De Novo Discovery of Pseudo-Natural Prenylated Macrocyclic Peptide Ligands.

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether-macrocyclic peptide (teMP) library construction/selection technology, so-called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp-C3-prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product. This unique enzyme exhibited remarkably broad substrate tolerance, capable of modifying various Trp-containing teMPs to install a prenylated residue with tricyclic constrained structure. We constructed a vast library of prenylated teMPs and subjected it to in vitro selection against a phosphoglycerate mutase. This selection platform has led to the identification of a pseudo-natural prenylated teMP inhibiting the target enzyme with an IC50 of 30 nM. Importantly, the prenylation was essential for the inhibitory activity, enhanced serum stability, and cellular uptake of the peptide, highlighting the benefits of peptide prenylation. This work showcases the de novo discovery platform for pseudo-natural prenylated peptides, which is readily applicable to other drug targets.

Extratesticular masses focusing on MRI findings.

Scrotal masses, whether cystic or solid lesions, are routinely evaluated using ultrasonography. Magnetic resonance imaging (MRI) may be used for further investigation in cases with atypical findings, difficult diagnoses, large masses, and/or unclear relationships with the surrounding tissues. Scrotal solid masses are divided into intra- and extra-testicular masses. A staggering 90% of the intratesticular masses are malignant, whereas 75% of extratesticular masses are benign. Extratesticular masses are less common than intratesticular masses; however, some extratesticular masses present characteristic MRI findings. Familiarity with these specific MRI features of extratesticular masses is beneficial to radiologists, as appropriate diagnoses can help avoid unnecessary invasive treatments such as orchiectomy. In this review, we describe fibrous pseudotumors, polyorchidism, adenomatoid tumors, and scrotal leiomyoma as benign paratesticular masses, focusing on their characteristic imaging features on MRI. Although these tumors are extremely rare, their MRI findings are distinctive, and accurate diagnoses can prevent unnecessary orchiectomy. In addition, to demonstrate the pitfalls of diagnosing extratesticular masses, we present a case of seminoma misidentified as extratesticular masses due to large extensions outside the testis. Spermatic cord sarcoma, including rhabdomyosarcoma, leiomyosarcoma, and liposarcoma, and metastasis to the spermatic cord are described as malignant extratesticular masses. This review focused on extratesticular masses and elaborates the imaging findings that can aid in the accurate diagnosis using MRI.

Next-generation sequencing of primary testicular lymphoma and relapse in the glans penis after prophylactic radiation therapy: a rare case report.

BACKGROUND: Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse. CASE PRESENTATION: A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens. CONCLUSIONS: We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.

Unexpected change in hydrogel spacer volume during external-beam radiation therapy.

PURPOSE: To reduce the rectal radiation dose during local radiation therapy of prostate cancer, a hydrogel spacer is typically implanted between the prostate and rectum. However, the spacer volume can change during external beam radiation therapy (EBRT). Therefore, we used magnetic resonance imaging (MRI) to determine changes in the spacer volume during EBRT and analyzed the data to identify patient factors influencing this change. MATERIALS AND METHODS: A hydrogel spacer was implanted in each enrolled patient diagnosed with prostate cancer (n = 22, age = 69-86 years) for EBRT with a total dose of 70 Gy over 35 fractions. T2-weighted MRI images were acquired before (median = 8 days) and during EBRT, when the radiation dose of 48 Gy (median) was given at 55 days (median) after implantation. MRI images were used to determine the spacer volume as well as the maximum and minimum distances between the prostate and anterior wall of the rectum at the middle height of the prostate. Scatterplots were created to determine whether correlations existed between changes in the spacer volume and these two distances, while uni- and multivariate analyses were conducted to determine if the spacer volume change was influenced by the following patient factors: age, body mass index, estimated glomerular filtration rate, and visceral fat areas at the umbilical and femoral head positions. RESULTS: The spacer volume increased in all 22 patients, with the smaller spacer volume before EBRT increasing by a larger amount during EBRT. This increase in the spacer volume was unaffected by other patient factors. However, it correlated with the change in the maximum distance between the prostate and anterior wall of the rectum. CONCLUSION: To avoid adverse changes in the rectal radiation dose during EBRT, hydrogel spacer volume should be monitored, especially if the pre-EBRT volume is small.

Evaluation of output factors of different radiotherapy planning systems using Exradin W2 plastic scintillator detector.

This study aims to evaluate the output factors (OPF) of different radiation therapy planning systems (TPSs) using a plastic scintillator detector (PSD). The validation results for determining a practical field size for clinical use were verified. The implemented validation system was an Exradin W2 PSD. The focus was to validate the OPFs of the small irradiation fields of two modeled radiation TPSs using RayStation version 10.0.1 and Monaco version 5.51.10. The linear accelerator used for irradiation was a TrueBeam with three energies: 4, 6, and 10 MV. RayStation calculations showed that when the irradiation field size was reduced from 10 × 10 to 0.5 × 0.5 cm2, the results were within 2.0% of the measured values for all energies. Similarly, the values calculated using Monaco were within approximately 2.0% of the measured values for irradiation field sizes between 10 × 10 and 1.5 × 1.5 cm2 for all beam energies of interest. Thus, PSDs are effective validation tools for OPF calculations in TPS. A TPS modeled with the same source data has different minimum irradiation field sizes that can be calculated. These findings could aid in verification of equipment accuracy for treatment planning requiring highly accurate dose calculations and for third-party evaluation of OPF calculations for TPS.

A case of bilateral adrenal infarction with preserved adrenal function diagnosed by dual-energy computed tomography.

We report a case wherein adrenal function remained preserved despite bilateral adrenal infarction, as evidenced by dual-energy computed tomography (DECT) iodine density images. The patient was a 37-year-old man with a history of antiphospholipid syndrome concomitant with systemic lupus erythematosus. The patient underwent contrast-enhanced DECT, which revealed bilateral adrenal infarction. Laboratory tests revealed preserved adrenal function. On the iodine density images, the infarcted and noninfarcted areas in the adrenal glands were visually different. The volume of the non-infarcted area was 8.9 mL, which was 41% of the total adrenal volume. DECT may be a useful complementary tool for assessing the preservation of adrenal function.

Water-Mediated On-Demand Detachable Solid-State Adhesive of Porous Hydroxyapatite for Internal Organ Retractions.

Novel adhesives for biological tissues offer an advanced surgical approach. Here, the authors report the development and application of solid-state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid-state adhesives are experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance is evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrate the holding ability of porcine livers and on-demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery.

Dysphagia in patients with severe COVID-19: a retrospective study.

To investigate dysphagia after extubation in patients with severe coronavirus disease 2019 (COVID-19). We retrospectively examined patients with severe COVID-19 treated in our hospital between August 2021 and March 2022. Feeding outcomes were categorized into two groups-(1) total oral intake, and (2) difficulty in oral intake. To assess the feeding outcome, we used modified water-swallowing test (MWST) for all patients. However, in cases where aspiration or recurrent laryngeal nerve palsy was suspected, we conducted the fiberoptic endoscopic evaluation of swallowing after MWST. Patient data were collected from medical records. Forty-six patients with severe COVID-19 were included. Among the 46 patients, 14 (30.4%) experienced difficulties with oral intake. Older age, longer length of hospitalization, duration of mechanical ventilation, tracheostomy, diabetes, and higher serum levels of C-reactive protein (CRP) and procalcitonin (PCT) at the time of intubation were associated with difficulty in oral intake. The rate of difficulty with oral intake in patients with severe COVID-19 was 30.4%, which is not as high as reported in previous studies. Older age, longer duration of mechanical ventilation, tracheostomy, diabetes, and higher levels of CRP and PCT were associated with the prevalence of oral intake difficulty, suggesting that early attention should be paid to high-risk patients who have preexisting deterioration of swallowing function due to aging and comorbidities, or who have prolonged intubation or tracheostomy to prevent aspiration pneumonia.

Multicenter prospective randomized controlled clinical trial comparing the pocket-creation method with and without single-clip traction of colonic endoscopic submucosal dissection.

BACKGROUND: The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial. METHODS: This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. RESULTS: 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI -38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI -20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P >0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups. CONCLUSION: ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates.

Lipids and Minerals, Interplay in Biomineralization: Nature's Alchemy.

The main focus of this article is the role of lipids in biomineralization. Much of the discussion on biomineralization focuses on proteins in these decades. Indeed, collagen and acidic noncollagenous proteins effectively serve as templates for mineralization. However, other macromolecules such as lipids and polysaccharides have received less attention despite their abundance at mineralization sites. The matrix vesicle (MV) theory is widely accepted as the induction of early mineralization. Although ion concentration within the vesicles has been discussed in the initial mineralization in this theory, the role of phospholipids that constitute the vesicle membrane has not been discussed much. Comprehensive considerations, including pathological mineralization, exist regardless of the localization of MVs, the involvement of bacteria in dental calculus formation, and biomineralization caused by marine organisms such as corals, suggesting that initial mineralization found in these biological conditions might be a common reaction relating to lipids. In contrast, despite the abundance of lipids, mineralization occurs only in the limited tissue within our body. In other words, gathering knowledge and creating a path to understanding about lipid-based mineralization is extremely important in proposing new bone disease treatment methods. This article describes how lipids influence nucleation, mineralization, and expansion during hard tissue formation.

Investigation on bacterial capture and antibacterial properties of acid-treated Ti surface.

OBJECTIVES: Utilizing Ti and Ti alloys as dental materials established a huge spurt in the field of dentistry. Since implantation is an invasive procedure that involves tissue penetration, infection control is mandatory for increasing the success rate of the implant treatment. In this study, we aimed to assess the impact of the surface physicochemical properties of acid-treated Ti on microorganisms specifically bacteria. METHODS: After investigating the surface morphology and characteristics of acid-treated and untreated Ti sheets, we evaluated their potential to capture Escherichia coli (E. coli.) as well as the latter's survival on the surface of both types of sheets. Finally, we assessed the efficiency of the antibacterial properties exhibited by Ti against the oral microflora. RESULTS: SEM images revealed surface roughening of the acid-treated Ti represented by significantly irregular shape. Moreover, the acid-treated Ti exhibited remarkable hydrophobicity. A quantitative evaluation confirmed that acid-treated Ti has higher bacterial capture and antibacterial properties than untreated Ti. Further experiments showed similar effects of both types of Ti not only on E. coli but also on oral microflora. SIGNIFICANCE: Results suggest that acid treatment of Ti surface is a potent technique for enhancing the antibacterial properties of Ti-derived materials.

Oral Intake Difficulty and Aspiration Pneumonia Assessment Using High-Resolution Manometry.

OBJECTIVE: The sequential generation of swallowing pressure (SP) from the nasopharynx to the proximal esophagus is important for the bolus to pass from the oral cavity to the esophagus. The purpose of this study was to investigate the correlation of the SP sequence mode on high-resolution manometry (HRM) with oral intake difficulty and aspiration pneumonia. METHODS: Consecutive patients with dysphagia who were admitted to our dysphagia clinic between November 2016 and November 2020 were enrolled in this cross-sectional study. We classified the HRM pressure topography data according to the SP sequence mode into type A, normal; B, partially decreased; C, totally decreased; and D, sequence disappeared, and according to the upper esophageal sphincter (UES) during pharyngeal swallowing into type 1, flattening and 2, non-flattening. Clinical dysphagia severity was determined based on oral intake difficulty and aspiration pneumonia. RESULTS: In total, 202 patients with dysphagia (mean [standard deviation] age, 68.3 [14.5] years; 140 [69.8%] male) were enrolled. Type C (odds ratio [OR], 10.48; 95% confidence interval [CI], 2.89-51.45), type D (OR, 19.90; 95% CI, 4.18-122.35), and type 2 (OR, 6.36; 95% CI, 2.88-14.57) were significantly related to oral intake difficulty. Type C (OR, 3.23; 95% CI, 1.08-11.12) and type 2 (OR, 4.18; 95% CI, 1.95-9.15) were significantly associated with aspiration pneumonia. CONCLUSION: The failure of sequential generation of SP was associated with higher risk of oral intake difficulty and aspiration pneumonia. These assessments are useful in understanding the pathophysiology and severity of dysphagia and in selecting safety nutritional management methods. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2127-2135, 2024.

Comparison between CT volumetry, technetium99m galactosyl-serum-albumin scintigraphy, and gadoxetic-acid-enhanced MRI to estimate the liver fibrosis stage in preoperative patients.

OBJECTIVES: To compare the efficacy of computed tomography volumetry (CTV), technetium99m galactosyl-serum-albumin (99mTc-GSA) scintigraphy, and gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI) in estimating the liver fibrosis (LF) stage in patients undergoing liver resection. METHODS: This retrospective study included 91 consecutive patients who had undergone preoperative dynamic CT and 99mTc-GSA scintigraphy. EOB-MRI was performed in 76 patients. CTV was used to measure the total liver volume (TLV), spleen volume (SV), normalised to the body surface area (BSA), and liver-to-spleen volume ratio (TLV/SV). 99mTc-GSA scintigraphy provided LHL15, HH15, and GSA indices. The liver-to-spleen ratio (LSR) was calculated in the hepatobiliary phase of EOB-MRI. Hyaluronic acid and type 4 collagen levels were measured in 65 patients. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify useful parameters for estimating the LF stage and laboratory data. RESULTS: According to the multivariable logistic regression analysis, SV/BSA (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003-1.02; p = 0.011), LSR (OR, 0.06; 95%CI, 0.004-0.70; p = 0.026), and hyaluronic acid (OR, 1.01; 95%CI, 1.001-1.02; p = 0.024) were independent variables for severe LF (F3-4). Combined SV/BSA, LSR, and hyaluronic acid correctly estimated severe LF, with an AUC of 0.91, which was significantly larger than the AUCs of the GSA index (AUC = 0.84), SV/BSA (AUC = 0.83), or LSR (AUC = 0.75) alone. CONCLUSIONS: Combined CTV, EOB-MRI, and hyaluronic acid analyses improved the estimation accuracy of severe LF compared to CTV, EOB-MRI, or 99mTc-GSA scintigraphy individually. CLINICAL RELEVANCE STATEMENT: The combined analysis of spleen volume on CT volumetry, liver-to-spleen ratio on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI, and hyaluronic acid can identify severe liver fibrosis associated with a high risk of liver failure after hepatectomy and recurrence in patients with hepatocellular carcinoma. KEY POINTS: • Spleen volume of CT volumetry normalised to the body surface area, liver-to-spleen ratio of EOB-MRI, and hyaluronic acid were independent variables for liver fibrosis. • CT volumetry and EOB-MRI enable the detection of severe liver fibrosis, which may correlate with post-hepatectomy liver failure and complications. • Combined CT volumetry, gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid-enhanced MRI (EOB-MRI), and hyaluronic acid analyses improved the estimation of severe liver fibrosis compared to technetium99m galactosyl-serum-albumin scintigraphy.

Solid-state inorganic and metallic adhesives for soft biological tissues.

Currently, the soft-tissue adhesives used in clinical practice are glue-type organic adhesives. However, there is a demand for new types of adhesives, because the current organic adhesives present challenges in terms of their biocompatibility and adhesion strength. This review summarizes the discovery and development of inorganic and metallic adhesives designed for soft biological tissues while focusing on immobilization of medical divices on soft tissues. These new types of adhesives are in a solid state and adhere directly and immediately to soft tissues. Therefore, they are called "solid-state adhesives" to distinguish them from the currently used glue-type adhesives. In previous studies on inorganic solid-state adhesives, oxides and calcium phosphates were used as raw materials in the form of nanoparticles, nanoparticle-coated films, or nanoparticle-assembled porous plates. In previous studies on metallic solid-state adhesives, only Ti and its alloys were used as raw materials. This review also discusses the future perspectives in this active research area.

Extracellular volume by dual-energy CT, hepatic reserve capacity scoring, CT volumetry, and transient elastography for estimating liver fibrosis.

Our purpose was to compare the efficacy of liver and splenic volumetry (LV and SV), extracellular volume (ECV) on dual-layer spectral-detector CT scoring systems for estimating liver fibrosis (LF) in 45 patients with pathologically staged LF. ECV measured on CT value (HU-ECV), iodine density (ID-ECV), atomic number (Zeff-ECV), and electron density (ED-ECV), LV or SV/body surface area (BSA), albumin bilirubin grade (ALBI), model for end-stage liver disease (MELD) score, aspartate aminotransferase platelet ratio index (APRI), and fibrosis index based on the four factors (FIB-4) were recorded. Transient elastography was measured in 22 patients, and compared to ECV. No correlation was found between transient elastography and all ECVs. Area under the curve (AUC) for estimating F4 on transient elastography was 0.885 (95% CI 0.745-1.000). ALBI was weakly associated with LF (p = 0.451), while MELD (p < 0.001), APRI (p = 0.010), and FIB-4 (p = 0.010) were significantly associated with LF. SV/BSA had a higher AUC than MELD, APRI, and FIB-4 for estimating F4 (AUC = 0.815, 95% CI 0.63-0.999), but MELD (AUC = 0.799, 95% CI 0.634-0.965), APRI (AUC = 0.722, 95% CI 0.561-0.883), and FIB-4 (AUC = 0.741, 95% CI 0.582-0.899) had higher AUCs than ALBI. SV/BSA significantly contributed to differentiation for estimating F4; odds ratio (OR) was 1.304-1.353 (Reader 1-2; R1-R2), whereas MELD significantly contributed to the differentiation between F0-2 and F3-4; OR was 1.528-1.509 (R1-R2). AUC for SV/BSA and MELD combined was 0.877 (95% CI 0.748-1.000). In conclusion, SV/BSA allows for a higher estimation of liver cirrhosis (F4). MELD is more suitable for assessing severe LF (≥ F3-4). The combination of SV/BSA and MELD had a higher AUC than SV/BSA alone for liver cirrhosis (F4).

Computed Tomography-guided Drainage with Modified Trocar Technique Using a Drainaway Drainage Kit.

Purpose: Image-guided percutaneous drainage for abscesses is known as a safe and effective treatment. The computed tomography-guided percutaneous drainage kit Drainaway (SB Kawasumi Co., Ltd.), developed on the basis of a modified trocar method, has made it possible to complete the procedure only under computed tomography guidance without radiographic fluoroscopy. This study investigated the feasibility and safety of Drainaway for abscess drainage. Material and Methods: In this retrospective observational study, 28 procedures in 27 patients (18 men and 9 women; age 67.0 ± 12.3 years) who underwent computed tomography-guided drainage using Drainaway between March and December 2021 at seven affiliated hospitals were analyzed. Patients with symptomatic, puncturable on computed tomography and refractory abscesses were included. Technical success (successful drainage with computed tomography alone), primary clinical success (successful drainage with Drainaway alone), secondary clinical success (avoidance of surgery), and complications were evaluated. Results: The sites of the abscesses were the intraperitoneal, retroperitoneal, and thoracic cavities in 19, 5, and 2 patients, respectively, and subcutaneous tissue in 1 patient. The mean size of the abscesses was 7.1 ± 3.4 cm. The technical success rate was 96.4%; the ligament of the puncture route could not be penetrated in one case. The primary clinical success rate was 77.8%, whereas the secondary clinical success rate of catheter upsizing or replacement was 96.3%. Complications included one case of biliary pleurisy that required drainage. Conclusions: Drainaway is a useful device that allows abscess drainage using only computed tomography guidance without radiographic fluoroscopy.

Comparison between Intravoxel Incoherent Motion and Splenic Volumetry to Predict Hepatic Fibrosis Staging in Preoperative Patients.

Intravoxel incoherent motion (IVIM) and splenic volumetry (SV) for hepatic fibrosis (HF) prediction have been reported to be effective. Our purpose is to compare the HF prediction of IVIM and SV in 67 patients with pathologically staged HF. SV was divided by body surface area (BSA). IVIM indices, such as slow diffusion-coefficient related to molecular diffusion (D), fast diffusion-coefficient related to perfusion in microvessels (D*), apparent diffusion-coefficient (ADC), and perfusion related diffusion-fraction (f), were calculated by two observers (R1/R2). D (p = 0.718 for R1, p = 0.087 for R2) and D* (p = 0.513, p = 0.708, respectively) showed a poor correlation with HF. ADC (p = 0.034, p = 0.528, respectively) and f (p < 0.001, p = 0.007, respectively) decreased as HF progressed, whereas SV/BSA increased (p = 0.015 for R1). The AUCs of SV/BSA (0.649-0.698 for R1) were higher than those of f (0.575-0.683 for R1 + R2) for severe HF (≥F3-4 and ≥F4), although AUCs of f (0.705-0.790 for R1 + R2) were higher than those of SV/BSA (0.628 for R1) for mild or no HF (≤F0-1). No significant differences to identify HF were observed between IVIM and SV/BSA. SV/BSA allows a higher estimation for evaluating severe HF than IVIM. IVIM is more suitable than SV/BSA for the assessment of mild or no HF.

Pulmonary interstitial glycogenosis in Birt-Hogg-Dubé syndrome-associated lung cysts: A new insight into the pathogenesis?

Multiple lung cysts are one of the major features of Birt-Hogg-Dubé syndrome (BHD), but little is known about their nature and pathogenesis. We report a case of a woman diagnosed with BHD lung cysts who exhibited pulmonary interstitial glycogenosis (PIG), a mesenchymal abnormality hitherto undescribed in this disease, in specimens resected at 14 and 29 years of age. Histopathologically, oval to spindle clear cells were seen in the subepithelial interstitial tissue of septal structures and the walls of the cysts. They had abundant periodic acid-Schiff-positive cytoplasmic glycogen. Immunohistochemically, these cells were positive for a few markers of mesenchymal stem cell-like lineage, including vimentin, CD44, and CD10, and negative for markers of epithelial or specific mesenchymal differentiation; these results were consistent with the reported immunophenotype of PIG cells. These PIG cells were more abundant in her specimen at age 14 years than in the second specimen from adulthood. The present case suggests that BHD lung cysts belong to a group of pulmonary developmental disorders characterized by combined PIG and alveolar simplification/cystic change. Disorders with PIG may persist until adulthood and may be of clinical and pathological significance.

Fabrication of a Fish-Bone-Inspired Inorganic-Organic Composite Membrane.

Biological materials have properties like great strength and flexibility that are not present in synthetic materials. Using the ribs of crucian carp as a reference, we investigated the mechanisms behind the high mechanical properties of this rib bone, and found highly oriented layers of calcium phosphate (CaP) and collagen fibers. To fabricate a fish-rib-bone-mimicking membrane with similar structure and mechanical properties, this study involves (1) the rapid synthesis of plate-like CaP crystals, (2) the layering of CaP-gelatin hydrogels by gradual drying, and (3) controlling the shape of composite membranes using porous gypsum molds. Finally, as a result of optimizing the compositional ratio of CaP filler and gelatin hydrogel, a CaP filler content of 40% provided the optimal mechanical properties of toughness and stiffness similar to fish bone. Due to the rigidity, flexibility, and ease of shape control of the composite membrane materials, this membrane could be applied as a guided bone regeneration (GBR) membrane.