Imbalance between the function of Na+-K+-2Cl and K+-Cl impairs Cl- homeostasis in human focal cortical dysplasia.

Objective: Altered expression patterns of Na+-K+-2Cl- (NKCC1) and K+-Cl- (KCC2) co-transporters have been implicated in the pathogenesis of epilepsy. Here, we assessed the effects of imbalanced NKCC1 and KCC2 on γ-aminobutyric acidergic (GABAergic) neurotransmission in certain brain regions involved in human focal cortical dysplasia (FCD). Materials and methods: We sought to map a micro-macro neuronal network to better understand the epileptogenesis mechanism. In patients with FCD, we resected cortical tissue from the seizure the onset zone (SOZ) and the non-seizure onset zone (non-SOZ) inside the epileptogenic zone (EZ). Additionally, we resected non-epileptic neocortical tissue from the patients with mesial temporal lobe epilepsy (MTLE) as control. All of tissues were analyzed using perforated patch recordings. NKCC1 and KCC2 co-transporters expression and distribution were analyzed by immunohistochemistry and western blotting. Results: Results revealed that depolarized GABAergic signals were observed in pyramidal neurons in the SOZ and non-SOZ groups compared with the control group. The total number of pyramidal neurons showing GABAergic spontaneous postsynaptic currents was 11/14, 7/17, and 0/12 in the SOZ, non-SOZ, and control groups, respectively. The depolarizing GABAergic response was significantly dampened by the specific NKCC1 inhibitor bumetanide (BUM). Patients with FCD exhibited higher expression and internalized distribution of KCC2, particularly in the SOZ group. Conclusion: Our results provide evidence of a potential neurocircuit underpinning SOZ epileptogenesis and non-SOZ seizure susceptibility. Imbalanced function of NKCC1 and KCC2 may affect chloride ion homeostasis in neurons and alter GABAergic inhibitory action, thereby contributing to epileptogenesis in FCDs. Maintaining chloride ion homeostasis in the neurons may represent a new avenue for the development of novel anti-seizure medications (ASMs).

Mechanistic Analysis of Micro-Neurocircuits Underlying the Epileptogenic Zone in Focal Cortical Dysplasia Patients.

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro-macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

OBJECTIVE: We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. METHODS: Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2 weeks of treatment. RESULTS: After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. SIGNIFICANCE: Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

lncRNA AK054386 Functions as a ceRNA to Sequester miR-199 and Induce Sustained Endoplasmic Reticulum Stress in Hepatic Reperfusion Injury.

Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a "competing endogenous RNA (ceRNA)" and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

High-Efficiency Perovskite Light-Emitting Diodes with Synergetic Outcoupling Enhancement.

Perovskite light-emitting diodes (PeLEDs) show great application potential in high-quality flat-panel displays and solid-state lighting due to their steadily improved efficiency, tunable colors, narrow emission peak, and easy solution-processing capability. However, because of high optical confinement and nonradiative charge recombination during electron-photon conversion, the highest reported efficiency of PeLEDs remains far behind that of their conventional counterparts, such as inorganic LEDs, organic LEDs, and quantum-dot LEDs. Here a facile route is demonstrated by adopting bioinspired moth-eye nanostructures at the front electrode/perovskite interface to enhance the outcoupling efficiency of waveguided light in PeLEDs. As a result, the maximum external quantum efficiency and current efficiency of the modified cesium lead bromide (CsPbBr3 ) green-emitting PeLEDs are improved to 20.3% and 61.9 cd A-1 , while retaining spectral and angular independence. Further reducing light loss in the substrate mode using a half-ball lens, efficiencies of 28.2% and 88.7 cd A-1 are achieved, which represent the highest values reported to date for PeLEDs. These results represent a substantial step toward achieving practical applications of PeLEDs.

Repression of let-7a cluster prevents adhesion of colorectal cancer cells by enforcing a mesenchymal phenotype in presence of liver inflammation.

The liver is the most common site of metastasis in patients with colorectal cancer, and colorectal cancer liver metastasis (CRLM) is associated with poor rates of survival. However, CRLM occurs infrequently in livers exhibiting signs of hepatitis or cirrhosis, suggesting a role for inflammation in attenuating CRLM. The molecular mechanisms driving this phenomenon remain unclear. The aim of this study was to confirm the mechanism by which liver inflammation inhibits CRLM. We used BALB/c animal models of inflammatory liver diseases to confirm that liver inflammation inhibits CRLM, and then elucidated the molecular mechanisms governing that process. Out data showed that liver inflammation induces IFN-γ expression, which then downregulates expression of the let-7a cluster through IRF-1 in colorectal cancer cells. Finally, we showed that modulation of let-7a expression regulated the epithelial-mesenchymal transition in colorectal cancer cell lines, and inhibited their capacity to metastasize in vivo. Cumulatively, we clarified the critical role played by the IFN-γ/IRF-1/let-7a cluster/EMT pathway in regulating the spread of circulating colorectal cancer cells to the liver, and highlighted the critical role that the hepatitis microenvironment plays in modulating that process.