Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate.

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.

QTc prolongation after aneurysmal subarachnoid hemorrhage might be associated with worse neurologic outcome in patients receiving microsurgical clipping or embolization of the intracranial aneurysms: a retrospective observational study.

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

Metformin protects human lens epithelial cells from high glucose-induced senescence and autophagy inhibition by upregulating SIRT1.

PURPOSE: The aim of this study is to explore whether metformin (MET) protects the human lens epithelial cells (HLECs) from high glucose-induced senescence and to identify the underlying mechanisms. METHODS: A cellular senescence model was established by treating HLE-B3 cells with D-glucose and then intervened with MET. Concentrations of high glucose (HG) and MET were detected using CCK-8 and western blot. qRT-PCR, western blot, and senescence-associated ß-galactosidase (SA-ß-gal) were performed to verify the protective effect of MET on senescent HLE-B3 cells. Additionally, western blot and qRT-PCR were conducted to detect the effects of MET on autophagy-related markers p62 and LC3, as well as SIRT1. RESULTS: In vitro, we observed apparent senescence in human lens epithelial cells (HLECs) under high glucose conditions. This was characterized by increased senescence-associated genes p21 and p53. However, the addition of MET significantly reduced the occurrence of HLECs senescence. We also observed that high glucose inhibited both autophagy and SIRT1, which could be restored by MET. Moreover, we verified that the anti-senescence effect of MET was mediated by SIRT1 using SIRT1 activators and inhibitors. CONCLUSION: We have demonstrated that autophagy and SIRT1 activity are inhibited in HLE-B3 cells using the HG induced senescence model. Furthermore, our results showed that MET can delay senescence by activating SIRT1 and autophagy. These findings suggest that MET may be a promising candidate for alleviating cataract development and provide a direction for further investigation into the underlying molecular mechanisms.

Correction: Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems.

Correction for 'Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems' by Jongyun Kim et al., Analyst, 2023, 148, 5133-5143, https://doi.org/10.1039/D3AN01286G.

Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems.

Proper regulation of the in vitro cell culture environment is essential for disease modelling and drug toxicity screening. The main limitation of well plates used for cell culture is that they cannot accurately maintain energy sources and compounds needed during cell growth. Herein, to understand the importance of perfusion in cardiomyocyte culture, changes in contractile force and heart rate during cardiomyocyte growth are systematically investigated, and the results are compared with those of a perfusion-free system. The proposed perfusion system consists of a Peltier refrigerator, a peristaltic pump, and a functional well plate. A functional well plate with 12 wells is made through injection moulding, with two tubes integrated in the cover for each well to continuously circulate the culture medium. The contractile force of cardiomyocytes growing on the cantilever surface is analysed through changes in cantilever displacement. The maturation of cardiomyocytes is evaluated through fluorescence staining and western blot; cardiomyocytes cultured in the perfusion system show greater maturity than those cultured in a manually replaced culture medium. The pH of the culture medium manually replaced at intervals of 3 days decreases to 6.8, resulting in an abnormal heartbeat, while cardiomyocytes cultured in the perfusion system maintained at pH 7.4 show improved contractility and a uniform heart rate. Two well-known ion channel blockers, verapamil and quinidine, are used to measure changes in the contractile force of cardiomyocytes from the two systems. Cardiomyocytes in the perfusion system show greater stability during drug toxicity screening, proving that the perfusion system provides a better environment for cell growth.

Two-dimensional material-based complementary ambipolar field-effect transistors with ohmic-like contacts.

Ambipolar field-effect transistors (FETs) possessing both electron and hole carriers enable implementation of novel reconfigurable transistors, artificial synaptic transistors, and output polarity controllable (OPC) amplifiers. Here, we fabricated a two-dimensional (2D) material-based complementary ambipolar FET and investigated its electrical characteristics. Properties of ohmic-like contacts at source/drain sides were verified from output characteristics and temperature-dependent measurements. The symmetry of electron and hole currents can be easily achieved by optimization of the MoS2or WSe2channels, different from the conventional ambipolar FET with fundamental issues related to Schottky barriers. In addition, we demonstrated successful operation of a complementary inverter and OPC amplifier, using the fabricated complementary ambipolar FET based on 2D materials.

Mohs Micrographic Surgery With Digital Pathology Improves Surgical Quality and Efficiency: A Retrospective Cohort Study.

BACKGROUND: Mohs micrographic surgery, involving pathology of the surgical margin, has the lowest recurrence rate for skin cancer. Moreover, because of technological advances, digital pathology systems are gradually being adopted in hospitals. Yongin Severance Hospital was the first hospital to construct a fully digitalized pathology system in Korea. OBJECTIVE: To evaluate the efficiency and characteristics of the digital pathology system for Mohs micrographic surgery. METHODS: The medical records of 80 patients with skin cancer who underwent Mohs micrographic surgery from March 2020 to August 2022 were analyzed for the number of frozen margins, number of stages, operation time, and recurrence rate to compare cases based on the pathology system. RESULTS: Overall, 23 and 57 patients were examined using the conventional and digital pathology systems, respectively. The mean number of final stages was 0.494 lower ( p -value = .008), the time from the previous to the next stage was 0.687-fold shorter ( p = .002), and the rate of switching from positive to negative margins was 1.990 times higher ( p = .044) in the digital than the conventional group. LIMITATIONS: Retrospective single-center experience; short follow-up time. CONCLUSION: Digital pathology reduces operative time and increases accuracy in Mohs micrographic surgery.

Utility of fetal cardiac magnetic resonance imaging in assessing the cardiac axis in fetuses with congenital heart disease.

BACKGROUND: Fetal dedicated echocardiography is the standard to measure the fetal cardiac axis. However, fetal screening ultrasound (US) or fetal dedicated echocardiography may be technically limited. OBJECTIVE: The purpose of this study was to explore the accuracy of fetal cardiac magnetic resonance imaging (MRI) to measure the cardiac axis in fetuses with congenital heart disease as an adjunct to fetal dedicated echocardiography and to assess the predictive value of fetal cardiac MRI measurements in distinguishing healthy fetuses from fetuses with congenital heart disease. MATERIALS AND METHODS: This is a retrospective study of fetuses referred to our hospital for a fetal cardiac MRI from November 2019 to December 2021. Cardiac axes were measured in the 4-chamber view of the fetal heart using fetal cardiac MRI and dedicated echocardiography, or only using fetal cardiac MRI when screening US was technically limited. The fetuses were divided into a congenital heart disease group and a healthy control group. We used Bland-Altman analysis and the intraclass correlation coefficient (ICC) to assess the agreement of cardiac axis measurements in fetuses with congenital heart disease obtained by cardiac MRI and by fetal dedicated echocardiography. Receiver operating characteristic (ROC) curve analysis of the fetal cardiac axes in the congenital heart disease and healthy fetus groups assessed the predictive value of the cardiac axis measurements. RESULTS: This retrospective study included 431 women (162 carrying fetuses with congenital heart disease, 269 carrying healthy fetuses). Cardiac axes were measured in the 162 fetuses with congenital heart disease using fetal cardiac MRI and dedicated echocardiography. Cardiac axes were measured in the 269 healthy control fetuses using fetal cardiac MRI when fetal screening US was technically limited. The interobserver analysis and intraobserver analysis showed that the cardiac axis measured by fetal cardiac MRI and fetal dedicated echocardiography was repeatable (ICC>0.90). In 162 fetuses with congenital heart disease, Bland-Altman analysis showed a strong agreement between cardiac MRI and fetal dedicated echocardiography measurements for the cardiac axis. The ICC for the cardiac axis values between cardiac MRI and fetal dedicated echocardiography measurements was 0.99. In fetuses with congenital heart disease, 64.2% (104/162) had an abnormal cardiac axis. For the fetal cardiac axis in both the 162 fetuses with congenital heart disease and the 269 healthy fetuses, the area under the ROC curve reached 0.85 (95% confidence interval: 0.80-0.89; P<0.0001). CONCLUSION: The cardiac axis can be accurately measured using fetal cardiac MRI when fetal dedicated echocardiography/fetal screening US is technically limited. The cardiac axis measurements by fetal cardiac MRI are consistent with known cardiac axis measurements by fetal dedicated echocardiography. The frequency of abnormal cardiac axis depends on the type of congenital heart disease.

Significance of cholecystectomy in cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: There have been no studies concerning the complications or benefits of cholecystectomy in ovarian cancer. In this study, we aimed to evaluate the outcomes of cholecystectomy performed during various time periods of the disease course and suggest a management strategy for cholecystectomy in ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with advanced ovarian cancer who underwent cholecystectomy during the cytoreductive surgery from 2009 to 2020. Cholecystectomy was primarily indicated when the gallbladder and surrounding structures were considered to have metastatic tumor invasion. If the final pathologic results showed free of malignant tumor, patients were placed into the no-infiltration group. Clinical outcomes including the recurrence rate and complications were analyzed. RESULTS: A total of 62 patients underwent cholecystectomy, 48 of whom (77.4%) underwent cholecystectomy during primary or interval debulking surgery, whereas 14 (22.6%) underwent cholecystectomy during the follow-up period (five with benign disease and 9 with disease recurrence). Among the patients, 32 (51.6%) patients were included in the no-infiltration group in the final pathology. There were no complications observed in the no-infiltration group (n = 32). Seven (78%) of the nine patients who received cholecystectomy for disease recurrence had metastatic disease in the porta-hepatis or lesser sac at the time of primary surgery. However, no recurrent lesions were observed around the porta-hepatis in patients who received cholecystectomy during primary treatment. CONCLUSION: Considering the safety of the procedure, as well as the risk of disease recurrence or cholecystitis, a cholecystectomy can be offered to patients with ovarian cancer who have metastatic lesions around the gallbladder and porta-hepatis at the time of primary surgery.

Carboxylate-functionalized dragon fruit peel powder as an effective adsorbent for the removal of Rhodamine B (cationic dye) from aqueous solution: adsorption behavior and mechanism.

In this study, we used a simple and low-toxicity chemical treatment to make a carboxylate-functionalized dragon fruit peel powder (CF-DFPP) from dragon fruit peel to improve its capacity for adsorbing Rhodamine B (RhB) from an aqueous medium. Field Emission-Scanning Electron Microscopy/Energy-Dispersive X-ray (FE-SEM/EDX), point of zero charges (pHPZC), Brunauer-Emmett-Teller (BET), and Fourier Transform Infrared (FT-IR) analyses were performed to characterize the adsorbent materials. The adsorption performance and mechanism for the removal of RhB were examined. The kinetic, isotherm and thermodynamic parameters were employed to evaluate the adsorption mechanism. Compared to other models, the Langmuir isotherm and PSO kinetic models better defined the experimental data. CF-DFPP adsorbent exhibited a maximum adsorption efficiency of 228.7 mg/g at 298 K for RhB adsorption. Thermodynamic analysis revealed that the adsorption of RhB by CF-DFPP was spontaneous (ΔGo < 0) and exothermic (ΔHo < 0) nature of the process. Different eluting agents were used in desorption tests, and NaOH was revealed to have greater desorption efficiency (96.8%). Furthermore, regeneration examinations revealed that the biosorbent could effectively retain RhB, even after six adsorption/desorption cycles. These findings demonstrated that the CF-DFPP might be a novel material for removing RhB from an aqueous medium.

Zaluzanin C Alleviates Inflammation and Lipid Accumulation in Kupffer Cells and Hepatocytes by Regulating Mitochondrial ROS.

Zaluzanin C (ZC), a sesquiterpene lactone isolated from Laurus nobilis L., has been reported to have anti-inflammatory and antioxidant effects. However, the mechanistic role of ZC in its protective effects in Kupffer cells and hepatocytes has not been elucidated. The purpose of this study was to elucidate the efficacy and mechanism of action of ZC in Kupffer cells and hepatocytes. ZC inhibited LPS-induced mitochondrial ROS (mtROS) production and subsequent mtROS-mediated NF-κB activity in Kupffer cells (KCs). ZC reduced mRNA levels of pro-inflammatory cytokines (Il1b and Tnfa) and chemokines (Ccl2, Ccl3, Ccl4, Cxcl2 and Cxcl9). Tumor necrosis factor (TNF)-α-induced hepatocyte mtROS production was inhibited by ZC. ZC was effective in alleviating mtROS-mediated mitochondrial dysfunction. ZC enhanced mitophagy and increased mRNA levels of fatty acid oxidation genes (Pparα, Cpt1, Acadm and Hadha) and mitochondrial biosynthetic factors (Pgc1α, Tfam, Nrf1 and Nrf2) in hepatocytes. ZC has proven its anti-lipid effect by improving lipid accumulation in hepatocytes by enhancing mitochondrial function to facilitate lipid metabolism. Therefore, our study suggests that ZC may be an effective compound for hepatoprotection by suppressing inflammation and lipid accumulation through regulating mtROS.

Stress induced self-rollable smart-stent-based U-health platform for in-stent restenosis monitoring.

To date, several smart stents have been proposed to continuously detect biological cues, which is essential for tracking patients' critical vital signs and therapy. However, the proposed smart stent fabrication techniques rely on conventional laser micro-cutting or 3D printing technologies. The sensors are then integrated into the stent structure using an adhesive, conductive epoxy, or laser micro-welding process. The sensor packaging method using additional fabrication processes can cause electrical noise, and there is a possibility of sensor detachment from the sent structure after implantation, which may pose a significant risk to patients. Herein, we are demonstrating for the first time a single-step fabrication method to develop a smart stent with an integrated sensor for detecting in-stent restenosis and assessing the functional dynamics of the heart. The smart stent is fabricated using a microelectromechanical system (MEMS)-based micromachining technology. The proposed smart stent can detect biological cues without additional power and wirelessly transmit the signal to the network analyzer. The cytocompatibility of the smart stent is confirmed through a cytotoxicity test by monitoring the cell growth, proliferation, and viability of the cultured cardiomyocytes. The capacitance of the smart stent exhibits an excellent linear relationship with the applied pressure. The exceptional sensitivity of the pressure sensor enabled the proposed smart stent to detect biological cues during in vivo analysis. The preliminary findings confirmed the proposed smart stent's higher level of structural integrity, durability and repeatability. Finally, the practical feasibility of the smart stent is demonstrated by monitoring diastole and systole at various beat rates using a phantom. The results of the phantom study showed a similar pattern to the human model, indicating the potential use of the proposed multifunctional smart stent for real-time applications.

Prenatal diagnosis of fetal ectopia cordis by fetal cardiovascular magnetic resonance imaging.

OBJECTIVE: The purpose of this retrospective study was to report our cases of fetal ectopia cordis (EC) and to evaluate the utility of fetal cardiovascular magnetic resonance imaging (MRI) for the diagnosis of this rare anomaly. METHOD: This retrospective study included 11 fetuses with EC. The multiplane steady-state free precession (SSFP) sequence, single-shot turbo spin-echo sequence and non-gated SSFP cine cardiovascular magnetic resonance were used to evaluate the fetal heart and abdomen. RESULTS: The 11 fetal cases with EC were examined by fetal cardiovascular MRI and confirmed by postnatal or post-mortem findings. Of these 11 cases, two were isolated thoracic EC, six had pentalogy of Cantrell, and three had an omphalocele and EC. Among all 11 fetuses, nine were associated with congenital heart defects. In four cases, fetal MRI added additional information compared to fetal ultrasound, however, in two cases, fetal MRI missed the diagnosis of a ventricular septal defect noted by echocardiography. CONCLUSION: Fetal MRI combined with prenatal echocardiography can improve the accuracy of the prenatal diagnosis of EC.

Outcomes of bone marrow aspirate concentrate and matrix-induced chondrogenesis (BMIC) for treatment of osteochondral lesions of the talus.

BACKGROUND: To analyze the outcomes of Bone marrow aspirate concentrate and Matrix-Induced Chondrogenesis (BMIC) in Osteochondral Lesions of the Talus (OLTs). METHODS: Patients with OLTs treated with BMIC from June 2013 to July 2020 were included. Visual Analogue Scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Score (FAOS) before treatment and at last follow-up were subjected to analysis. RESULTS: Forty-five patients were included and mean follow-up was 39.1 months (range, 13-97 months). Mean lesion size and depth were 180.7 ± 110.4 mm2 and 9.6 ± 3.7 mm, respectively. BMIC was performed without malleolar osteotomy in 36 patients (80%) and bone graft was performed in 42 (93.3%). VAS, FFI, and FAOS improved significantly. No complication occurred and no revision was required. CONCLUSIONS: The BMIC procedure is feasible and should be considered a viable treatment option for OLTs associated with large subchondral bone defects.

A blocking peptide stabilizes lysophosphatidic acid receptor 1 and promotes lysophosphatidic acid-induced cellular responses.

G protein-coupled receptors regulate a variety of cellular responses and have been considered as therapeutic targets for human diseases. Lysophosphatidic acid receptor 1 (LPA1) is a receptor for bioactive lysophospholipid, LPA. LPA/LPA1-mediated signaling contributes to inflammatory and fibrotic responses in lung diseases; thus understanding regulation of LPA1 stability is important for modulating LPA/LPA1 signaling. Our previous study has shown that LPA1 is degraded in the Nedd4 like (Nedd4L) E3 ubiquitin ligase-mediated ubiquitin-proteasome system. In the current study, we attempt to identify a peptide that stabilizes LPA1 through disrupting LPA1 association with Nedd4L. LPA treatment induces both endogenous and overexpressed LPA1 degradation, which is attenuated by a proteasome inhibitor, suggesting that LPA1 is degraded in the proteasome. LPA increases phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and I-κB kinase in lung epithelial cells, and this effect is promoted by overexpression of a peptide (P1) that mimics C-terminal of LPA1. P1, not a control peptide, attenuates LPA-induced LPA1 ubiquitination and degradation, suggesting that P1 stabilizes LPA1. Further, P1 diminishes Nedd4L-mediated degradation of LPA1 and Nedd4L/LPA1 association. In addition to increasing LPA1 signaling, P1 enhances LPA-induced cell migration and gene expression of Elafin, matrix metallopeptidase 1, and serpin family B member 2 in lung epithelial cells. These data suggest that disruption of LPA1 interaction with Nedd4L by P1 increases LPA1 stability and LPA/LPA1 signaling.

SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration.

The Skp1-Cul1-F-box protein (SCF) E3 ligase complex is one of the largest ubiquitin E3 ligase families. FBXL19, a F-box protein in SCFFBXL19 E3 ligase complex, regulates a variety of cellular responses including cell migration. We have shown that FBXL19 is not stable and its degradation is mediated by the ubiquitin-proteasome system, while the ubiquitin E3 ligase for FBXL19 ubiquitination and degradation has not been identified. In the study, we discovered that a new ubiquitin E3 ligase, SCFFBXW17 , ubiquitinates and induces FBXL19 degradation. Exogenous FBXW17 targets FBXL19 for its ubiquitination and degradation. Lysine 114 in FBXL19 is a potential ubiquitin acceptor site. Acetylation of FBXL19 attenuated SCFFBXW17 -mediated FBXL19 degradation. SCFFBXL19 E3 ligase reduced Rac1 levels and cell migration, while the effects were attenuated by exogenous FBXW17. Downregulation of FBXW17 attenuated lysophosphatidic acid-induced lamellipodia formation and Rac1 accumulation at migration leading edge. Taken together with our previous studies, FBXL19 is degraded by the ubiquitin-proteasome system and its site-specific ubiquitination is mediated by SCFFBXW17 E3 ligase, which promotes cell migration.

Increasing the Energy Gap between Band-Edge and Trap States Slows Down Picosecond Carrier Trapping in Highly Luminescent InP/ZnSe/ZnS Quantum Dots.

Non-toxic InP-based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, compared to Cd-based quantum dots (QDs), for better device efficiency and long-term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state-of-the-art InP-based QD with near-unity luminescence. Here, it is shown that using time-resolved spectroscopic measurements of systematically size-controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band-edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band-edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP-based QDs.

Three-Dimensional Volumetric Magnetic Resonance Imaging Detects Early Alterations of the Brain Growth in Fetuses With Congenital Heart Disease.

BACKGROUND: Several published studies have shown alterations of brain development in third-trimester fetuses with congenital heart disease (CHD). However, little is known about the timing and pattern of altered brain development in fetuses with CHD. PURPOSE: To investigate the changes in the volume of intracranial structures in fetuses with CHD by three-dimensional (3D) volumetric magnetic resonance imaging (MRI) in the earlier stages of pregnancy (median gestational age [GA], 26 weeks). STUDY TYPE: Retrospective. POPULATION: Forty women carrying a fetus with CHD (including 20 fetuses with GA <26 weeks) and 120 pregnant women carrying a healthy fetus (including 50 fetuses with GA <26 weeks). FIELD STRENGTH/SEQUENCE: Two-dimensional single-shot turbo spin echo sequence at 1.5 -T. ASSESSMENT: Three-dimensional volumetric parameters from slice-to-volume registered images, including cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum, brainstem, and extra-cerebrospinal fluid (e-CSF) were quantified by manual segmentation from one primary and two secondary observers. STATISTICAL TESTS: Volumes were presented graphically with quadratic curve fitting. Scatterplots were produced mapping volumes against GA in normal and CHD fetuses. For GA <26 weeks, Z scores were calculated and Student's t-tests were conducted to compare volumes between the normal and CHD fetuses. RESULTS: In fetuses with CHD GMV, SBV, cerebellum, and brainstem were significantly reduced (all P < 0.05) in early stages of pregnancy (GA <26 weeks), with differences becoming progressively greater with increasing GA. Compared with normal fetuses, e-CSF, e-CSF to ICV ratio, and VV were higher in fetuses with CHD (all P < 0.05). However, ICV volume and the GMV to SBV ratio were not significantly reduced in the CHD group (P = 0.94 and P = 0.13, respectively) during the middle gestation (GA <26 weeks). DATA CONCLUSION: There appear to be alterations of brain development trajectory in CHD fetuses that can be detected by 3D volumetric MRI in the earlier stages of pregnancy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Multi-layered polymer cantilever integrated with full-bridge strain sensor to enhance force sensitivity in cardiac contractility measurement.

In this study, we developed a multi-layered functional cantilever for real-time force measurement of cardiomyocytes in cell culture media. The functional cantilever with a full-bridge circuit configuration was composed of one polydimethylsiloxane (PDMS) and two polyimide (PI) layers, forming two resistive sensors on each upper side of the two PI layers. The PI layers were chemically bonded using an oxygen plasma treatment, with a thin composite layer consisting of Cr/SiO2/PDMS. These greatly improved the force sensitivity and the long-term reliability of the integrated strain sensor operating in liquids. The nanogrooved PDMS top layer bonded on the upper PI layer was employed to further improve the growth of cardiomyocytes on the functional cantilever. The difference in resistance changes and response characteristics was confirmed by evaluating the characteristics of the multi-layered polymer cantilevers with half-bridge and full-bridge circuit configurations. We also employed the cantilever devices to measure the contraction force of cardiomyocytes for 16 days and side effects in real time in human-induced pluripotent stem cells treated with the cardiovascular drug verapamil. The sensor-integrated cantilever devices are expected to be utilized as a novel biomedical sensor for evaluating the mechanobiology of cardiomyocytes, as well as in drug screening tests.

Chiral Recognition by Flexible Coordination Polymers of Ag+ with a Cysteine-Based Chiral Thiol Ligand That Bears a Binding Site.

We report a new scheme for chiral recognition using coordination polymers of Ag+ with a chiral thiol ligand that contains a binding group. N-Benzoyl-l-cysteine ethyl ester equipped with a boronic acid group at the para position of the phenyl ring forms coordination polymers with Ag+ in alkaline aqueous solutions that exhibit excellent selectivity toward a d-glucose enantiomer over l-glucose, while the coordination polymers from the d-cysteine-based thiol ligand are specific for l-glucose. It is assumed that a conformation change occurs upon interaction of a saccharide molecule with the polymeric chain receptor, for which the next binding is promoted, leading to the highly effective chiral recognition, despite the flexible nature of the polymeric receptor.