Reconstructing interfacial manganese deposition for durable aqueous zinc-manganese batteries.

Low-cost, high-safety, and broad-prospect aqueous zinc-manganese batteries (ZMBs) are limited by complex interfacial reactions. The solid-liquid interfacial state of the cathode dominates the Mn dissolution/deposition process of aqueous ZMBs, especially the important influence on the mass and charge transfer behavior of Zn2+ and Mn2+. We proposed a quasi-eutectic electrolyte (QEE) that would stabilize the reversible behavior of interfacial deposition and favorable interfacial reaction kinetic of manganese-based cathodes in a long cycle process by optimizing mass and charge transfer. We emphasize that the initial interfacial reaction energy barrier is not the main factor affecting cycling performance, and the good reaction kinetics induced by interfacial deposition during the cycling process is more conducive to the stable cycling of the battery, which has been confirmed by theoretical analysis, quartz crystal microbalance with dissipation monitoring, depth etching X-ray photon-electron spectroscopy, etc. As a result, the QEE electrolyte maintained a stable specific capacity of 250 mAh g-1 at 0.5 A g-1 after 350 cycles in zinc-manganese batteries. The energy density retention rate of the ZMB with QEE increased by 174% compared to that of conventional aqueous electrolyte. Furthermore, the multi-stacked soft-pack battery with a cathodic mass load of 54.4 mg maintained a stable specific capacity of 200 mAh g-1 for 100 cycles, demonstrating its commercial potential. This work proves the feasibility of adapting lean-water QEE to the stable aqueous ZMBs.

Deep learning-based classification and segmentation for scalpels.

PURPOSE: Scalpels are typical tools used for cutting in surgery, and the surgical tray is one of the locations where the scalpel is present during surgery. However, there is no known method for the classification and segmentation of multiple types of scalpels. This paper presents a dataset of multiple types of scalpels and a classification and segmentation method that can be applied as a first step for validating segmentation of scalpels and further applications can include identifying scalpels from other tools in different clinical scenarios. METHODS: The proposed scalpel dataset contains 6400 images with labeled information of 10 types of scalpels, and a classification and segmentation model for multiple types of scalpels is obtained by training the dataset based on Mask R-CNN. The article concludes with an analysis and evaluation of the network performance, verifying the feasibility of the work. RESULTS: A multi-type scalpel dataset was established, and the classification and segmentation models of multi-type scalpel were obtained by training the Mask R-CNN. The average accuracy and average recall reached 94.19% and 96.61%, respectively, in the classification task and 93.30% and 95.14%, respectively, in the segmentation task. CONCLUSION: The first scalpel dataset is created covering multiple types of scalpels. And the classification and segmentation of multiple types of scalpels are realized for the first time. This study achieves the classification and segmentation of scalpels in a surgical tray scene, providing a potential solution for scalpel recognition, localization and tracking.

Autonomous aspirating robot for removing saliva blood mixed liquid in oral surgery.

Saliva blood mixed liquid (SBML) appears in oral surgery, such as scaling and root planning, and it affects surgical vision and causes discomfort to the patient. However, removing SBML, i.e. frequent aspiration of the mixed liquid, is a routine task involving heavy workload and interruption of oral surgery. Therefore, it is valuable to alternate the manual mode by autonomous robotic technique. The robotic system is designed consisting of an RGB-D camera, a manipulator, a disposable oral aspirator. An algorithm is developed for detection of SBML. Path planning method is also addressed for the distal end of the aspirator. A workflow for removing SBML is presented. 95% of the area of the SBML in the oral cavity was removed after liquid aspiration among a group of ten SBML aspiration experiments. This study provides the first result of the autonomous aspirating robot (AAR) for removing SBML in oral surgery, demonstrating that SBML can be removed by the autonomous robot, freeing stomatology surgeon from tedious work.

A novel nomogram for early prediction of death in severe neurological disease patients with electroencephalographic periodic discharges.

OBJECTIVE: To investigate death-related factors in patients with electroencephalographic (EEG) periodic discharges (PDs) and to construct a model for death prediction. METHODS: This case-control study enrolled a total of 80 severe neurological disease patients with EEG PDs within 72 h of admission to the neuroscience intensive care unit (NICU). According to modified Rankin scale (mRS) scores half a year after discharge, patients were divided into a survival group (<6 points) and a death group (6 points). Their relevant clinical and biochemical indicators as well as EEG characteristics were retrospectively analyzed. Logistic regression analysis was used to identify the risk factors associated with the death of patients with EEG PDs. A death risk prediction model and an individualized nomogram prediction model were constructed, and the prediction performance and concordance of the models were evaluated. RESULTS: Multivariate logistic regression analysis showed that the involvement of both gray and white matter in imaging, disappearance of EEG reactivity, occurrence of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and an interval time of 0.5-4 s were independent risk factors for death. A regression model was established according to the multivariate logistic regression analysis, and the area under the curve of this model was 0.9135. The accuracy of the model was 87.01%, the sensitivity was 87.17%, and the specificity was 89.17%. A nomogram model was constructed, and a concordance index of 0.914 was obtained after internal validation. CONCLUSION: The regression model based on risk factors has high accuracy in predicting the risk of death of patients with EEG PDs. SIGNIFICANCE: This model can help clinicians in the early assessment of the prognosis of severe neurological disease patients with EEG PDs.

Biopsy Needle System With a Steerable Concentric Tube and Online Monitoring of Electrical Resistivity and Insertion Forces.

OBJECTIVE: Biopsies are the gold standard for clinical diagnosis. However, a discrepancy between the biopsy sample and target tissue because of misplacement of the biopsy spoon can lead to errors in the diagnosis and subsequent treatment. Thus, correctly determining whether the needle tip is in the tumor is crucial for accurate biopsy results. METHODS: A biopsy needle system was designed with a steerable, flexible, and superelastic concentric tube; electrodes to monitor the electrical resistivity; and load cells to monitor the insertion force. The degrees of freedom were analyzed for two working modes: straight-line and deflection. RESULTS: Experimental results showed that the system could perceive the tissue type in online based on the electrical resistivity. In addition, changes in the insertion force indicated transitions between the interfaces of adjacent tissue layers. CONCLUSION: The two monitoring methods guarantee that the biopsy spoon is at the desired position inside the tumor during an operation. SIGNIFICANCE: The proposed biopsy needle system can be integrated into an autonomous robotic biopsy system.

Coicis semen protects against focal cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting angiogenesis via the TGFß/ALK1/Smad1/5 signaling pathway.

BACKGROUND: Ischemic stroke is a devastating disease that causes long-term disability. However, its pathogenesis is unclear, and treatments for ischemic stroke are limited. Recent studies indicate that oxidative stress is involved in the pathological progression of ischemic stroke and that angiogenesis participates in recovery from ischemic stroke. Furthermore, previous studies have shown that Coicis Semen has antioxidative and anti-inflammatory effects in a variety of diseases. In the present study, we investigated whether Coicis Semen has a protective effect against ischemic stroke and the mechanism of this protective effect. RESULTS: Coicis Semen administration significantly decreased the infarct volume and mortality and alleviated neurological deficits at 3, 7 and 14 days after MCAO. In addition, cerebral edema at 3 days poststroke was ameliorated by Coicis Semen treatment. DHE staining showed that ROS levels in the vehicle group were increased at 3 days after reperfusion and then gradually declined, but Coicis Semen treatment reduced ROS levels. The levels of GSH and SOD in the brain were increased by Coicis Semen treatment, while MDA levels were reduced. Furthermore, Coicis Semen treatment decreased the extravasation of EB dye in MCAO mouse brains and elevated expression of the tight junction proteins ZO-1 and Occludin. Double immunofluorescence staining and western blot analysis showed that the expression of angiogenesis markers and TGFß pathway-related proteins was increased by Coicis Semen administration. Consistent with the in vivo results, cytotoxicity assays showed that Coicis Semen substantially promoted HUVEC survival following OGD/RX in vitro. Additionally, though LY2109761 inhibited the activation of TGFß signaling in OGD/RX model animals, Coicis Semen cotreatment markedly reversed the downregulation of TGFß pathway-related proteins and increased VEGF levels. METHODS: Adult male wild-type C57BL/6J mice were used to develop a middle cerebral artery occlusion (MCAO) stroke model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7 and 14 after staining. In addition, changes in superoxide dismutase (SOD), GSH and malondialdehyde (MDA) levels were detected with a commercial kit. Blood-brain barrier (BBB) permeability was assessed with Evans blue (EB) dye. Western blotting was also performed to measure the levels of tight junction proteins of the BBB. Additionally, ELISA was performed to measure the level of VEGF in the brain. The colocalization of CD31, angiogenesis markers, and Smad1/5 was assessed by double immunofluorescent staining. TGFß pathway-related proteins were measured by western blotting. Furthermore, the cell viability of human umbilical vein endothelial cells (HUVECs) following oxygen-glucose deprivation/reoxygenation (OGD/RX) was measured by Cell Counting Kit (CCK)-8 assay. CONCLUSIONS: Coicis Semen treatment alleviates brain damage induced by ischemic stroke through inhibiting oxidative stress and promoting angiogenesis by activating the TGFß/ALK1 signaling pathway.

Role of Fractalkine in promoting inflammation in sepsis-induced multiple organ dysfunction.

OBJECTIVE: Fractalkine, CX3CL1, is involved in the directional movement of chemokine cells, immune response, inflammatory response, tissue repair, and other processes. However, its role in sepsis is not well known. METHODS: We measured circulating Fractalkine in adult patients with sepsis. Effects of Fractalkine on the survival, inflammation, tissue injury, and bacterial clearance were assessed using the WT or CX3CL-/- murine model of cecal ligation and puncture (CLP)-induced sepsis. RESULTS: Serum Fractalkine concentrations were significantly elevated in adult patients with sepsis compared to healthy adults. Increased Fractalkine correlated positively with the number of blood leukocytes and the level of inflammatory cytokines, including IL-6, IL-1ß, IL-17A, IFN-γ, and TNF-α, and correlated negatively with IL-10 in clinical sepsis. Recombinant Fractalkine impaired survival whereas Fractalkine gene knockout or anti-Fractalkine antibody improved survival in the murine model of CLP-induced sepsis. Fractalkine administration increased inflammatory response, evident by higher levels of cytokines (TNF-α, IL-1ß, IL-17A, IFN-γ, and IL-6 but not IL-10), and tissue damage (lung, liver, and kidney) in CLP-induced sepsis. Fractalkine reduced bacterial clearance in CLP-induced polymicrobial sepsis by reducing macrophage or neutrophil phagocytosis and intracellular elimination of E. coli. CONCLUSIONS: Fractalkine aggravates sepsis by increasing inflammation and decreasing bacterial clearance, and is a potential tool for anti-sepsis therapy.

Peroxiredoxin-1 Overexpression Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Cardiomyocyte Apoptosis.

Background. Previous research has shown that peroxiredoxin 1 (Prdx1) is an important modulator of physiological and pathophysiological cardiovascular events. This study is aimed at investigating the role and underlying mechanism of Prdx1 in doxorubicin- (DOX-) induced cardiotoxicity. Cardiac-specific expression of Prdx1 was induced in mice, and the mice received a single dose of DOX (15 mg/kg) to generate cardiotoxicity. First, our study demonstrated that Prdx1 expression was upregulated in the heart and in cardiomyocytes after DOX treatment. Second, we provided direct evidence that Prdx1 overexpression ameliorated DOX-induced cardiotoxicity by attenuating oxidative stress and cardiomyocyte apoptosis. Mechanistically, we found that DOX treatment increased the phosphorylation level of apoptosis signal-regulating kinase-1 (ASK1) and the downstream protein p38 in the heart and in cardiomyocytes, and these effects were decreased by Prdx1 overexpression. In contrast, inhibiting Prdx1 promoted DOX-induced cardiac injury via the ASK1/p38 pathway. These results suggest that Prdx1 may be an effective therapeutic option to prevent DOX-induced cardiotoxicity.

Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca2+-STIM1/Orai1 Signaling.

Dexmedetomidine (DEX), a potent and highly selective agonist for α2-adrenergic receptors (α2AR), exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca2+ influx. However, the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation (OGD/R) injury in vitro are unknown. We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells, as evidenced by decreased oxidative stress, autophagy, and neuronal apoptosis. Specifically, DEX pretreatment decreased the expression levels of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), and reduced the concentration of intracellular calcium pools. In addition, variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions, which were modulated through STIM1/Orai1 signaling. Moreover, DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3), hallmark markers of autophagy, and the formation of autophagosomes. In conclusion, these results suggested that DEX exerts neuroprotective effects against oxidative stress, autophagy, and neuronal apoptosis after OGD/R injury via modulation of Ca2+-STIM1/Orai1 signaling. Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

Predictors of Outcome in Clinically Diagnosed Viral Encephalitis Patients: A 5-Year Prospective Study.

BACKGROUND: Viral encephalitis is the most common infectious disease of the central nervous system and is associated with high morbidity, mortality, and disability. The objective of this study was to analyze the clinical characteristics, auxiliary examinations, therapeutic management, and outcomes of patients clinically diagnosed with viral encephalitis and identify the outcome predictors. METHODS: We conducted a prospective observational study by collecting information from patients clinically diagnosed with viral encephalitis at the First Affiliated Hospital of Chongqing Medical University and Yongchuan Hospital of Chongqing Medical University from January 2013 to December 2018. Univariate and multivariate analyses were performed to identify factors that influenced good patient outcomes (mRS < 3) and poor patient outcomes (mRS ≥ 3) at discharge. RESULTS: In total, 216 patients were enrolled in the study. The multivariate analysis suggested that the following factors were associated with a poor outcome: Glasgow Coma Scale (GCS) score (OR 0.154, 95% CI (0.078-0.302), and P < 0.001), focal neurological deficits (OR 9.403, 95% CI (1.581-55.928), and P = 0.014), and total length of hospital stay (OR 1.119, 95% CI (1.002-1.250), and P = 0.045). However, neurological intensive care unit (NICU) treatment, status epilepticus, and abnormal electroencephalogram (EEG) findings did not influence the prognosis of patients. CONCLUSION: Our study suggests that low GCS scores at admission, focal neurological deficits at admission, and a prolonged total hospital stay are predictors of a poor outcome at discharge in clinically diagnosed viral encephalitis patients. Whether early and effective neurological rehabilitation can improve the prognosis of viral encephalitis patients with focal neurological deficits remains to be confirmed in further studies.

Dexmedetomidine pretreatment attenuates myocardial ischemia reperfusion induced acute kidney injury and endoplasmic reticulum stress in human and rat.

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) often develop acute kidney injury (AKI) caused by myocardial ischemia reperfusion (MI/R), and this renal injury can be resolved notably by dexmedetomidine. Endoplasmic reticulum (ER) stress was reported to get involved in organ injury including AKI. OBJECTIVES: The current study aimed to address the correlation between MI/R induced AKI with ER stress and to assess the effects of dexmedetomidine pretreatment on AKI protection. METHOD: Patients selected for heart valve replacement surgery were randomly assigned to NS group (pre-anesthesia with 0.9% NaCl) and DEX group (pre-anesthesia with dexmedetomidine). Rat MI/R model was induced by occluding coronary artery for 30 min followed by 48-hour reperfusion. Rats were randomized into Sham (0.9% NaCl), I/R (MI/R + 0.9% NaCl) and I/R + DEX (MI/R + dexmedetomidine). Organ function and ER stress condition were evaluated by blood chemistry, pathology, and molecular test. RESULTS: Clinical data indicated dexmedetomidine pretreatment attenuated AKI and oxidative stress as well as postischemic myocardial injury in patients. Accordingly animal results suggested dexmedetomidine reduced cellular injury and improved postischemic myocardial and renal function. Dexmedetomidine also reduced myocardial and renal cells apoptosis and down-regulated ER stress. CONCLUSIONS: These results suggested that dexmedetomidine pretreatment attenuates MI/R injury-induced AKI by relieving the ER stress.

Neuroprotective effects of 1-O-hexyl-2,3,5-trimethylhydroquinone on ischaemia/reperfusion-induced neuronal injury by activating the Nrf2/HO-1 pathway.

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a lipophilic phenolic agent, has an antioxidant activity and reactive oxygen species (ROS) scavenging property. However, the role of HTHQ on cerebral ischaemic/reperfusion (I/R) injury and the underlying mechanisms remain poorly understood. In the present study, we demonstrated that HTHQ treatment ameliorated cerebral I/R injury in vivo, as demonstrated by the decreased infarct volume ration, neurological deficits, oxidative stress and neuronal apoptosis. HTHQ treatment increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant protein, haeme oxygenase-1 (HO-1). In addition, HTHQ treatment decreases oxidative stress and neuronal apoptosis of PC12 cells following hypoxia and reperfusion (H/R) in vitro. Moreover, we provided evidence that PC12 cells were more vulnerable to H/R-induced oxidative stress after si-Nrf2 transfection, and the HTHQ-mediated protection was lost in PC12 cells transfected with siNrf2. In conclusion, these results suggested that HTHQ possesses neuroprotective effects against oxidative stress and apoptosis after cerebral I/R injury via activation of the Nrf2/HO-1 pathway.

Dexmedetomidine with sufentanil in intravenous patient-controlled analgesia for relief from postoperative pain, inflammation and delirium after esophageal cancer surgery.

BACKGROUND AND AIMS: Postoperative pain can cause serious adverse reactions that severely affect postoperative outcome. The present study evaluated the effect of dexmedetomidine (DEX) added to sufentanil in intravenous patient-controlled analgesia (PCA) on the relief of pain and inflammatory responses during postoperative recovery of patients undergoing a combined thoracoscopic-laparoscopic esophagectomy (TLE). METHODS: Sixty patients undergoing TLE were randomly allocated to receive 1 µg/ml of sufentanil alone (Group S) or 1 µg/ml of sufentanil plus 2.5 µg/ml of DEX (Group D) for postoperative intravenous (IV) PCA. Postoperative pain relief, cumulative PCA requirements, inflammatory marker levels, delirium and recovery were assessed. RESULTS: A joint DEX and sufentanil regimen significantly reduced the area under the curve of numerical rating scores for pain at rest (NRSR) and coughing (NRSC) at 1-48 h postoperatively (P = 0.000) that were associated with lower PCA-delivered cumulative sufentanil consumption and less PCA frequency until 48 h postoperatively (P < 0.05 and P < 0.0001, respectively). The simultaneous administration of DEX and sufentanil significantly reduced plasma IL-6 and TNF-α concentrations and increased IL-10 level (P < 0.0001, P = 0.0003 and P = 0.0345, respectively), accompanied by better postoperative delirium categories and health statuses of patients (P = 0.024 and P < 0.05, respectively). There was no hypotension, bradycardia, respiratory depression or oversedation in Group D. CONCLUSION: Patients receiving DEX in addition to IV PCA sufentanil for TLE exhibited better postoperative analgesia, fewer inflammatory responses and lower postoperative delirium categories and better health statuses.

Role of activin receptor-like kinase 1 in vascular development and cerebrovascular diseases.

Activin receptor-like kinase 1 (ALK1) is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta (TGFß) receptor superfamily. ALK1 is specifically expressed in vascular endothelial cells, and its dynamic changes are closely related to the proliferation of endothelial cells, the recruitment of pericytes to blood vessels, and functional differentiation during embryonic vascular development. The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells. Indeed, mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation. Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms, arteriovenous malformations, and cerebral atherosclerosis. In this review, we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis, and we discuss its relationship to functional dysregulation in cerebrovascular diseases. This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis, treatment, and prevention.

A Rare KIF1A Missense Mutation Enhances Synaptic Function and Increases Seizure Activity.

Although genetic factors are considered a main etiology of epilepsy, the causes of genetic epilepsy in the majority of epilepsy patients remain unknown. Kinesin family member 1A (KIF1A), a neuron-specific motor protein that moves along with microtubules, is responsible for the transport of membranous organelles and synaptic vesicles. Variants of KIF1A have recently been associated with hereditary spastic paraplegia (HSP), hereditary sensory and autonomic neuropathy type 2 (HSANII), and intellectual disability. However, mutations in KIF1A have not been detected in patients with epilepsy. In our study, we conducted customized sequencing of epilepsy-related genes of a family with six patients with generalized epilepsy over three generations and identified a rare heterozygous mutation (c.1190C > A, p. Ala397Asp) in KIF1A. Whole-cell recordings from primary cultured neurons revealed that the mutant KIF1A increases the excitatory synaptic transmission but not the intrinsic excitability of neurons, and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. These results provide new evidence demonstrating that KIF1A dysfunction is involved in epileptogenesis.

Inhibition of Nwd1 activity attenuates neuronal hyperexcitability and GluN2B phosphorylation in the hippocampus.

BACKGROUND: NACHT and WD repeat domain-containing protein 1 (Nwd1) is a member of the innate immune protein subfamily. Nwd1 contributes to the androgen receptor signaling pathway and is involved in axonal growth. However, the mechanisms that underlie pathophysiological dysfunction in seizures remain unclear. METHODS: Biochemical methods were used to assess Nwd1 expression and localization in a mouse model of kainic acid (KA)-induced acute seizures and temporal lobe epilepsy (TLE) patients. Electrophysiological recordings were used to measure the role of Nwd1 in regulating synaptic transmission and neuronal hyperexcitability in a model of magnesium-free-induced seizure in vitro. Behavioral experiments were performed, and seizure-induced pathological changes were evaluated in a KA-induced seizure model in vivo. GluN2B expression was measured and its correlation with Tyr1472-GluN2B phosphorylation was analyzed in primary hippocampal neurons. FINDINGS: We demonstrated high protein levels of Nwd1 in brain tissues obtained from mice with acute seizures and TLE patients. Silencing Nwd1 in mice using an adeno-associated virus (AAV) profoundly suppressed neuronal hyperexcitability and the occurrence of acute seizures, which may have been caused by reducing GluN2B-containing NMDA receptor-dependent glutamatergic synaptic transmission. Moreover, the decreased activation of Nwd1 reduced GluN2B expression and the phosphorylation of the GluN2B subunit at Tyr1472. INTERPRETATION: Here, we report a previously unrecognized but important role of Nwd1 in seizure models in vitro and in vivo, i.e., modulating the phosphorylation of the GluN2B subunit at Tyr1472 and regulating neuronal hyperexcitability. Meanwhile, our findings may provide a therapeutic strategy for the treatment of epilepsy or other hyperexcitability-related neurological disorders. FUND: The funders have not participated in the study design, data collection, data analysis, interpretation, or writing of the report.

Transgenic overexpression of furin increases epileptic susceptibility.

The proprotein convertase Furin plays crucial roles in the pathology of many diseases. However, the specific role of furin in epilepsy remains unclear. In our study, furin protein was increased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. The furin transgenic (TG) mice showed increased susceptibility to epilepsy and heightened epileptic activity compared with wild-type (WT) mice. Conversely, lentivirus-mediated knockdown of furin restrained epileptic activity. Using whole-cell patch clamp, furin knockdown and overexpression influenced neuronal inhibitory by regulating postsynaptic gamma-aminobutyric acid A receptor (GABAAR)-mediated synaptic transmission. Importantly, furin influenced the expression of GABAAR ß2/3 membrane and total protein in epileptic mice by changing transcription level of GABAAR ß2/3, not the protein degradation. These results reveal that furin may regulate GABAAR-mediated inhibitory synaptic transmission by altering the transcription of GABAAR ß2/3 subunits in epilepsy; this finding could provide new insight into epilepsy prevention and treatment.

ZDHHC8 critically regulates seizure susceptibility in epilepsy.

Epilepsy is one of the most prevalent and drug-refractory neurological disorders. Zinc finger DHHC-type containing 8 (ZDHHC8) is a putative palmitoyltransferase that is highly expressed in the brain. However, the impact of ZDHHC8 on seizures remains unclear. We aimed to explore the association of ZDHHC8 with epilepsy and investigate its in epileptogenesis in in vivo and in vitro models through behavioral, electrophysiological, and pathological studies. We used kainic acid- and pilocarpine-induced C57BL/6 mice and magnesium-free-induced pyramidal neurons as experimental epileptic models in this study. We first found increased ZDHHC8 expression in the brains of temporal lobe epilepsy (TLE) patients, similar to that observed in chronic epileptic mice, strongly suggesting that ZDHHC8 is correlated with human epilepsy. In the in vitro seizure models, knocking down ZDHHC8 using recombinant adeno-associated virus (rAAV) delayed seizure precipitation and decreased chronic spontaneous recurrent seizures (SRSs) and epileptiform-like discharges, while ZDHHC8 overexpression had the opposite effect. ZDHHC8 levels were consistent with seizure susceptibility in induced mice with SRSs. In an in vitro magnesium-free model, neuronal hyperexcitability and hypersynchrony were reduced in ZDHHC8-knockdown neurons but were increased in ZDHHC8-overexpressing neurons. To further explore the potential mechanisms, we observed that ZDHHC8 had a significant modulatory effect on 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-related excitatory, but not inhibitory, glutamatergic synaptic neurotransmission, further affecting the inward rectification of AMPA currents in acute hippocampal slices in whole-cell recordings. ZDHHC8 facilitated GluA1 trafficking to the neuronal surface in the hippocampus, as shown by immunoprecipitation and Western blotting. These results suggest that ZDHHC8 may promote the generation and propagation of seizures in humans and that knocking down ZDHHC8 might produce anti-epileptogenic effects in drug-resistant epilepsy. Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.

A novel scoring system to predict the outcomes of adult patients with hypoxic-ischemic encephalopathy.

BACKGROUND: Adult patients with hypoxic-ischemic encephalopathy (HIE) often incur large costs, but their outcomes are poor. Currently, there is lack of a comprehensive quantitative approach to predict patient prognoses. METHODS: A total of 73 adult patients with HIE participated in this prospective, observational study. Clinical assessments, laboratory tests, and electrophysiological examinations were conducted within 3 days after HIE occurred. Logistic regression model was used to identify independent factors associated with patient outcomes. RESULTS: After a 6-month follow-up, 44 (61.1%) patients survived, 28 (38.9%) patients died, and one patient was lost to follow-up. The level of blood calcium and lactate, the presence of electroencephalography reactivity, and Glasgow Coma Scale (GCS) score were significantly associated with the patient's outcome. Based on the regression coefficients from logistic regression analysis, we constructed a scoring system (CEGL; C: calcium, E: EEG reactivity, G: GCS, L: lactate) to predict the possibility of a patient's death. The area under the receiver operating characteristic curve was 0.91 (P < 0.001, 95% CI [0.87-0.95]) with a specificity of 97.7% and a positive predictive value of 97.4%. CONCLUSION: CEGL score can provide clinicians useful information for assessment of patient prognosis within 6 months after HIE.

Altered resting-state voxel-level whole-brain functional connectivity in depressed Parkinson's disease.

BACKGROUND: Depression is one of the most common non-motor symptoms in Parkinson's disease (PD), but its pathogenesis is still not very clear. Recently, degree centrality, a voxel-level whole-brain functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging, has provided the most promising way to explore the neural network mechanisms underlying depressed PD. METHODS: Degree centrality, voxel-wise image and clinical symptoms correlation and secondary seed-based FC analyses were performed in twenty-seven drug-naïve, early stage depressed PD patients, 27 non-depressed PD patients and 27 healthy controls (HCs) to reveal voxel-level whole-brain FC changes in depressed PD. RESULTS: Compared with the HCs, depressed PD and non-depressed PD patients shared similar brain degree centrality abnormalities mainly in the basal ganglia, insular cortex, motor cortices, default mode network, prefrontal gyrus and the cerebellum. However, compared with non-depressed PD, depressed PD showed degree centrality abnormalities in the right middle prefrontal gyrus, anterior cingulate cortices, supplementary motor cortices and cerebellum lobule VI. The right middle prefrontal gyrus degree centrality abnormalities were correlated with the clinical depression severity, and using it as a seed, a secondary seed-based FC analysis further revealed the FC changes in the anterior cingulate cortices and the cerebellum lobule VI. CONCLUSIONS: Our findings revealed that dysfunction in extensive brain areas were involved in depressed PD, and among these regions, the right middle prefrontal gyrus, anterior cingulate cortices and the cerebellum may pose as pathogenesis hubs underlying depressed PD.