Microglial SCAP deficiency protects against diabetes-associated cognitive impairment through inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.

Atmospheric Mercury Isotope Shifts in Response to Mercury Emissions from Underground Coal Fires.

Pollutant emissions from coal fires have caused serious concerns in major coal-producing countries. Great efforts have been devoted to suppressing them in China, notably at the notorious Wuda Coalfield in Inner Mongolia. Recent surveys revealed that while fires in this coalfield have been nearly extinguished near the surface, they persist underground. However, the impacts of Hg volatilized from underground coal fires remain unclear. Here, we measured concentrations and isotope compositions of atmospheric Hg in both gaseous and particulate phases at an urban site near the Wuda Coalfield. The atmospheric Hg displayed strong seasonality in terms of both Hg concentrations (5-7-fold higher in fall than in winter) and isotope compositions. Combining characteristic isotope compositions of potential Hg sources and air mass trajectories, we conclude that underground coal fires were still emitting large amounts of Hg into the atmosphere that have been transported to the adjacent urban area in the prevailing downwind direction. The other local anthropogenic Hg emissions were only evident in the urban atmosphere when the arriving air masses did not pass directly through the coalfield. Our study demonstrates that atmospheric Hg isotope measurement is a useful tool for detecting concealed underground coal fires.

Mercury Isotopes in Deep-Sea Epibenthic Biota Suggest Limited Hg Transfer from Photosynthetic to Chemosynthetic Food Webs.

Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.

Mercury Isotope Variations in Lake Sediment Cores in Response to Direct Mercury Emissions from Non-Ferrous Metal Smelters and Legacy Mercury Remobilization.

Nature archives record atmospheric mercury (Hg) depositions from directly emitted Hg and re-emitted legacy Hg. Tracing the legacy versus newly deposited Hg is still, however, challenging. Here, we measured Hg isotope compositions in three dated sediment cores at different distances from the Flin Flon smelter, the largest Canadian Hg sources to the atmosphere during the 1930s-2000s. During the smelter's operative period, Hg isotope compositions showed limited variations in the near-field lake (<10 km) sediments but were rather variable in middle- (20-75 km) and far-field lake (∼800 km) sediments. Only the post-2000 sediments in middle/far-field lakes showed significantly negative Hg isotope shifts, while sediments from the 1970s-1990s had Hg isotope values resembling those of near-field lake post-1930 sediments. We suggest that the smelter's peak Hg emissions during the 1970s-1990s, which coincided with the deployment of a super stack in the mid-1970s, largely increased the long-range dispersion of smelter plumes. For the top post-2000 sediments, the fugitive dust from ore tailings and terrestrial legacy Hg re-emissions dominated Hg deposition in near-field lakes and middle/far-field lakes, respectively. Our study demonstrates that legacy Hg remobilization now exports substantial amounts of Hg to ecosystems, highlighting the need for aggressive remediation measures of Hg-contaminated sites.

Stable Isotopes Reveal Photoreduction of Particle-Bound Mercury Driven by Water-Soluble Organic Carbon during Severe Haze.

Haze with high loading of particles may result in significant enrichment of particle-bound Hg (PBM), potentially impacting the atmospheric Hg transformation and transport. However, the dynamics of Hg transformation and the relative environmental effect during severe haze episodes remain unclear. Here, we report Hg isotopic compositions of atmospheric particles (PM2.5, PM10, and TSP) collected during a severe haze episode in Tianjin, China, to investigate the transformation and fate of Hg during haze events. All severe haze samples display significantly higher Δ199Hg (up to 1.50‰) than global urban PBM, which cannot be explained by primary anthropogenic emissions. The high Δ199Hg is likely caused by photoreduction of PBM promoted by water-soluble organic carbon (WSOC) during the particle accumulation period, as demonstrated by the positive correlations of Δ199Hg with WSOC and relative humidity and confirmed by our laboratory-controlled photoreduction experiment. The results show that, on average, 21% of PBM are likely photoreduced and re-emitted back to the atmosphere as Hg(0), potentially requiring revision of atmospheric Hg budgeting and modeling. This study highlights the release of large portions of PBM back to the gas phase through photoreduction, which needs to be taken into account while evaluating the atmospheric Hg cycle and the relative ecological effects.

Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

BACKGROUND: Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. METHODS: In the VRONI study, children aged 5-14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. RESULTS: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. CONCLUSIONS: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

Mercury in sediment reflecting the intensive coal mining activities: Evidence from stable mercury isotopes and Bayesian mixing model analysis.

Severe environmental issues are caused by long-term coal mining activities; however, the process of mercury (Hg) response in mining subsidence area sediments (MSAS) is still unclear, and direct evidence showing the relationship between Hg accumulation mechanism in sediments and mining activities is lacking. In this study, the characteristics of total mercury (THg) content in MSAS were investigated. Moreover, Hg isotopes were obtained to determine the main sources and environmental process of mercury in MSAS, and a MixSIAR mixing model was first used to estimate the potential Hg sources. The THg content ranged from 27.5 to 113.9 ng/g, with a mean of 65.8 ± 29.4 ng/g, exceeding the local soil background value (19.7 ng/g). The Hg in MSAS was affected by clay and organic matter. The Δ199Hg and Δ201Hg in the sediments varied from - 0.05-0.05‰ (mean: -0.01 ± 0.03‰) and - 0.07-0.01‰ (mean: -0.02 ± 0.03‰), respectively, with the fitting results suggesting that a photochemical reaction occurred in some of the Hg in the sediments prior to deposition. The results of the MixSIAR mixing model revealed that the Hg in MSAS was mainly derived from gangue, soil erosion, coal, fly ash, and feed, and their corresponding percentage contribution was 51.5 ± 9.6%, 23.8 ± 13.1%, 13.9 ± 7.9%, 8.1 ± 5.4%, and 3.1 ± 1.4%, respectively. Hg isotopes can be used to trace the transport and transformation of environmental pollutants, and this may provide an important reference for the assessment and prevention of Hg pollution in typical areas such as coal mining and coal-fired.

Looking at young millennials' risk perception and purchase intention toward GM foods: Exploring the role of source credibility and risk attitude.

This study investigated young millennials' risk perception, benefit perception, and purchase intention toward GM foods by testing the effects of source credibility and risk attitude. By comparing two samples collected in the U.S. (N = 207) and China (N = 242), we found that source credibility positively influenced benefit perceptions of GM foods among Chinese millennial consumers. Results also revealed risk attitude significantly influenced both American and Chinese millennial consumers' intention to purchase GM foods. Furthermore, a significant interaction effect between source credibility and risk attitude was found on Chinese millennial consumers' risk perception of GM foods.

Enhancing Employee Engagement via Leaders' Motivational Language in times of crisis: Perspectives from the COVID-19 outbreak.

By bridging theoretical perspectives from diverse disciplines including public relations, organizational communication, psychology, and management, this study advances a sequential mediation process model that links leaders' motivational communication-specifically, direction-giving, empathetic, and meaning-making language-to employees' organizational engagement during times of crisis. The model incorporates employees' psychological needs satisfaction and their subsequent crisis coping strategies so as to explain the process that underlies the effects of leader communication on employee engagement. We tested the model in a unique yet underexplored crisis context: organizational crises triggered by the global pandemic of COVID-19. The results of an online survey of 490 full-time U.S. employees provide strong support to the model's predictions. Our research extends internal crisis communication scholarship in public relations by addressing what types of leader communication strategies as well as how these strategies contribute to employee engagement in a holistic fashion. It also advances theoretical development of the motivational language theory, self-determination theory, transactional model of stress and coping, and organizational engagement-the four theoretical bases of our study-in the context of organizational crises. Lastly, the study results provide timely practical insights on effective internal crisis communication.

Millimeter-wave Channel-Sounder Performance Verification using Vector Network Analyzer in a Controlled RF Channel.

A new comparison-to-reference performance verification technique compares an E-band channel-sounder and reference vector network analyzer measurements of the same controlled, static channel. This new technique reduces the number of inaccurate assumptions that exist in other methods providing a stronger verification of the channel-sounder hardware and processing performance. This technique compares the channel-sounder and VNA derived channel metrics from these measurements. Using mechanical switches, we established a controlled, static RF channel. The vector network analyzer has a comprehensive uncertainty analysis that propagates systematic and random uncertainties through to the power delay profiles. The method is suitable for millimeter-wave channel-sounder hardware with removable antennas.

Employee coping with organizational change in the face of a pandemic: The role of transparent internal communication.

The COVID-19 pandemic has caused many businesses and organizations to implement changes to manage operational and economic challenges. Understanding how employees manage such changes during the process is critical to the success of organizations. Integrating the literature from transparent internal communication, the transactional theory of stress and coping, and organizational change research, this study proposes a theoretical model to understand the role of internal communication and its effects on employees' management of organizational change. An online survey was conducted with 490 full-time employees in the U.S. during the second and third weeks of April 2020. The findings of this study demonstrate that transparent internal communication can help encourage problem-focused control coping, reduce uncertainty, and foster employee-organization relationships during organizational change. Theoretical and practical implications are discussed.

Mercury isotope compositions in large anthropogenically impacted Pearl River, South China.

Rivers integrate natural and anthropogenic mercury (Hg), and are important vectors of terrestrial Hg to the oceans. Here, we report the total Hg concentration and Hg isotope compositions of dissolved load in the Pearl River, the second largest river in China, in order to understand the processes and sources affecting Hg systematics in large anthropogenically-impacted river water. The dissolved Hg showed a concentration varying from 0.45 to 2.44 ng/L, within the range reported for natural background lake and river waters. All river water samples showed significantly negative δ202Hg (-2.89‰ to -0.57‰), slightly positive Δ200Hg (-0.05‰ to 0.52‰), and mostly positive Δ199Hg (0.10‰ to 0.57‰), except for three extremely negative values (-2.25‰ to -0.76‰). Combined with other geochemical parameters, we suggest that the influence of in-river processes, such as sorption and reduction, on the Hg isotope compositions is very limited, and the dissolved Hg in the Pearl River mainly comes from atmospheric precipitation and surface soil weathering. Although the whole river basin is largely affected by urban, industrial and mining activities, unlike other heavy metals, their direct contributions to dissolved Hg seem limited. It is worth noting that the three samples with very negative Δ199Hg values (down to -2.25‰) are derived from special source which attribute to the input of Hg released from the local incineration of electronic wastes. This study demonstrates that isotope approach is a powerful tool for tracing sources and pathways of Hg in large complex river systems.

172-fs, 27-µJ, Yb-doped all-fiber-integrated chirped pulse amplification system based on parabolic evolution by passive spectral amplitude shaping.

Parabolic pulses with linear self-phase-modulation-induced frequency chirp are attractive in ultrafast laser fiber amplification system for the functionality of nonlinearities suppression. In this paper, we present an effective way of parabolic pulse evolution by passive spectral amplitude shaping with a pair of chirped fiber Bragg gratings (CFBG). By this approach, a high-energy high-peak-power Yb-doped fiber chirped pulse amplification (CPA) system is demonstrated. The oscillator is a dispersion-managed passively mode-locked Yb-doped fiber laser with a broadband Gaussian-shaped spectrum which is evolved to parabola in a following preamplifier with pre-chirping management by a CFBG compressor. The pulses are then stretched with a CFBG stretcher, based on frequency-to-time mapping, the temporal profiles of the pulses show an identical parabolic envelope to the spectrum. The shaped pulses are further amplified with three stages of all-fiber amplifiers and compressed by a grating-pair compressor. The pulse duration is compressed to 172 fs with a pulse energy of 27 µJ. The central pulse encompasses 72% of total pulse energy, corresponding to a pulse peak power of 113 MW. No obvious pulse degeneration is noticed at nonlinearity accumulation B-integral as high as 12 rad. This configuration shows a significant potential for nonlinearity tolerance in high-energy operation compared with conventional CPA system.

An Integrated Model for Input and Migration of Mercury in Chinese Coastal Sediments.

Coastal sediments are a major sink of the global mercury (Hg) biogeochemical cycle, bridging terrestrial Hg migration to the open ocean. It is thus of substantial interest to quantify the Hg contributors to coastal sediments and the extents to which the Hg sequestered into coastal sediments affects the ocean. Here, we measured concentrations and isotope compositions of Hg in Chinese coastal sediments and found that estuary sediments had distinctly higher δ202Hg and lower Δ199Hg values than marine sediments. Hg isotope compositions of marine sediments followed a latitudinal trend where δ202Hg decreases and Δ199Hg increases from north to south. An integrated model was developed based on a Hg isotope mixing model and urban distance factor (UDF), which revealed a significant difference in Hg source contributions among the estuary and marine sediments and a gradual change of dominant Hg sources from terrestrial inputs (riverine and industrial wastewater discharges) to atmospheric deposition with a decrease in urban impact. A UDF value of 306 ± 217 was established as the critical point where dominant Hg sources started to change from terrestrial inputs to atmospheric deposition. Our study helps explain the input and migration of Hg in Chinese marginal seas and provides critical insights for targeted environmental management.

Temporal trends of polybrominated diphenyl ethers in the sediment cores from different areas in China.

This paper presented the historical data on the temporal trends of polybrominated diphenyl ethers (PBDEs) in the sediment cores collected from the Huaihe River, Yellow River and Chaohu Lake, China. Among the 40 targeted PBDE congeners, only 10, 6, and 9 of them were detected respectively in the samples from the Huaihe River, Yellow River and Chaohu Lake. On average, the total PBDEs concentrations in sediments were highest in Chaohu Lake followed by the Huaihe River and the Yellow River. As compared to other PBDE congeners, BDE-209 had higher concentrations and detection rates. The similar down core variation between PBDEs and total organic carbon (TOC) suggests that TOC is an important factor influencing PBDEs distribution in the sediments. The total PBDEs concentrations showed an increasing trend from bottom to upper sediments before a decreasing trend in the topmost sediments. The rapid urbanization and industrialization of these regions in recent decades may cause the historically increasing concentrations of sedimentary PBDEs, especially BDE-209. The decreasing PBDEs concentrations in topmost sediments was probably related to the strict environmental policies at present.

Mercury emission from underground coal fires in the mining goaf of the Wuda Coalfield, China.

The Wuda Coalfield, Inner Mongolia suffers from serious coal fires for more than half a century. Fire-extinguishing projects have been carried out to suppress the coal fires since the last decade, but sporadic surface fires still occur and underground fires are more prevailing. Here, we used a real-time RA-915M Mercury Analyzer with modified inlet to monitor gaseous Hg concentrations in fumes emitted from boreholes that were designed to detect and control the underground coal fires. Meanwhile, offline methods were used to collect the fumes and analyze the contents of the gases including CO, CO2, CH4, C2H6, C2H4 and C2H2. The results showed that gaseous Hg concentrations in fumes from boreholes ranged from 6.42 ±â€¯0.73 to 123.53 ±â€¯34.66 ng m-3, with an average value of 49 ±â€¯44 ng m-3. We suggest that the amounts of coal left for burning or smoldering mainly accounted for the large variation in fume Hg concentrations of underground coal fires. The gaseous Hg concentrations in near-surface air surrounding boreholes varied from 2.38 ±â€¯0.28 to 13.10 ±â€¯0.97 ng m-3, with a mean value of 6.68 ±â€¯3.09 ng m-3. They were higher than the ambient air Hg concentrations measured at a background site near the Yellow River (<2 ng m-3), suggesting underground coal fires were one significant Hg pollution source. Importantly, we found that gaseous Hg concentrations in the boreholes had significantly positive correlations with temperatures and CO (a traditional coal-fire index gas) contents, implying that Hg has the potential to serve as an index gas to monitor the occurrences of underground coal fires in mining goafs.

Mercury Stable Isotope Fractionation During Coal Combustion in Coal-Fired Boilers: Reconciling Atmospheric Hg Isotope Observations with Hg Isotope Fractionation Theory.

Mercury (Hg) stable isotope is a useful tool to understand the transformation of atmospheric Hg. The observation on the enrichment of heavier isotopes in gaseous elemental Hg (GEM) relative to oxidized HgII species in atmosphere cannot be convincingly explained by isotope fractionation of Hg redox processes. This review shows that the large Hg isotope mass dependent fractionation (MDF) in coal-fired boilers is one of the underlying reasons. The reported Hg isotope data of feed coals and their combustion products are first summarized to give a general overview of how Hg isotopes fractionate before Hg discharge from coal-fired boilers. Then, predictive MDF models are discussed to simulate δ202Hg values of different Hg species in coal combustion flue gases. The discharged GEM is predicted to have the highest δ202Hg followed by gaseous HgII and particulate-bound HgII, which is in consistent with the observed MDF pattern of atmospheric Hg species.

Historical Pollution and Source Contributions of PAHs in Sediment Cores from the Middle Reach of Huai River, China.

To investigate the spatial and historical distributions, and source contributions of polycyclic aromatic hydrocarbon (PAHs) from the middle reach of Huai River, 15 surface sediments and two sediment cores were analyzed. The Σ16 PAHs levels in surface sediments varied from 533.15 to 1422.83 ng/g dw, and from 413.27 to 43951.56 ng/g dw in individual sediment layer of sediment cores. The temporal trends of PAHs in sediment cores are the good indicators of the anthropogenic emissions over the last 60 years. The stable carbon isotope ratios of PAHs indicate the primary PAHs sources were the combustion of wood and coal during 1950s-1970s, and automobile exhausts and the coal combustion emissions in recent decades.

Sources and Assessment of Mercury and Other Heavy Metal Contamination in Soils Surrounding the Wuda Underground Coal Fire Area, Inner Mongolia, China.

Concentrations of mercury and other heavy metals were measured in soils surrounding the Wuda Coalfield, Inner Mongolia where underground coal fires are regarded as an important contamination source. Soil samples at the downwind direction were nearly all enriched mercury in surface layers, with their concentrations ~ 10 times higher than those from upwind soils. Mercury concentrations generally increased along soil profiles upward, indicative of increasing atmospheric mercury deposition in recent decades. We suggest that underground coal fire emissions were the potential mercury contamination source and the key factor controlling mercury enrichment in soils. Other heavy metals showed no clear spatial and vertical trends, suggesting that underground coal fire emissions may not the main factor for their enrichment in soils. Antimony showed the highest enrichment followed by tin, while chromium, mercury and cadmium only exhibited slight enrichment. Risk evaluation indicated that heavy metals in the studied soils pose no ecological threats.

Express incorporation of membrane proteins from various human cell types into phospholipid bilayer nanodiscs.

Analysis of membrane proteins is still inadequately represented in diagnostics despite their importance as drug targets and biomarkers. One main reason is the difficult handling caused by their insolubility in aqueous buffer solutions. The nanodisc technology was developed to circumvent this challenge and enables analysis of membrane proteins with standard research methods. However, existing nanodisc generation protocols rely on time-consuming membrane isolation and protein purification from overexpression systems. In the present study, we present a novel, simplified procedure for the rapid generation of nanodiscs directly from intact cells. Workflow and duration of the nanodisc preparation were shortened without reducing the reconstitution efficiency, and all the steps were modified for the use of only standard laboratory equipment. This protocol was successfully applied to various human cell types, such as cultivated human embryonic kidney 293 (HEK-293) cells, as well as freshly isolated human red blood cells and platelets. In addition, the reconstitution of membrane proteins from cell organelles was achieved. The use of endogenous lipids ensures a native-like environment, which promotes native protein (re)folding. Nanodisc generation was verified by size exclusion chromatography and EM, whereas incorporation of different membrane proteins was demonstrated by Western blot analysis. Our protocol enabled the rapid incorporation of endogenous membrane proteins from human cells into nanodiscs, which can be applied to analytical approaches.