Linguistic experience acquisition for novel stimuli selectively activates the neural network of the visual word form area

The human ventral visual cortex is functionally organized into different domains that sensitively respond to different categories, such as words and objects. There is heated debate over what principle constrains the locations of those domains. Taking the visual word form area (VWFA) as an example, we tested whether the word preference in this area originates from the bottom-up processes related to word shape (the shape hypothesis) or top-down connectivity of higher-order language regions (the connectivity hypothesis). We trained subjects to associate identical, meaningless, non-word-like figures with high-level features of either words or objects. We found that the word-feature learning for the figures elicited the neural activation change in the VWFA, and learning performance effectively predicted the activation strength of this area after learning. Word-learning effects were also observed in other language areas (i.e., the left posterior superior temporal gyrus, postcentral gyrus, and supplementary motor area), with increased functional connectivity between the VWFA and the language regions. In contrast, object-feature learning was not associated with obvious activation changes in the language regions. These results indicate that high-level language features of stimuli can modulate the activation of the VWFA, providing supportive evidence for the connectivity hypothesis of words processing in the ventral occipitotemporal cortex

Comparative Studies Between the Murine Immortalized Brain Endothelial Cell Line (bEnd.3) and Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells for Paracellular Transport

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of the ihBMECs and bEnd.3 cells for key paracellular diffusional transport characteristics. The TEER across the ihBMECs was 45- to 68-fold higher than the bEnd.3 monolayer. The ihBMECs had significantly lower tracer permeability than the bEnd.3 cells. Both, however, could discriminate between the paracellular permeabilities of two tracers: sodium fluorescein (MW: 376 Da) and fluorescein isothiocyanate (FITC)–dextran (MW: 70 kDa). FITC-dextran permeability was a strong inverse-correlate of TEER in the bEnd.3 cells, whereas sodium fluorescein permeability was a strong inverse-correlate of TEER in the ihBMECs. Both bEnd.3 cells and ihBMECs showed the typical cobblestone morphology with robust uptake of acetylated LDL and strong immuno-positivity for vWF. Both models showed strong claudin-5 expression, albeit with differences in expression location. We further confirmed the vascular endothelial- (CD31 and tube-like formation) and erythrophagocytic-phenotypes and the response to inflammatory stimuli of ihBMECs. Overall, both bEnd.3 cells and ihBMECs express key brain endothelial phenotypic markers, and despite differential TEER measurements, these in vitro models can discriminate between the passage of different molecular weight tracers. Our results highlight the need to corroborate TEER measurements with different molecular weight tracers and that the bEnd.3 cells may be suitable for large molecule transport studies despite their low TEER

AIE-active Ir(iii) complexes functionalised with a cationic Schiff base ligand: synthesis, photophysical properties and applications in photodynamic therapy

Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (1O2) yield of PSs in the aggregated state. Ir(III) complexes are promising PSs with long excited-state lifetime, good photophysical and photochemical properties and large Stokes shifts. Aggregation-induced emission (AIE) characteristics could reduce the nonradiative recombination and improve the ISC ability of excited states through the restriction of the intramolecular motions in aggregated states. Accordingly, two AIE-active Ir(III) complexes Ir-1-N+ and Ir-2-N+ were successfully designed and obtained based on Schiff base ligands. Experimental results showed that Ir-1-N+ and Ir-2-N+ have good photophysical properties and the corresponding nanoparticles (NPs) have good water solubility and 1O2 generation ability. Notably, Ir-2-N+ NPs can be efficiently taken up by mouse breast cancer cells (4T1 cells) with good biocompatibility, low dark toxicity and excellent phototoxicity. This work demonstrates a versatile strategy for exploiting efficient transition metal PSs with a cationic ligand in PDT

Prevalence and changes of anemia among young children and women in 47 low- and middle-income countries, 2000-2018

BackgroundAnemia remains a major public health issue, particularly for children and women in low- and middle-income countries (LMICs). However, the current prevalence and recent changes of anemia among young children and women of reproductive age, particularly for pregnant women in different trimesters are unclear. We examined the current prevalence of anemia among children aged less than 5 years by age (6-35 months vs. 36-59 months) and women of reproductive age by pregnant status (pregnant vs. non-pregnant) and trimesters (the third vs. the second vs. the first trimester) between 2010 and 2018 and further examined changes in the prevalence from 2000-2009 to 2010-2018.MethodsData were from the cross-sectional Demographic and Health Surveys performed between 2000 and 2018. A total of 47 countries were included to examine the current prevalence of anemia (weighted prevalence and 95% confidence interval [CI]) among young children aged less than 5 years (N = 459,785) and 46 countries among women of reproductive age (N = 1,079,805) between 2010 and 2018. To examine changes in the prevalence of anemia, a total of 29 countries with at least two Demographic and Health Surveys performed between 2000 and 2009 (children: N = 130,772; women: N = 371,845) and 2010-2018 (children: N = 386,202; women: N = 928,889) were included. Modified Poisson regression analyses with robust error variance were used to examine changes in anemia between 2000-2009 and 2010-2018 in participants by child age (6-5 months vs. 36-59 months), women pregnant status (pregnant vs. non-pregnant), trimesters (the second or third trimester vs. the first trimester) with the adjustment for potential covariates.FindingsIn 47 LMICs for children aged less than 5 years between 2010 and 2018, the total prevalence of anemia was 56.5% (95% CI 56.2, 56.8). Younger children aged 6-35 months were more likely to have anemia than older children aged 36-59 months (adjusted odds ratio [OR] 1.38, 95% CI 1.36-1.39, P InterpretationThe prevalence of anemia among children aged less than 5 years and women of reproductive age was still high in LMICs, particularly for younger children and pregnant women. The relative change among women of reproductive age was far away from the WHO goal of reduction of anemia by 50% by 2025 (i.e., prevalence reduction to about 15.2% by 2025 from 30.3% at 2012 baseline). Continued and effective efforts, particularly for high-risk populations, are needed to improve the general health of the population.</p

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation

Background Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD. Methods CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and gut-derived uremic toxins on brain microvascular endothelial barrier. Results CKD was induced in aged C57BL/6J mice with significant increases in both serum creatinine and cystatin C levels (p \u3c 0.0001) without elevation of systolic or diastolic blood pressure. CMH was significantly increased and positively correlated with serum creatinine level (Spearman r = 0.37, p \u3c 0.01). Moreover, CKD significantly increased Iba-1-positive immunoreactivity by 51% (p \u3c 0.001), induced a phenotypic switch from resting to activated microglia, and enhanced fibrinogen extravasation across the blood–brain barrier (BBB) by 34% (p \u3c 0.05). On analysis stratified by sex, the increase in CMH number was more pronounced in male mice and this correlated with greater creatinine elevation in male compared with female mice. Microglial depletion with PLX3397 diet significantly decreased CMH formation in CKD mice without affecting serum creatinine levels. Incubation of CKD serum significantly reduced transendothelial electrical resistance (TEER) (p \u3c 0.01) and increased sodium fluorescein permeability (p \u3c 0.05) across the endothelial monolayer. Uremic toxins (i.e., indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide) in combination with urea and lipopolysaccharide induced a marked drop in TEER compared with the control group (p \u3c 0.0001). Conclusions CKD promotes the development of CMH in aged mice independent of blood pressure but directly proportional to the degree of renal impairment. These effects of CKD are likely mediated in part by microglia and are associated with BBB impairment. The latter is likely related to gut-derived bacteria-dependent toxins classically associated with CKD. Overall, these findings demonstrate an important role of CKD in the development of cerebral small vessel disease

Sociophonetic variation in a long-term language contact situation: /l/-darkening in Welsh-English bilingual speech

This study investigates /l/-darkening in the Welsh and English speech of bilinguals in North Wales. Although it is claimed that /l/ is dark in all syllable positions in northern varieties of both languages, there have been no quantitative investigations of this feature which consider cross-linguistic phonetic differences, the differing nature of language contact between North East and North West Wales, and differences in the way both languages are acquired by speakers. The dataset of 32 Welsh-English bilinguals, aged 16-18, was stratified by speaker sex, home language, and area. Tokens of /l/ in word-initial onset and word-final coda positions were analysed acoustically. The results show cross-linguistic differences in onset position and that such differences were found to be greater in the speech of female participants and those from North West Wales. Differences were also found between Welsh-dominant and English-dominant communities. These results are discussed with reference to the influence of extra-linguistic factors on speech production and the possible social meaning associated with dark /l/

Synthesized trade-off analysis of flood control solutions under future deep uncertainty: An application to the central business district of Shanghai.

Coastal mega-cities will face increasing flood risk under the current protection standard because of future climate change. Previous studies seldom evaluate the comparative effectiveness of alternative options in reducing flood risk under the uncertainty of future extreme rainfall. Long-term planning to manage flood risk is further challenged by uncertainty in socioeconomic factors and contested stakeholder priorities. In this study, we conducted a knowledge co-creation process together with infrastructure experts, policy makers, and other stakeholders to develop an integrated framework for flexible testing of multiple flood-risk mitigation strategies under the condition of deep uncertainties. We implemented this framework to the reoccurrence scenarios in the 2050s of a record-breaking extreme rainfall event in central Shanghai. Three uncertain factors, including precipitation, urban rain island effect and the decrease of urban drainage capacity caused by land subsidence and sea level rise, are selected to build future extreme inundation scenarios in the case study. The risk-reduction performance and cost-effectiveness of all possible solutions are examined across different scenarios. The results show that drainage capacity decrease caused by sea-level rise and land subsidence will contribute the most to the rise of future inundation risk in central Shanghai. The combination of increased green area, improved drainage system, and the deep tunnel with a runoff absorbing capacity of 30% comes out to be the most favorable and robust solution which can reduce the future inundation risk by 85% (±8%). This research indicates that to conduct a successful synthesized trade-off analysis of alternative flood control solutions under future deep uncertainty is bound to be a knowledge co-creation process of scientists, decision makers, field experts, and other stakeholders

Temperature distribution of Collins Ice Cap, King George Island, Antarctica

Temperature measurements in boreholes show that ice is of temperate state in accumulation area and of cold state in ablation area in Collins Ice Cap. Ice temperature of active layer is significantly influenced by seasonal variations of air temperature. The warming of ice by the melt water infiltration is remarkable. Snow cover also noticeably affects thermal regimes of the Collins Ice Cap. The measurements also reveal that temperature below the active layer is approximate to the melting point in the majority of the glacier except in the vicinity of the Little Dome, where ice temperature varies sharply within a surface distance of more than 10 meters. Significant water oozing from the ice cores was observed at a depth of 30m during the drilling near the Little Dome, which is probably caused by the combined effects such as internal runoffs, differential movement and high salinity of the glacier

The Flotation Separation of Magnesite and Limonite Using an Amine Collector

In order to reduce the iron impurities in magnesite ore and improve the purity of magnesium products, the difference in floatability between magnesite and limonite has been studied by using mixtures with a collecting agent—KD (cationic amine collectors, containing soluble components). Sodium hexametaphosphate, pH, sodium silicate, and sodium carboxymethyl cellulose were used as regulators. Adsorption mechanisms of the reagents on minerals were analyzed by a zeta potential analyzer and infrared spectroscopy. Sodium silicate increased the floatability of both minerals at 11.6. All the three regulators reduced the zeta potential of both minerals, while KD increased the zeta potential of magnesite and decreased the zeta potential of limonite. All the three regulators were likely chemically adsorbed on the surface of both minerals; KD has electrostatic adsorption on the surface of the minerals