Monolayer SnS2 Schottky barrier field effect transistors: effects of electrodes.

Achieving Ohmic contacts with low resistance is quite desirable for two-dimensional (2D) Schottky barrier field effect transistors (SBFETs). We verify the electrode effect on monolayer (ML) SnS2 SBFETs using ab initio calculations. With the aforeselected ML electrodes from matching lattices and work functions, we obtain n-type Ohmic contacts or quasi-Ohmic contacts to ML SnS2 with ML 1T-NbTe2, Sc2NF2, Mo2NF2, Nb2CF2, and graphene electrodes. The n-type ML SnS2 SBFET with the Ohmic-contact 1T-NbTe2 electrode exhibits remarkably better device performance than that with a Schottky-contact 2H-NbTe2 electrode, and their on-state currents of 629/1048 µA µm-1, delay times of 0.236/0.169 ps, and power dissipations of 0.074/0.089 fJ µm-1 exceed the International Roadmap for Devices and Systems targets for low-power/high-performance application. This study reports on Ohmic-contact electrodes for n-type ML SnS2 SBFETs and can give hints for future theoretical and experimental studies on 2D SBFETs.

Sex-dimorphic functions of orexin in neuropsychiatric disorders.

The orexin system regulates a variety of physiological functions, including the sleep-wake cycle, addiction, foraging behavior, stress and cognitive functioning. Orexin levels in central and peripheral are related to the pathogenesis of many diseases, most notably the narcolepsy, eating disorders, stress-related psychiatric disorders, and neurodegenerative diseases. Recently, it has been reported that the orexin system is distinctly sexually dimorphic, and is strongly associated with neuropsychiatric disorders. In this review, we analyzed advancements in the sex differences in the orexin system and their connection to psychoneurological conditions. Considering the scarcity of research in this domain, more research is imperative to reveal the underlying mechanisms.

Fine-Tuned Large Language Model for Visualization System: A Study on Self-Regulated Learning in Education.

Large Language Models (LLMs) have shown great potential in intelligent visualization systems, especially for domainspecific applications. Integrating LLMs into visualization systems presents challenges, and we categorize these challenges into three alignments: domain problems with LLMs, visualization with LLMs, and interaction with LLMs. To achieve these alignments, we propose a framework and outline a workflow to guide the application of fine-tuned LLMs to enhance visual interactions for domain-specific tasks. These alignment challenges are critical in education because of the need for an intelligent visualization system to support beginners' self-regulated learning. Therefore, we apply the framework to education and introduce Tailor-Mind, an interactive visualization system designed to facilitate self-regulated learning for artificial intelligence beginners. Drawing on insights from a preliminary study, we identify self-regulated learning tasks and fine-tuning objectives to guide visualization design and tuning data construction. Our focus on aligning visualization with fine-tuned LLM makes Tailor-Mind more like a personalized tutor. Tailor-Mind also supports interactive recommendations to help beginners better achieve their learning goals. Model performance evaluations and user studies confirm that Tailor-Mind improves the self-regulated learning experience, effectively validating the proposed framework.

Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure-Like Activities.

The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.

The influence of forest types including native and non-native tree species on soil macrofauna depends on site conditions.

The ongoing climate change calls for managing forest ecosystems in temperate regions toward more drought-resistant and climate-resilient stands. Yet ecological consequences of management options such as planting non-native tree species and mixing coniferous and deciduous tree species have been little studied, especially on soil animal communities, key in litter decomposition and pest control. Here, we investigated the taxonomic and trophic structure of soil macrofauna communities in five forest types including native European beech (Fagus sylvatica), range-expanding Norway spruce (Picea abies) and non-native Douglas fir (Pseudotsuga menziesii) as well as conifer-beech mixtures across loamy and sandy sites in northern Germany. Abundance of primary decomposers (feeding predominantly on litter) was high in Douglas fir and beech forests, benefiting from less acidic soil and more favorable litter resources compared to spruce forests, while secondary decomposers (feeding predominantly on microorganisms and microbial residues) reached highest densities in spruce forests. Differences in abundance and species richness among forest types generally varied between regions and were most pronounced in Douglas fir of the sandy region. However, trophic guilds differed more between regions than between forest types, indicating that environmental factors outweigh the importance of forest type on soil macrofauna communities. The analysis of stable isotopes (δ15N and δ13C values) supported the general robustness in trophic position of macrofauna trophic guilds against variations in forest types and regions, but indicated reduced detrital shifts and food-chain lengths in coniferous compared to European beech forests with mixtures mitigating these effects. Overall, for evaluating consequences of future forest management practices on the structure and functioning of soil animal communities, regional factors need to be considered, but in particular at loamy sites the taxonomic and trophic structure of soil macrofauna communities are resistant against changes in forest types.

Optimizing Skin Surface Metabolomics: A Comprehensive Evaluation of Sampling Methods, Extraction Solvents, and Analytical Techniques.

Characterizing the metabolite fingerprint from the skin surface provides invaluable insights into skin biology and microbe-host interactions. To ensure data accuracy and reproducibility, it is essential to develop standard operating procedures (SOPs) for skin surface metabolomics. However, there is a notable lack of studies in this area. Here, we thoroughly evaluated different sampling materials, extraction solvents, taping methods (frequency and number of tapes) and analytical techniques to optimize skin surface metabolomics. Our results showed that the combination of D-Squame® D100 tape with a methyl tert-butyl ether/methanol extractant is optimal for skin surface lipidomics. Performing the skin taping procedure five times with one tape yields sufficient biomass for lipid analysis, while the optimal taping procedure varies for water-soluble compounds. In addition, our study identified associations among the skin surface metabolites, some of which potentially underlie the formation of microbial cutotypes and offer insights into host-microbe interactions.

Inhibition of ubiquitin-specific protease 7 ameliorates ferroptosis-mediated myocardial infarction by contrasting oxidative stress: An in vitro and in vivo analysis.

BACKGROUND: Our prior research determined that USP7 exacerbates myocardial injury. Additionally, existing studies indicate a strong connection between USP7 and ferroptosis. However, the influence of USP7 on ferroptosis-mediated myocardial infarction (MI) remains unclear. Given these findings, we are particularly interested in USP7's regulatory role in ferroptosis-mediated MI and its underlying mechanisms. METHODS: In this study, we established MI models and lentivirus-transfected groups to inhibit USP7 expression both in vivo and in vitro. Cardiac function was detected with Echocardiography. TTC and HE staining were employed to assess myocardial alterations. The expression of ferroptosis markers (PTGS2, ACSL4, GPX4) were analyzed by RT-qPCR and Western blotting. Flow cytometry and ELISA were used for measuring Fe2+, lipid ROS, GSH, and GSSG levels. TEM and Prussian blue staining were used to observe mitochondrial alterations and iron deposition. RT-qPCR, Western blotting, and immunofluorescence were conducted to analyze Keap1, Nrf2, and nuclear Nrf2 expression in vitro and in vivo. RESULTS: In the MI model group, USP7 expression significantly increased, worsening ferroptosis-mediated MI. Conversely, in the USP7-inhibited group, activation of the Keap1-Nrf2 signaling pathway improved ferroptosis-mediated MI outcomes. In vitro, the MI model exhibited a marked decline in cardiomyocyte viability and notable mitochondrial damage. However, these issues improved in the USP7-inhibited groups. In vivo, USP7 intensified MI and iron deposition within the MI model group, with decreased values of LVEF, LVFS, SV, LVAWd, and LVPWs, all of which showed improvement in the USP7-inhibited group, except for LVPWd and LVPWs, which showed no significant variation. Importantly, both the in vitro and in vivo experiments revealed analogous results: a reduction in Keap1 expression and an increase in both Nrf2 and nuclear Nrf2 post USP7 inhibition. Additionally, GPX4 expression decreased while PTGS2 and ACSL4 expressions increased. Notably, concentrations of Fe2+, lipid ROS, GSH, and GSSG significantly decreased. CONCLUSION: In vitro and in vivo studies have found that inhibition of USP7 attenuates iron deposition and suppresses oxidative stress, resulting in amelioration of ferroptosis-induced MI.

Specific physiological responses to alkaline carbonate stress in rice (Oryza sativa) seedlings: organic acid metabolism and hormone signalling.

In recent years, alkaline soda soil has stimulated numerous biological research on plants under carbonate stress. Here, we explored the difference in physiological regulation of rice seedlings between saline (NaCl) and alkaline carbonate (NaHCO3 and Na2 CO3 ) stress. The rice seedlings were treated with 40mM NaCl, 40mM NaHCO3 and 20mM Na2 CO3 for 2h, 12h, 24h and 36h, their physiological characteristics were determined, and organic acid biosynthesis and metabolism and hormone signalling were identified by transcriptome analysis. The results showed that alkaline stress caused greater damage to their photosynthetic and antioxidant systems and led to greater accumulation of organic acid, membrane damage, proline and soluble sugar but a decreased jasmonic acid content compared with NaCl stress. Jasmonate ZIM-Domain (JAZ), the probable indole-3-acetic acid-amido synthetase GH3s, and the protein phosphatase type 2Cs that related to the hormone signalling pathway especially changed under Na2 CO3 stress. Further, the organic acid biosynthesis and metabolism process in rice seedlings were modified by both Na2 CO3 and NaHCO3 stresses through the glycolate/glyoxylate and pyruvate metabolism pathways. Collectively, this study provides valuable evidence on carbonate-responsive genes and insights into the different molecular mechanisms of saline and alkaline stresses.

The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study.

Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66-1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72-0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03-1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00-1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05-1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.

Bioinspired triple-layered membranes for periodontal guided bone regeneration applications.

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

Double hook-type aptamer-based colorimetric and electrochemical biosensor enables rapid and robust analysis of EpCAM expression.

Epithelial cell adhesion molecule (EpCAM), which is overexpressed in breast cancer cells and participates in cell signaling, migration, proliferation, and differentiation, has been utilized as a biomarker for cancer diagnosis and therapeutic prognosis. Here, a dual-signal readout nonenzymatic aptasensor is fabricated for the evaluation of EpCAM at the level of three breast cancer cell lines. The central principle of this enzyme-free aptasensor is the use of double hook-type aptamers (SYL3C and SJ3C2)-functionalized magnetic iron oxide (Fe3O4) as capture probes and quasi-CoFe prussian blue analogs (QCoFe PBAs) as nonenzymatic signal probes for colorimetric and electrochemical analysis. Following ligand detachment, the CoFe PBA was transformed to QCoFe PBA (calcined at 350 °C for 1 h), with its metal active sites exposed by controllable pyrolysis. We found that the enhanced sensitivity was attributed to the resonance effect of QCoFe PBA with the remarkable enzymatic properties. The dual-signal readout nonenzymatic aptasensor exhibited limits of detection for EpCAM as low as 0.89 pg mL-1 and 0.24 pg mL-1, within a wide linear range from 0.001 to 100 ng mL-1, respectively. We successfully employed this nonenzymatic aptasensor for monitoring EpCAM expression in three breast cancer cell lines, which provides an economical and robust alternative to costly and empirical flow cytometry. The dual-signal readout nonenzymatic aptasensor provides rapid, robust, and promising technological support for the accurate management of tumors.

Functional network modules overlap and are linked to interindividual connectome differences during human brain development.

The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.

Electrical Contacts in Monolayer MoSi2N4 Transistors.

The latest synthesized monolayer (ML) MoSi2N4 material exhibits stability in ambient conditions, suitable bandgap, and high mobilities. Its potential as a next-generation transistor channel material has been demonstrated through quantum transport simulations. However, in practical two-dimensional (2D) material transistors, the electrical contacts formed by the channel and the electrode must be optimized, as they are crucial for determining the efficiency of carrier injection. We employed the density functional theory (DFT) combined with the nonequilibrium Green's function (NEGF) method to systematically explore the vertical and horizontal interfaces between the typical metal electrodes and the ML MoSi2N4. The DFT+NEGF method incorporates the coupling between the electrode and the channel, which is crucial for quantum transport. Among these metals, Sc and Ti form n-type Ohmic contacts with zero tunneling barriers at both vertical and horizontal interfaces with ML MoSi2N4, making them optimal for contact metals. In-ML MoSi2N4 contacts display zero Schottky barriers but a 3.11 eV tunneling barrier. Cu and Au establish n-type Schottky contacts, while Pt forms a p-type contact. The Fermi pinning factors of the metal-ML MoSi2N4 contacts for both electrons and holes are above 0.51, much higher than the typical 2D semiconductors. Moreover, there is a strong positive correlation between the Fermi pinning factor and the band gap, with a Spearman rank correlation coefficient of 0.897 and a p-value below 0.001. Our work provides insight into the contact optimization for the ML MoSi2N4 transistors and highlights the promising potential of ML MoSi2N4 as the channel material for the next-generation FETs.

Study of the intensive care unit activity scale in the early rehabilitation of patients after direct cardiac surgery.

BACKGROUND: Direct cardiac surgery often necessitates intensive post-operative care, and the intensive care unit (ICU) activity scale represents a crucial metric in assessing and guiding early rehabilitation efforts to enhance patient recovery. AIM: To clarify the clinical application value of the ICU activity scale in the early recovery of patients after cardiac surgery. METHODS: One hundred and twenty patients who underwent cardiac surgery between September 2020 and October 2021 were selected and divided into two groups using the random number table method. The observation group was rated using the ICU activity scale and the corresponding graded rehabilitation interventions were conducted based on the ICU activity scale. The control group was assessed in accordance with the routine rehabilitation activities, and the postoperative rehabilitation indexes of the patients in both groups were compared (time of tracheal intubation, time of ICU admission, occurrence of complications, and activity scores before ICU transfer). The two groups were compared according to postoperative rehabilitation indicators (time of tracheal intubation, length of ICU stay, and occurrence of complications) and activity scores before ICU transfer. RESULTS: In the observation group, tracheal intubation time lasted for 18.30 ± 3.28 h and ICU admission time was 4.04 ± 0.83 d, which were significantly shorter than the control group (t-values: 2.97 and 2.038, respectively, P < 0.05). The observation group also had a significantly lower number of complications and adverse events compared to the control group (P < 0.05). Before ICU transfer, the observation group (6.7%) had few complications and adverse events than the control group (30.0 %), and this difference was statistically significant (P < 0.05). Additionally, the activity score was significantly higher in the observation (26.89 ± 0.97) compared to the control groups (22.63 ± 1.12 points) (t-value; -17.83, P < 0.05). CONCLUSION: Implementation of early goal-directed activities in patients who underwent cardiac surgery using the ICU activity scale can promote the recovery of cardiac function.

Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Exploring the correlation between innate immune activation of inflammasome and regulation of pyroptosis after intracerebral hemorrhage: From mechanism to treatment.

Stroke has emerged as the primary cause of disability and death globally in recent years. Intracerebral hemorrhage (ICH), a particularly severe kind of stroke, is occurring in an increasing number of people. The two main clinical treatments for ICH now in use are conservative pharmaceutical therapy and surgical intervention, both of which have risks and drawbacks. Consequently, it is crucial to look into the pathophysiology of ICH and consider cutting-edge therapeutic approaches. Recent research has revealed that pyroptosis is a newly identified type of cell death distinguished by the break of the cell membrane and the discharge of pro-inflammatory substances through different routes. Following ICH, glial cells experience pyroptosis, which worsens neuroinflammation. Hence, the onset and progression of ICH are strongly linked to pyroptosis, which is facilitated by different inflammasomes. It is essential to conduct a comprehensive investigation of ICH damage processes and uncover new targets for treatment. The impact and function of pyroptosis in ICH, as well as the activation and regulation of inflammasomes and their mediated pyroptosis pathways will be fully discussed in this review.

Development and validation of a nomogram for individualizing fall risk in patients with hematologic malignancies.

Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.

Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.

Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin-1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin-1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain-derived neurotrophic factor (BDNF) expression by hypoxia-inducible factor-1α (HIF-1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin-1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin-1 and microPET-CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin-1-HCRTR1 in altered cognitive function in depression.