Challenges in drug development of neurological diseases remain mainly ascribed to the blood-brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains ...difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.
Zebrafish model of posttraumatic epilepsy Cho, Sung‐Joon; Park, Eugene; Telliyan, Tamar ...
Epilepsia (Copenhagen),
August 2020, 2020-08-00, 20200801, Volume:
61, Issue:
8
Journal Article
Peer reviewed
Objective
Posttraumatic epilepsy (PTE) is defined as recurrent and unprovoked seizures occurring >1 week after traumatic brain injury (TBI). Animal studies of PTE are lengthy and expensive. In this ...study, we developed a cost‐effective PTE animal model using zebrafish to bridge the gap between in vitro studies and low‐throughput animal studies.
Methods
We used two different sets of parameters (G1 and G2) to induce closed‐head TBI in adult zebrafish using pulsed high‐intensity focused ultrasound. Injured fish and naive controls were evaluated for behavioral deficits and spontaneous behavioral seizure activity up to 21 days postinjury (DPI). We also assessed behavioral seizure susceptibility to a subconvulsive dose of pentylenetetrazole (PTZ; 2.5 mmol·L–1) and recorded electrophysiological signals to confirm seizure activity up to 40 DPI. In addition, we investigated injury‐related changes in the blood‐brain barrier and expression levels of various proteins altered in rodent and human TBI.
Results
The G2 parameters resulted in a more severe TBI, with a mortality rate of 25%, as well as motor dysfunction and heightened anxiety persisting at 21 DPI. One hundred percent of the G2 group showed spontaneous myocloniclike behavior, and 80% demonstrated tonic‐clonic–like behavioral seizures by 21 DPI. Such activities were not detected in the naive group. After the application of 2.5 mmol·L–1 PTZ, 100% of injured zebrafish had cloniclike seizures at 21 DPI, versus 30% of the naive group. We also demonstrated electrographic seizure activity at 40 DPI, which was not detected in the naive controls. Lastly, we observed acute blood‐brain barrier dysfunction and increased levels of HMGB1 and ratios of phosphorylated/total Akt and tau through 21 DPI.
Significance
Together, the results indicate that severe TBI in the adult zebrafish leads to similar behavioral and physiological changes to those of more traditional models, including the development of PTE, and suggest this may be a useful model that can accelerate research in TBI/PTE.
Abstract
For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and ...large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm
2
and a greater than 8% efficiency for a cell area larger than 2 cm
2
of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.
A high salt diet is associated with the development of hypertension, one of the most important cardiovascular risk factors. A reduction in sodium intake seems to have an effect on increasing serum ...triglycerides (TGs). Elevated TGs are independently linked to cardiovascular risk. However, there is limited evidence of a possible interactive effect of sodium intake and serum TGs on high blood pressure (BP).
We conducted a nationwide, population-based interaction analysis using the Kawasaki method for estimating 24-h urinary sodium excretion (e24hUNaEKawasaki) as a candidate indicator of dietary sodium intake. All native Koreans aged 20 years or older without significant medical illness were eligible for inclusion.
A total of 16936 participants were divided into quintiles according to their e24hUNaEKawasaki results. Participants in the highest quintile were more obese and hypertensive and had higher white blood cell count, lower hemoglobin, greater glycemic exposure, and poor lipid profiles compared to the same parameters of individuals in other quintiles. Linear regression revealed that e24UNaEKawasaki was related to systolic BP, diastolic BP, and TGs. Multiple logistic regression, adjusted for dietary sodium intake and various conventional risk factors for chronic vascular diseases, showed that both e24UNaEKawasaki and TGs were significant predictors of hypertension. Our interaction analysis demonstrated that increased sodium intake was associated with higher risk of hypertension in participants with elevated TGs than in those without (adjusted RERI = 0.022, 95% CI = 0.017-0.027; adjusted AP = 0.017, 95% CI = 0.006-0.028; adjusted SI = 1.010, 95% CI = 1.007-1.014).
Our findings suggest that the interaction between a high salt diet and elevated TGs may exert synergistic biological effects on the risk of hypertension.
This article critically examines the unknowing of the source of the Ebola epidemic in Northern Uganda, in 2000/1, by asking how this unknowing has been achieved and has shaped the disease situation. ...Specifically, this article follows my informants’ explanation that soldiers of the Uganda People's Defence Force had brought the disease from the Democratic Republic of the Congo to Uganda. This account is widely rejected as a rumour by scientists, who insist that the source of the epidemic remains unknown. By contrast, I suggest that following these stories, as embodied experiences of the multiple connections between war and epidemics, human and nonhuman lives, provides crucial insights into the political ecology of Ebola in the wider region – a region where, even today, conflict and Ebola outbreaks are intricately interwoven. Understanding how unknowing is achieved and shapes a disease situation directs attention to forms of silent knowing, which illuminate what preparedness means in the political ecology of Ebola.
Abstrait
Secret mortel : situer la non‐connaissance et la connaissance de l'origine de l’épidémie d'Ebola dans le nord de l'Ouganda
Résumé
Cet article propose un examen critique de la non‐connaissance de l'origine de l’épidémie d'Ebola qui a sévi dans le nord de l'Ouganda en 2000 et 2001, en cherchant à déterminer comment cette non‐connaissance a été atteinte et a façonné la situation sanitaire. Plus spécifiquement, l'auteur retrace les explications de ses informateurs, selon lesquels des militaires de la Force de défense du peuple ougandais auraient rapporté la maladie de la République démocratique du Congo. Les scientifiques réfutent largement cette rumeur et soutiennent que la source de l’épidémie est à ce jour inconnue. L'auteur suggère en revanche que ces histoires, en tant qu'expériences incarnées des connexions multiples entre guerre et épidémies, vies humaines et non humaines, apportent un éclairage crucial de l’écologie politique d'Ebola dans cette région du monde où, aujourd'hui encore, conflits et épidémies d'Ebola sont intimement liés. Comprendre comment la non‐connaissance est atteinte et façonne une situation sanitaire attire l'attention sur des formes de connaissance silencieuse, qui viennent éclairer ce que signifie l’état de préparation dans l’écologie politique d'Ebola.
The uniform growth of single-crystal graphene over wafer-scale areas remains a challenge in the commercial-level manufacturability of various electronic, photonic, mechanical, and other devices based ...on graphene. Here, we describe wafer-scale growth of wrinkle-free single-crystal monolayer graphene on silicon wafer using a hydrogen-terminated germanium buffer layer. The anisotropic twofold symmetry of the germanium (110) surface allowed unidirectional alignment of multiple seeds, which were merged to uniform single-crystal graphene with predefined orientation. Furthermore, the weak interaction between graphene and underlying hydrogen-terminated germanium surface enabled the facile etch-free dry transfer of graphene and the recycling of the germanium substrate for continual graphene growth.
The effects of basicity and amphoteric oxides (Al2O3 and FetO) on the structure–property relationships of CaO–SiO2–(Al2O3 and FetO) and CaO–SiO2–Al2O3–FetO slags were investigated to determine the ...constitutional effects on the structure of high‐temperature ionic melts. The proportion of Qn species, which is determined by Raman spectroscopy, and the viscosity measured by the rotating cylinder method are both correlated and shown together with the slag structure index (NBO/T) concept. The NBO/T of CaO‐SiO2 binary slags showed a linear relationship with basicity (CaO/SiO2), including an inflection point at CaO/SiO2 = 1.0 resulting from the stability and Qn‐dominant unit of the melt, which changes close to the wollastonite (CaSiO3) congruent point. This inflection point changes with the increasing amphoteric oxide content (Al2O3 and FetO) because of the change in the dominant polymeric unit (Si4+–O–Si4+→M4+–O–Si4+; M: Al and Fe), in accordance with the equilibrated primary phases. As the Al2O3 content increased, the viscosity and activation energy of slags both drastically increased owing to the change in the flow unit (Si–O–Si, Al–O–Si, and Al–O–Al). In contrast, as FetO increased, the viscosity and activation energy (Eη) of slags decreased because of the change in the flow unit (Si–O–Si, Fe–O–Si, and Fe–O–Fe). Ultimately, the flow unit (T–O–T; T = Si, Al, and Fe) and activation energy of the slags were found to be closely related to the solid primary phase on the phase diagram, and the physical‐property–structure relationship was determined from the phase stability.
Dual-layer slot coating (DSC) is a state-of-the-art technique that can fabricate thin film composite membranes by simultaneously spreading two monomer solutions to form an unsupported ultrathin ...polyamide (PA) selective layer, which is subsequently adhered to a support. To demonstrate its versatility, DSC was applied to polyethylene and polysulfone supports modified with O2 plasma and/or polydopamine (PDA) coating for the fabrication of high-performance reverse osmosis (RO) membranes. PDA coating enabled the uniform and robust PA deposition by uniformly hydrophilizing supports and reinforcing PA-support interfacial adhesion through the introduction of oxygen-containing and amine groups that promote hydrogen bonding with the PA layer, thus achieving good RO performance. The O2 plasma treatment on PDA-coated supports further strengthened PA-support interfacial adhesion by increasing the number of carboxyl groups with a higher hydrogen bonding ability, hence fabricating long-term stable, high-performance RO membranes that outperform a commercial RO membrane. This superior RO performance was enabled by the extremely thin (~7 nm) and highly crosslinked PA structure as well as strong PA-support interfacial adhesion. The surface tension analysis suggested that the work of adhesion at the PA-support interface of >~110 mJ m−2 is required to achieve high membrane performance.
Display omitted
•Dual-slot coating (DSC) is applied to PE and PSF supports to fabricate RO membranes.•Polydopamine coating combined with O2 plasma greatly enhances interfacial adhesion.•An extreme thin (~7 nm) and dense polyamide selective layer is formed via DSC.•DSC-assembled RO membranes have superior performance than a commercial RO membrane.•DSC-assembled RO membranes also exhibit the high long-term stability.
The aim of this study was to establish ethnic- and gender-specific cut-off values of triglycerides and glucose index (TyG index) for clinical usefulness in a representative sample of Mexican ...American, Non-Hispanic White, Non-Hispanic Black, and Korean adolescents. The data were collected from datasets of the National Health and Nutrition Examination Survey between 1999 and 2012, and the Korean National Health and Nutrition Examination Survey between 2005 and 2013. Receiver operating characteristic curve analysis was used to find valid cut-off values of the TyG index for metabolic syndrome. The total number of eligible participants was 3,164 in the US and 4,873 in Korea. The optimal cut-off value with the Cook et al. definition revealed 8.55 in Mexican American, 8.55 in Non-Hispanic White, 8.35 in Non-Hispanic Black, and 8.45 in Korean, respectively. The cut-off value with the de Ferranti et al. definition was 8.45, 8.45, 8.15, and 8.35, and the cut-off value with the International Diabetes Federation definition was 8.65, 8.65, 8.15, and 8.55, respectively. These findings may be clinically useful for evaluating insulin resistance for determining metabolic abnormalities in adolescents.
PDF
