We performed surgery to remove the kinked section instead of revision surgery consisting of total arch replacement. OUTCOMES: The patient's postoperative course was uneventful and there were no complications. Postoperative enhanced computed tomography findings showed that the repaired graft had an adequate length and smoothly curved shape. The 4D flow MRI findings revealed smooth flow in the ascending portion and decreased viscous energy loss. LESSONS: Based on the 4D flow MRI findings, we adopted a less invasive approach, repairing only the ascending portion of the graft, instead of performing revision surgery comprising total arch replacement.

Cell-repellent polyampholyte for conformal coating on microstructures.

Repellent coatings are critical for the development of biomedical and analytical devices to prevent nonspecific protein and cell adhesion. In this study, prevelex (polyampholytes containing phosphate and amine units) was synthesized for the fine coating of microdevices for cell culture. The dip-coating of the prevelex on hydrophobic substrates altered their surfaces to be highly hydrophilic and electrically neutral. The range of prebake temperature (50-150 °C) after dip-coating was moderate and within a preferable range to treat typical materials for cell culture such as polystyrene and polydimethylsiloxane. Scanning electron microscopy revealed a conformal and ultra-thin film coating on the micro/nano structures. When compared with poly(2-hydroxyethyl methacrylate) and poly(2-methacryloyloxyethyl phosphorylcholine), prevelex exhibited better characteristics for coating on microwell array devices, thereby facilitating the formation of spheroids with uniform diameters using various cell types. Furthermore, to examine cellular functionalities, mouse embryonic epithelial and mesenchymal cells were seeded in a prevelex-coated microwell array device. The two types of cells formed hair follicle germ-like aggregates in the device. The aggregates were then transplanted to generate de novo hair follicles in nude mice. The coating material provided a robust and fine coating approach for the preparation of non-fouling surfaces for tissue engineering and biomedical applications.