Dysfunction of astrocytic glycophagy exacerbates reperfusion injury in ischemic stroke.

Glycophagy has evolved from an alternative glycogen degradation pathway into a multifaceted pivot to regulate cellular metabolic hemostasis in peripheral tissues. However, the pattern of glycophagy in the brain and its potential therapeutic impact on ischemic stroke remain unknown. Here, we observed that the dysfunction of astrocytic glycophagy was caused by the downregulation of the GABA type A receptor-associated protein like 1 (GABARAPL1) during reperfusion in ischemic stroke patients and mice. PI3K-Akt pathway activation is involved in driving GABARAPL1 downregulation during cerebral reperfusion. Moreover, glycophagy dysfunction-induced glucosamine deficiency suppresses the nuclear translocation of specificity protein 1 and TATA binding protein, the transcription factors for GABARAPL1, by decreasing their O-GlcNAcylation levels, and accordingly feedback inhibits GABARAPL1 in astrocytes during reperfusion. Restoring astrocytic glycophagy by overexpressing GABARAPL1 decreases DNA damage and oxidative injury in astrocytes and improves the survival of surrounding neurons during reperfusion. In addition, a hypocaloric diet in the acute phase after cerebral reperfusion can enhance astrocytic glycophagic flux and accelerate neurological recovery. In summary, glycophagy in the brain links autophagy, metabolism, and epigenetics together, and glycophagy dysfunction exacerbates reperfusion injury after ischemic stroke.

Evaluation of stored red blood cell quality after washing using immune indices.

Washed red blood cells (RBCs) can be used to treat immune-related diseases. However, whether the washing process changes the quality of RBCs and affects the curative effect of transfusion therapy remains unclear. We retrospectively analysed the clinical data of patients who received blood transfusion. The physiological and biochemical parameters of RBCs were tested on an automated haematology-biochemical analyser. CD47 and phosphatidylserine (PS) plasma membrane expression were analysed using flow cytometry. Morphological changes in RBCs were observed using scanning electron microscopy. The results showed that the curative effect on patients who received washed RBCs was weaker than that on those who received non-washed RBCs. Physiological and biochemical parameters of RBCs were not significantly different. RBC immune indices changed significantly after washing. The expression of "don't eat me" signals was weakened, whereas the intensity of "eat me" signals was enhanced. This study suggests that the current use of physiological and biochemical parameters as indicators to evaluate the quality of RBCs may not be comprehensive and that evaluation of the real status of RBCs requires other effective parameters. Immune molecules in RBCs are expected to become supplementary markers for evaluating RBC quality.

Ventral Tegmental Area Glutamatergic Neurons Facilitated Emergence From Isoflurane Anesthesia Involves Excitation of Lateral Septum γ-Aminobutyric Acid-ergic Neurons in Mice.

BACKGROUND: Ventral tegmental area (VTA) glutamatergic neurons promote wakefulness in the sleep-wake cycle; however, their roles and neural circuit mechanisms during isoflurane (ISO) anesthesia remain unclear. METHODS: Fiber photometry and in vivo electrophysiology were used to observe the changes in neuronal or terminal activity during ISO anesthesia and arousal processes. Optogenetic and anesthesia behaviors were used to investigate the effects of VTA glutamatergic neurons and their projections to the lateral septum (LS) during ISO anesthesia and arousal. Anterograde and retrograde tracings were performed to identify the connections between VTA glutamatergic neurons and the LS. RESULTS: Population activity and firing rates of VTA glutamatergic neurons decreased during ISO anesthesia (ISO: 95% confidence interval [CI], 0.83-2.06 Spikes.s-1 vs wake: 95% CI, 3.53-7.83 Spikes.s-1; P =.0001; n = 34 from 4 mice). Optogenetic activation of VTA glutamatergic neurons reduced the burst-suppression ratio in electroencephalography (laser: 95% CI, 13.09%-28.76% vs pre: 95% CI, 52.85%-71.59%; P =.0009; n = 6) and facilitated emergence (ChR2: 95% CI, 343.3-388.0 seconds vs mCherry: 95% CI, 447.6-509.8 seconds; P < .0001; n = 11/12) from ISO anesthesia. VTA glutamatergic neurons monosynaptically innervated LS γ-aminobutyric acid (GABA)-ergic neurons. The activity of VTA glutamatergic terminals in the LS decreased during ISO anesthesia, and optogenetic activation of the VTA glutamatergic terminals in the LS facilitated emergence from ISO anesthesia. Furthermore, optogenetic activation of VTA glutamatergic terminals increased the firing rates of LS γ-aminobutyric acid-ergic (GABAergic) neurons (laser: 95% CI, 0.85-4.03 Spikes.s-1 vs pre: 95% CI, 0.24-0.78 Spikes.s-1; P =.008; n = 23 from 4 mice) during ISO anesthesia. CONCLUSIONS: VTA glutamatergic neurons facilitated emergence from ISO anesthesia involving excitation of LS GABAergic neurons.

Differences in the EEG Power Spectrum and Cross-Frequency Coupling Patterns between Young and Elderly Patients during Sevoflurane Anesthesia.

Electroencephalography (EEG) is widely used for monitoring the depth of anesthesia in surgical patients. Distinguishing age-related EEG features under general anesthesia will help to optimize anesthetic depth monitoring during surgery for elderly patients. This retrospective cohort study included 41 patients aged from 18 to 79 years undergoing noncardiac surgery under general anesthesia. We compared the power spectral signatures and phase-amplitude coupling patterns of the young and elderly groups under baseline and surgical anesthetic depth. General anesthesia by sevoflurane significantly increased the spectral power of delta, theta, alpha, and beta bands and strengthened the cross-frequency coupling both in young and elderly patients. However, the variation in EEG power spectral density and the modulation of alpha amplitudes on delta phases was relatively weaker in elderly patients. In conclusion, the EEG under general anesthesia using sevoflurane exhibited similar dynamic features between young and elderly patients, and the weakened alteration of spectral power and cross-frequency coupling patterns could be utilized to precisely quantify the depth of anesthesia in elderly patients.

Percutaneous cortical bone trajectory screw fixation versus traditional open pedicle screw fixation for type A thoracolumbar fractures without neurological deficit.

Retrospective matched-cohort comparative study. Cortical bone trajectory screw (CBT) technique is a new insertion technique in terms of fixation strength and less invasiveness. The purposes of this study were to compare the clinical and radiological outcomes of percutaneous CBT fixation (PCBT) with traditional open posterior pedicle screw fixation (OPPS) technique. Between September 2019 and October 2020, patients undergoing posterior stabilization were matched for age, sex, diagnosis, fractured level, and AO classification. 24 control patients with OPPS were identified and appropriately matched to 24 consecutive patients with PCBT technique. Clinical outcomes and radiographic assessments including vertebral wedge angle (VWA) and sagittal index were recorded and compared between the two groups. Incision length, intraoperative blood loss and hospital stay in the PCBT group were significantly better than the OPPS group (P < 0.05). The VAS scores 5 days after operation for PCBT patients were significantly lower than those for OPPS patients (P = 0.003), but these differences lost significance at last follow-up. There was no significant difference in VWA and sagittal index between OPPS and PCBT group (P > 0.05). While no complications were noted in the PCBT group, there were four cases with complications in the traditional OPPS group. The present study showed that PCBT is a safe and feasible method for the treatment of thoracolumbar fractures without neurological deficits. This new surgical treatment was more minimally invasive, yet yielded equivalent or superior clinical and radiographic outcomes compared to the traditional open pedicle screw fixation surgery.

Recyclable magnetic Fe3O4@C for methylene blue removal under microwave-induced reaction system.

The reclamation and removal of organic pollutants are difficult issues of world concern. In this study, a microwave-induced reaction system (MIRS) is applied to synthesize the multifunctional composite of Fe3O4@C, which is employed to adsorb, separate and catalytic oxide the typical organic dye of methylene blue (MB). SEM, TEM, VSM, XPS, pHpzc, and N2 adsorption performances are carried out to characterize the Fe3O4@C. Results show that the Fe3O4@C mainly consists of activated Fe-O-C microspheres, which possess plentiful mesopore and macropore structures on surfaces. Batch adsorption experiments were carried out by varying key reaction conditions to optimize these. The maximum adsorption capacity of MB onto the Fe3O4@C was 305.0 mg g-1 in 120 min, at pH 10, and at a temperature of 323 K. MIRS was also assisted to regenerate the spent Fe3O4@C which presented good regeneration efficiency by sustaining 16 regeneration cycles without any oxidizing agent. SEM images and FTIR spectrum verified that MB would translate into greater or smaller-sized carbon microspheres. What's more, the adsorption of MB onto both initial and the 16th regenerated Fe3O4@C obeyed the Langmuir isotherm model and followed the pseudo-second-order adsorption kinetics, indicating the adsorptive stability after regeneration. In this study, the Fe3O4@C combined with MIRS may be one innovative strategy for organic pollutants' complete removal in the future.

[Effects of Different Treatment Methods on the Contents of Related Growth Factors Released by Platelet Rich Plasma].

OBJECTIVE: To evaluate the effect of sonication, repeated freeze-thaw cycles, calcium salt solution and their combination on the content of related growth factors (GFs) released by platelet rich plasma (PRP). METHODS: Twenty PRPs from healthy blood donors were divided into 9 groups, including sonication group, freeze-thaw group, calcium gluconate group, calcium chloride group, sonication + calcium gluconate group, sonication + calcium chloride group, freeze-thaw + calcium gluconate group, freeze-thaw + calcium chloride group, and sonication + freeze-thaw group. After PRP activated by above 9 methods, the content of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) were detected by ELISA. RESULTS: The platelet concentration of the samples was (966.7±202.6)×109/L. The content of TGF-ß1 in sonication + freeze-thaw group was the highest, while the lowest was in freeze-thaw group. The content of VEGF in freeze-thaw + calcium chloride group was the highest, while the lowest was in calcium gluconate group. The content of PDGF-BB in sonication + freeze-thaw group was the highest, while the lowest was in calcium gluconate group. There was no significant differences in the three GFs between calcium gluconate group and calcium chloride group. CONCLUSION: Among the 9 activated methods of PRP, there is no difference between two calcium salt solutions. And the combination of repeated freeze-thaw cycles and sonication may be the best treatment method to promote PRP to release GFs, while calcium gluconate is the weakest way.

In Situ Synthetic ZIF-8/Carbon Aerogel Composites as Solid-Phase Microextraction Coating for the Detection of Phthalic Acid Esters in Water Samples.

In this study, a hybrid composite featuring zeolitic imidazolate framework-8/carbon aerogel (ZIF-8/CA) was synthesized via in situ nucleation and growth of ZIF-8 nanoparticles inside carbon aerogels. The novel material was used as the solid-phase microextraction (SPME) coating for the five phthalic acid esters (PAEs) detection by coupling with a gas chromatography-flame ionization detector (GC-FID). Compared with bare carbon aerogel, the ZIF-8/CA presented the best performance, which is attributed to the unique advantages between the high surface area of CA and high hydrophobic properties, the thermal stability of ZIF-8, and their synergistic adsorption effects, such as molecular penetration, hydrogen bond, and π-π stacking interactions. Under the optimized conditions, the as-proposed ZIF-8/CA fiber provided a wide linearity range from 0.2 to 1000 µg L-1 and a low detection limit of 0.17-0.48 µg L-1 for PAEs analysis. The intra-day and inter-day of signal fiber and the fiber-fiber relative standard deviations were observed in the ranges of 3.50-8.16%, 5.02-10.57%, and 5.66-12.11%, respectively. The method was applied to the determination of five PAEs in plastic bottled and river water samples.

Electroencephalogram Features of Perioperative Neurocognitive Disorders in Elderly Patients: A Narrative Review of the Clinical Literature.

Postoperative neurocognitive disorder (PND) is a common postoperative complication, particularly in older patients. Electroencephalogram (EEG) monitoring, a non-invasive technique with a high spatial-temporal resolution, can accurately characterize the dynamic changes in brain function during the perioperative period. Current clinical studies have confirmed that the power density of alpha oscillation during general anesthesia decreased with age, which was considered to be associated with increased susceptibility to PND in the elderly. However, evidence on whether general anesthesia under EEG guidance results in a lower morbidity of PND is still contradictory. This is one of the reasons that common indicators of the depth of anesthesia were limitedly derived from EEG signals in the frontal lobe. The variation of multi-channel EEG features during the perioperative period has the potential to highlight the occult structural and functional abnormalities of the subcortical-cortical neurocircuit. Therefore, we present a review of the application of multi-channel EEG monitoring to predict the incidence of PND in older patients. The data confirmed that the abnormal variation in EEG power and functional connectivity between distant brain regions was closely related to the incidence and long-term poor outcomes of PND in older adults.

Efficient Reduction of Cr(VI) with Carbon Quantum Dots.

Hexavalent chromium (Cr(VI)) pollution is a global problem, and the reduction of highly toxic Cr(VI) to less toxic Cr(III) is considered to be an effective method to address Cr(VI) pollution. In this study, low-toxicity carbon quantum dots (CQDs) were used to reduce Cr(VI) in wastewater. The results show that CQDs can directly reduce Cr(VI) at pH 2 and can achieve a reduction efficiency of 94% within 120 min. It is observed that under pH higher than 2, CQDs can activate peroxymonosulfate (PMS) to produce reactive oxygen species (ROS) for the reduction of Cr(VI) and the reduction efficiency can reach 99% within 120 min even under neutral conditions. The investigation of the mechanism shows that the hydroxyl groups on the surface of CQDs can be directly oxidized by Cr(VI) because of the higher redox potential of Cr(VI) at pH 2. As the pH increases, the carbonyl groups on the surface of CQDs can activate PMS to generate ROS, O2 •-, and 1O2, which result in Cr(VI) being reduced. To facilitate the practical application of CQDs, the treatment of Cr(VI) in real water samples by CQDs was simulated and the method reduced Cr(VI) from an initial concentration of 5 mg/L to only 8 µg/L in 150 min, which is below the California water quality standard of 10 µg/L. The study provides a new method for the removal of Cr(VI) from wastewater and a theoretical basis for practical application.

Seroprevalence of Transfusion Transmissible Infections and Associated Risk Factors in Hospitalized Patients before Transfusion in Jinling Hospital Nanjing University: A Three-Year Retrospective Study.

Transfusion-transmitted infections (TTIs), such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and treponema pallidum (TP), must be detected before blood transfusion. However, few studies have been conducted on the prevalence and accuracy of positive results in hospitalized patients. The purpose of this study was to investigate the real seroprevalence of TTIs among patients before blood transfusion and analyze the characteristics of false-positive results in Jinling Hospital, Nanjing University, China. TTI results were collected from medical records and analyzed retrospectively. Additionally, we also used confirmatory assays to verify the accuracy of positive results. The overall prevalence of TTI was 8.96%, which was related to gender and age. The real positive rates were 86.67% (HBV), 35.09% (HCV), 20.75% (HIV), and 100% (TP). Our results also showed that high-speed centrifugation can reduce the false-positive rate of HBsAg. In summary, the results demonstrated that the positive rates of TTIs in hospitalized patients are higher than those in the general population. We also confirmed the existence of false-positive results in serological screening for TTIs. The method of processing specimens through high-speed centrifugation could reduce the false-positive results of detecting antigens effectively.

A specific circuit in the midbrain detects stress and induces restorative sleep.

In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep could enable resilience, but how stress promotes sleep is unclear. Activity-dependent tagging revealed a subset of ventral tegmental area γ-aminobutyric acid (GABA)-somatostatin (VTAVgat-Sst) cells that sense stress and drive non-rapid eye movement (NREM) and REM sleep through the lateral hypothalamus and also inhibit corticotropin-releasing factor (CRF) release in the paraventricular hypothalamus. Transient stress enhances the activity of VTAVgat-Sst cells for several hours, allowing them to exert their sleep effects persistently. Lesioning of VTAVgat-Sst cells abolished SDS-induced sleep; without it, anxiety and corticosterone concentrations remained increased after stress. Thus, a specific circuit allows animals to restore mental and body functions by sleeping, potentially providing a refined route for treating anxiety disorders.

Improving stability and oral bioavailability of hydroxycamptothecin via nanocrystals in microparticles (NCs/MPs) technology.

This study developed a nanocrystals-in-microparticles (NCs/MPs) technology for improving dissolution and oral absorption of poorly soluble drugs. Hydroxycamptothecin (HCPT) was selected as a model drug and prepared to be nanocrystals (HCPT-NCs) by acid-alkali based precipitation. The HCPT-NCs were rod like shape with the length of 250 nm and the width of 50 nm. Then, the chitosan and sodium alginate were selected as microparticles matrix to encapsulate the HCPT-NCs. The HCPT-NCs were entrapped in microparticles with a D50 value of 15 µm. The drug loading capacity of microparticles achieved more than 40% (w/w) by NCs/MPs technology. The powder X-ray diffraction showed the crystal structure of HCPT in microparticles was same as nanocrystals, indicating that the preparation of microparticles could not destroy the nanocrystals. The in vitro release demonstrated that microparticles could protect the NCs in gastric fluid and release NCs in intestinal fluid. Furthermore, the oral bioavailability of HCPT in NCs/MPs was improved by 18-fold compared to bulk HCPT and 2.1-fold compared to HCPT-NCs as tested by a rat model. Therefore, NCs/MPs technology is a promising and high effective approach to improve the oral bioavailability of poorly soluble drugs.

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

AIMS: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating. METHODS: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods. RESULTS: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons. CONCLUSION: Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.

Current applications of platelet gels in wound healing-A review.

Human platelets play important roles in several physiologic and pathologic processes. Platelet concentrates are activated with thrombin or calcium, resulting in a viscous coagulum (platelet gel [PG]), composed of 95% platelets at least. PG is increasingly used for the treatment of a variety of soft and hard tissue defects, most notably in the management of chronic non-healing wounds. During wound healing, platelets not only play a critical role in primary hemostasis and thrombosis, but also release growth factors and cytokines to promote tissue regeneration, enhance collagen synthesis, and trigger an immune response. This review addresses a variety of aspects relevant to the functions of well-known platelet growth factors, animal and clinical studies of PG in the last decade, and different sources of platelets for PG. PG is used for non-healing chronic wounds, such as oral ulcerations related to epidermolysis bullosa and chronic graft-versus-host disease, for those, the traditional treatment effect is poor. PG maybe provide a new therapeutic direction for these diseases. Nevertheless, some uncertainty is present, the number of clinical studies is not enough. Hence, randomized controlled trials are still required to study the potential of the use of PG in the near future.

Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress.

Social stress, a common stressor, causes multiple forms of physical and mental dysfunction. Prolonged exposure to social stress is associated with a higher risk of psychological disorders, including anxiety disorders and major depressive disorder (MDD). The orexinergic system is involved in the regulation of multiple motivated behaviors. The current study examined the regulatory effect of orexinergic projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) in depression- and anxiety-like behaviors after chronic social defeat stress. When mice were defeated during social interaction, both orexinergic neurons in the LHA and glutamatergic neurons in the LHb were strongly activated, as indicated by the FosTRAP strategy. Infusion of orexin in the LHb significantly alleviated social avoidance and depression-like behaviors induced by chronic social defeat stress. Administration of an orexin receptor 2 antagonist in the LHb further aggravated the depressive phenotype. Photoactivation of orexinergic cell bodies in the LHA or terminals in the LHb relieved anxiety-like behaviors induced by chronic social defeat stress. Collectively, we identified the antidepressant and anxiolytic effects of the circuit from LHA orexinergic neurons to the LHb in response to chronic social stress, providing new evidence of the antidepressant properties of LHA orexin circuits.

Carboxylation modified meso-porous carbon aerogel templated by ionic liquid for solid-phase microextraction of trace tetracyclines residues using HPLC with UV detection.

A carbon aerogel composite templated and catalyzed by ionic liquid was fabricated to obtain a meso-porous and cross-linked structure while avoiding the freeze and supercritical drying. It was then carboxylated to obtain favorable surface groups. The easily prepared material displayed excellent extraction effect of six tetracyclines (TCs) compared to the non-carboxylated carbon aerogel. A direct immersion solid-phase microextraction method to determine six TCs in aqueous samples was developed coupling with high-performance liquid chromatography (HPLC) with UV-Vis detector set at 355 nm. The experimental parameters affecting the analytical performance of this method, including sample pH, ionic strength, extraction and desorption time, extraction volume, and temperature, were optimized. Adsorption kinetics and thermodynamics models were used to clarify the extraction mechanism. Under the optimized conditions, this method has a wide linear range of 2-1000 µg L-1, low limits of detection of 0.36-0.71 µg L-1, repeatability of 1.85-10.96%, and reproducibility of 4.92-13.47% for six TCs. The method was successfully applied to detect TC residues in egg and poultry farm wastewater samples.

Carbon aerogel as a solid-phase microextraction fiber coating for the extraction and detection of trace tetracycline residues in food by coupling with high-performance liquid chromatography.

A direct immersion solid-phase microextraction method for determining tetracyclines (TCs) was developed by coupling with high-performance liquid chromatography. A carbon aerogel (CA) was synthesized as a fiber coating with high extractive properties and a low density of 0.1855 g cm-3via ambient pressure drying and carbonization. The as-synthesized CA exhibited a high specific surface area and a cross-linked structure; it was characterized via scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller analysis, etc. The extraction performance for six TCs was investigated, and the main experimental parameters were optimized by the Box-Behnken design. Adsorption kinetics, Langmuir and Freundlich models were used to clarify the extraction mechanism. This method showed wide linear ranges of 1-500 µg L-1, low limits of detection of 0.52-1.05 µg L-1, good repeatability of 1.37-12.47%, and satisfactory inter-fiber reproducibility of 8.51-15.81% relative standard deviation for the detection of six TCs. Moreover, this study provided an interesting insight into the detection of TCs residues in food samples.

Simultaneous Oxidation and Sequestration of Arsenic(III) from Aqueous Solution by Copper Aluminate with Peroxymonosulfate: A Fast and Efficient Heterogeneous Process.

The major problem in arsenic (As(III)) removal using adsorbents is that the method is time-consuming and inefficient owing to the fact that most of the adsorbents are more effective for As(V). Herein, we report a new discovery regarding the significant simultaneous oxidation and sequestration of As(III) by a heterogeneous catalytic process of copper aluminate (CuAl2O4) coupled with peroxymonosulfate (PMS). Oxidation and adsorption promote each other. With the help of the active radicals, the As(III) removal efficiency can be increased from 59.4 to 99.2% in the presence of low concentrations of PMS (50 µM) and CuAl2O4 (300 mg/L) in solution. CuAl2O4/PMS can work effectively in a wide pH range (3.0-9.0). Other substances, such as nitrate, sulfate, chloride, carbonate, and humic acid, exert an insignificant effect on As(III) removal. Based on X-ray photoelectron spectroscopy (XPS) analysis, the exposed reductive copper active sites might drive the redox reaction of Cu(II)/Cu(I), which plays a key role in the decomposition of PMS and the oxidation of As(III). The exhausted CuAl2O4 could be refreshed for cycling runs with insignificant capacity loss by the combined regeneration strategy because of the stable spinel structure. According to all results, the CuAl2O4/PMS with favorable oxidation ability and stability could be employed as a promising candidate in real As(III)-contaminated groundwater treatment.

Dysfunction of ventral tegmental area GABA neurons causes mania-like behavior.

The ventral tegmental area (VTA), an important source of dopamine, regulates goal- and reward-directed and social behaviors, wakefulness, and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTAVgat) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTAVgat neurons did not catch up on lost sleep, even though they were starting from a sleep-deprived baseline, suggesting that sleep homeostasis was bypassed. The mania-like behaviors, including the sleep loss, were reversed by valproate, and re-emerged when treatment was stopped. Lithium salts and lamotrigine, however, had no effect. Low doses of diazepam partially reduced the hyperlocomotion and fully recovered the immobility time during tail suspension. The mania like-behaviors mostly depended on dopamine, because giving D1/D2/D3 receptor antagonists reduced these behaviors, but also partially on VTAVgat projections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTAVgat terminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTAVgat neurons help set an animal's (and perhaps human's) mental and physical activity levels. Inputs inhibiting VTAVgat neurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival. In the extreme, however, decreased or failed inhibition from VTAVgat neurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).