1T'-transition metal dichalcogenide monolayers stabilized on 4H-Au nanowires for ultrasensitive SERS detection.

Unconventional 1T'-phase transition metal dichalcogenides (TMDs) have aroused tremendous research interest due to their unique phase-dependent physicochemical properties and applications. However, due to the metastable nature of 1T'-TMDs, the controlled synthesis of 1T'-TMD monolayers (MLs) with high phase purity and stability still remains a challenge. Here we report that 4H-Au nanowires (NWs), when used as templates, can induce the quasi-epitaxial growth of high-phase-purity and stable 1T'-TMD MLs, including WS2, WSe2, MoS2 and MoSe2, via a facile and rapid wet-chemical method. The as-synthesized 4H-Au@1T'-TMD core-shell NWs can be used for ultrasensitive surface-enhanced Raman scattering (SERS) detection. For instance, the 4H-Au@1T'-WS2 NWs have achieved attomole-level SERS detections of Rhodamine 6G and a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins. This work provides insights into the preparation of high-phase-purity and stable 1T'-TMD MLs on metal substrates or templates, showing great potential in various promising applications.

Recent Progress on Phase Engineering of Nanomaterials.

As a key structural parameter, phase depicts the arrangement of atoms in materials. Normally, a nanomaterial exists in its thermodynamically stable crystal phase. With the development of nanotechnology, nanomaterials with unconventional crystal phases, which rarely exist in their bulk counterparts, or amorphous phase have been prepared using carefully controlled reaction conditions. Together these methods are beginning to enable phase engineering of nanomaterials (PEN), i.e., the synthesis of nanomaterials with unconventional phases and the transformation between different phases, to obtain desired properties and functions. This Review summarizes the research progress in the field of PEN. First, we present representative strategies for the direct synthesis of unconventional phases and modulation of phase transformation in diverse kinds of nanomaterials. We cover the synthesis of nanomaterials ranging from metal nanostructures such as Au, Ag, Cu, Pd, and Ru, and their alloys; metal oxides, borides, and carbides; to transition metal dichalcogenides (TMDs) and 2D layered materials. We review synthesis and growth methods ranging from wet-chemical reduction and seed-mediated epitaxial growth to chemical vapor deposition (CVD), high pressure phase transformation, and electron and ion-beam irradiation. After that, we summarize the significant influence of phase on the various properties of unconventional-phase nanomaterials. We also discuss the potential applications of the developed unconventional-phase nanomaterials in different areas including catalysis, electrochemical energy storage (batteries and supercapacitors), solar cells, optoelectronics, and sensing. Finally, we discuss existing challenges and future research directions in PEN.

Uniform and Persistent Jumping Detachment of Condensed Nanodroplets.

Realizing jumping detachment of condensed droplets from solid surfaces at the smallest sizes possible is vital for applications such as antifogging/frosting and heat transfer. For instance, if droplets uniformly jump at sizes smaller than visible light wavelengths of 400-720 nm, antifogging issues could be resolved. In comparison, the smallest droplets experimentally observed so far to jump uniformly were around 16 µm in radius. Here, we show molecular dynamics (MD) simulations of persistent droplet jumping with a uniform radius down to only 3.6 nm on superhydrophobic thin-walled lattice (TWL) nanostructures integrated with superhydrophilic nanospots. The size cutoff is attributed to the preferential cross-lattice coalescence of island droplets. As an application, the MD results exhibit a 10× boost in the heat transfer coefficient (HTC), showing a -1 scaling law with the maximum droplet radius. We provide phase diagrams for jumping and wetting behaviors to guide the design of lattice structures with advanced antidew performance.

Ratiometric Imaging of Catecholamine Neurotransmitters with Nanosensors.

Neurotransmitters are important signaling molecules in the brain and are relevant in many diseases. Measuring them with high spatial and temporal resolutions in biological systems is challenging. Here, we develop a ratiometric fluorescent sensor/probe for catecholamine neurotransmitters on the basis of near-infrared (NIR) semiconducting single wall carbon nanotubes (SWCNTs). Phenylboronic acid (PBA)-based quantum defects are incorporated into them to interact selectively with catechol moieties. These PBA-SWCNTs are further modified with poly(ethylene glycol) phospholipids (PEG-PL) for biocompatibility. Catecholamines, including dopamine, do not affect the intrinsic E11 fluorescence (990 nm) of these (PEG-PL-PBA-SWCNT) sensors. In contrast, the defect-related E11* emission (1130 nm) decreases by up to 35%. Furthermore, this dual functionalization allows tuning selectivity by changing the charge of the PEG polymer. These sensors are not taken up by cells, which is beneficial for extracellular imaging, and they are functional in brain slices. In summary, we use dual functionalization of SWCNTs to create a ratiometric biosensor for dopamine.

StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.

Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field. Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry. An algorithm named StrucGP is also developed to automate the interpretation process for large-scale analysis. By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes. Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures. The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.

Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China.

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.

Root endophyte-mediated alteration in plant H2O2 homeostasis regulates symbiosis outcome and reshapes the rhizosphere microbiota.

Endophytic symbioses between plants and fungi are a dominant feature of many terrestrial ecosystems, yet little is known about the signaling that defines these symbiotic associations. Hydrogen peroxide (H2O2) is recognized as a key signal mediating the plant adaptive response to both biotic and abiotic stresses. However, the role of H2O2 in plant-fungal symbiosis remains elusive. Using a combination of physiological analysis, plant and fungal deletion mutants, and comparative transcriptomics, we reported that various environmental conditions differentially affect the interaction between Arabidopsis and the root endophyte Phomopsis liquidambaris, and link this process to alterations in H2O2 levels and H2O2 fluxes across root tips. We found that enhanced H2O2 efflux leading to a moderate increase in H2O2 levels at the plant-fungal interface is required for maintaining plant-fungal symbiosis. Disturbance of plant H2O2 homeostasis compromises the symbiotic ability of plant roots. Moreover, the fungus-regulated H2O2 dynamics modulate the rhizosphere microbiome by selectively enriching for the phylum Cyanobacteria, with strong antioxidant defenses. Our results demonstrated that the regulation of H2O2 dynamics at the plant-fungal interface affects the symbiotic outcome in response to external conditions and highlight the importance of the root endophyte in reshaping the rhizosphere microbiota.

BLSTM convolution and self-attention network enabled recursive and direct prediction for optical chaos.

Chaotic time series prediction has attracted much attention in recent years because of its important applications, such as security analysis for random number generators and chaos synchronization in private communications. Herein, we propose a BLSTM convolution and self-attention network model to predict the optical chaos. We validate the model's capability for direct and recursive prediction, and the model dramatically reduces the accumulation of errors. Moreover, the time duration prediction of optical chaos is increased with comparative accuracy where the predicted sequence length reaches 4 ns with normalized mean squared error (NMSE) of less than 0.01.

Scaling Laws for the Influence of Gravity and Its Gradient on Dropwise Condensation: A Simulation Study.

Gravity is essential for the shedding of condensed droplets on hydrophobic surfaces, whose influences on condensation parameters under unconventional gravity conditions remain unclear and are hard to probe through experiments. A simulation framework is designed here to investigate such phase-change processes. We find clear scaling laws between heat flux Q, residual volume V, gravitational acceleration g, and nucleation density N0 with Q ∼ g1/6N01/3 and V ∼ g-1/2N00. We also identify a critical gravitational acceleration determined by nucleation density, above which a counterintuitive trend emerges: the heat flux decreases with increasing gravitational acceleration. This deviation is attributed to the sharp decrease in heat flux contributed by droplets larger than the effective radius. In addition, for zero-gravity scenarios, a centrifugal strategy is proposed to simulate Earth's gravity by introducing artificial gravity with a spatial gradient. We reveal that the gradients have a significant influence on the residual volume but a minor one on the heat flux. The conclusions are informative for the estimation and design of condensation heat transfer systems for future space applications.

Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/ß-Catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

Seed-borne bacterial synthetic community resists seed pathogenic fungi and promotes plant growth.

AIMS: In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated. METHODS AND RESULTS: Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia. CONCLUSIONS: Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings.

Growth performance, nutrient digestibility, fecal microbial diversity and volatile fatty acid, and blood biochemical indices of suckling donkeys fed diets supplemented with multienzymes.

BACKGROUND: As the foal grows, the amount of breast milk produced by the donkey decreases. In such cases, early supplemental feeding is particularly important to meet the growth needs of the foal. Foals have an incompletely developed gastrointestinal tract with a homogenous microbiota and produce insufficient amounts of digestive enzymes, which limit their ability to digest and utilize forage. Improving the utilization of early supplemental feeds, promoting gastrointestinal tract development, and enriching microbial diversity are the hotspots of rapid growth research in dairy foals. Plant-based feeds usually contain non-starch polysaccharides (NSPs), including cellulose, xylan, mannan, and glucan, which hinder nutrient digestion and absorption. In addition, proteins and starch (both biomolecules) form a composite system mainly through non-covalent interactions. The proteins wrap around the surface of starch granules and act as a physical obstacle, thereby inhibiting water absorption and expansion of starch and decreasing the enzyme's catalytic effect on starch. Glyanase, ß-mannanase, ß-glucanase, cellulase, protease, and amylase added to cereal diets can alleviate the adverse effects of NSPs. The current study determined the effects of adding multienzymes (glyanase, ß-mannanase, ß-glucanase, cellulase, protease, and amylase) to the diet of 2-month-old suckling donkeys on their growth performance, apparent nutrient digestibility, fecal volatile fatty acid (VFA) and pH, fecal bacterial composition, and blood biochemical indices. RESULTS: On day 120 of the trial, fecal samples were collected from the rectum of donkeys for determining bacterial diversity, VFA content, and pH. Moreover, fresh fecal samples were collected from each donkey on days 110 and 115 to determine apparent digestibility. The multienzymes supplementations did not affect growth performance and apparent nutrient digestibility in the donkeys; however, they tended to increase total height gain (P = 0.0544). At the end of the study, the multienzymes supplementations increased (P < 0.05) the Observed species, ACE, Chao1, and Shannon indices by 10.56%, 10.47%, 10.49%, and 5.01%, respectively. The multienzymes supplementations also increased (P < 0.05) the abundance of Firmicutes, Oscillospiraceae, Lachnospiraceae, Christensenellaceae, Christensenellaceae_R-7_group, and Streptococcus in feces, whereas decreased (P = 0.0086) the abundance of Proteobacteria. CONCLUSIONS: Multienzymes supplementations added to a basal diet for suckling donkeys can increase fecal microbial diversity and abundance.

Considering climate change impact on the global potential geographical distribution of the invasive Argentine ant and little fire ant.

The Argentine ant (Linepithema humile) and the little fire ant (Wasmannia auropunctata) are among the top 100 invasive alien species globally, causing significant ecological and economic harm. Therefore, it is crucial to study their potential geographic distribution worldwide. This study aimed to predict their global distribution under current and future climate conditions. We used distribution data from various sources, including CABI, GBIF, and PIAKey, and key climate variables selected from 19 environmental factors to model their potential geographic distribution using MaxEnt. The AUC values were 0.925 and 0.937 for L. humile and W. auropunctata, respectively, indicating good predictive performance. Suitable areas for L. humile were mainly in southern North America, northern South America, Europe, central Asia, southern Oceania, and parts of Africa, while W. auropunctata suitable areas were mostly in southern North America, most of South America, a small part of Europe, southern Asia, central Africa, and some parts of Oceania. Under climate change scenario, suitable areas for L. humile increased, while highly suitable areas for W. auropunctata decreased. The top four countries with the largest areas of overlapping suitable habitat under current climate were Brazil, China, Australia, and Argentina, while under future SSP585 climate scenario, the top four countries were Brazil, China, Indonesia, and Argentina. Some countries, such as Estonia and Finland, will see an overlapping adaptation area under climate change. In conclusion, this study provides insight into controlling the spread and harm of L. humile and W. auropunctata.

Study on trade-offs and synergies of rural ecosystem services in the Tacheng-Emin Basin, Xinjiang, China: Implications for zoning management of rural ecological functions.

Rural areas are the main source of ecosystem services in arid and semi-arid areas, and ecosystem services are the background conditions for rural revitalization. In this study, the spatial pattern of key ecosystem services in the countryside was assessed, and the trade-offs and synergistic relationships among ecosystem services were investigated, using the Tacheng-Emin Basin in China as the study area. Finally, the types of ecological function zoning and development strategies for the countryside are proposed. The results showed that: (1) the area of ecological land was large, and the average land use intensity was 2.48, which belonged to the medium intensity. (2) The mean values of the six ecosystem services are all in the middle and lower classes, and the spatial distribution of the five ecosystem services is similar, except for food production. (3) Except for grain production, the other five ecosystem services showed positive feedback to elevation. The other five ecosystem services are synergistic, and there are trade-offs between grain production and other ecosystem services. In the nonlinear interaction mechanism of ecosystem services, the fluctuation constraint occupies the largest proportion. (4) At smaller spatial scales, there are more types of ecosystem service clusters. Combining the results of the study, the villages in the study area can be categorized into five types. This study formulates five priority levels of rural ecological revitalization and proposes different development recommendations for the sustainable development of each type of village. This study is helpful for the fine management of land resources and the revitalization of rural ecology and provides a reference for the sustainable development of ecosystem services in arid and semi-arid areas.

Design, Synthesis and Antitumor Activity of Quercetin Derivatives Containing a Quinoline Moiety.

Quercetin is a flavonoid with significant biological and pharmacological activity. In this paper, quercetin was modified at the 3-OH position. Rutin was used as a raw material. We used methyl protection, Williamson etherification reactions, and then substitution reactions to prepare 15 novel quercetin derivatives containing a quinoline moiety. All these complexes were characterized by 1H NMR, 13C NMR, IR and HRMS. Of these, compound 3e (IC50 = 6.722 µmol·L-1) had a better inhibitory effect on human liver cancer (HepG-2) than DDP (Cisplatin) (IC50 = 26.981 µmol·L-1). The mechanism of the action experiment showed that compound 3e could induce cell apoptosis.

Signal Amplification and Near-Infrared Translation of Enzymatic Reactions by Nanosensors.

Enzymatic reactions are used to detect analytes in a range of biochemical methods. To measure the presence of an analyte, the enzyme is conjugated to a recognition unit and converts a substrate into a (colored) product that is detectable by visible (VIS) light. Thus, the lowest enzymatic turnover that can be detected sets a limit on sensitivity. Here, we report that substrates and products of horseradish peroxidase (HRP) and ß-galactosidase change the near-infrared (NIR) fluorescence of (bio)polymer modified single-walled carbon nanotubes (SWCNTs). They translate a VIS signal into a beneficial NIR signal. Moreover, the affinity of the nanosensors leads to a higher effective local concentration of the reactants. This causes a non-linear sensor-based signal amplification and translation (SENSAT). We find signal enhancement up to ≈120x for the HRP substrate p-phenylenediamine (PPD), which means that reactions below the limit of detection in the VIS can be followed in the NIR (≈1000 nm). The approach is also applicable to other substrates such as 3,3'-5,5'-tetramethylbenzidine (TMB). An adsorption-based theoretical model fits the observed signals and corroborates the sensor-based enhancement mechanism. This approach can be used to amplify signals, translate them into the NIR and increase sensitivity of biochemical assays.

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides.

An efficient and practical method for the synthesis of C5-brominated 8-aminoquinoline amides via a copper-promoted selective bromination of 8-aminoquinoline amides with alkyl bromides was developed. The reaction proceeds smoothly in dimethyl sulfoxide (DMSO) under air, employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields.

CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice.

Hepatocyte transplantation has the potential to treat acute liver failure and correct liver-based metabolic disorders. Proliferating human hepatocytes (ProliHHs) provide a large-scale source as an alternative to primary human hepatocytes. However, host rejection led to inefficient graft survival and function, which hindered the clinical application of cell therapy. Herein, we employed the lentiviral system to overexpress immunomodulatory factors programmed death-ligand 1 (cluster of differentiation 274) (CD274) and cluster of differentiation 47 (CD47) in ProliHHs. CD47+274 overexpression inhibited macrophage and T cell responses in vitro. After transplantation into mice via the spleen without immunosuppression, CD47+274 ProliHHs accumulation in the liver significantly increased for 48 hours compared with ProliHHs. Consistent with the in vitro results, CD47+274 ProliHHs were less aggregated and infiltrated by macrophages and also recruited fewer T cells in the liver. Seven days after transplantation, the human albumin level of engineered ProliHHs doubled compared with control group. CD47+274 ProliHHs further ameliorated the liver injury induced using concanavalin A. Overall, our results suggested CD47+274 overexpression reduced innate and adaptive immune responses during hepatocyte transplantation, and the survival rate and graft function of transplanted hepatocyte-like cells were all significantly improved.

RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.

Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-ß-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-ß-induced cell viability, decreased TGF-ß-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-ß-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-ß, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

Distinct Neural Representations and Cognitive Behaviors Attributable to Naturally Developed Active Avoidance or Reactive Escape Strategies in the Male Rat.

BACKGROUND: The high individual variability in coping with stress is often attributed to genetic background differences, sustained environmental conditions, or a combination of both. However, the neural mechanisms underlying coping style variability are still poorly understood. METHODS: Here we examined the impact of a single extended emotional challenge on coping style variability and the associated involvement of the hippocampus, medial prefrontal cortex (mPFC), and periaqueductal gray (PAG). Male Sprague-Dawley rats (n = 170) were trained in an extended 2-way shuttle avoidance (eTWSA) task for 7 days, and daily avoidance rates were measured. Forced swim test, elevated plus maze, or Morris water maze was tested before or after eTWSA exposure. Excitotoxic lesion of the hippocampal dentate gyrus (DG) was performed by Ibotenic infusion. Transient pharmacological blocking of DG, mPFC, or PAG was performed by muscimol or CNQX+TTX infusion. RESULTS: Exposing rats to eTWSA was found to lead to naturally developing dichotomous, not continuous, coping styles, which we termed active avoidance (AA) or reactive escape (RE). Prior emotional responses did not predict the developing coping style. AA was associated with beneficial outcomes, including reduced behavioral despair and improved spatial learning. RE led to impaired spatial retrieval. AA was abolished by lesioning or pharmacological blocking of the DG. RE was prevented by blocking mPFC or PAG. CONCLUSION: The results indicate that a single exposure to a significant emotional challenge can lead, in otherwise healthy individuals, to dichotomous development of an active or reactive coping style with distinctive neural correlates and subsequent behavioral significance.