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

Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain

Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced spinal LTP, microglial activation, and upregulation of BDNF are inhibited by antibodies against colony-stimulating factor 1 (CSF-1). Together, our results show that microglial CSF1 and BDNF signaling are indispensable for spinal LTP and chronic pain. The microglia-dependent transition of synaptic potentiation to structural alterations in pain pathways may underlie pain chronicity

The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury

Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT). Hv1 mediated voltage-gated proton currents in spinal microglia and mice lacking Hv1 (Hv1 KO) display attenuated pain hypersensitivities after SNT compared with wildtype (WT) mice. In addition, microglial production of reactive oxygen species (ROS) and subsequent astrocyte activation in the spinal cord was reduced in Hv1 KO mice after SNT. Cytokine screening and immunostaining further revealed that IFN-γ expression was compromised in spinal astrocytes in Hv1 KO mice. These results demonstrate that Hv1 proton channel contributes to microglial ROS production, astrocyte activation, IFN-γ upregulation, and subsequent pain hypersensitivities after SNT. This study suggests Hv1-dependent microglia-astrocyte communication in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.The work was supported by the National Institutes of Health grants (R01NS110825 and R01NS088627) to L.J.W and National Research Founda‑tion of Korea grants (NRF-2017M3C7A1025602, 2018R1A5A2024418 and 2021R1A2C3003334) from Korean government MSIT (Ministry of Science and ICT) to S.B.O

Strain-activated light-induced halide segregation in mixed-halide perovskite solids

Abstract Light-induced halide segregation limits the bandgap tunability of mixed-halide perovskites for tandem photovoltaics. Here we report that light-induced halide segregation is strain-activated in MAPb(I1−xBrx)3 with Br concentration below approximately 50%, while it is intrinsic for Br concentration over approximately 50%. Free-standing single crystals of CH3NH3Pb(I0.65Br0.35)3 (35%Br) do not show halide segregation until uniaxial pressure is applied. Besides, 35%Br single crystals grown on lattice-mismatched substrates (e.g. single-crystal CaF2) show inhomogeneous segregation due to heterogenous strain distribution. Through scanning probe microscopy, the above findings are successfully translated to polycrystalline thin films. For 35%Br thin films, halide segregation selectively occurs at grain boundaries due to localized strain at the boundaries; yet for 65%Br films, halide segregation occurs in the whole layer. We close by demonstrating that only the strain-activated halide segregation (35%Br/45%Br thin films) could be suppressed if the strain is properly released via additives (e.g. KI) or ideal substrates (e.g. SiO2)

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

An Improved Evaluation Scheme for Performing Quality Assessments of Unconsolidated Cultivated Land

Socioeconomic factors are extrinsic factors that drive spatial variability. They play an important role in land resource systems and sometimes are more important than that of the natural setting. The study aims to build a comprehensive framework for assessing unconsolidated cultivated land (UCL) in the south-central and southwestern portions of Hubei Province, China, which have not experienced project management and land consolidation, to identify the roles of natural and especially socioeconomic factors. Moreover, the study attempts to identify the attributes and indicators that describe the characteristics of the extrinsic factors affecting land spatial variability. Assessment supplement 12 proposed land use indicators on the basis of natural factors using the method of gradation of agricultural land quality (GALQ). The overall level of cultivated land quality (CLQ) in the two study areas is moderate, and this quantity is significantly correlated with topography. Excellent and high-quality UCL are mainly distributed in the south-central plain division of Hubei Province (SCPDHP), whereas lower grades are mainly distributed in the area of the southwestern mountainous division of Hubei Province (SWMDHP). These results suggest that the pattern of small-scale agricultural development depends strongly on the labor force and is the key land use-related factor that limits the improvement of regional CLQ. Such assessments and their findings are essential for the protection of cultivated land and the adjustment of agricultural structure to promote the sustainable use of UCL

Identification of two novel PRPF31 mutations in Chinese families with non‐syndromic autosomal dominant retinitis pigmentosa

Abstract Background Retinitis pigmentosa is a heterogeneous group of inherited retinal diseases leading to progressive vision loss. It has been estimated that the etiology is still unclear in 22%‐40% of cases, indicating that many novel pathogenic variations related to RP remain unidentified in many patients. In this study, our aim was to investigate the disease‐causing variants and function of the variants in two Chinese families with non‐syndromic autosomal dominant retinitis pigmentosa (adRP). Methods Clinical data and peripheral blood DNA samples were collected. Whole exome sequencing (WES) was conducted to screen for variations. Then, the expression of green fluorescent protein (GFP)‐fused wild‐type PRPF31 protein and its variants was evaluated via western blotting and GFP fluorescence detection in vitro. Results Two novel heterozygous variants of PRPF31 (NM_015629.4): c.855+5G>A and c.849_855del (p.Pro284Ilefs*35) were identified respectively in two families. The variant c.855+5G>A is co‐segregated with the disease in adRP‐01 family. The pedigree analysis result for c.849_855del (p. Pro284Ilefs*35) shows an inheritance pattern with incomplete penetrance for adRP‐02 family. The RT‐PCR analysis shows the PRPF31 gene c.855+5G>A leading to the missing from the 997th to the 1405th positions of the PRPF31 gene (NM_015629.4) cDNA. The expressions of the mutant GFP‐fused PRPF31 protein were not detected in HEK293 cells or Cos7 cells via western blotting and immunofluorescence. Conclusions Our findings identified two novel variants in PRPF31 in two Chinese families with adRP, expanding the mutational spectrum of this gene. Functional analysis reveals that these variants lead to the truncation of the PRPF31 protein

Study on Angular Free Vibration Stability and Parameters Influence of Dry Gas Seal Based on the Characteristic Equation

Based on Laplace transform and Hurwitz stability criterion, the system characteristic equation and algebraic stability criterion of the two degree-of-freedom angular free vibration of dry gas seal are derived. The effects of rotational inertia, stiffness and damping parameters on the angular free vibration stability of dry gas seal are analyzed by using the root locus method and the concept of the closed-loop dominant pole. The results show that the constraint condition of rotational inertia is the most demanding of all stability conditions. Both the angular main damping and main stiffness are not simply the larger the better, but there are preferred values in the interval greater than the stability threshold. The approach of the absolute value of the cross coefficient to zero is beneficial to the suppression of angular free vibration. There is a threshold of rotational inertia, which makes the cross stiffness change from having only the lower limit value to both the upper and lower critical values at the same time