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This study introduces a novel paradigm for achieving widely tunable many-body Fano quantum interference in low-dimensional semiconducting nanostructures, beyond the conventional requirement of closely matched energy levels between discrete and continuum states observed in atomic Fano systems. Leveraging Floquet engineering, the remarkable tunability of Fano lineshapes is demonstrated, even when the original discrete and continuum states are separated by over 1 eV. Specifically, by controlling the quantum pathways of discrete phonon Raman scattering using femtosecond laser pulses, the Raman intermediate states across the excitonic Floquet band are tuned. This manipulation yields continuous transitions of Fano lineshapes from antiresonance to dispersive and to symmetric Lorentzian profiles, accompanied by significant variations in Fano parameter q and Raman intensity spanning 2 orders of magnitude. A subtle shift in the excitonic Floquet resonance is further shown, achieved by controlling the intensity of the femtosecond laser, which profoundly modifies quantum interference strength from destructive to constructive interference. The study reveals the crucial roles of Floquet engineering in coherent light-matter interactions and opens up new avenues for coherent control of Fano quantum interference over a broad energy spectrum in low-dimensional semiconducting nanostructures., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: Although delirium is well described in patients with sepsis, there are limited data on other neurologic complications. We aimed to systematically review the prevalence, neuromonitoring tools, and neurocognitive outcomes in sepsis patients with neurologic complications., Data Sources: MEDLINE and six other databases (Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov ) were searched through January 2023., Study Selection: Studies of adult patients with sepsis reported neurologic complications, use of neuromonitoring tools, neuropathology, and cognitive outcomes., Data Extraction: Two independent reviewers extracted the data. Random-effect meta-analyses were used to pool data., Data Synthesis: Seventy-four studies ( n = 146,855) were included. Neurologic complications were reported in 38 studies ( n = 142,193) including septic encephalopathy (36%, 95% CI, 27-46%; I 2 = 99%), ischemic stroke (5%, 95% CI, 2.1-11.5; I 2 = 99%), intracranial hemorrhage (2%, 95% CI, 1.0-4.4%; I 2 = 96%), seizures (1%, 95% CI, 0.2-7%; I 2 = 96%), posterior reversible encephalopathy syndrome (9%), and hypoxic-ischemic brain injury (7%). In the meta-regression analysis, pulmonary infection, sepsis induced by a gram-positive organism, higher sequential organ failure assessment score, acute physiology and chronic health evaluation II score at admission, and longer ICU length of stay were associated with higher risk of developing septic encephalopathy. Three studies ( n = 159) reported postmortem neuropathological findings, acute brain injury was noted in 47% of patients. Twenty-six studies ( n = 1,358) reported the use of neuromonitoring tools, electroencephalogram was the most used tool for seizure detection. Transcranial Doppler and near infrared spectroscopy were used for monitoring cerebral hemodynamic changes to detect early ischemia. Six studies reported cognitive outcomes ( n = 415) up to 12 months postdischarge and cognitive impairment (≥ one domain) was reported in 30%., Conclusions: In-hospital neurologic complications are common in patients with sepsis. However, the mechanism and timing of those sepsis-associated complications are poorly understood and there are limited data on standardized neuromonitoring in this population., Competing Interests: Dr .Cho is funded by National Heart Lung and Blood Institute 1K23HL157610. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Left ventricular assist device (LVAD) use has revolutionised the care of patients with advanced heart failure, allowing more patients to survive until heart transplantation and providing improved quality for patients unable to undergo transplantation. Despite these benefits, improvements in device technology, and better clinical care and experience, LVADs are associated with neurologic complications. This review provides information on the incidence, risk factors, and management of neurologic complications among LVAD patients. Although scant guidelines exist for the evaluation and management of neurologic complications in LVAD patients, a high index of suspicion can prompt early detection of neurologic complications which may improve overall neurologic outcomes. A better understanding of the implications of continuous circulatory flow on systemic and cerebral vasculature is necessary to reduce the common occurrence of neurologic complications in this population., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Neurocritical care management of acute brain injury (ABI) is focused on identification, prevention, and management of secondary brain injury (SBI). Physiologic monitoring of the brain and other organ systems has a role to predict patient recovery or deterioration, guide individualized therapeutic interventions, and measure response to treatment, with the goal of improving patient outcomes. In this review, we detail how specific physiologic markers of brain injury and neuromonitoring tools are integrated and used in ABI patients to develop therapeutic approaches to prevent SBI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Silica aerogel composite is an excellent thermal insulator for spacecraft under high-temperature and complex air environments. This study intends to evaluate SiC-doped silica aerogel’s thermal insulation performance under large temperature and air pressure differences. In this paper, the hot surface’s temperature response of SiC-doped silica aerogel with different content was studied at significant temperature differences (ΔT) when pressure changes instantaneously. Their thermal insulation performance was evaluated by analyzing the influence of pressure gradients on the unsteady-state heat transfer. When the cold surface’s temperature of the specimen keeps constant at 15 °C and ΔT = 171~912 K, the results demonstrate that the correlative thermal conductivities of silica aerogel with 1% and 5.84% SiC are 0.02223~0.04077 W·m−1·K−1 at P ≈ 10 Pa and 0.03165~0.04665 W·m−1·K−1 at P = 1 atm, respectively. The aerogel composite with 0% SiC showed the best thermal insulation performance at ΔT < 200 K and P ≈ 10 Pa, while the aerogel with 5.84% SiC became the best at ΔT > 700 K and P = 1 atm. In addition, the transient pressure decreases will significantly impair the heat transfer of the gas inside the aerogel, thereby weakening the gaseous thermal conductivity and improving the thermal insulation performance.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis., (© 2021. The Author(s).)

Strokes are common among patients with left ventricular devices (LVAD). We hypothesize that there is ongoing cerebral microvascular injury with LVAD support and aim to describe this among LVAD-implanted patients through post-mortem neuropathologic evaluation. We identified and reviewed medical records of LVAD patients who underwent brain autopsy between January 2006 and December 2019 at a tertiary center. Cerebral injury was defined as both gross and microscopic injuries within the intracranial space including cerebral infarct (CI), hypoxic-ischemic brain injury (HIBI), intracranial hemorrhage (ICH), and cerebral microvascular injury. Cerebral microvascular injury was defined as microscopic brain intraparenchymal or perivascular hemorrhage, perivascular hemosiderin deposition, and perivascular inflammation. Twenty-one patients (median age = 57 years, 67% male) had autopsy after LVAD support (median LVAD support = 51 days). The median time from death to autopsy was 19 h. All 21 patients had cerebral injuries and 19 (90%) patients had cerebral microvascular injuries. Fourteen patients (78%) harbored more than one type of cerebral injury. On gross examination, 8 patients (38%) had CI, and 6 patients (29%) had ICH. On microscopic exam, 12 patients (57%) had microscopic intraparenchymal hemorrhage, 3 patients (14%) had perivascular hemorrhage, 11 patients (43%) had perivascular hemosiderin deposition, 5 patients (24%) had meningeal hemorrhage, 13 patients had chronic perivascular inflammation (62%), and 2 patients had diffuse HIBI (10%). Among patients with LVAD, there is a high prevalence of subclinical microvascular injuries and cerebral microbleeds (CMBs), which may provide some insights to the cause of frequent cerebral injury in LVAD population., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: We aim to provide the current evidence on utility and application of neuromonitoring tools including electroencephalography (EEG), transcranial Doppler (TCD), pupillometry, optic nerve sheath diameter (ONSD), cerebral near-infrared spectroscopy (cNIRS), somatosensory-evoked potentials (SSEPs), and invasive intracranial monitoring in COVID-19. We also provide recent evidence on management strategy of COVID-19-associated neurological complications., Recent Findings: Despite the common occurrence of neurological complications, we found limited use of standard neurologic monitoring in patients with COVID-19. No specific EEG pattern was identified in COVID-19. Frontal epileptic discharge was proposed to be a potential marker of COVID-19 encephalopathy. TCD, ONSD, and pupillometry can provide real-time data on intracranial pressure. Additionally, TCD may be useful for detection of acute large vessel occlusions, abnormal cerebral hemodynamics, cerebral emboli, and evolving cerebral edema at bedside. cNIRS was under-utilized in COVID-19 population and there are ongoing studies to investigate whether cerebral oxygenation could be a more useful parameter than peripheral oxygen saturation to guide clinical titration of permissive hypoxemia. Limited data exists on SSEPs and invasive intracranial monitoring., Summary: Early recognition using standardized neuromonitoring and timely intervention is important to reduce morbidity and mortality. The management strategy for neurological complications is similar to those without COVID-19., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Governments around the world have implemented numerous policies in response to the COVID-19 pandemic. This research examines the political issues resulting in public opinion concerning their responses to the pandemic via an international perspective. The objectives of this study are to: (1) measure the association and determine whether differences in political support can be attributed to the presence of approval ratings during the pandemic, and to (2) identify exceptional cases based on statistical predictions., Methods: We collect information from several open-sourced surveys conducted between June and September 2020 of public sentiment concerning governments' response toward COVID-19. The 11 countries in our sample account for over 50% of the world's Gross Domestic Product (GDP). The study includes country-specific random effects to take into account the data's clustered structure. We consider "political partisanship" and "pre-pandemic approval ratings in 2019" as two potential explanatory variables and employ a mix-effect regression for bounded responses via variable transformation and the wild bootstrap resampling method., Results: According to the wild bootstrap method, the mixed-effect regression explains 98% of the variation in approval ratings during the pandemic in September 2020. The findings reveal partisan polarization on COVID-19 policies in the U.S., with opposing supporters most likely to express negative sentiments toward the governing party., Conclusions: The evidence suggests that approval ratings during the pandemic correlate to differences in political support and pre-pandemic approval ratings, as measured by approval ratings from the views between governing coalition supporters and opponents., Competing Interests: The author has declared that no competing interests exist.

Objectives: Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population., Data Sources: PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020., Study Selection: Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old., Data Extraction: Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI)., Data Synthesis: We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I 2  = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I 2  = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I 2  = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS., Conclusion: In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute respiratory distress syndrome (ARDS) has been associated with secondary acute brain injury (ABI). However, there is sparse literature on the mechanism of lung-mediated brain injury and prevalence of ARDS-associated secondary ABI. We aimed to review and elucidate potential mechanisms of ARDS-mediated ABI from preclinical models and assess the prevalence of ABI and neurological outcome in ARDS with clinical studies. We conducted a systematic search of PubMed and five other databases reporting ABI and ARDS through July 6, 2020 and included studies with ABI and neurological outcome occurring after ARDS. We found 38 studies (10 preclinical studies with 143 animals; 28 clinical studies with 1175 patients) encompassing 9 animal studies (n = 143), 1 in vitro study, 12 studies on neurocognitive outcomes (n = 797), 2 clinical observational studies (n = 126), 1 neuroimaging study (n = 15), and 13 clinical case series/reports (n = 15). Six ARDS animal studies demonstrated evidence of neuroinflammation and neuronal damage within the hippocampus. Five animal studies demonstrated altered cerebral blood flow and increased intracranial pressure with the use of lung-protective mechanical ventilation. High frequency of ARDS-associated secondary ABI or poor neurological outcome was observed ranging 82-86% in clinical observational studies. Of the clinically reported ABIs (median age 49 years, 46% men), the most common injury was hemorrhagic stroke (25%), followed by hypoxic ischemic brain injury (22%), diffuse cerebral edema (11%), and ischemic stroke (8%). Cognitive impairment in patients with ARDS (n = 797) was observed in 87% (range 73-100%) at discharge, 36% (range 32-37%) at 6 months, and 30% (range 25-45%) at 1 year. Mechanisms of ARDS-associated secondary ABI include primary hypoxic ischemic injury from hypoxic respiratory failure, secondary injury, such as lung injury induced neuroinflammation, and increased intracranial pressure from ARDS lung-protective mechanical ventilation strategy. In summary, paucity of clinical data exists on the prevalence of ABI in patients with ARDS. Hemorrhagic stroke and hypoxic ischemic brain injury were commonly observed. Persistent cognitive impairment was highly prevalent in patients with ARDS., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: We aim to report the incidence and clinical characteristics of patients who were found to have diffusion restricting lesions of the corpus callosum (CC) on Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) following intracranial hemorrhage (ICH)., Design/methods: A retrospective cross-sectional analysis was performed of medical records of all adult patients admitted to a single tertiary center with a primary diagnosis of ICH and received nicardipine infusion over a 2-year period. Patients without MRI brain available or patients who underwent digital subtraction angiography (DSA) prior to MRI were excluded. ICH and intraventricular hemorrhage (IVH) volumes and scores were calculated. MRI brain scans were evaluated for presence and locations of DWI lesions., Results: Among 162 patients who met inclusion criteria, 6 patients (4%, median age 53, range 37-71, 100% male, 33% white) were found to have DWI lesions in the CC with a median ICH volume of 17ml (range 1-105ml). The ICH locations were lobar (n=3), deep (n=2) and cerebellum (n=1). All patients (100%) had intraventricular hemorrhage (IVH) with median IVH volume of 25ml (range 2.7-55ml). Four patients were on levetiracetam. No identifiable infections or metabolic abnormalities were found among these patients. All but one patient had normal DSA. Follow up MRI was only available in one patient and showed no reversibility at 14 days., Conclusion: Although rare, diffusion restricting corpus callosum lesions can be seen in patients with ICH, especially in patients with IVH. The etiology and clinical significance of these lesions remains unknown and warrant further research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Despite the common occurrence of brain injury in patients with left ventricular assist device (LVAD), optimal neuromonitoring methods are unknown. A systematic review of PubMed and six electronic databases from inception was conducted until June 5, 2019. Studies reporting methods of neuromonitoring while on LVAD were extracted. Of 5,190 records screened, 37 studies met the inclusion criteria. The neuromonitoring methods include Transcranial Doppler ultrasound for emboli monitoring (TCD-e) (n = 13) and cerebral autoregulation (n = 3), computed tomography and magnetic resonance imaging (n = 9), serum biomarkers (n = 7), carotid ultrasound (n = 3), and near-infrared spectroscopy (n = 2). Of 421 patients with TCD-e, thromboembolic events (TEs) were reported in 79 patients (20%) and microembolic signals (MES) were detected in 105 patients (27%). Ischemic stroke was more prevalent in patients with MES compared to patients without MES (43% vs.13%, p < 0.001). Carotid ultrasound for assessing carotid stenosis was unreliable after LVAD implantation. Elevated lactate dehydrogenase (LDH) levels were associated with TEs. Significant heterogeneity exists in timing, frequency, and types of neuromonitoring tools. TCD-e and serial LDH levels appeared to have potential for assessing the risk of ischemic stroke. Future prospective research incorporating protocolized TCD-e and LDH may assist in monitoring adverse events in patients with LVAD., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Objective: Herpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections., Methods: We reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement., Results: Of 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement., Conclusion: Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

First discovered on the natural killer (NK) cell, the cell surface inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is known for regulating many important biological activities. However, the detail regulatory mechanism for Siglec-7 expression in NK cells currently remains unclear. In this study, we aimed to investigate how cell surface Siglec-7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK-92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5' Siglec-7 promoter became noticeably hypomethylated, and Siglec-7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec-7 expression. Additionally, by using histone deacetylases (HDAC) inhibitor, butyric acid, we showed that Siglec-7 expression was also subjected to the histone modification. And a combined treatment with both 5-azacytidine and butyric acid showed an additive effect on Siglec-7 transcript expression in peripheral NK cells., (© 2020 John Wiley & Sons Ltd.)

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria play significant roles in the biomedical field as they can be facilely functionalized using genetic engineering tools and thus often serve as a versatile multifunctional nanoparticles for a variety of applications. In this study, we investigated the multifaceted bioluminescence kinetics of a NanoLuc luciferase-expressed outer membrane vesicle produced by E. coli . This multifunctional OMV emits strong blue luminescence at 460 nm after mixing with the substrate furimazine, which potentially can be used for bioluminescence-based optical imaging. Characterization of the vesicles was performed via dynamic light scattering and nanoparticle tracking analysis. A murine animal model was used to observe the in vivo behavior of the bioluminescence produced by outer membrane vesicles through post subcutaneous administration. The bioluminescence signal was tracked by noninvasive in vivo optical imaging, while in vitro cytotoxicity and ex vivo tissue histopathology were studied to demonstrate the biocompatibility of the engineered OMVs. A theoretical model was also developed to simulate the relevant enzyme-substrate reaction kinetics along with absorption of the in vivo system. The interplay of the reaction and absorption is in good agreement with the experimental results. The study shows a great potential of the genetically engineered vesicles as an interesting class of functional nanomaterials for imaging-related biomedical applications.

Background: The risk-benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown., Objective: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients., Methods: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy. Pre- and post-discontinuation comparisons of Performance Scales (PS), Timed 25-Foot Walk, and Patient Health Questionnaire-9 (PHQ9) were analyzed using linear mixed models., Results: A total of 600 patients were included, with 178 (29.7%) discontinuing. Discontinuers were 2.2 years older, had 3.2 years longer disease duration, and 1.6 years lesser treatment exposure. Providers initiated discontinuation more than patients (68.0%). Only one clinical relapse occurred in discontinuers. A proportion (10.7%) reinitiated DMT. Provider-initiated discontinuers restarted less often (hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.12-0.9). In discontinuers, relapsing-remitting patients had lower PS on average than primary progressive. Provider-initiated discontinuation was associated with lower PS than patient- initiated discontinuation. PHQ9 scores appeared higher in those stopping intravenous (IV) therapies than interferons. Lower PS and PHQ9 indicate better outcomes., Conclusion: Most patients over age 60, who discontinued DMT, remained off DMT. This study provides real-world data that may guide clinicians considering discontinuing DMT.

A smart hydrogel with dual self-healing and autofluoresent functionalities is presented. The protein hydrogel is fabricated by denaturing bovine serum albumin in a basic environment. Upon gelation, autofluorescence is induced and the protein hydrogel can be excited by a wide range of spectrum, ranging from 320 to 520 nm. It was also found that the as-prepared autofluorescent protein hydrogel possessed rapid and repetitive self-healing capability. Without any external stimulus, more than 90% recovery of the mechanical strength can be obtained within 10 min after destruction. Moreover, the as-prepared hydrogel exhibits excellent biocompatibility and cell attachment property after its pH adjustment to neutral pH, while both autofluorescence and self-healing properties were still retained. This study suggests a promising means to prepare multi-functional protein hydrogel with dual physicochemical functionalities, which holds great potential in biomedical related applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 81-91, 2019., (© 2018 Wiley Periodicals, Inc.)

Bulk solutions of therapeutic proteins are often frozen for long-term storage. During the freezing process, proteins in liquid solution redistribute and segregate in the interstitial space between ice crystals. This is due to solute exclusion from ice crystals, higher viscosity of the concentrated solution, and space confinement between crystals. Such segregation may have a negative impact on the native conformation of protein molecules. To better understand the mechanisms, we developed a phase-field model to describe the growth of ice crystals and the dynamics of freeze concentration at the mesoscale based on mean field approximation of solute concentration and the underlying heat, mass and momentum transport phenomena. The model focuses on evolution of the interfaces between liquid solution and ice crystals, and the degree of solute concentration due to partition, diffusive, and convective effects. The growth of crystals is driven by cooling of the bulk solution, but suppressed by a higher solute concentration due to increase of solution viscosity, decrease of freezing point, and the release of latent heat. The results demonstrate the interplay of solute exclusion, space confinement, heat transfer, coalescence of crystals, and the dynamic formation of narrow gaps between crystals and Plateau border areas along with correlations of thermophysical properties in the supercooled regime.

Altered sialic acid processing that leads to upregulation of cell surface sialylation is recognized as a key change in malignant tissue glycosylation. This cancer-associated hypersialylation directly impacts the signaling interactions between tumor cells and their surrounding microenvironment, especially the interactions mediated by immune cell surface sialic acid-binding immunoglobulin-like lectins (Siglecs) to relay inhibitory signals for cytotoxicity. First, we obtained a Siglec-7 neg NK-92MI cell line, NK-92MI-S7N, by separating a group of Siglec-7 neg cell population from an eight-month-long-term NK-92MI in vitro culture by fluorescence-activated cell sorting (FACS). The effect of Siglec-7 loss on NK-92MI-S7N cells was characterized by the cell morphology, proliferation, and cytotoxic activity via FACS, MTS assay, cytotoxic assay, and natural killer (NK) degranulation assay. We found the expression levels of Siglec-7 in NK-92MI were negatively correlated with NK cytotoxicity against leukemia cells. This NK-92MI-S7N cell not only shared very similar phenotypes with its parental cells but also possessed a high and sustainable killing activity. Furthermore, this Siglec-7 neg NK line was unexpectedly capable of eliminating a NK-92MI-resistant leukemia cell, THP-1, through enhancing the effector-target interaction. In this study, a NK cell line with high and sustainable cytotoxicity was established and this cell may provide a potential application in NK-based treatment for leukemia patients.

Autofluorescent bovine serum albumin (BSA) hydrogel microspheres were prepared through the spray-drying of glutaraldehyde cross-linked BSA nanoparticles and then used for a proteinase K based degradation study in an aqueous solution. Experimental results and empirical models are presented to characterize the kinetics of BSA hydrogel microsphere degradation, as well as the accompanying release of synthesized fluorophore. The BSA gel degradation dynamics is primarily controlled by the concentration of proteinase K within the Tris buffer. The coupling of swelling dynamics and the transient distributions of fluorophore are traced by confocal microscopy. Models are developed based on the linear theory of elastic deformation coupled to enzyme and fluorophore transport. This study represents a fundamental investigation of the degradation and release kinetics of protein-based materials, which can potentially be applied for the dynamic and photostable tracking of relevant in vivo systems.

Background: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors., Study Design and Methods: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector-target interactions by cytotoxic analysis and conjugate formation assay., Results: We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I- cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis., Conclusion: In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector-target interaction., (© 2016 AABB.)

Self-healing is a capacity observed in most biological systems in which the healing processes are autonomously triggered after the damage. Inspired by this natural behavior, researchers believed that a synthetic material possessing similar self-recovery capability could also be developed. Albeit various intrinsic self-healing systems have been developed over the past few decades, restriction on the biocompatibility due to the required synthetic conditions under extreme pH and with poisonous cross-linker significantly limits their application in biomedical field. In this study, a highly biocompatible nanocomposite protein hydrogel with excellent biomimetic self-healing property is presented. The self-healing protein gel is made by inducing calcium ions into the mixture of heat-induced BSA nano-aggregates and pristine BSA molecules at room temperature and under physiological pH due to the ion-mediated protein-protein association and the bridging effect of divalent Ca(2+) ions. The as-prepared protein hydrogel shows excellent repetitive self-healing properties without using any external stimuli at ambient condition. Such outstanding self-recovery performance was quantitatively evaluated/validated by both dynamic and oscillatory rheological analysis. Moreover, with the presence of calcium ions, the self-healing behavior can be significantly facilitated/enhanced. Finally, the superior biocompatibility demonstrated by in vitro cytotoxicity analysis suggests that it is a promising self-healing material well-suited for biomedical applications.

Bovine serum albumin (BSA) microspheres were prepared through a facile and low-cost route including a high-speed dispersion of BSA in cross-linking solution followed by spray drying. Interestingly the as-prepared BSA microspheres possess unique blue-green, green, green-yellow, and red fluorescence when excited by specific wavelengths of laser or LED light. The studies of UV-visible reflectance spectra and fluorescence emission spectra indicated that four classes of fluorescent compounds are presumably formed during the fabrication processes. The formation and the potential contributors for the unique green and red autofluorescence were also discussed and proposed though the exact structures of the fluorophores formed remain elusive due to the complexity of the protein system. The effect of spray-drying conditions on the morphology of spray-dried samples was investigated and optimized. FTIR was further employed to characterize the formation of the functional groups in the as-prepared autofluorescent microspheres. Good in vitro and in vivo biocompatibility was demonstrated by the cytotoxicity test on the A549 cancer cells and tissue histological analysis, respectively. The autofluorescent BSA microspheres themselves were then applied as a novel tracer for convenient tracking/modeling of the biodegradation of autofluorescent BSA microspheres injected into mouse model based on noninvasive, time-dependent fluorescence images of the mice, in which experimental data are in good agreement with the proposed mathematical model. All these studies indicate that the as-developed protein microspheres exhibiting good biocompatibility, biodegradability, and unique autofluorescence, can significantly broaden biomedical applications of fluorescent protein particles.

Dilated cardiomyopathy is a major cause of heart failure (HF) that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and HF in experimental dilated cardiomyopathy. Yet, patients with significant HF unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels, and the stages of HF. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D HF. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B HF and remained low through Stages C and D (P<0.001). Cardiac corin levels were positively correlated with systolic function (r=0.96, P=0.003) and inversely with lung water (r=-0.92, P=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stages C and D) and plasma levels rose only with terminal HF (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate levels (r=0.82, P=0.01 and r=0.8, P=0.02, respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of HF, whereas significant increases in plasma ANP, BNP, and cyclic guanosine monophosphate levels were found only in later stage (C and D) HF. This dyssynchrony in expression of corin versus ANP/BNP may impair cleavage activation of pro-natriuretic peptides, and thereby promote the transition from earlier to later stage HF., (© 2015 American Heart Association, Inc.)

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Pumping is a vital natural process, imitated by humans for thousands of years. We demonstrate that a hitherto undocumented mechanism of fluid transport pumps nectar onto the hummingbird tongue. Using high-speed cameras, we filmed the tongue-fluid interaction in 18 hummingbird species, from seven of the nine main hummingbird clades. During the offloading of the nectar inside the bill, hummingbirds compress their tongues upon extrusion; the compressed tongue remains flattened until it contacts the nectar. After contact with the nectar surface, the tongue reshapes filling entirely with nectar; we did not observe the formation of menisci required for the operation of capillarity during this process. We show that the tongue works as an elastic micropump; fluid at the tip is driven into the tongue's grooves by forces resulting from re-expansion of a collapsed section. This work falsifies the long-standing idea that capillarity is an important force filling hummingbird tongue grooves during nectar feeding. The expansive filling mechanism we report in this paper recruits elastic recovery properties of the groove walls to load nectar into the tongue an order of magnitude faster than capillarity could. Such fast filling allows hummingbirds to extract nectar at higher rates than predicted by capillarity-based foraging models, in agreement with their fast licking rates., (© 2015 The Author(s).)

Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione (E h GSH) and cysteine (E h CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p = 0.04), higher body mass index (BMI) (p = 0.003), less oxidized E h CyS (p = 0.001), lower DROMs (p = 0.02), and lower IsoP (p = 0.03). Higher BMI (OR: 1.3; 95% CI: 1.1-1.6) and less oxidized E h CyS (OR: 1.2; 95% CI: 1.1-1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01-1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF.

A newly-designed drug carrier composed of an internal droplet core and a thickness-controllable shell was successfully developed. By co-delivering paclitaxel, doxorubicin and quantum dots simultaneously, this combinational drug delivery system could achieve in vitro fluorescence imaging, chemotherapeutic and oxidation therapy.

Lipid-based nanodiscs (bicelles) are able to form in mixtures of long- and short-chain lipids. Initially, they are of uniform size but grow upon dilution. Previously, nanodisc growth kinetics have been studied using time-resolved small angle neutron scattering (SANS), a technique which is not well suited for probing their change in size immediately after dilution. To address this, we have used dynamic light scattering (DLS), a technique which permits the collection of useful data in a short span of time after dilution of the system. The DLS data indicate that the negatively charged lipids in nanodiscs play a significant role in disc stability and growth. Specifically, the charged lipids are most likely drawn out from the nanodiscs into solution, thereby reducing interparticle repulsion and enabling the discs to grow. We describe a population balance model, which takes into account Coulombic interactions and adequately predicts the initial growth of nanodiscs with a single parameter - i.e., surface potential. The results presented here strongly support the notion that the disc coalescence rate strongly depends on nanoparticle charge density. The present system containing low-polydispersity lipid nanodiscs serves as a good model for understanding how charged discoidal micelles coalesce.

A quantitative analysis is presented for the stochastic interactions of a pair of Brownian hard spheres in non-adsorbing polymer solutions. The hard spheres are hypothetically trapped by optical tweezers and allowed for random motion near the trapped positions. The investigation focuses on the long-time correlated Brownian motion. The mobility tensor altered by the polymer depletion effect is computed by the boundary integral method, and the corresponding random displacement is determined by the fluctuation-dissipation theorem. From our computations it follows that the presence of depletion layers around the hard spheres has a significant effect on the hydrodynamic interactions and particle dynamics as compared to pure solvent and uniform polymer solution cases. The probability distribution functions of random walks of the two interacting hard spheres that are trapped clearly shift due to the polymer depletion effect. The results show that the reduction of the viscosity in the depletion layers around the spheres and the entropic force due to the overlapping of depletion zones have a significant influence on the correlated Brownian interactions.

Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

Purpose: To investigate the feasibility and indication of condylectomy for treatment of comminuted fractures of the condyle above the neck., Methods: Sixty-one patients with condylar fractures, treated between September 2007 and September 2011 were reviewed respectively. Among them, 30 underwent open reduction and internal fixation, 15 underwent conservative therapy, and 16 patients (18 sides) who had comminuted fractures of the condyle above the neck underwent condylectomy. All the patients were followed up for 5 to 48 months after treatment to evaluate the outcomes., Results: Among the 16 patients with condylectomy, poor wound healing due to rejection of hemostatic gauze was noted in 1 patient, occlusal deviation occurred in 1 patient, mild mouth opening limitation happened in 1 patient, and anterior open bite was present in 1 patient. The other patients recovered well, without apparent discomfort, malocclusion and facial asymmetry., Conclusions: For patients with finished maxillofacial growth, condylectomy is a feasible and effective way for management of comminuted fractures of the condyle above the neck. Postoperative occlusal deviation, open bite and limited mouth opening can be corrected with further expectant treatment.

A theoretical model is developed for predicting dynamic polymer depletion under the influence of fluid flow. The results are established by combining the two-fluid model and the self-consistent field theory. We consider a uniform fluid flow across a slit containing a solution with polymer chains. The two parallel and infinitely long walls are permeable to solvent only and the polymers do not adsorb to these walls. For a weak flow and a narrow slit, an analytic expression is derived to describe the steady-state polymer concentration profiles in a Θ-solvent. In both Θ- and good-solvents, we compute the time evolution of the concentration profiles for various flow rates characterized by the Peclet number. The model reveals the interplay of depletion, solvent condition, slit width, and the relative strength of the fluid flow.

Myopia is becoming a significant public health problem, affecting more and more people. Studies indicate that there are two main factors, hereditary and environmental, suspected to have strong impact on myopia. Motivated by the increase in the number of people affected by this problem, this paper focuses primarily on the utilization of mathematical methods to gain further insight into their relationship with myopia. Accordingly, utilizing multidimensional longitudinal myopia data with correlation between both eyes, we develop a Bayesian structural equation model including random effects. With the aid of the MCMC method, it is capable of expressing the correlation between repeated measurements as well as the two-eye correlation and can be used to explore the relational structure among the variables in the model. We consider four observed factors, including intraocular pressure, anterior chamber depth, lens thickness, and axial length. The results indicate that the genetic effect has much greater influence on myopia than the environmental effects., (Copyright © 2011 John Wiley & Sons, Ltd.)

In the intracytoplasmic sperm injection (ICSI) process, a piezoelectric actuator is commonly used to assist the piercing of cell membrane. The longitudinal pulses that are performed by the piezo actuator, however, cause undesired lateral vibrations at the drawn tip of the injection micropipette. This mechanism is not well understood, despite its critical role in piezo-assisted cellular microinjection. We provide an analytical model to characterize the micropipette tip vibrations under assumed base excitation arising from the piezoelectric pulses. The resulting dynamic response is determined by using the Duhamel integral method. This study quantifies the effect of fluid damping, embedded mercury, and the apparent cell membrane elasticity. We found that, in practice, a small mercury droplet filled in pipette essentially creates higher shear forces at the membrane-pipette interface. The increased shear due to underdamped eigenmodes is conceived to assist the piercing of the cell membrane.

In this paper, a series of PANI nanocomposites have been successfully prepared by in situ oxidative polymerization. The as-prepared PANI nanocomposites were subsequently characterized by WAXRD patterns and TEM. It should be noted that the nanocomposite coating containing 3 wt-% of organophilic clay loading was found to exhibit an observable enhanced corrosion protection on cold-rolled steel (CRS) electrode at higher operational temperature of 50 degrees C, which was even better than that of uncoated and electrode-coated with PANI or PANI nanocomposites with 3 wt-% of amino-modified silica nanoparticles alone at room temperature of 30 degrees C based on the electrochemical parameter evaluations (e.g., E(corr), R(p), I(corr), R(corr) and impedance). The vapor permeability property at three different operational temperatures of PANI and PANI nanocomposite membranes were investigated by vapor permeability analyzer (VPA). Effect of material composition on the molecular weight, optical properties and surface hydrophobicity of neat PANI and PANI nanocomposite, in the form of membrane and solution, were studied by gel permeation chromatography (GPC), ultraviolet-visible absorption spectra and contact-angle measurements, respectively. Finally, electrical conductivity at three different operational temperatures of PANI and PANI nanocomposite powder-pressed pellets was also investigated through the measurements of standard four-point-probe technique.

Intracytoplasmic sperm injection (ICSI) is a broadly utilized assisted reproductive technology. A number of technologies for this procedure have evolved lately, such as the most commonly utilized piezo-assisted ICSI technique (P-ICSI). An important problem with this technique, however, is that it requires a small amount of mercury to stabilize the tip of the penetration micropipette. A completely different and mercury-free injection technology, called the rotationally oscillating drill (Ros-Drill) (RD-ICSI), was recently developed. It uses microprocessor-controlled rotational oscillations of a spiked micropipette after the pipette deforms the membrane to a certain tension level. Inappropriate selection of this initiation instant typically results in cell damage, which ultimately leads to unsuccessful ICSI. During earlier manual clinical tests of Ros-Drill, the technicians' expertise determined this instant in an ad hoc fashion. In this paper, we introduce a computer-vision-based tool to mechanize this process with the objective of maintaining the repeatability and introducing potential automation. Computer images are used for monitoring the membrane deformations and curvature variations as the basis for decision making. The main contribution of this paper is in the specifics of the computer logic to perform the monitoring. These new tools are expected to provide a practicable means for automating the Ros-Drill-assisted ICSI operation.

We present optimal perfusion conditions for the growth of primary mouse embryonic fibroblasts (mEFs) and mouse embryonic stem cells (mESCs) using a microfluidic perfusion culture system. In an effort to balance nutrient renewal while ensuring the presence of cell secreted factors, we found that the optimal perfusion rate for culturing primary embryonic fibroblasts (mEFs) in our experimental setting is 10 nL/min with an average flow velocity 0.55 microm/s in the microchannel. Primary mEFs may have a greater dependence on cell secreted factors when compared to their immortalized counterpart 3T3 fibroblasts cultured under similar conditions. Both the seeding density and the perfusion rate are critical for the proliferation of primary cells. A week long cultivation of mEFs and mESCs using the microculture system exhibited similar morphology and viability to those grown in a petri dish. Both mEFs and mESCs were analyzed using fluorescence immunoassays to determine their proliferative status and protein expression. Our results demonstrate that a perfusion-based microculture environment is capable of supporting the highly proliferative status of pluripotent embryonic stem cells.

We demonstrate that hydrogel functionalization with DNA aptamers can be applied for developing a novel sustained-release system.

The ameloblastoma mainly occurs in the mandible, rarely seen in the soft tissues. This paper reported 1 case of mandibular gingival peripheral ameloblastoma, and discussed its treatment based on literature review.

Obstructive sleep apnea, characterized by intermittent periods of hypoxemia, is an independent risk factor for the development of pulmonary hypertension. However, the exact mechanisms of this disorder remain to be defined. Enhanced NADPH oxidase expression and superoxide (O2(-).) generation in the pulmonary vasculature play a critical role in hypoxia-induced pulmonary hypertension. Therefore, the current study explores the hypothesis that chronic intermittent hypoxia (CIH) causes pulmonary hypertension, in part, by increasing NADPH oxidase-derived reactive oxygen species (ROS) that contribute to pulmonary vascular remodeling and hypertension. To test this hypothesis, male C57Bl/6 mice and gp91phox knockout mice were exposed to CIH for 8 hours per day, 5 days per week for 8 weeks. CIH mice were placed in a chamber where the oxygen concentration was cycled between 21% and 10% O2 45 times per hour. Exposure to CIH for 8 weeks increased right ventricular systolic pressure (RVSP), right ventricle (RV):left ventricle (LV) + septum (S) weight ratio, an index of RV hypertrophy, and thickness of the right ventricular anterior wall as measured by echocardiography. CIH exposure also caused pulmonary vascular remodeling as demonstrated by increased muscularization of the distal pulmonary vasculature. CIH-induced pulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of platelet-derived growth factor receptor beta and its associated downstream effector, Akt kinase. These CIH-induced derangements were attenuated in similarly treated gp91phox knockout mice. These findings demonstrate that NADPH oxidase-derived ROS contribute to the development of pulmonary vascular remodeling and hypertension caused by CIH.

Purpose: The purpose of this study is to investigate the relation between age, gender and thickening and nodules in port wine stains(PWS) patients., Methods: The gender and age of 193 cases with port wine stains were compared between those with flat, those with thickening, those with thickening and nodules, in 0-19, 20-year age group. SAS6012 software package was used for Fisher's exact test and Kruskal-Wallis test., Results: There were 165 cases with flat (85.49%), 10 cases with thickening (5.18%), 18 cases with thickening and nodules (9.33%). Kruskal-Wallis test demonstrated significant difference between 2 age groups(P<0.01).There was an increase incidence of thickening, and thickening and nodule formation in 0-19, 20-year age group(P<0.01), but there was no gender difference between thickening and nodules.The data were analyzed by SAS6.12 Fisher's exact test and Kruskal-Wallis test., Conclusion: The incidence of thickening and nodule formation in PWS increase with age.

We analyze the scaling law for the polymer-induced retardation a nanoparticle experiences as it moves through a semi-dilute polymer solution. The translational friction is calculated from a modified Stokes flow using a local viscosity near the nanosphere. The results rationalize a general retardation factor, R = exp(Kaµcν) [T. Odijk, Biophys. J., 2000, 79, 2314], revealing scaling exponents µ = 0.77 and ν = 1, which are in agreement with experiment. We find that rotational motion also has a self-similar behavior and R can be described too by a stretched exponential with slightly different exponents.