Background: Electroconvulsive therapy (ECT) endures as a definitive treatment for refractory depression and catatonia and is also considered an effective treatment for a number of other severe psychiatric disorders (Lisanby, N Engl J Med 357:1939-1945, 2007)(Weiner and Prudic, Biol Psychiatry 73:105-106, 2013). GA is an essential component of the ECT procedure for various reasons (Lee, Jenkins and Sparkle, Life 11, 2021). Monitoring anesthetic effects on the brain is desirable as anesthetic agents affect seizure duration and recovery (Rasulo, Hopkins, Lobo, et al, Neurocrit Care 38:296-311, 2023) (Jones , Nittur , Fleming and Applegate, BMC Anesthesiol 21:105, 2021) (Soehle , Kayser , Ellerkmann and Schlaepfer, BJA 112:695-702, 2013).
View Article and Find Full Text PDFInsects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs).
View Article and Find Full Text PDFPharmacological activation of voltage-gated ion channels by ligands serves as the basis for therapy and mainly involves a classic gating mechanism that augments the native voltage-dependent open probability. Through structure-based virtual screening, we identified a new scaffold compound, Ebio1, serving as a potent and subtype-selective activator for the voltage-gated potassium channel KCNQ2 and featuring a new activation mechanism. Single-channel patch-clamp, cryogenic-electron microscopy and molecular dynamic simulations, along with chemical derivatives, reveal that Ebio1 engages the KCNQ2 activation by generating an extended channel gate with a larger conductance at the saturating voltage (+50 mV).
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2023
KCNQ (Kv7) channels are voltage-gated, phosphatidylinositol 4,5-bisphosphate- (PIP-) modulated potassium channels that play essential roles in regulating the activity of neurons and cardiac myocytes. Hundreds of mutations in KCNQ channels are closely related to various cardiac and neurological disorders, such as long QT syndrome, epilepsy, and deafness, which makes KCNQ channels important drug targets. During the past several years, the application of single-particle cryo-electron microscopy (cryo-EM) technique in the structure determination of KCNQ channels has greatly advanced our understanding of their molecular mechanisms.
View Article and Find Full Text PDFThe human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation.
View Article and Find Full Text PDFThe P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive disorder of copper metabolism. Here, we present cryoelectron microscopy (cryo-EM) structures of human ATP7B in the E1 state in the apo, the putative copper-bound, and the putative cisplatin-bound forms.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2022
The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown.
View Article and Find Full Text PDFObjectives: To compare the safety and efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) for such hemangiomas (5-9.9 cm in diameter).
Methods: This multicenter retrospective cohort study investigated the differences in technical success, ablation time, complete ablation, complications, hospital stay, and clinical response between MWA and RFA.
Background: To report the safety and effectiveness of laparoscopic intratumoral resection facilitated by coagulation (LIRC) compared with laparoscopic hepatectomy (LH) in treating giant hepatic hemangioma.
Methods: From 2017 to 2020, 19 consecutive patients with giant hepatic hemangioma (≥ 10 cm) received LIRC in one center. We selected a subgroup of 103 patients treated by LH in other four centers who well matched the 19 consecutive patients treated with LIRC, in a 1:1 fashion based on the tumor location, tumor size, and body mass index.
The photosynthetic bacterial phycobiliprotein lyases, also called CpcT lyases, catalyze the biogenesis of phycobilisome, a light-harvesting antenna complex, through the covalent attachment of chromophores to the antenna proteins. The Arabidopsis CRUMPLED LEAF (CRL) protein is a homolog of the cyanobacterial CpcT lyase. Loss of CRL leads to multiple lesions, including localized foliar cell death, constitutive expression of stress-related nuclear genes, abnormal cell cycle, and impaired plastid division.
View Article and Find Full Text PDFA new concept and solution of architecture of the intelligent POCT network, based on Internet of Things and intelligent POCT devices, is proposed. This network's topology structure and components with basic requirements are introduced. Through the experience of clinical application scenario, the main characteristics of the network and superiority over traditional POCT device have been analyzed.
View Article and Find Full Text PDFWorld J Surg Oncol
October 2016
Background: More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in gastric cancer cell lines and to evaluate the role of CXCR7 in the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells.
View Article and Find Full Text PDFAblative and chronic stimulation procedures targeting the internal pallidum (GPi) and the subthalamic nucleus (STN) have led to major advancements in the treatment of Parkinson's disease and other movement disorders. Although these procedures have evolved to primarily target the posterior ventrolateral sensorimotor portion of GPi and to less selectively target STN, centrally, the ideal targets within these structures remain to be fully established. In this study, we sought to identify the optimal targeting sites in GPi and STN for reversal of parkinsonian signs through a series of reversible injections of the GABA(A) agonist muscimol in these nuclei in parkinsonian primates.
View Article and Find Full Text PDF