Akt and AMPK activators rescue hyperexcitability in neurons from patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric illness affecting ∼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive. METHODS: In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies. FINDINGS: We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with changes to Na+ conductance. Whole transcriptome sequencing in BD neurons revealed altered gene expression pathways related to glutamate transmission, alterations in cell signalling and ion transport/channel activity. We found altered Akt signalling as a potential therapeutic effect of Li in LR neurons from patients with BD, and that Akt activation mimics Li effect in LR neurons. Furthermore, the increased neural network activity observed in both LR & LNR neurons from patients with BD were reversed by AMP-activated protein kinase (AMPK) activation. INTERPRETATION: These results suggest potential for new treatment strategies in BD, such as Akt activators in LR cases, and the use of AMPK activators for LNR patients with BD. FUNDING: Supported by funding from ERA PerMed, Bell Brain Canada Mental Research Program and Brain & Behavior Research Foundation.

A facile single-cell patterning strategy based on harbor-like microwell microfluidics.

Single-cell analysis is an effective method for conducting comprehensive heterogeneity studies ranging from cell phenotype to gene expression. The ability to arrange different cells in a predetermined pattern at single-cell resolution has a wide range of applications in cell-based analysis and plays an important role in facilitating interdisciplinary research by researchers in various fields. Most existing microfluidic microwell chips is a simple and straightforward method, which typically use small-sized microwells to accommodate single cells. However, this method imposes certain limitations on cells of various sizes, and the single-cell capture efficiency is relatively low without the assistance of external forces. Moreover, the microwells limit the spatiotemporal resolution of reagent replacement, as well as cell-to-cell communication. In this study, we propose a new strategy to prepare a single-cell array on a planar microchannel based on microfluidic flip microwells chip platform with large apertures (50 µm), shallow channels (50 µm), and deep microwells (50 µm). The combination of three configuration characteristics contributes to multi-cell trapping and a single-cell array within microwells, while the subsequent chip flipping accomplishes the transfer of the single-cell array to the opposite planar microchannel for cells adherence and growth. Further assisted by protein coating of bovine serum albumin and fibronectin on different layers, the single-cell capture efficiency in microwells is achieved at 92.1 ± 1%, while ultimately 85 ± 3.4% on planar microchannel. To verify the microfluidic flip microwells chip platform, the real-time and heterogeneous study of calcium release and apoptosis behaviors of single cells is carried out. To our knowledge, this is the first time that high-efficiency single-cell acquisition has been accomplished using a circular-well chip design that combines shallow channel, large aperture and deep microwell together. The chip is effective in avoiding the shearing force of high flow rates on cells, and the large apertures better allows cells to sedimentation. Therefore, this strategy owns the advantages of easy preparation and user-friendliness, which is especially valuable for researchers from different fields.

Autophagy in hematopoietic stem cell development of the embryo.

Hematopoietic stem cells (HSC) emerge from hemogenic endothelial cells (HEC) in the aorta-gonad-mesonephros (AGM) region of embryos, which go through the pre-HSC process. Various intrinsic and extrinsic factors are involved in this process. We recently discovered that the existence of distinct macroautophagic/autophagic statuses in hematopoietic precursors is related to the hematopoietic potential of pre-HSCs and the depletion of the Atg5 (autophagy related 5) gene specifically in endothelial cells impaired in the transition of endothelial to pre-HSCs, by hampering the autophagic process, likely via the NCL (nucleolin) pathway.Abbreviation: Atg5: autophagy related 5; EGFP: enhanced green fluorescent protein; EHT: endothelial-to-hematopoietic transition; HEC: hemogenic endothelial cell; HSC: hematopoietic stem cell; NCL: nucleolin; RFP: red fluorescent protein.

A Network Pharmacology-Based Method to Explore the Therapeutic Effect of Honokiol on Diabetes with Comorbid Depression in Mice.

The effective treatment of diabetes with comorbid depression is a big challenge so far. Honokiol, a bioactive compound from the dietary supplement Magnolia officinalis extract, possesses multiple health benefits. The present study aims to propose a network pharmacology-based method to elucidate potential targets of honokiol in treating diabetes with comorbid depression and related mechanisms. The antidepressant-like efficacy of honokiol was evaluated in high-fat diet (HFD) induced diabetic mice using animal behavior testing, immuno-staining and western blotting assay. Through network pharmacology analysis, retinoid X receptor alpha (RXRα) and vitamin D receptor (VDR) were identified as potential targets related to diabetes and depression. The stable binding conformation between honokiol and RXR/VDR was determined by molecular docking simulation. Moreover, hononkiol effectively alleviated depression-like behaviors in HFD diabetic mice, presented anti-diabetic and anti-neuroinflammatory functions, and protected the hippocampal neuroplasticity. Importantly, honokiol could activate RXR/VDR heterodimer in vivo. The beneficial effects of honokiol on HFD mice were significantly suppressed by UVI3003 (a RXR antagonist), while enhanced by calcitriol (a VDR agonist). Additionally, the disruption of autophagy in the hippocampus of HFD mice was ameliorated by honokiol, which was attenuated by UVI3003 but strengthened by calcitriol. Taken together, the data provide new evidence that honokiol exerts the antidepressant-like effect in HFD diabetic mice via activating RXR/VDR heterodimer to restore the balance of autophagy. Our findings indicate that the RXR/VDR-mediated signaling might be a potential target for treating diabetes with comorbid depression.

Heat-Localized and Salt-Resistant 3D Hierarchical Porous Ceramic Platform for Efficient Solar-Driven Interfacial Evaporation.

Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.

Response of plants and soils to inundation duration and construction of the plant‒soil association mode in the hydro‒fluctuation belt of the reservoir wetland.

Hydro-Fluctuation Belt (HFB), a periodically exposed bank area formed by changes in water level fluctuations, is critical for damaging the reservoir wetland landscape and ecological balance. Thus, it is important to explore the mechanism of hydrological conditions on the plant-soil system of the HFB for protection of the reservoir wetland and landscape restoration. Here, we investigated the response of plant community characteristics and soil environment of the HFB of Tonghui River National Wetland Park (China), is a typical reservoir wetland, to the duration of inundation, as well as the correlation between the distribution of dominant plants and soil pH, nutrient contents, and enzyme activity by linear regression and canonical correlation analyses. The results show that as the duration of inundation decreases, the vegetation within the HFB is successional from annual or biennial herbs to perennial herbs and shrubs, with dominant plant species prominent and uneven distribution of species. Soil nutrient contents and enzyme activities of HFB decreased with increasing inundation duration. Dominant species of HFB plant community are related to soil environment, with water content, pH, urease, and available potassium being principle soil environmental factors affecting their distribution. When HFB was inundated for 0-30 days, soil pH was strongly acidic, with available potassium content above 150 mg kg-1 and higher urease activity, distributed with Arundo donax L., Polygonum perfoliatum L., Alternanthera philoxeroides (Mart.) Griseb., and Daucus carota L. communities. When inundated for 30-80 days, soil pH was acidic, with lower available potassium content (50-150 mg kg-1) and urease activity, distributed with Beckmannia syzigachne (Steud.) Fern.+ Polygonum lapathifolium L., Polygonum lapathifolium L., Medicago lupulina L. + Dysphania ambrosioides L. and Leptochloa panicea (Retz.) Ohwi communities. Using the constructed HFB plant-soil correlation model, changes in the wetland soil environment can be quickly judged by the succession of plant dominant species, which provides a simpler method for the monitoring of the soil environment in the reservoir wetland, and is of great significance for the scientific management and reasonable protection of the reservoir-type wetland ecosystem.

A subset of megakaryocytes regulates development of hematopoietic stem cell precursors.

Understanding the regulatory mechanisms facilitating hematopoietic stem cell (HSC) specification during embryogenesis is important for the generation of HSCs in vitro. Megakaryocyte emerged from the yolk sac and produce platelets, which are involved in multiple biological processes, such as preventing hemorrhage. However, whether megakaryocytes regulate HSC development in the embryonic aorta-gonad-mesonephros (AGM) region is unclear. Here, we use platelet factor 4 (PF4)-Cre;Rosa-tdTomato+ cells to report presence of megakaryocytes in the HSC developmental niche. Further, we use the PF4-Cre;Rosa-DTA (DTA) depletion model to reveal that megakaryocytes control HSC specification in the mouse embryos. Megakaryocyte deficiency blocks the generation and maturation of pre-HSCs and alters HSC activity at the AGM. Furthermore, megakaryocytes promote endothelial-to-hematopoietic transition in a OP9-DL1 coculture system. Single-cell RNA-sequencing identifies megakaryocytes positive for the cell surface marker CD226 as the subpopulation with highest potential in promoting the hemogenic fate of endothelial cells by secreting TNFSF14. In line, TNFSF14 treatment rescues hematopoietic cell function in megakaryocyte-depleted cocultures. Taken together, megakaryocytes promote production and maturation of pre-HSCs, acting as a critical microenvironmental control factor during embryonic hematopoiesis.

Association between triglyceride-glucose index and intracranial/extracranial atherosclerotic stenosis: findings from a retrospective study.

OBJECTIVE: The association of the triglyceride-glucose (TyG) index with intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) is unclear. This study aimed to investigate the relationship of TyG index with the distribution and severity of ICAS and ECAS. METHOD: Patients who underwent digital subtraction angiography (DSA) for evaluating ICAS/ECAS in Zhongnan Hospital of Wuhan University from January 2017 to October 2021 were retrospectively enrolled in our study. Clinical characteristics, DSA data, blood routine, lipid profile and fasting glucose were recorded. The association of TyG index and ICAS/ECAS status were investigated in four aspects: location and distribution of stenosis, stenosis severity and whether stenosis is symptomatic. Logistic regression models were used to evaluate the association. Restricted cubic splines were constructed to model the non-linear relationship between the TyG index and different arterial stenosis status. RESULTS: Among 1129 included patients, the median age was 62 (IQR 55-68) years, and 71.3% were male. The median TyG index was 8.81 (8.40, 9.21). Elevated TyG index was significantly associated with ICAS, combined ICAS/ECAS, anterior circulation stenosis, posterior circulation stenosis, combined anterior/posterior circulation stenosis, severe stenosis, both asymptomatic and symptomatic stenosis. This association was maintained after adjusting for age, sex, smoking, drinking, medical history of hypertension and stroke, platelet, total cholesterol, high-density lipoprotein, and low-density lipoprotein. Multivariable-adjusted spline regression models showed that a progressively increasing risk of arterial stenosis was related to an elevated TyG index. CONCLUSION: Elevated TyG index was associated with ICAS/ECAS. TyG index might be a useful indicator of ICAS and severe stenosis.

Autophagy regulates the maturation of hematopoietic precursors in the embryo.

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.

Solid-Phase Microextraction/Gas Chromatography-Time-of-Flight Mass Spectrometry Approach Combined with Network Pharmacology Analysis to Evaluate the Quality of Agarwood from Different Regions against Anxiety Disorder.

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.

Successful hybrid endovascular treatment for refractory cerebral venous sinus thrombosis in pregnancy: A case report.

Background: Cerebral venous sinus thrombosis (CVST) in pregnancy was common and endovascular treatment (EVT) could be an effective and safe treatment for patients with severe and refractory CVST. However, the efficacy and safety of hybrid EVT (craniotomy + endovascular treatment) for CVST were unknown. We represented a rare case of hybrid EVT through the incision of the superior sagittal sinus in a pregnant woman with CVST who failed to EVT through the femoral vein pathway. Case presentation: A 26-year-old woman, in her second month of pregnancy, complained of a headache for 5 days and aggravation with coma combined with convulsions for 2 days. She was diagnosed with CVST in the local hospital by digital subtraction angiography (DSA) and treated with anticoagulation. She had no history of illness and the biochemical tests were normal. Hybrid EVT (craniotomy + EVT) was attempted after failing to conduct EVT through the femoral vein pathway due to difficulty to reach the target cerebral venous sinus. Briefly, a small hole was made in the frontotemporal head to expose the superior sagittal sinus and a 6F sheath was inserted into 2cm of superior sagittal sinus incision and fixed on the scalp, after repeated aspiration by 5F intermediate catheter and balloon dilatation of stenosis in the right transverse sinus and right sigmoid sinus, the cerebral venous system got successful recanalization. No obvious complications were found and the patient recovered very well after the surgery. Conclusion: Anticoagulation was the standard treatment for CVST. EVT could rapidly restore venous flow and improve the prognosis for refractory and severe CVST. EVT by hybrid surgery through the superior sagittal sinus incision may be safe and effective for desperate patients with severe CVST.

Salicylic Acid Modulates the Osmotic System and Photosynthesis Rate to Enhance the Drought Tolerance of Toona ciliata.

Toona ciliata M. Roem. is a valuable and fast-growing timber species which is found in subtropical regions; however, drought severely affects its growth and physiology. Although the exogenous application of salicylic acid (SA) has been proven to enhance plant drought tolerance by regulating the osmotic system and photosynthesis rate, the physiological processes involved in the regulation of drought tolerance by SA in various plants differ. Therefore, drought mitigation techniques tailored for T. ciliata should be explored or developed for the sustainable development of the timber industry. We selected 2-year-old T. ciliata seedlings for a potting experiment, set the soil moisture at 45%, and subjected some of the T. ciliata seedlings to a moderate drought (MD) treatment; to others, 0.5 mmol/L exogenous SA (MD + SA) was applied as a mitigation test, and we also conducted a control using a normal water supply at 70% soil moisture (CK). Our aim was to investigate the mitigating effects of exogenous SA on the growth condition, osmotic system, and photosynthesis rate of T. ciliata under drought stress conditions. OPLS-VIP was used to analyze the main physiological factors that enable exogenous SA to alleviate drought-induced injury in T. ciliata. The results indicated that exogenous SA application increased the growth of the ground diameter, plant height, and leaf blades and enhanced the drought tolerance of the T. ciliata seedlings by maintaining the balance of their osmotic systems, improving their gas exchange parameters, and restoring the activity of their PSII reaction centers. The seven major physiological factors that enabled exogenous SA to mitigate drought-induced injury in the T. ciliata seedlings were the soluble proteins (Sp), net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), stomatal opening window (Sow), activity of the photosystem II reaction center (ΦPSII), and electron transfer rate (ETR). Of these, Sp was the most dominant factor. There was a synergistic effect between the osmotic system and the photosynthetic regulation of drought injury in the T. ciliata seedlings. Overall, our study confirms that exogenous SA enhances the drought tolerance of T. ciliata by modulating the osmotic system and photosynthesis rate.

Recurrent stroke shortly after mechanical thrombectomy secondary to carotid web: A case report.

RATIONALE: Carotid web, a known source of thrombus for embolic stroke, presents a considerable risk of stroke recurrence. While case reports have demonstrated the safety and effectiveness of mechanical thrombectomy in treating carotid web-related stroke, the need for concurrent carotid artery stenting to prevent recurrent stroke immediately after thrombectomy remains unclear. This study aims to underscore the importance of immediate carotid artery stenting in preventing recurrent stroke following mechanical thrombectomy in patients with carotid web-related stroke. PATIENT CONCERNS: A 43-year-old woman with acute onset of left limb weakness and slurred speech within 3 hours was admitted to the emergency department. DIAGNOSES: Computed tomographic angiography confirmed the M1 segment occlusion of the right middle cerebral artery. INTERVENTIONS: The patient received intravenous thrombolysis in the local hospital and mechanical thrombectomy in our stroke center. OUTCOMES: Three days post-mechanical thrombectomy, there was a sudden exacerbation of her neurological deficit symptoms. A reexamination via computed tomographic angiography revealed a re-occlusion in M1 segment of the right middle cerebral artery, despite the implementation of stringent anticoagulation therapy for carotid web-related stroke. LESSONS: Stroke patients with carotid web had a high risk of stroke recurrence and it was necessary to conduct carotid artery stenting to prevent stroke recurrence secondary to the carotid web immediately after mechanical thrombectomy.

Predicting functional outcome in acute ischemic stroke patients after endovascular treatment by machine learning.

Background: Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we aimed to explore a predictive model for patients after EVT. Method: A total of 156 patients were retrospectively enrolled. The primary outcome was functional dependence (defined as a 90-day modified Rankin Scale score ≤ 2). Least absolute shrinkage and selection operator and univariate logistic regression were used to select predictive factors. Various machine learning algorithms, including multivariate logistic regression, linear discriminant analysis, support vector machine, k-nearest neighbors, and decision tree algorithms, were applied to construct prognostic models. Result: Six predictive factors were selected, namely, age, baseline National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT (ASPECT) score, modified thrombolysis in cerebral infarction score, symptomatic intracerebral hemorrhage (sICH), and complications (pulmonary infection, gastrointestinal bleeding, and cardiovascular events). Based on these variables, various models were constructed and showed good discrimination. Finally, a nomogram was constructed by multivariate logistic regression and showed a good performance. Conclusion: Our nomogram, which was composed of age, baseline NIHSS score, ASPECT score, recanalization status, sICH, and complications, showed a very good performance in predicting outcome after EVT.

Development and validation of a predictive model for white matter lesions in young- and middle-aged people.

Background: White matter lesion (WML) is an age-related disorder associated with stroke and cognitive impairment. This study aimed to investigate the risk factors and build a predictive model of WML in young- and middle-aged people. Methods: We performed a second analysis of the data from the Dryad Digital Repository. We selected those people who are <60 years old and randomly divided them into the training group and the validation group. We investigated the risk factors of WML in the training group with logistic regression analysis and built a prediction nomogram based on multivariate logistic regression analysis; finally, the performance of the prediction nomogram was evaluated for discrimination, accuracy, and clinical utility. Results: There were 308 people in the training group and 723 people in the validation group. Multivariate regression analysis showed that the age (OR = 1.49, 95% CI: 1.31-1.70), diastolic blood pressure (OR = 1.02, 95% CI: 1.00-1.03), carotid plaque score (OR = 1.31, 95% CI: 1.14-1.50), female gender (OR = 2.27, 95% CI: 1.56-3.30), and metabolic syndrome (OR = 2.12, 95% CI: 1.22-3.70) were significantly associated with white matter lesions. The area under the curve value (AUC) of the receiver operating curve (ROC) was 0.734 for the training group and 0.642 for the validation group. The calibration curve and clinical impact curve showed that the prediction nomogram has good accuracy and clinical application value. Conclusion: Age, diastolic blood pressure, carotid plaque score, female gender, and metabolic syndrome were risk factors in young- and middle-aged people <60 years old with WML, and the nomogram based on these risk factors showed good discrimination, accuracy, and clinical utility.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Facile Synthesis of Co Nanoparticles Embedded in N-Doped Carbon Nanotubes/Graphitic Nanosheets as Bifunctional Electrocatalysts for Electrocatalytic Water Splitting.

Developing robust and cost-effective electrocatalysts to boost hydrogen evolution reactions (HERs) and oxygen evolution reactions (OERs) is crucially important to electrocatalytic water splitting. Herein, bifunctional electrocatalysts, by coupling Co nanoparticles and N-doped carbon nanotubes/graphitic nanosheets (Co@NCNTs/NG), were successfully synthesized via facile high-temperature pyrolysis and evaluated for water splitting. The morphology and particle size of products were influenced by the precursor type of the cobalt source (cobalt oxide or cobalt nitrate). The pyrolysis product prepared using cobalt oxide as a cobalt source (Co@NCNTs/NG-1) exhibited the smaller particle size and higher specific surface area than that of the pyrolysis products prepared using cobalt nitrate as a cobalt source (Co@NCNTs/NG-2). Notably, Co@NCNTs/NG-1 displayed much lower potential -0.222 V vs. RHE for HER and 1.547 V vs. RHE for OER at the benchmark current density of 10 mA cm-2 than that of Co@NCNTs/NG-2, which indicates the higher bifunctional catalytic activities of Co@NCNTs/NG-1. The water-splitting device using Co@NCNTs/NG-1 as both an anode and cathode demonstrated a potential of 1.92 V to attain 10 mA cm-2 with outstanding stability for 100 h. This work provides a facile pyrolysis strategy to explore highly efficient and stable bifunctional electrocatalysts for water splitting.

Branched DNA-Based Electrochemical Biosensor for Sensitive Nucleic Acids Analysis with Gold Nanoparticles as Amplifier.

A branched DNA-based electrochemical biosensor was designed to sensitively detect specific nucleic acids. On this platform, novel a branched DNA with three sticky ends could be used as a biosensor to sensitively and specifically detect nucleic acids. Meanwhile, we also employed branched DNA-modified AuNPs as a signal amplifier to further improve the sensitivity. Branched DNA sensors, target DNA, and DNA-modified AuNPs formed a sandwich structure to produce an electronic signal for target DNA detection. The reaction primarily involved DNA hybridization without bulky thermal cyclers and enzymes. We proved that the hybridization reaction easily occurred under different conditions, such as the NaCl concentration, reaction time, pH, and temperature, except for a pH lower than 4. The limit of detection could go as low as 0.09 pM (S/N = 3) with excellent specificity and selectivity. There was a correlation curve relationship between the peak current and the logarithm of the target DNA concentration (0.10 pM to 10 nM). The correlation coefficient reached 0.987. The electrochemical platform enables a branched DNA nanostructure to determine nucleic acids for disease diagnosis.

Mechanical thrombectomy for acute ischemic stroke with large vessel occlusion in pregnancy with mechanical heart valves： A case report.

Background: The management of anticoagulation for mechanical heart valves (MHVs) during pregnancy posed a special challenge. Mechanical thrombectomy (MT) was the standard treatment for acute ischemic stroke (AIS) in anterior circulation with large vessel occlusion. However, the efficacy and safety of MT in the treatment of acute ischemic stroke in pregnancy were unknown. Case presentation: A 29-year-old woman with MHVs in her first pregnancy at 7 weeks' gestation underwent MT because of a large occlusive thrombus in the end of the internal carotid artery despite therapeutic anticoagulation with low-molecular-weight heparin. This pregnant woman recovered well after MT with a modified rank score (mRS) of 0 at 90 days. Conclusion: At present, there was no standard protocol of anticoagulation therapy for pregnant women with MHVs. Acute ischemic stroke with large vessel occlusion in pregnancy was rare, but could bring devastating consequences for both mother and infant. Our case report demonstrated that MT could be safe and effective in pregnancy.

An adult progressive Langerhans cell histiocytosis with central nervous system involvement for 10 years: A case report.

Introduction: Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines and studies mainly focused on pediatric patients. The rarity and also insufficient knowledge of LCH in adults, especially central neuvous system (CNS) involvement of LCH, often resulted in missed and delayed diagnosis. Case presentation: A 35-year-old woman presented with cognitive impairment, anxietydepression, decreased eyesight, skin rash, hypernatremia, gonadal hormone deficiency and hypothyroidism. She had experienced menstrual disturbance and infertility since 10 years ago. MRI examination showed a mass lesion in the hypothalamic-pituitary region. Sighs of radiologic neurodegeneration were not found on brain MRI scans, however. Biopsy of skin rash confirmed the the diagnosis of multisystem LCH. BRAF V600E mutation was detected in the peripheral blood mononuclear cells. She accepted combination chemotherapy of vindesine and prednisone and accquired partial remission. The patient died of severe pneumonia during the second course of chemotherapy. Conclusion: Given the complicated differential diagnoses of neuroendocrine disorders, it was essential to be aware of CNS involvement of LCH at first, especially in adults. BRAF V600E mutation may participated in disease progression.