Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice

The P2Y12 receptor (P2Y12R) is a purinoceptor that is selectively expressed in microglia in the central nervous system. As a signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and is engaged in several neurological diseases including chronic pain, stroke and seizures. However, the role of microglial P2Y12R in regulating neuronal excitability and innate behaviors is not fully understood. Here, we generated P2Y12-floxed mice to delete microglial P2Y12R beginning in development (CX3CR1Cre/+:P2Y12f/f; “constitutive knockout”), or after normal development in adult mice (CX3CR1CreER/+:P2Y12f/f; “induced knockout”). Using a battery of behavioral tests, we found that both constitutive and induced P2Y12R knockout mice exhibited innate fear but not learned fear behaviors. After mice were exposed to the elevated plus maze, the c-fos expression in ventral hippocampus CA1 neurons was robustly increased in P2Y12R knockout mice compared with wild-type mice. Consistently, using whole cell patch clamp recording, we found the excitability of ventral hippocampus CA1 neurons was increased in the P2Y12R knockout mice. The results suggest that microglial P2Y12R regulates neuronal excitability and innate fear behaviors in developing and adult mice

Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice

The P2Y12 receptor (P2Y12R) is a purinoceptor that is selectively expressed in microglia in the central nervous system. As a signature receptor, microglial P2Y12R mediates process chemotaxis towards ADP/ATP gradients and is engaged in several neurological diseases including chronic pain, stroke and seizures. However, the role of microglial P2Y12R in regulating neuronal excitability and innate behaviors is not fully understood. Here, we generated P2Y12-floxed mice to delete microglial P2Y12R beginning in development (CX3CR1Cre/+:P2Y12f/f; “constitutive knockout”), or after normal development in adult mice (CX3CR1CreER/+:P2Y12f/f; “induced knockout”). Using a battery of behavioral tests, we found that both constitutive and induced P2Y12R knockout mice exhibited innate fear but not learned fear behaviors. After mice were exposed to the elevated plus maze, the c-fos expression in ventral hippocampus CA1 neurons was robustly increased in P2Y12R knockout mice compared with wild-type mice. Consistently, using whole cell patch clamp recording, we found the excitability of ventral hippocampus CA1 neurons was increased in the P2Y12R knockout mice. The results suggest that microglial P2Y12R regulates neuronal excitability and innate fear behaviors in developing and adult mice

Precise Control of Process Parameters for >23% Efficiency Perovskite Solar Cells in Ambient Air Using an Automated Device Acceleration Platform

Achieving high-performance perovskite photovoltaics, especially in ambient air relies heavily on optimizing process parameters. However, traditional manual methods often struggle to effectively control the key variables. This inherent challenge requires a paradigm shift toward automated platforms capable of precise and reproducible experiments. Herein, we use a fully automated device acceleration platform (DAP) to optimize the process parameters for preparing full perovskite devices using a two-step method in ambient air. Eight process parameters that have the potential to significantly influence device performance are systematically optimized. Specifically, we delve into the impact of the dispense speed of organic ammonium halide, a parameter that is difficult to control manually, on both perovskite film and device performance. Through the targeted design of experiments, we reveal that the dispense speed significantly affects device performance primarily by adjusting the residual PbI2 content in the films. We find that moderate dispense speeds, e.g., 50 {\mu}l/s, contribute to top-performance devices. Conversely, too fast or too slow speeds result in devices with relatively poorer performance and lower reproducibility. The optimized parameter set enables us to establish a Standard Operation Procedure (SOP) for additive-free perovskite processing under ambient conditions, which yield devices with efficiencies surpassing 23%, satisfactory reproducibility, and state-of-the-art photo-thermal stability. This research underscores the importance of understanding the causality of process parameters in enhancing perovskite photovoltaic performance. Furthermore, our study highlights the pivotal role of automated platforms in discovering innovative workflows and accelerating the development of high-performing perovskite photovoltaic technologies

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease

IntroductionObesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.MethodsDiagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data.Results and discussionThe results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population

What is the future for nuclear fission technology? A technical opinion from the Guest Editors of VSI NFT series and the Editor of the Journal Nuclear Engineering and Design

The Nuclear Fission Technology (NFT) series of Virtual Special Issues (VSIs) for the Journal Nuclear Engineering and Design (J NED) was proposed in 2023, including the request to potential authors of manuscript to address the following questions: o For how long will (water-cooling based) large size nuclear reactor survive? o Will water-technology based SMRs displace large reactors? o Will non-water-cooling technology SMRs and micro-reactors have an industrial deployment? o Will breeding technology, including thorium exploitation, have due relevance? o Will ‘nuclear infrastructure’ (fuel supply, financial framework, competence by regulators for new designs, waste management, etc.) remain or be sufficiently robust? Several dozen Guest Editors (GEs), i.e., the authors of the present document, managed the activity together with the Editor-in-Chief (EiC) of the journal. More than one thousand scientists contributed 470+ manuscripts, not evenly distributed among the geographical regions of the world and not necessarily addressing directly the bullet-questions, but certainly providing a view of current research being done. Key conclusions are as follows: (a) Large size reactors are necessary for a sustainable and safe exploitation of nuclear fission technology; (b) The burning of 233U (from thorium) and 239Pu (from uranium) is unavoidable, as well as recycling residual uranium currently part of waste; (c) Nuclear infrastructures in countries that currently use, or are entering the use of, fission energy for electricity production need a century planning; (d) The adoption of small reactors for commercial naval propulsion, hydrogen production and desalination is highly recommended

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Atomic insight into tribological behavior of AlCoCrFeNi high entropy alloy at various nanoscratching conditions

High-entropy alloys (HEAs) have garnered significant interest in recent years due to their exceptional properties. Among the HEAs, the AlCoCrFeNi HEA has been extensively studied due to its outstanding thermal stability and mechanical properties. However, limited attention has been given to its tribological behavior under high temperature and high velocity conditions. In this study, we first investigate the effect of temperature, scratching velocity, and scratching depth on the tribological behavior of AlCoCrFeNi HEA at the atomic level employing molecular dynamics method. The AlCoCrFeNi HEA exhibits good wear resistance at high temperature due to fewer dislocations to nucleation and slip. Regardless of a significant increase in scratching velocity, there is little difference in the wear volume, indicating that the AlCoCrFeNi HEA still maintains excellent wear resistance even under extremely high scratching velocity. The stacking fault tetrahedron is generated in the AlCoCrFeNi HEA under the large scratching depths of 1.5 nm and 2.0 nm, implying that the wear resistance of AlCoCrFeNi HEA would be improved after the nanoscratching with a relatively large scratching depth. These findings are highly significant for expanding the application potential of AlCoCrFeNi HEA under extreme conditions and provide profound insights into the tribological behavior of the HEA

Heat Transfer Enhancement of Nanofluids with Non-Spherical Nanoparticles: A Review

This article reviews the heat transfer enhancement of nanofluids with non-spherical nanoparticles. We divided the non-spherical nanoparticles suspended in nanofluids into three categories based on the dimension of geometric particle structure. Based on the measured data in experimental studies, we then evaluated the shape effect of non-spherical nanoparticles on thermal conductivity and convective heat transfer enhancement of nanofluids. Recent studies explored the numerical predictions and related heat transfer mechanisms. Due to large aspect ratios, thermal conductivity is abnormally enhanced only for nanofluids with carbon nanotubes/nanofibers/nanowires. The approximate enhancement effect exerted by three types of non-spherical nanoparticles on thermal conductivity was 4.5:2.5:1. Thermal conductivity enhancement per concentration was larger for nanorods/ellipsoids with small aspect ratios. The convective heat transfer coefficient was increased by suspending non-spherical nanoparticles in the base fluid. Consequently, no significant thermohydraulic performance was discovered for convective heat transfer of non-spherical nanoparticle nanofluid flow, specifically for turbulent flows, due to increased pumping power. However, the temperature and particle concentration effect on convective heat transfer remains unclear. In addition, no perfect model for predicting the thermal conductivity and convective heat transfer of non-spherical nanoparticle nanofluids has been reported

Heat Transfer Enhancement of Nanofluids with Non-Spherical Nanoparticles: A Review

This article reviews the heat transfer enhancement of nanofluids with non-spherical nanoparticles. We divided the non-spherical nanoparticles suspended in nanofluids into three categories based on the dimension of geometric particle structure. Based on the measured data in experimental studies, we then evaluated the shape effect of non-spherical nanoparticles on thermal conductivity and convective heat transfer enhancement of nanofluids. Recent studies explored the numerical predictions and related heat transfer mechanisms. Due to large aspect ratios, thermal conductivity is abnormally enhanced only for nanofluids with carbon nanotubes/nanofibers/nanowires. The approximate enhancement effect exerted by three types of non-spherical nanoparticles on thermal conductivity was 4.5:2.5:1. Thermal conductivity enhancement per concentration was larger for nanorods/ellipsoids with small aspect ratios. The convective heat transfer coefficient was increased by suspending non-spherical nanoparticles in the base fluid. Consequently, no significant thermohydraulic performance was discovered for convective heat transfer of non-spherical nanoparticle nanofluid flow, specifically for turbulent flows, due to increased pumping power. However, the temperature and particle concentration effect on convective heat transfer remains unclear. In addition, no perfect model for predicting the thermal conductivity and convective heat transfer of non-spherical nanoparticle nanofluids has been reported