ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury.

Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.

Non-concordant epigenetic and transcriptional responses to acute thermal stress in western mosquitofish (Gambusia affinis).

Climate change is intensifying the frequency and severity of extreme temperatures. Understanding the molecular mechanisms underlying the ability to cope with acute thermal stress is key for predicting species' responses to extreme temperature events. While many studies have focused on the individual roles of gene expression, post-transcriptional processes and epigenetic modifications in response to acute thermal stress, the relative contribution of these molecular mechanisms remains unclear. The wide range of thermal limits of western mosquitofish (Gambusia affinis) provides an opportunity to explore this interplay. Here, we quantified changes in gene expression, alternative splicing, DNA methylation and microRNA (miRNA) expression in muscle tissue dissected from mosquitofish immediately after reaching high (CTmax) or low thermal limit (CTmin). Although the numbers of genes showing expression and splicing changes in response to acute temperature stress were small, we found a possibly larger and non-redundant role of splicing compared to gene expression, with more genes being differentially spliced (DSGs) than differentially expressed (DEGs), and little overlap between DSGs and DEGs. We also identified a small proportion of CpGs showing significant methylation change (i.e. differentially methylated cytosines, DMCs) in fish at thermal limits; however, there was no overlap between DEGs and genes annotated with DMCs in both CTmax and CTmin experiments. The weak interplay between epigenetic modifications and gene expression was further supported by our discoveries of no differentially expressed miRNAs. These findings provide novel insights into the relative role of different molecular mechanisms underlying immediate responses to extreme temperatures and demonstrate non-concordant responses of epigenetic and transcriptional mechanisms to acute temperature stress.

Increased serum levels of high-mobility group box 1 protein and the location characteristics in the patients of intracranial aneurysms.

OBJECTIVE: Inflammation-related factors play a crucial role in intracranial aneurysms (IA) initiation, progression, and rupture. High mobility group box 1 (HMGB-1) serves as an alarm to drive the pathogenesis of the inflammatory disease. This study aimed to evaluate the role of HMGB-1 in IA and explore the correlation with other inflammatory-related factors. METHODS: A total of twenty-eight adult male Japanese white rabbits were included in with elastase-induced aneurysms, n = 18) and the control group (normal rabbits, n = 10). To assess the expression of HMGB-1, both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) was performed on serum samples obtained from human subjects (10 patients with IA and 10 healthy donors) as well as from rabbits (aneurysm group and control group). Immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of elastic fibers, HMGB-1, tumor necrosis factor-alpha (TNF-α), and triggering receptor expressed on myeloid cells-1 (TREM-1). RESULTS: The expression of HMGB-1 was found to be significantly higher in the IA group compared to the control group, both at the mRNA and protein levels (P < 0.0001). Similar findings were observed in the rabbit aneurysm model group compared to the control group (P < 0.0001). HMGB-1 expression was observed to be more abundant in the inner wall of the aneurysm compared to the external wall, whereas in the control group, it was rarely scattered. Additionally, the localization patterns of TNF-α and TREM-1 exhibited similar characteristics to HMGB-1. CONCLUSION: Our findings demonstrate that HMGB-1 is highly expressed in both IA patients and rabbit aneurysm models. Furthermore, the similar localization patterns of HMGB-1, TNF-α, and TREM-1 suggest their potential involvement in the inflammatory processes associated with IA. These results highlight the potential of HMGB-1 as a novel therapeutic target for IA.

Targeting and Microenvironment-Activated Nanoreactor for Diabetic Chronic Wound Healing via Multienzyme Cascade Reactions.

The development of cell-like nanoreactors with the ability to initiate biocatalytic cascades under special conditions holds tremendous potential for therapeutic applications. Herein, conformationally gated nanoreactors that respond to the acidic microenvironment of infected diabetic wounds were developed by cucur[8]bituril (CB[8])-based supramolecular assembly. The bioinspired nanoreactors exhibit not only self-regulated permeability and selectivity to control internal enzyme activities by substance exchange but also distinct binding specificities toward Gram-positive and Gram-negative bacteria via noncovalent modification with different ligands. The encapsulation of glucose oxidase (GOx), Fe3O4 nanozyme, and l-arginine (l-Arg) into the nanocarriers enables intelligent activation of multienzyme cascade reactions upon glucose (Glu) uptake to produce gluconic acid (GA) and hydrogen peroxide (H2O2), which is further converted into highly toxic hydroxyl radicals (·OH) for selective antibacterial activity. Moreover, acidic H2O2 promotes the oxidization of l-Arg, leading to the release of nitric oxide (NO). Consequently, this nanoreactor provides a multifunctional and synergistic platform for diabetic chronic wound healing by combining enzyme dynamic therapy with NO gas therapy to combat bacterial infections and inflammation under high blood Glu levels.

Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

Buried-Metal-Grid Electrodes for Efficient Parallel-Connected Perovskite Solar Cells.

The limited conductivity of existing transparent conducting oxide (TCO) greatly restricts the further performance improvement of perovskite solar cells (PSCs), especially for large-area devices. Herein, buried-metal-grid tin-doped indium oxide (BMG ITO) electrodes are developed to minimize the power loss caused by the undesirable high sheet resistance of TCOs. By burying 140-nm-thick metal grids into ITO using a photolithography technique, the sheet resistance of ITO is reduced from 15.0 to 2.7 Ω sq-1 . The metal step of BMG over ITO has a huge impact on the charge carrier transport in PSCs. The PSCs using BMG ITO with a low metal step deliver power conversion efficiencies (PCEs) significantly better than that of their counterparts with higher metal steps. Moreover, compared with the pristine ITO-based PSCs, the BMG ITO-based PSCs show a smaller PCE decrease when scaling up the active area of devices. The parallel-connected large-area PSCs with an active area of 102.8 mm2 reach a PCE of 22.5%. The BMG ITO electrodes are also compatible with the fabrication of inverted-structure PSCs and organic solar cells. The work demonstrates the great efficacy of improving the conductivity of TCO by BMG and opens up a promising avenue for constructing highly efficient large-area PSCs.

[Evaluation of extravascular lung water index in critically ill patients based on lung ultrasound radiomics analysis combined with machine learning].

OBJECTIVE: To explore lung ultrasound radiomics features which related to extravascular lung water index (EVLWI), and to predict EVLWI in critically ill patients based on lung ultrasound radiomics combined with machine learning and validate its effectiveness. METHODS: A retrospective case-control study was conducted. The lung ultrasound videos and pulse indicated continuous cardiac output (PiCCO) monitoring results of critically ill patients admitted to the department of critical care medicine of the First Affiliated Hospital of Guangxi Medical University from November 2021 to October 2022 were collected, and randomly divided into training set and validation set at 8:2. The corresponding images from lung ultrasound videos were obtained to extract radiomics features. The EVLWI measured by PiCCO was regarded as the "gold standard", and the radiomics features of training set was filtered through statistical analysis and LASSO algorithm. Eight machine learning models were trained using filtered radiomics features including random forest (RF), extreme gradient boost (XGBoost), decision tree (DT), Naive Bayes (NB), multi-layer perceptron (MLP), K-nearest neighbor (KNN), support vector machine (SVM), and Logistic regression (LR). Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of models on EVLWI in the validation set. RESULTS: A total of 151 samples from 30 patients were enrolled (including 906 lung ultrasound videos and 151 PiCCO monitoring results), 120 in the training set, and 31 in the validation set. There were no statistically significant differences in main baseline data including gender, age, body mass index (BMI), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), cardiac index (CI), cardiac function index (CFI), stroke volume index (SVI), global end diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), pulmonary vascular permeability index (PVPI) and EVLWI. The overall EVLWI range in 151 PiCCO monitoring results was 3.7-25.6 mL/kg. Layered analysis showed that both datasets had EVLWI in the 7-15 mL/kg interval, and there was no statistically significant difference in EVLWI distribution. Two radiomics features were selected by using LASSO algorithm, namely grayscale non-uniformity (weight was -0.006 464) and complexity (weight was -0.167 583), and they were used for modeling. ROC curve analysis showed that the MLP model had better predictive performance. The area under the ROC curve (AUC) of the prediction validation set EVLWI was higher than that of RF, XGBoost, DT, KNN, LR, SVM, NB models (0.682 vs. 0.658, 0.657, 0.614, 0.608, 0.596, 0.557, 0.472). CONCLUSIONS: The gray level non-uniformity and complexity of lung ultrasound were the most correlated radiomics features with EVLWI monitored by PiCCO. The MLP model based on gray level non-uniformity and complexity of lung ultrasound can be used for semi-quantitative prediction of EVLWI in critically ill patients.

Preoperative Fibrinogen Levels and Function as Predictive Factors for Acute Bleeding in the Hematoma Cavity After Burr Hole Drainage in Patients with CSDH.

OBJECTIVE: Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. METHODS: This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. RESULTS: The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. CONCLUSIONS: The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH.

Recent advances in ß-cyclodextrin-based materials for chiral recognition.

In nature, enantiomers are pairs of chiral compounds, and have semblable chemical and physical properties but mostly show opposite biological effects when they enter an organism. Therefore, chiral recognition has a crucial research value in the fields of medicine, food, biochemistry, etc. Cyclodextrins (CDs) are produced by cyclodextrin glucosyltransferase in some species of bacillus on starch and include three main members α-, ß-, and γ-CD with six, seven and eight units of glucose, respectively. With a hydrophilic external cavity and a hydrophobic internal cavity, ß-CD can also combine with a variety of materials (e.g., graphene, nanoparticles, COFs, and OFETs) to enhance the chiral recognition of guest molecules in a chiral sensor. This review presents the progress of ß-CD modification with different materials for chiral recognition and describes in detail how different materials assist ß-CD in chiral recognition and improve the effect of ß-CD chiral discrimination.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report.

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Generation of high-dimensional caustic beams via phase holograms using angular spectral representation.

Using angular spectral representation, we demonstrate a generalized approach for generating high-dimensional elliptic umbilic and hyperbolic umbilic caustics by phase holograms. The wavefronts of such umbilic beams are investigated via the diffraction catastrophe theory determined by the potential function, which depends on the state and control parameters. We find that the hyperbolic umbilic beams degenerate into classical Airy beams when the two control parameters are simultaneously equal to zero, and elliptic umbilic beams possess an intriguing autofocusing property. Numerical results demonstrate that such beams exhibit clear umbilics in 3D caustic, which link the two separated parts. The dynamical evolutions verify that they both possess prominent self-healing properties. Moreover, we demonstrate that hyperbolic umbilic beams follow along a curve trajectory during propagation. As the numerical calculation of diffraction integral is relatively complex, we have developed an effective approach for successfully generating such beams by using phase hologram represented by angular spectrum. Our experimental results are in good agreement with the simulations. Such beams with intriguing properties are likely to be applied in emerging fields such as particle manipulation and optical micromachining.

Prognostic analysis of posterior fossa decompression with or without cerebellar tonsillectomy for Chiari malformation type I: a multicenter retrospective study.

OBJECTIVE: The purpose of this study was to compare the prognosis of patients with Chiari malformation type I (CM-I) treated with posterior fossa decompression with duraplasty (PFDD) and posterior fossa decompression with resection of tonsils (PFDRT). METHODS: The clinical data of patients with CM-I treated using these two procedures in three medical centers between January 2016 and June 2021 were retrospectively analyzed and divided into PFDD and PFDRT groups according to the procedures. The Chicago Chiari Outcome Scale (CCOS) was used to score the patients and compare the prognosis of the two groups. RESULTS: A total of 125 patients with CM-I were included, of whom 90 (72.0%) were in the PFDD group, and 35 (28.0%) were in the PFDRT group. There was no significant difference in the overall essential characteristics of the two groups. Moreover, there was no significant difference in complication rates (3.3% vs 8.6%, p = 0.348), CCOS scores (13.5 ± 1.59 vs 14.0 ± 1.21, p = 0.111), and the probability of poor prognosis (25.6% vs 11.4%, p = 0.096) between the two groups. Nevertheless, a subgroup of patients who had CM-I combined with syringomyelia (SM) revealed higher CCOS scores (13.91 ± 1.12 vs 12.70 ± 1.64, p = 0.002) and a lower probability of poor prognosis (13.0% vs 40.4%, p = 0.028) in the PFDRT than in the PFDD group. Also, SM relief was more significant in patients in the PFDRT compared to the PFDD group. A logistic multifactor regression analysis of poor prognosis in patients with CM-I and SM showed that the PFDRT surgical approach was a protective factor compared to PFDD. Furthermore, by CCOS analysis, it was found that the main advantage of PFDRT in treating patients with CM-I and SM was to improve patients' nonpain and functionality scores. CONCLUSIONS: Compared with PFDD, PFDRT is associated with a better prognosis for patients with CM-I and SM and is a protective factor for poor prognosis. Therefore, the authors suggest that PFDRT may be considered for patients with CM-I and SM.

ChIP-seq profiling of H3K4me3 and H3K27me3 in an invasive insect, Bactrocera dorsalis.

Introduction: While it has been suggested that histone modifications can facilitate animal responses to rapidly changing environments, few studies have profiled whole-genome histone modification patterns in invasive species, leaving the regulatory landscape of histone modifications in invasive species unclear. Methods: Here, we screen genome-wide patterns of two important histone modifications, trimethylated Histone H3 Lysine 4 (H3K4me3) and trimethylated Histone H3 Lysine 27 (H3K27me3), in adult thorax muscles of a notorious invasive pest, the Oriental fruit fly Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), using Chromatin Immunoprecipitation with high-throughput sequencing (ChIP-seq). Results: We identified promoters featured by the occupancy of H3K4me3, H3K27me3 or bivalent histone modifications that were respectively annotated with unique genes key to muscle development and structure maintenance. In addition, we found H3K27me3 occupied the entire body of genes, where the average enrichment was almost constant. Transcriptomic analysis indicated that H3K4me3 is associated with active gene transcription, and H3K27me3 is mostly associated with transcriptional repression. Importantly, we identified genes and putative motifs modified by distinct histone modification patterns that may possibly regulate flight activity. Discussion: These findings provide the first evidence of histone modification signature in B. dorsalis, and will be useful for future studies of epigenetic signature in other invasive insect species.

Suppressed phase segregation for triple-junction perovskite solar cells.

The tunable bandgaps and facile fabrication of perovskites make them attractive for multi-junction photovoltaics1,2. However, light-induced phase segregation limits their efficiency and stability3-5: this occurs in wide-bandgap (>1.65 electron volts) iodide/bromide mixed perovskite absorbers, and becomes even more acute in the top cells of triple-junction solar photovoltaics that require a fully 2.0-electron-volt bandgap absorber2,6. Here we report that lattice distortion in iodide/bromide mixed perovskites is correlated with the suppression of phase segregation, generating an increased ion-migration energy barrier arising from the decreased average interatomic distance between the A-site cation and iodide. Using an approximately 2.0-electron-volt rubidium/caesium mixed-cation inorganic perovskite with large lattice distortion in the top subcell, we fabricated all-perovskite triple-junction solar cells and achieved an efficiency of 24.3 per cent (23.3 per cent certified quasi-steady-state efficiency) with an open-circuit voltage of 3.21 volts. This is, to our knowledge, the first reported certified efficiency for perovskite-based triple-junction solar cells. The triple-junction devices retain 80 per cent of their initial efficiency following 420 hours of operation at the maximum power point.

Customizing non-diffracting structured beams.

We demonstrate a universal approach to designing and generating non-diffracting structured light beams with arbitrary shapes. Such light beams can be tailored by predefining suitable spectral phases that match the corresponding beam shapes in the transverse plane. We develop a practical spectral superposition algorithm to discuss the non-diffracting properties and experimentally confirm our numerical results. Our proposed approach differs from that of classical non-diffracting beams, which are always constructed from wave equation solutions. The various non-diffracting structured beams could help manipulate particles following arbitrary transverse shapes and are likely to give rise to new applications in optical micromachining.

Mild Hypothermia Alleviates CLP-induced Multiple Organ Dysfunction by Mitigating Pyroptosis Through the TLR4/NF-κB/NLRP3 Signaling Pathway.

BACKGROUND: Multiple organ failure secondary to severe sepsis leads to increased morbidity and mortality and is often accompanied by inflammation and immune system dysfunction. Mild hypothermia has been shown to have anti-inflammatory properties, but whether it can exert a protective effect in cases of multiple organ failure remains unclear. Thus, in this study, we investigated the protective effect of mild hypothermia on septic multiple organ failure and the underlying mechanism for this effect. METHOD: Sepsis was induced through the cecal ligation and puncture (CLP) method. Rats were then housed at normal (36-38°C) or mild hypothermic (32-34°C) temperature for 10 h. RESULTS: CLP-induced effects on inflammatory cytokines and biochemical markers in serum were reversed by mild hypothermia. The pathological injury score and the expressions of pyroptosis markers, including TLR4, MyD88 and NF-κB signaling molecules, showed a similar trend. Moreover, 3 d survival of CLP rats was improved by mild hypothermia. CONCLUSIONS: Mild hypothermia alleviated CLP-induced organ failure and the downstream effects on pyroptosis, probably through the TLR4/NF-κB/NLRP3 signaling pathway.

Increases in intraspecific body size variation are common among North American mammals and birds between 1880 and 2020.

Many studies have documented the average body size of animals declining over time. Compared to mean body size, less is known about long-term changes in intraspecific trait variation (ITV), which is also important to understanding species' ability to cope with environmental challenges. On the basis of 393,499 specimen records from 380 species collected in North America between 1880 and 2020, we found that body size ITV increased by 9.59% for mammals (n = 302) and 30.67% for birds (n = 78); human-harvested species had higher probability of ITV increase. The observed increasing ITV in many species suggests possible niche expansion and potential buffering effects against downsizing but it risks increased maladaptation to rapidly changing environments. The results demonstrate that trait mean and variance do not necessarily respond in similar ways to anthropogenic pressures and both should be considered.

Enhanced Organic Thin-Film Transistor Stability by Preventing MoO3 Diffusion with Metal/MoO3/Organic Multilayered Interface Source-Drain Contact.

The source-drain electrode with a MoO3 interfacial modification layer (IML) is considered the most promising method to solve electrical contact issues impeding organic thin-film transistors (OTFTs) from commercialization. However, this method raises many concerns because MoO3 might diffuse into organic materials, which causes device instability. In this work, we observed a significant device stability degradation by damaging on/off switching performance caused by MoO3 diffusion. To prevent the MoO3 diffusion, a source-drain electrode with a multilayered interface contact (MIC) consisting of a top-down stack of metal, MoO3 IML, and organic buffer layer (OBL) is proposed. In the MIC device, the MoO3 IML serves well for its intended functions of reducing contact resistance and suppressing minority carrier injection to the OTFT channel. The inclusion of OBL to the MIC helps block MoO3 diffusion and thereby leads to better device stability and an increased on/off ratio. Through combinations with several organic compounds as a buffer layer, the MoO3 diffusion related electrical behaviors of OTFTs are systematically studied. Key parameters related to MoO3 diffusion such as the Fick coefficient and bias-stress stability such as carrier trapping time are extracted from numerical device analysis. Finally, we summarize a general rule of material selection for making robust source-drain contact.

The role of plastic and evolved DNA methylation in parallel adaptation of threespine stickleback (Gasterosteus aculeatus).

Repeated phenotypic patterns among populations undergoing parallel evolution in similar environments provide support for the deterministic role of natural selection. Epigenetic modifications can mediate plastic and evolved phenotypic responses to environmental change and might make important contributions to parallel adaptation. While many studies have explored the genetic basis of repeated phenotypic divergence, the role of epigenetic processes during parallel adaptation remains unclear. The parallel evolution of freshwater ecotypes of threespine stickleback fish (Gasterosteus aculeatus) following colonization of thousands of lakes and streams from the ocean is a classic example of parallel phenotypic and genotypic adaptation. To investigate epigenetic modifications during parallel adaptation of threespine stickleback, we reanalysed three independent data sets that investigated DNA methylation variation between marine and freshwater ecotypes. Although we found widespread methylation differentiation between ecotypes, there was no significant tendency for CpG sites associated with repeated methylation differentiation across studies to be parallel versus nonparallel. To next investigate the role of plastic versus evolved changes in methylation during freshwater adaptation, we explored if CpG sites exhibiting methylation plasticity during salinity change were more likely to also show evolutionary divergence in methylation between ecotypes. The directions of divergence between ecotypes were generally in the opposite direction to those observed for plasticity when ecotypes were challenged with non-native salinity conditions, suggesting that most plastic responses are likely to be maladaptive during colonization of new environments. Finally, we found a greater number of CpG sites showing evolved changes when ancestral marine ecotypes are acclimated to freshwater environments, whereas plastic changes predominate when derived freshwater ecotypes transition back to their ancestral marine environments. These findings provide evidence for an epigenetic contribution to parallel adaptation and demonstrate the contrasting roles of plastic and evolved methylation differences during adaptation to new environments.

Microglia activation in the hippocampus mediates retinal degeneration-induced depressive-like behaviors via the NLRP3/IL-1ß pathway.

Epidemiological studies have shown that patients with glaucoma are more prone to depression, but the mechanism of comorbid depression in patients with glaucoma remains unknown. Excessive neuroinflammation has been shown to participate in glaucoma-induced retinal degeneration and hippocampal neural apoptosis in depression. However, little research has been conducted to determine whether neuroinflammation contributes to glaucoma-induced depression. Since the degeneration of retinal ganglion cells is a hallmark of glaucoma, we investigated the role of microglia-induced neuroinflammation in retinal degeneration-induced depression and its potential mechanism. An N-methyl-D-aspartate (NMDA)-induced retinal degeneration model was established, and behavioral tests were conducted at 3, 7, 14, and 21 days after retinal degeneration. After tissue collection, we used immunohistochemistry to assess the activation of microglia and real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines and the NOD-, LRR-, and pyrin-domain containing protein 3 (NLRP3) inflammasome. The mice exhibited depressive-like behaviors 14 and 21 days after retinal degeneration, based on the open field test, tail suspension test, and forced swimming test. Mice also displayed a lower body weight gain than the control group. In addition, microglial activation was observed in the hippocampus. Microglial proliferation was first observed in the dentate gyrus on day 3, while the number of microglia in cornu ammonis 1 grew the most. Moreover, not only was the expression of pro-inflammatory cytokines, including interleukin-1ß, interleukin-18, and interleukin-6 promoted, but the messenger ribonucleic acid levels of the NLRP3 inflammasome were also increased. In conclusion, our research shows that NMDA-induced retinal degeneration can induce depressive-like behaviors, which may be attributed to hippocampal neuroinflammation.