Dissolved carbon in effluent of wastewater treatment plants and its potential impacts in the receiving karst river.

The dissolved carbon cycling in river system fueled by wastewater treatment plant effluent have been a research hotspot. However, the composition of dissolved carbon (DC) in wastewater effluents from karst regions remains poorly understood, resulting in a lack of clarity regarding its impact on the dynamics of dissolved carbon in karst rivers. To address this knowledge gap, this study investigated variations of dissolved inorganic (DIC) and organic C (DOC) components in effluent in karst regions and preliminarily discussed their influence on the DC cycling in karst rivers. The results showed that bicarbonate (HCO3-) in WWTP effluents makes more than 90% of the total dissolved inorganic carbon (DIC). The partial pressure of aqueous CO2 (pCO2) of the effluent reached 14450 ± 10084µtam, and pCO2 level declined with increasing river distance from the effluent discharge, effluent acted as a strong CO2 emitter to the atmosphere. Stable carbon isotope and water chemistry evidence revealed that organic matter degradation made important contributions to the high CO2 concentrations in effluent. PHREEQC mixing simulation together with filed samples data indicated that the DIC species can be changed, and pCO2 increased in receiving karst river water after mixed with effluent. The dissolved organic carbon (DOC) of effluent contained humic-like and protein-tryptophan-like, both of them appeared important and recent autochthonous, which could interfere the distinguish the sources of DOC in receiving karst river water. Thus, these findings highlight that the effluent can be an essential factor for the changes of the karst riverine DC pool, which advance our understanding on karst riverine DC evolution under anthropogenic activities. As more than 30% of the earth surface in China, northern America, and Europe are covered by carbonate rocks, this study has relevant implications for other karst regions as it underscores the influence of WWTP effluents on the carbon cycle in karst rivers. Such information and knowledge are valuable for monitoring and managing effluent-receiving river in other karst regions in the world.

Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.

Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.

DNA nanostructure-based fluorescence thermometer with silver nanoclusters.

DNA nanostructure-based fluorescence thermometers were fabricated by linking fluorescent silver nanoclusters (AgNCs) and guanine-rich（G-rich）DNA chains via a thermally sensitive DNA stem-loop at terminals 5' and 3'. Variations of temperature alter the distance between the AgNCs and G-rich DNA chain, affecting the interaction between them. As a result, the intensity of fluorescence emission from the AgNCs at 636 nm can be sensitively modulated. It was found that the intensity of such red emission is more temperature sensitive than the equivalent green emission at 543 nm; sensitivity of -3.6%/°C was achieved. Through variation of the melting temperature of the DNA stem-loop, the response temperature range of the thermometers could be readily adjusted. Novel DNA nanostructure-based fluorescence thermometers as described in this work are anticipated to be able to measure the temperature of biological systems at small scales-even a single cell.

Electrospinning Preparation of La-Doped SnO2 Hollow Nanofibers: An Improvement of Their Gas Sensing Properties.

SnO2 hollow nanofibers with different amount of La-doped were prepared by electrostatic spinning method. Their composition, morphology and structure were characterized by XRD, SEM, BET and XPS respectively and their gas sensing properties were also investigated. The results showed that the hollow nanofibers with the molar ratio of tin to La of 7% had the best sensitivity to ammonia of 500 ppm at the temperature of 300 °C, and the sensitivity value reached 480, which was 10 times that of pure SnO2. And its response time was also significantly shortened.

Construction of a NETosis-related gene signature for predicting the prognostic status of sepsis patients.

Background: Sepsis is a common traumatic complication of response disorder of the body to infection. Some studies have found that NETosis may be associated with the progression of sepsis. Methods: Data of the sepsis samples were acquired from Gene Expression Omnibus (GEO) database. Gene set enrichment score was calculated using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks analysis, and stepwise multivariable regression analysis were performed to identify NETosis-associated genes for sepsis prognosis. To assess the infiltration of immune cells, the ESTIMATE and CIBERPSORT algorithms were used. Functional enrichment analysis was conducted in the clusterProfiler package. Results: Different programmed death pathways were abnormally activated in sepsis patients as compared to normal samples. We screened five important NETosis associated genes, namely, CEACAM8, PGLYRP1, MAPK14, S100A12, and LCN2. These genes were significantly positively correlated with entotic cell death and ferroptosis and negatively correlated with autophagy. A clinical prognostic model based on riskscore was established using the five genes. The ROC curves of the model at 7 days, 14 days and 21 days all had high AUC values, indicating a strong stability of the model. Patients with high riskscore had lower survival rate than those with low riskscore. After the development of a nomogram, calibration curve and decision curve evaluation also showed a strong prediction performance and reliability of the model. As for clinicopathological features, older patients and female patients had a relatively high riskscore. The riskscore was significantly positively correlated with cell cycle-related pathways and significantly negatively correlated with inflammatory pathways. Conclusion: We screened five NETosis-associated genes that affected sepsis prognosis, and then established a riskscore model that can accurately evaluate the prognosis and survival for sepsis patients. Our research may be helpful for the diagnosis and clinical treatment of sepsis.

Experimental insights into the formation of secondary minerals in acid mine drainage-polluted karst rivers and their effects on element migration.

Acid mine drainage (AMD) threatens the water quality and safety of karst river water (KRW), and the formation of secondary iron or aluminum-bearing minerals during the mixing of AMD with KRW plays a crucial role in the migration of elements. However, the variations in the mineralogical, morphological and elemental compositions of secondary minerals and their influences on the migration of elements during AMD-KRW mixing have not been systematically studied. In this study, we mixed different proportions of AMD and KRW in a laboratory experiment to simulate seasonal hydrological conditions in a river to understand the major and trace elemental distributions in the mixed water and in precipitates and we discuss the formation process for the secondary minerals. The results showed that AMD can lead to a decrease in pH and DO and an increase in heavy metals and rare earth elements (REEs) in KRW. With the biological or chemical oxidation of Fe2+, Fe3+ combines with SO42- to form schwertmannite or hydrolyzes to form Fe(OH)3(s) and FeOOH(s), accompanied by the formation of amorphous Al hydroxide, resulting in a decrease in pH and an increase in Eh. Schwertmannite had strong adsorption and coprecipitation effects on Mn, Cr, Cu and As, so the adsorption and coprecipitation effects of schwertmannite on REEs were inhibited, while the migration of REEs were mainly affected by Al hydroxides. Therefore, after the AMD mixes with KRW, it not only causes severe water and sediment pollution but also adsorbs and enriches high concentrations of heavy metals in the secondary minerals formed during the mixing process, creating a major ecological hazard that requires further attention.

Spatial and temporal distribution characteristics of pCO2 and CO2 evasion in karst rivers under the influence of urbanization.

Surface rivers play an essential role in carbon cycle processes in karst regions. However, the CO2 diffusion flux from karst rivers under the influence of urbanization has been scarcely examined in the literature. Along these lines, in this work, the CO2 partial pressure (pCO2) and its degassing in a typical karst river (Nanming River and its tributaries) were thoroughly investigated, which are significantly affected by urbanization in Southwest China. From the acquired results, it was demonstrated that the average values of pCO2 in the main stream of the Nanming River in the wet season, dry season, and flat season were 1975.77 ± 714.45 µatm, 1116.08 ± 454.24 µatm, and 976.89 ± 746.37 µatm, respectively. On the other hand, the tributary showed mean pCO2 values of 1770.46 ± 1120.79 µatm, 1638.13 ± 1121.82 µatm, and 1107.74 ± 824.03 µatm in the three different hydrographic periods. Overall, the pCO2 of the Nanming River basin decreased in the following order: wet season > dry season > flat season, while the mainstream of the Nanming River was slightly higher than that of the tributaries in the wet season. However, it was lower than that of the tributaries in the dry and flat seasons. Additionally, more than 90% of the samples displayed a supersaturated state of CO2, which acted as an important source of CO2 in the atmosphere. From a spatial point of view, pCO2 tended to be higher in the western region than in the eastern region, higher in the middle than in the immediate vicinity, and higher in the south during the three seasons. The higher urban areas showed also relatively higher pCO2 than the lower urban areas. The urban land along with the Nanming River's mainstream exhibited a weaker correlation with pCO2 than the urban land along with the main tributaries due to the mainstream's regular management in recent years. Moreover, the pCO2 was mainly influenced by the carbonate rocks dissolution, aquatic organism metabolic processes, and human activities. In the Nanming River basin, the average CO2 diffusion fluxes in the wet season, dry season, and flat season were 147.02 ± 100.3 mmol·m-2·d-1, 76.02 ± 67.45 mmol·m-2·d-1, and 119.28 ± 168.22 mmol·m-2·d-1, respectively, which indicates high potential CO2 emissions. In addition, it was found that urban construction could increase the pCO2 of karst rivers and cause an increase in the CO2 release flux during the regional urban expansion. In view of the increasing intensive and extensive urbanization in karst regions, our findings are helpful to elucidate the characteristics of carbon dioxide emissions from karst rivers under the disturbance of human activities and further deepen the understanding of the carbon balance in karst river basins.

Temporal and spatial distribution characteristics and source analysis of dissolved organic nitrogen in the surface sediment of the Caohai Lake, southwest China.

Caohai Lake is a typical natural lake-type karst plateau wetland, which is sensitive to environmental changes, and the release of dissolved organic nitrogen (DON) in sediment is a potential factor of nitrogen pollution in this lake. Therefore, we aimed to reveal the temporal and spatial distribution characteristics and source analysis of DON in karst lake sediment. Surface sediment samples were collected from Caohai Lake in southwest China, and the sample locations were distributed across almost the entire wetland area, during both the wet and dry seasons. The DON content and fluorescence spectroscopy were determined and analysed using a three-dimensional fluorescence-parallel factor analysis (3DEEM-PARAFAC) model. The mean DON content in the sediment during the dry season (67.79 ± 42.96 mg/kg) was higher than that in the wet season (28.57 ± 20.97 mg/kg). There were four fluorescent components of DON in the sediment: C1 (tyrosine-like protein), C2 (terrestrial humus), C3 (tryptophan-like protein) and C4 (terrestrial humus). The DON in the surface sediment of Caohai Lake was influenced by terrestrial sources and biological activities. These findings help reveal the circulation mechanism of endogenous nitrogen in the lake and provide theoretical support for the prevention and control of nitrogen pollution in Caohai Lake.

Spatio-temporal characterization of dissolved organic matter in karst rivers disturbed by acid mine drainage and its correlation with metal ions.

Dissolved organic matter (DOM) is widely present in surface water environments and plays a critical role in the biogeochemical cycling of metal ions. Metal ions in acid mine drainage (AMD) have seriously polluted karst surface water environments, but few studies have explored interactions between DOM and metal ions in AMD-disturbed karst rivers. Here, the composition and sources of DOM in AMD-disturbed karst rivers were investigated by fluorescence excitation-emission spectroscopy combined with parallel factor analysis. In addition, correlations between metal ions and other factors (DOM components, total dissolved carbon (TDC) and pH) were determined using structural equation modeling (SEM). Results showed that there were evident differences in the seasonal distribution of TDC and metal ion concentrations in AMD-disturbed karst rivers. The concentrations of DOC, dissolved inorganic carbon (DIC), and metal ions were generally higher in the dry season than in the wet season, with Fe and Mn pollution being the most pronounced. The DOM in AMD contained two types of protein-like substances that were mainly from autochthonous inputs, while DOM in AMD-disturbed karst rivers contained two additional types of humic-like substances from both autochthonous and allochthonous inputs. The SEM results showed that the influence of DOM components on the distribution of metal ions was greater than that of TDC and pH. Among the DOM components, the influence of humic-like substances was greater than that of protein-like substances. Additionally, DOM and TDC had direct positive effects on metal ions, while pH had a direct negative effect on these. These results further elucidated the geochemical interactions between DOM and metal ions in AMD-disturbed karst rivers, which will assist in the pollution prevention of metal ions in AMD.

Revealing the role of calcium alginate-biochar composite for simultaneous removing SO42- and Fe3+ in AMD: Adsorption mechanisms and application effects.

The remediation of acid mine drainage (AMD) is particularly challenging because it contains a large amount of Fe3+ and a high concentration of SO42-. To reduce the pollution caused by SO42- and Fe3+ in AMD and realize the recycling of solid waste, this study used distillers grains as raw materials to prepare biochar at different pyrolysis temperatures. Calcium alginate-biochar composite (CA-MB) was further synthesized via the entrapment method and used to simultaneously remove SO42- and Fe3+ from AMD. The effects of different influencing factors on the sorption process of SO42- and Fe3+ were studied through batch adsorption experiments. The adsorption behaviors and mechanisms of SO42- and Fe3+ were investigated with different adsorption models and characterizations. The results showed that the adsorption process of CA-MDB600 on SO42- and Fe3+ could be well described by Elovich and Langmuir-Freundlich models. It was further proved by the site energy analysis that the adsorption mechanisms of SO42- onto CA-MDB600 were mainly surface precipitation and electrostatic attraction, while that of Fe3+ removal was attributed to ion exchange, precipitation, and complexation. The applications of CA-MDB600 in actual AMD proved its good application potential. This study indicates that CA-MDB600 could be applied as a promising eco-friendly adsorbent for the remediation of AMD.

Dimorpholinium tetra-chlorido-cobaltate(II).

In the title mol-ecular salt, (C(4)H(10)NO)(2)[CoCl(4)], the morpholinium cations adopt chair conformations and the tetra-chloridocobaltate(II) anion is significantly distorted from regular tetra-hedral geometry [Cl-Co-Cl = 102.183 (19)-117.59 (2)°]. The Co-Cl bond lengths for the chloride ions not accepting hydrogen bonds are significantly shorter than those for the chloride ions accepting such bonds. In the crystal, the components are linked by N-H⋯O and N-H⋯Cl and bifurcated N-H⋯(O,Cl) hydrogen bonds to generate (100) sheets.

[Acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke depression: a randomized controlled trial].

OBJECTIVE: To observe the curative effect of Shugan Tiaoshen (soothing liver and regulating mind) acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke depression (PSD), and to explore its mechanism. METHODS: Ninety patients of PSD were randomly divided into an acupuncture+rTMS combination group (30 cases), a rTMS combination group (30 cases, 1 case dropped off) and a western medication group (30 cases, 1 case dropped off). The western medication group was treated with escitalopram oxalate tablets, 10 mg orally each time, once a day; on the basis of the treatment in the western medication group, the rTMS combination group was additionally given rTMS, and the frequency was 20 Hz, 20 min each time, once a day, 5 times a week; on the basis of the treatment in the rTMS combination group, the acupuncture+rTMS combination group was additionally treated with Shugan Tiaoshen acupuncture at Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 24+), Shenting (GV 24), etc. for 40 min each time, once a day, weekly 5 times, and each group was treated for 4 weeks. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Montreal cognitive assessment scale (MoCA), Pittsburgh sleep quality index (PSQI) were observed, and serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were detected in each group. RESULTS: After treatment, the HAMD-17 scores in the three groups were lower than those before treatment (P<0.01), and the PSQI scores in the acupuncture+rTMS combination group and the rTMS combination group were lower than those before treatment (P<0.01); the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were lower than those in the western medication group (P<0.05), and the PSQI score in the acupuncture+rTMS combination group was lower than that in the rTMS combination group (P<0.05). After treatment, the MoCA scores and serum BDNF levels in the acupuncture+rTMS combination group and the rTMS combination group were higher than those before treatment (P<0.01), and the serum 5-HT levels in the three groups were higher than those before treatment (P<0.01); and the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were higher than those in the western medication group (P<0.05), and which in the acupuncture+rTMS combination group were higher than those in the rTMS combination group (P<0.05). CONCLUSION: On the basis of western medication escitalopram oxalate, the addition of Shugan Tiaoshen acupuncture combined with rTMS therapy can effectively improve cognitive function and sleep quality in patients with PSD, and the effect is better than that of western medication alone or rTMS combined with western medication. Its mechanism of action may be related to the increase of peripheral serum 5-HT and BDNF levels.

ADAM Challenge: Detecting Age-Related Macular Degeneration From Fundus Images.

Age-related macular degeneration (AMD) is the leading cause of visual impairment among elderly in the world. Early detection of AMD is of great importance, as the vision loss caused by this disease is irreversible and permanent. Color fundus photography is the most cost-effective imaging modality to screen for retinal disorders. Cutting edge deep learning based algorithms have been recently developed for automatically detecting AMD from fundus images. However, there are still lack of a comprehensive annotated dataset and standard evaluation benchmarks. To deal with this issue, we set up the Automatic Detection challenge on Age-related Macular degeneration (ADAM), which was held as a satellite event of the ISBI 2020 conference. The ADAM challenge consisted of four tasks which cover the main aspects of detecting and characterizing AMD from fundus images, including detection of AMD, detection and segmentation of optic disc, localization of fovea, and detection and segmentation of lesions. As part of the ADAM challenge, we have released a comprehensive dataset of 1200 fundus images with AMD diagnostic labels, pixel-wise segmentation masks for both optic disc and AMD-related lesions (drusen, exudates, hemorrhages and scars, among others), as well as the coordinates corresponding to the location of the macular fovea. A uniform evaluation framework has been built to make a fair comparison of different models using this dataset. During the ADAM challenge, 610 results were submitted for online evaluation, with 11 teams finally participating in the onsite challenge. This paper introduces the challenge, the dataset and the evaluation methods, as well as summarizes the participating methods and analyzes their results for each task. In particular, we observed that the ensembling strategy and the incorporation of clinical domain knowledge were the key to improve the performance of the deep learning models.

Coupling stable isotopes to evaluate sources and transformations of nitrate in groundwater and inflowing rivers around the Caohai karst wetland, Southwest China.

Nitrate is one of the most common pollutants in aquatic ecosystems, particularly in highly vulnerable karst aquifers. In Caohai Lake, an important karst wetland in southwestern China, karst surface water and groundwater are important recharge water sources, and nitrates flow into the wetland along with the surface water and groundwater, degrading the wetland water quality. Therefore, identifying the sources of nitrate in the surface water and groundwater in the Caohai catchment is of great significance to the protection of the wetland water environment. In this study, the nitrate concentrations, hydrochemistry and multiple stable isotope ratios (δ18O-H2O, δD-H2O, δ15N-NO3- and δ18O-NO3-) were used to identify the sources and fate of the NO3- in the groundwater and inflowing rivers around the Caohai wetland. The results showed that the NO3- concentrations in the groundwater samples from the southern side exceeded the WHO limit during the wet season, while other samples did not exceed the limit. The mean concentrations of NO3- in groundwater were higher than those in the inflowing river water, and NO3- concentrations decreased in the order of wet season>dry season>normal season in the groundwater and inflowing rivers. The hydrochemistry and multiple isotope ratios suggest that the nitrate transformation was dominated by nitrification processes, while denitrification had an influence on the transformation of NO3- (as evidenced by isotopes) in groundwater during the dry season. According to the analyses based on a stable isotope analysis in R (SIAR), sewage and manure were the main sources of NO3- in the groundwater, while sewage, manure and chemical fertilizer were the major sources of NO3- in the inflowing river water; therefore, the scientific use of farmland fertilizers and the treatment of domestic sewage should be strengthened to safeguard groundwater quality and control the NO3- concentrations in rivers.

[Hydrochemistry Characteristics and Estimation of the Dissolved Inorganic Carbon Flux in the Caohai Lake Wetland Catchment of Guizhou Province].

The Caohai Lake wetland in Weining County, Guizhou Province, is the largest karst wetland in China, and karst groundwater is an essential source of recharge and material. This study collected groundwater from the Caohai Lake catchment during the wet season, dry season, and flat season, and the main ion components of the groundwater were analyzed. The hydrochemistry characteristics and main ion sources of the groundwater were revealed, and the preliminary estimates of the karst carbon sink flux in the Caohai Lake catchment were calculated based on the solute load method. The results indicated that the water chemistry of the groundwater in the Caohai Lake catchment is primarily the HCO3-Ca type, and individual groundwater points in the southeast are the SO4-Ca type during the flat season. The dominant ions in the groundwater are Ca2+, Mg2+, and HCO3-. Seasonally, the average concentrations of SO42- and Mg2+ decreased in the order of flat season>dry season>wet season, while the average concentration of NO3- decreased in the order of wet season>dry season>flat season, and the seasonal variation of the other ions were not significant. Spatially, the concentrations of Ca2+ and HCO3- in the groundwater in the northern part of Caohai Lake, of K+, Na+, and Cl- in the southwest, and of Mg2+, NO3-, and SO42- in the southeast were relatively high. Ca2+, Mg2+, and HCO3- in the groundwater were primarily controlled by the dissolution of carbonate rocks, and carbonic acid, sulfuric acid and nitric acid were all involved in the weathering of carbonate rocks in the catchment. Most of the NO3- in the groundwater was affected mostly by the soil nitrogen and domestic sewage, while NO3- in the southeast groundwater was primarily affected by agricultural activities. The sources of K+, Na+, Cl-, and SO42- exhibited no obvious temporal and spatial differences, and the K+, Na+, and Cl- were mainly affected by human activities, while SO42- was mostly derived from the dissolution of sulfur compounds in the formation. The studied area has a high proportion of allogenic acids (sulfuric acid and nitric acid) participating in the weathering of carbonate rocks, which is the highest in the flat season and the lowest in wet season. After deducting the proportion of allogenic acids participating in the weathering of carbonate rocks, the average inorganic carbon flux in the Caohai Lake catchment is preliminarily estimated to be approximately 181.5 t·a-1, and the average karst groundwater transport of HCO3- to Caohai Lake is approximately 1144.1 t·a-1.

Alternation in Effective Connectivity With Cognitive Aging: A Longitudinal Study of Elderly Populations.

In this research, we investigated the alterations in the directionality and strength of regional interactions within functionally changed brain networks and their relationship to cognitive decline during the aging process in normal elderly individuals. Thirty-seven cognitively normal elderly people received resting-state fMRI scans and cognitive assessments at baseline (age = 78.65 ± 3.56 years) and at 4-year follow-up. Functional connectivity analyses were used to identify networks containing brain regions whose functions changed with age as regions of interest. The spectral dynamic causal modeling (spDCM) method was used to estimate the causal interactions within networks in subjects at different time points and in subjects with different cognitive levels to explore the alterations with cognitive aging. The results showed that, at both time points, all the networks, except the frontal-parietal network (FPN) at baseline, had mutual interactions between each pair of nodes. Furthermore, when the subjects were divided with global cognition level, lost connections were only found in the subgroup with better performance. These indicated that elderly people appeared to need more interaction pathways between brain areas with cognitive decline. We also observed that the strength of the flow of information from the left angular gyrus to the precuneus, which is associated with activation of memory retrieval and the functional hub involved in various cognitive domains, was predictive of declines in executive function with the aging process, making it a potential predictor of such situation.

High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production.

BACKGROUND: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. OBJECTIVE: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. METHODS: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. RESULTS: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1ß, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. CONCLUSION: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

A Single Silicon Nanowire-Based Ratiometric Biosensor for Ca2+ at Various Locations in a Neuron.

Ionic calcium (Ca2+) is an important second messenger in cells, particularly in the neuron. A deficiency or excess of Ca2+ would lead to neuronal apoptosis and further injury to the brain. For accurate analysis of intracellular Ca2+, a single silicon nanowire (SiNW)-based ratiometric biosensor was constructed by simultaneously anchoring Ru(bpy)2(mcbpy-O-Su-ester)(PF6)2, as a reference molecule, and Fluo-3, as a response molecule, onto the surface of a single SiNW. The SiNW-based biosensor exhibits high sensitivity and favorable selectivity for detecting Ca2+. With the assistance of a micromanipulator and laser scanning confocal microscope, two single SiNW sensors were placed in the body and the neurites of an individual neuron to detect Ca2+. The difference between the concentrations of Ca2+ in the body and neurites was identified. The results from the present study provide new insights into Ca2+ in neurons at a high spatial resolution, and the strategy used in this study provides a new opportunity to investigate cellular metabolism by combining the advantages of a single-cell detection technique and physiology.

Altered Prefrontal-Basal Ganglia Effective Connectivity in Patients With Poststroke Cognitive Impairment.

We investigated the association between poststroke cognitive impairment and a specific effective network connectivity in the prefrontal-basal ganglia circuit. The resting-state effective connectivity of this circuit was modeled by employing spectral dynamic causal modeling in 11 poststroke patients with cognitive impairment (PSCI), 8 poststroke patients without cognitive impairment (non-PSCI) at baseline and 3-month follow-up, and 28 healthy controls. Our results showed that different neuronal models of effective connectivity in the prefrontal-basal ganglia circuit were observed among healthy controls, non-PSCI, and PSCI patients. Additional connected paths (extra paths) appeared in the neuronal models of stroke patients compared with healthy controls. Moreover, changes were detected in the extra paths of non-PSCI between baseline and 3-month follow-up poststroke, indicating reorganization in the ipsilesional hemisphere and suggesting potential compensatory changes in the contralesional hemisphere. Furthermore, the connectivity strengths of the extra paths from the contralesional ventral anterior nucleus of thalamus to caudate correlated significantly with cognitive scores in non-PSCI and PSCI patients. These suggest that the neuronal model of effective connectivity of the prefrontal-basal ganglia circuit may be sensitive to stroke-induced cognitive decline, and it could be a biomarker for poststroke cognitive impairment 3 months poststroke. Importantly, contralesional brain regions may play an important role in functional compensation of cognitive decline.

AGE challenge: Angle Closure Glaucoma Evaluation in Anterior Segment Optical Coherence Tomography.

Angle closure glaucoma (ACG) is a more aggressive disease than open-angle glaucoma, where the abnormal anatomical structures of the anterior chamber angle (ACA) may cause an elevated intraocular pressure and gradually lead to glaucomatous optic neuropathy and eventually to visual impairment and blindness. Anterior Segment Optical Coherence Tomography (AS-OCT) imaging provides a fast and contactless way to discriminate angle closure from open angle. Although many medical image analysis algorithms have been developed for glaucoma diagnosis, only a few studies have focused on AS-OCT imaging. In particular, there is no public AS-OCT dataset available for evaluating the existing methods in a uniform way, which limits progress in the development of automated techniques for angle closure detection and assessment. To address this, we organized the Angle closure Glaucoma Evaluation challenge (AGE), held in conjunction with MICCAI 2019. The AGE challenge consisted of two tasks: scleral spur localization and angle closure classification. For this challenge, we released a large dataset of 4800 annotated AS-OCT images from 199 patients, and also proposed an evaluation framework to benchmark and compare different models. During the AGE challenge, over 200 teams registered online, and more than 1100 results were submitted for online evaluation. Finally, eight teams participated in the onsite challenge. In this paper, we summarize these eight onsite challenge methods and analyze their corresponding results for the two tasks. We further discuss limitations and future directions. In the AGE challenge, the top-performing approach had an average Euclidean Distance of 10 pixels (10 µm) in scleral spur localization, while in the task of angle closure classification, all the algorithms achieved satisfactory performances, with two best obtaining an accuracy rate of 100%. These artificial intelligence techniques have the potential to promote new developments in AS-OCT image analysis and image-based angle closure glaucoma assessment in particular.