A prototype protein nanocage minimized from carboxysomes with gated oxygen permeability.

Protein nanocages (PNCs) in cells and viruses have inspired the development of self-assembling protein nanomaterials for various purposes. Despite the successful creation of artificial PNCs, the de novo design of PNCs with defined permeability remains challenging. Here, we report a prototype oxygen-impermeable PNC (OIPNC) assembled from the vertex protein of the ß-carboxysome shell, CcmL, with quantum dots as the template via interfacial engineering. The structure of the cage was solved at the atomic scale by combined solid-state NMR spectroscopy and cryoelectron microscopy, showing icosahedral assembly of CcmL pentamers with highly conserved interpentamer interfaces. Moreover, a gating mechanism was established by reversibly blocking the pores of the cage with molecular patches. Thus, the oxygen permeability, which was probed by an oxygen sensor inside the cage, can be completely controlled. The CcmL OIPNC represents a PNC platform for oxygen-sensitive or oxygen-responsive storage, catalysis, delivery, sensing, etc.

Molecular characterization of solitary pulmonary nodules in dual-energy CT nonlinear image fusion technology.

OBJECTIVE: To investigate the feasibility and to optimize the parameters of nonlinear blending technique in dual-energy CT on solitary pulmonary nodules (SPN). METHODS: The simulated enhanced SPN were used the mixture of nonionic iodinated contrast agent (Iopromide 370mgI/100 ml) and normal saline and then randomly placed inside an anthropomorphic chest phantom. The phantom was examined on SOMATOM definition flash with dual mode (80/140 kV) and single energy mode (120 kV) (the same CTDIvol). Nonlinear blending images and linear blending images with a weighting factor of 0.3 were generated and the image qualities were analyzed. RESULTS: For different simulated density SPN, when 0 HU was chosen as the Blending Center (BC) and 0 to 30 HU were chosen as the Blending width (BW), the nonlinear blending images yielded a higher contrast-to-noise (CNR). There were significant differences in the image noise and signal-to-noise (SNR) of different simulated density SPN at non-linear blending images, linear blending images and 120 kV images (p < .05); But the differences of CNR between the three groups were not statistically significant (p > .05). The SNR of different simulated density SPN at non-linear blending images was significantly increased compared with it at linear blending images and 120 kV images (p < .05); And the image noise at non-linear blending was lower than it at linear blending images (p < .05). CONCLUSION: Nonlinear blending technique in dual-energy CT can increase the SNR of enhanced SPN, and it is helpful in diagnosis of SPN.

Extensively sparse 13C labeling to simplify solid-state NMR 13C spectra of membrane proteins.

Solid-state Nuclear Magnetic Resonance (ssNMR) is an emerging technique to investigate the structures and dynamics of membrane proteins in an artificial or native membrane environment. However, the structural studies of proteins by ssNMR are usually prolonged or impeded by signal assignments, especially the assignments of signals for collection of distance restraints, because of serious overlapping of signals in 2D 13C-13C spectra. Sparse labeling of 13C spins is an effective approach to simplify the 13C spectra and facilitate the extractions of distance restraints. Here, we propose a new reverse labeling combination of six types of amino acid residues (Ile, Leu, Phe, Trp, Tyr and Lys), and show a clean reverse labeling effect on a model membrane protein E. coli aquaporin Z (AqpZ). We further combine this reverse labeling combination and alternate 13C-12C labeling, and demonstrate an enhanced dilution effect in 13C-13C spectra. In addition, the influences of reverse labeling on the labeling of the other types of residues are quantitatively analyzed in the two strategies (1, reverse labeling and 2, reverse labeling combining alternate 13C-12C labeling). The signal intensities of some other types of residues in 2D 13C-13C spectra are observed to be 20-50% weaker because of the unwanted reverse labeling. The extensively sparse 13C labeling proposed in this study is expected to be useful in the collection of distance restraints using 2D 13C-13C spectra of membrane proteins.

ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) patients have relatively poor clinical outcomes. A marker predicting the prognosis of patients with TNBC could help guide treatment. Extensive evidence demonstrates that angiopoietin-like 4 (ANGPTL4) is involved in the regulation of cancer growth, metastasis and angiogenesis. Therefore, its role in TNBC is of interest. METHODS: We tested the ANGPTL4 expression level in tumor tissues by immunohistochemistry (IHC) and detected its association with the clinical features of TNBC patients. Next, the effects and mechanisms of ANGPTL4 on TNBC cell migration and adhesion were investigated. RESULTS: We found that ANGPTL4 overexpression was associated with favorable outcomes in TNBC patients. ANGPTL4 upregulation inhibited cell adhesion, migration and invasion in vitro. Further analyses demonstrated that the possible mechanism might involve suppression of TNBC progression by interacting with extracellular matrix-related genes. CONCLUSIONS: The present findings demonstrated that enhancement of ANGPTL4 expression might inversely correlate with TNBC progression. ANGPTL4 is a promising marker of TNBC and should be evaluated in further studies. TRIAL REGISTRATION: Retrospectively registered.

Synthesis and characterization of a photoresponsive doxorubicin/combretastatin A4 hybrid prodrug.

To explore the application of photoremovable protecting groups (PPGs) in the field of combination chemotherapy, we designed and synthesized a photoresponsive hybrid prodrug 4 that bearing both doxorubicin (DOX) and combretastatin A4 (CA4). Light triggered drug release investigation found that DOX release was mainly accomplished by 405 nm light while CA4 release was mainly triggered by 365 nm light, i.e., prodrug 4 exhibited a quasi-sequential release behavior when a sequential light irradiation strategy was applied. Cell viability evaluation confirmed the increased cytotoxicity of prodrug 4 compared with individual drugs towards MDA-MB-231cells, indicating that a synergistic effect was achieved.

Consistency of Multiple Renal Functional MRI Measurements Over 18 Months.

BACKGROUND: Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies. PURPOSE/HYPOTHESIS: To investigate the consistency of repeated functional MRI measurements in healthy subjects. STUDY TYPE: Prospective, longitudinal study. SUBJECTS: Seventeen healthy subjects were examined on two different occasions, 18 months apart. FIELD STRENGTH/SEQUENCE: Multiple gradient-recalled-echo, 2D navigator-gated flow-sensitive alternating inversion recovery True-FISP and spin-echo planar diffusion-weighted sequences were used on a 3T scanner. Images were acquired on two different scanner configurations. ASSESSMENT: Blood oxygenation level-dependent (BOLD) R2*, arterial spin labeling (ASL) perfusion-derived blood flow (BF) and apparent diffusion coefficient (ADC) maps were analyzed using a custom image processing toolbox. Regions of interest (ROIs) were placed on renal cortex, medulla, and whole kidney. Multiple researchers were involved in defining the ROIs. STATISTICAL TESTS: Intra- and intersubject coefficients of variation (CV) and Bland-Altman plots were used to measure consistency and evaluate bias in the measurements. A nonparametric Wilcoxon test was used to compare differences between two timepoints. RESULTS: The intrasubject CV for R2* and ADC were 6.8% and 5.3% with small (-3.8 and 5.3%) bias, respectively, comparing baseline and 18-month data. Intrasubject CV for renal cortex BF was higher (18.7%) compared to R2* and ADC, but comparable to prior literature values over shorter durations. It also exhibited a larger bias (-15.4%) between two timepoints and significantly lower values (P = 0.022) at 18-month data. DATA CONCLUSION: All three MRI parameters over 18 months, even with a scanner upgrade and involving multiple observers, showed good consistency. These results are useful for the interpretation of longitudinal data and support the use of these methods to monitor progression in patients with CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:514-521.

Quantitative susceptibility mapping as a monitoring biomarker in cerebral cavernous malformations with recent hemorrhage.

BACKGROUND: Quantitative Susceptibility Mapping (QSM) MRI allows accurate assessment of iron content in cerebral cavernous malformations (CCM), and a threshold increase by 6% in QSM has been shown to reflect new symptomatic hemorrhage (SH) in previously stable lesions. PURPOSE/HYPOTHESIS: It is unclear how lesional QSM evolves in CCMs after recent SH, and whether this could serve as a monitoring biomarker in clinical trials aimed at preventing rebleeding in these lesions. STUDY TYPE: This is a prospective observational cohort study. POPULATION: 16 CCM patients who experienced a SH within the past year, whose lesion was not resected or irradiated. FIELD STRENGTH/SEQUENCE: The data acquisition was performed using QSM sequence implemented on a 3T MRI system ASSESSMENT: The lesional QSM assessments at baseline and yearly during 22 patient-years of follow-up were performed by a trained research staff including imaging scientists. STATISTICAL TESTS: Biomarker changes were assessed in relation to clinical events. Clinical trial modeling was performed using two-tailed tests of time-averaged difference (assuming within-patient correlation of 0.8, power = 0.9 and alpha = 0.1) to detect 20%, 30% or 50% effects of intervention on clinical and biomarkers event rates during two years of follow-up. RESULTS: The change in mean lesional QSM of index hemorrhagic lesions was +7.93% per patient-year in the whole cohort. There were 5 cases (31%) of recurrent SH or lesional growth, and twice as many instances (62%) with a threshold (6%) increase in QSM. There were no instances of SH hemorrhage or lesional growth without an associated threshold increase in QSM during the same epoch. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1133-1138.

Hierarchical Porous Protein Scaffold Templated from High Internal Phase Emulsion Costabilized by Gelatin and Gelatin Nanoparticles.

Recently, three-dimensional (3D) scaffolds produced using poly-Pickering high internal phase emulsions (polyHIPEs) technology are particularly attractive in biomedical application. However, until now the most investigated polyHIPEs are hydrophobic composites originating from synthetic polymers. Here we present an investigation of a hierarchical porous protein scaffold templated from oil-in-water (O/W) HIPEs costabilized by fully natural materials, gelatin, and gelatin nanoparticles. Fairly monodispersed gelatin nanoparticles were first synthesized through a two-step desolvation method, and then they were used as emulsifiers together with gelatin to fabricate stable HIPEs with adjustable droplet size distribution and rheology. Monolithic scaffolds were formed by cross-linking the HIPEs with polymers as low as 2.5 wt % in the continuous phase, which appropriately presented a general high porosity and had an interconnected porous morphology with smooth pore walls and textured structures. Furthermore, the scaffolds were degradable and showed reasonably good biocompatibility; L929 cells could adhere to the surface of the materials and exhibited intensive growth and well-spread morphology. This hierarchical porous protein scaffold could, therefore, have important application as a 3D scaffold that offers enhanced cell adhesion and functionality.

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. METHODS: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) were assessed by Western blot. RESULTS: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1ß significantly decreased (p < 0.01). CONCLUSION: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.

Interconnected macroporous 3D scaffolds templated from gelatin nanoparticle-stabilized high internal phase emulsions for biomedical applications.

Here we report on the successful preparation of open-cellular macroporous 3D scaffolds templated from gelatin nanoparticle-stabilized HIPEs with acrylamide (AM) as the monomer in the continuous phase. Tuning the gelatin nanoparticle concentration or AM content led to different porous structures with void diameters varying between 30 and 78 µm. More importantly, keeping HIPEs at room temperature to undergo a limited kinetic coarsening before polymerization could greatly improve the interconnectivity and pore size of the scaffolds, with the average diameters (approx. 118 µm) being enlarged 1.5-fold. Additionally, the scaffolds had a character of soft tissue with compressive modulus more than 150 kPa. The cell culture assay confirmed that HepG2 cells not only could adsorb on but also were grown inside the scaffolds, representing a characteristic of the good biocompatibility of the scaffolds. Our work suggests that the 3D scaffolds fabricated from gelatin nanoparticle-stabilized HIPE templates are promising culture substrates for a wide range of applications in the biomedical field.

Perception and Acceptability of Medical Photography in Chinese Dermatologic Patients: A Questionnaire Survey.

BACKGROUND: Medical photography is increasingly used by physicians, but studies assessing the perception and acceptability of medical photography by Chinese dermatologic patients are scarce. OBJECTIVE: To assess the perception and acceptability of medical photography in Chinese dermatologic patients. MATERIALS AND METHODS: From July to December 2014, adult patients visiting the Dermatology Clinic of The First Affiliated Hospital of Third Military Medical University were included in this study. They were required to fill an anonymous questionnaire regarding perception and acceptability of medical photography. RESULTS: A total of 509 consecutive patients completed the questionnaire, with 35 and 474 declining and undergoing medical photography, respectively. Meanwhile, 81.0% of the patients preferred to be photographed by attending physicians; 63.3% favored clinic-owned cameras, and 81.0% would rather have their photographs stored in the department's database. Besides, most patients allowed their photographs to be used in case studies (92.8%) or medical record keeping (90.3%). CONCLUSION: Most Chinese dermatologic patients accept medical photography. However, the principles of privacy protection and informed consent should be strictly enforced in clinical practice, and appropriate photographic devices and storage methods should be used, for better acceptance.

Trans-cinnamaldehyde protected PC12 cells against oxygen and glucose deprivation/reperfusion (OGD/R)-induced injury via anti-apoptosis and anti-oxidative stress.

Ischemia stroke is the major cause of mortality and permanent neurological disability with little definitive therapeutic options. This cerebral ischemic injury leads to the oxidative stress and eventually cell death. We hypothesized that treatment of this condition with the trans-cinnamaldehyde(TC) could protect cells from ischemic and reperfusion injury. Oxygen and glucose deprivation/reperfusion (OGD/R) was used as an in vitro model of hypoxic ischemic injury in present study. MTT was used to evaluate the protective effects of TC. Next, we tested whether TC reduced the production of reactive oxygen species (ROS). Besides, experiments were performed to determine whether or not the mitochondrial membrane potential was affected. Furthermore, the inhibiters of NO and PI3 K were used to determine the initial mechanisms. TC treatment improved cell viability, reduced intracellular ROS, and increased MMP. Further, the inhibition of NO or PI3 K significantly reduced TC's protective effects. These findings suggest that TC might be a promising agent for ischemic stroke.

Joint estimation of chemical shift and quantitative susceptibility mapping (chemical QSM).

PURPOSE: The purpose of this work is to address the unsolved problem of quantitative susceptibility mapping (QSM) of tissue with fat where both fat and susceptibility change the MR signal phase. THEORY AND METHODS: The chemical shift of fat was treated as an additional unknown and was estimated jointly with susceptibility to provide the best data fitting using an automated and iterative algorithm. A simplified susceptibility model was used to calculate an updated value of the chemical shift based on the local magnetic field in each iteration. Numerical simulation, phantom experiments and in vivo imaging were performed. Artifacts were assessed by measuring the susceptibility variance in uniform regions. Accuracy was assessed by comparison with ground truth in simulation, and using a susceptibility matching approach in phantom. RESULTS: Using the proposed method, artifacts on the QSM image were markedly suppressed in all tested datasets compared with results generated using fixed chemical shifts. Accuracy of the estimated susceptibility was also improved in numerical simulation and phantom experiments. CONCLUSION: A joint estimation of fat content and magnetic susceptibility using an iterative chemical shift update was shown to improve image quality and accuracy on QSM images.

Sensitivity of arterial spin labeling perfusion MRI to pharmacologically induced perfusion changes in rat kidneys.

PURPOSE: To investigate whether arterial spin labeling (ASL) MRI is sensitive to changes by pharmacologically induced vasodilation and vasoconstriction in rat kidneys. MATERIALS AND METHODS: Changes in renal cortical blood flow in seven rats were induced by adenosine infusion (vasodilation) and L-NAME injection (vasoconstriction). All imaging studies were performed on a 3 Tesla scanner using a FAIR-TrueFISP sequence for the ASL implementation. The acquisition time for each ASL scan was 6 min. Cortical perfusion rates were calculated using regions of interest analysis, and the differences in perfusion rates during baseline, vasodilation, and vasoconstriction were compared and assessed for statistical significance. RESULTS: Compared with the baseline, an average of 94 mL/100 g/min increase and 157 mL/100 g/min decrease in cortical perfusion was observed following adenosine infusion and L-NAME administration, respectively. The changes in cortical perfusion were significant between baseline and vasodilation (P < 0.05), baseline and vasoconstriction (P < 0.01), and vasodilation and vasoconstriction (P < 0.01). CONCLUSION: ASL is sensitive to pharmacologically induced perfusion changes in rat kidneys at doses comparable to current use. The preliminary results suggest the feasibility of ASL for investigating renal blood flow in a variety of rodent models.

Chromoblastomycosis due to Fonsecaea monophora in a man with nephritic syndrome.

Chromoblastomycosis is a chronic subcutaneous mycosis caused by dematiaceous fungi. Fonsecaea monophora, a new species segregated from F. pedrosoi, may be the most prevalent pathogen of chromoblastomycosis in southern China. Herein, we report a rare case of chromoblastomycosis in a man with nephritic syndrome. He presented with an asymptomatic red plaque on the back of his left wrist that had appeared and enlarged over a period of 1.5 years, without any prior trauma. He was initially diagnosed with sporotrichosis. However, he did not respond to a 6-month course of potassium iodide treatment. The lesion slowly enlarged and became verrucous instead. Concurrently, a similar maculopapule appeared on his left forearm. Histopathological examination of a biopsy specimen indicated the presence of sclerotic bodies in the dermis. The fungus was identified as Fonsecaea spp. based on the results of a slide culture; in addition, the agent was confirmed to be F. monophora by using molecular methods. The patient demonstrated marked improvement after receiving appropriate antifungal therapy for 3 months. To our knowledge, this is the first case of chromoblastomycosis caused by F. monophora in an immunosuppressed patient. The identification of the agent by molecular techniques is important for epidemiological purposes. Thus, we believe that combination therapy with itraconazole and terbinafine would be a suitable option for infections caused by F. monophora.

Dynamic permeability and quantitative susceptibility: related imaging biomarkers in cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in human cerebral cavernous malformation (CCM) disease. Here, we used 2 novel MRI techniques to establish a relationship between these phenomena. METHODS: Subjects with CCM disease (4 sporadic and 17 familial) underwent MRI imaging using the dynamic contrast-enhanced quantitative perfusion and quantitative susceptibility mapping techniques that measure hemodynamic factors of vessel leak and iron deposition, respectively, previously demonstrated in CCM disease. Regions of interest encompassing the CCM lesions were analyzed using these techniques. RESULTS: Susceptibility measured by quantitative susceptibility mapping was positively correlated with permeability of lesions measured using dynamic contrast-enhanced quantitative perfusion (r=0.49; P≤0.0001). The correlation was not affected by factors, including lesion volume, contrast agent, and the use of statin medication. Susceptibility was correlated with lesional blood volume (r=0.4; P=0.0001) but not with lesional blood flow. CONCLUSIONS: The correlation between quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion suggests that the phenomena of permeability and iron deposition are related in CCM; hence, more leaky lesions also manifest a more cumulative iron burden. These techniques might be used as biomarkers to monitor the course of this disease and the effect of therapy.

Renal perfusion imaging with two-dimensional navigator gated arterial spin labeling.

PURPOSE: To develop a navigator technique enabling free-breathing acquisition to afford sufficient signal averaging for quantitative renal perfusion measurement using arterial spin labeling MRI. METHODS: A novel two-dimensional (2D) navigator technique was implemented in concert with flow-sensitive alternating inversion recovery (FAIR) preparation and true fast imaging with steady precession (True-FISP) readout. The navigator images were obtained with a low-resolution fast low angle shot readout at end of each arterial spin labeling acquisition. A retrospective algorithm was developed to automatically detect respiratory motion for selective signal averaging. The 2D navigator-gated FAIR True-FISP sequence was performed in ten healthy volunteers and five patients with chronic kidney disease. RESULTS: Excellent image quality and comparable cortical perfusion rates (healthy: 276 ± 28 mL/100 g/min, patients: 155 ± 25 mL/100 g/min) to literature values were obtained. An average of 3-fold signal-to-noise ratio improvement was obtained in the 2D navigator-gated approach compared with the breath-hold acquisition in healthy volunteers. Good image quality was achieved in patients while the results from breath-hold acquisition were unusable. The quantitative perfusion rates were significantly lower in chronic kidney disease patients compared with the healthy volunteers. CONCLUSION: 2D navigator-gated free breathing arterial spin labeling is feasible and is a noninvasive method to evaluate renal perfusion both in healthy subjects and those with chronic kidney disease.

Endoscopic Management of Recurrent Epistaxis Caused by Retiform Hemangioendothelioma in a Child: A Case Report.

Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been reported in the inferior turbinate. A 10-year-old Chinese boy presented with recurrent epistaxis in his left nasal cavity and anemia for more than 2 years. Radiographic and electronic video laryngoscopic images showed an expansile mass in the left inferior turbinate. Endoscopic surgery and electrocautery were performed to resect the tumor beyond the macroscopic border. Histopathologically, the tissues were infiltrated by hyperplastic blood vessels arranged in a retiform pattern, and endothelial cells proliferate significantly in some areas. Immunohistochemistry showed a positive result for CD31, CD34, Fli-1, and ERG. No epistaxis, tumor recurrence, or metastasis was found on reexamination over 18 months after surgery.

Updated review of wet pack complications in pulse vacuum pressure steam sterilisation processes in central sterile supply departments.

The quality of sterilisation and disinfection in a central sterile supply department is directly related to the quality of the hospital services and the patients' safety. Wet packs occasionally occur following the process of pressure steam sterilisation; reducing this occurrence is an important issue. Therefore, the causes of wet pack following sterilisation were analysed to identify the influencing factors and suggest improvements to prevent its occurrence. Understanding the sterilisation process and possible causes of exposure helps with risk assessment and identifying necessary corrective measures.