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Journal of Colloid and Interface Science Jun 2024Exploring robust electrode materials which could permit fast and reversible insertion/extraction of large K is a crucial challenge for potassium-ion batteries (PIBs)....
Exploring robust electrode materials which could permit fast and reversible insertion/extraction of large K is a crucial challenge for potassium-ion batteries (PIBs). Smart interfacial design could facilitate electron/ion transport as well as assure the integrity of electrode. Herein, Cetyltrimethylammonium bromide (CTAB) was found to play bifunctional roles in construction of NbCT@MoSe heterostructure. Firstly, functionalization of CTAB on the surface of NbCT could influence the subsequent growth of MoSe by electrostatic effect, stereochemical effect and the synergetic Lewis acid-base interaction, leading to the formation of NbCT@MoSe with tiled heterostructure. Secondly, the interlayer spacing of NbCT was expanded from 0.77 to 1.21 nm owing to the pillar effect of CTAB. As excepted, the capacity retention was 80 % from 100 mA g (406 mA h g) to 1000 mA g concerning rate capability and the specific capacity maintained at 240 mA h g (at 2000 mA g) over 300 cycles. The calculated D values from Galvanostatic intermittent titration technique (GITT) measurement of the titled C-T-NbCT@MoSe@C electrode is two orders of magnitude larger than the traditional T-NbCT@MoSe@C electrode, further confirming intimate interface between MoSe and NbCT could provide convenient potassium-ion transport channels and fast diffusion kinetics. Finally, ex-situ characterizations at different charging and discharging voltage stages, including ex-situ XRD/Raman/HRTEM/XPS have been carried out to reveal the potassium storage mechanism. This work provides a facile strategy for the regulation of interface engineering by the assist of CTAB which could extend to other MXenes-TMDs (Transition metal dichalcogenides) hybrid electrodes.
PubMed: 38909591
DOI: 10.1016/j.jcis.2024.06.146 -
Journal of Forensic and Legal Medicine Jun 2024Sudden Cardiac Death (SCD) often shows negative anatomy results after a systemic autopsy and the gene mutations of potassium channel play a key role in the etiology of...
Sudden Cardiac Death (SCD) often shows negative anatomy results after a systemic autopsy and the gene mutations of potassium channel play a key role in the etiology of SCD. We established a feasible system to detect SCD-related mutations and investigated the mutations at KCNQ1 and KCNH2 genes in the Chinese population. We established a mutation detection system combined with multiplex PCR, SNaPshot technique, and capillary electrophoresis. We genotyped 101 putative mutations at KCNQ1 and KCNH2 genes in 60 SCD of negative anatomy and 50 controls using the established assay and compared Odd Ratio (OR). Four coding variants were identified in the KCNQ1 gene: S546S, I145I, P448R, and G643S. The mutations of I145I and S546S did not differ significantly in the SCD compared with controls. 21 SCD individuals (35 %) and 1 control individual (2 %) showed a genotype of C/G at P448R (OR = 17.5, 95 % CI [2.40-127.82]). 24 SCD individuals (40 %) and 1 control individual (2 %) showed a genotype of C/G at G643S (OR = 20.0, 95 % CI [2.75-145.25]). We established a robust assay for rapid screening the putative SCD-related mutations in KCNQ1 and KCNH2 genes. The new assay in our study is easily amenable to the majority of laboratories without the need for new specialized equipment. Our method will meet the increasing requirement of mutation screening for SCD in regular DNA laboratories and will help screen mutations in those dead of SCD and their relatives.
PubMed: 38908219
DOI: 10.1016/j.jflm.2024.102707 -
Pediatric Neurology May 2024Leucine-rich glioma-inactivated protein 1 (LGI-1) encephalitis is a rare form of autoimmune limbic encephalitis. Although relatively well documented in adults, pediatric...
BACKGROUND
Leucine-rich glioma-inactivated protein 1 (LGI-1) encephalitis is a rare form of autoimmune limbic encephalitis. Although relatively well documented in adults, pediatric cases are rare and remain poorly understood.
METHODS
We reviewed two pediatric cases of LGI-1 encephalitis from a single tertiary care facility retrospectively. The detailed analysis included assessment of the initial presentation, clinical progression, diagnostic challenges, treatments, and outcome. To contextualize the differences between pediatric and adult manifestations of disease, we compared these findings with existing literature.
RESULTS
Both cases illustrate the diagnostic challenges faced at initial presentation due to the rarity of this diagnosis in children and the absence of characteristic faciobrachial dystonic seizures, which is common in adults. The constellation of neuropsychiatric symptoms and refractory focal seizures led to a high clinical suspicion for autoimmune encephalitis, therefore, both cases were treated empirically with intravenous methylprednisolone. The diagnosis in both cases was confirmed with positive serum antibody testing, reinforcing that LGI-1 antibodies are more sensitive in the serum rather than the cerebrospinal fluid (CSF). Seizure control and improvement in cognitive symptoms was achieved through a combination of immunotherapy and antiseizure medications.
CONCLUSIONS
This case series underscores the significance of considering LGI-1 encephalitis in the differential diagnosis of pediatric patients exhibiting unexplained neuropsychiatric symptoms and focal seizures and emphasizes the importance of performing both serum and CSF antibody testing. It is necessary to conduct further research to identify the full range of pediatric presentations and to determine the optimal treatment protocol.
PubMed: 38905745
DOI: 10.1016/j.pediatrneurol.2024.04.031 -
PLoS Biology Jun 2024Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily...
Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.
Topics: Humans; Breast Neoplasms; Female; Cell Proliferation; Animals; Cell Line, Tumor; Histones; Mice; Gene Expression Regulation, Neoplastic; Up-Regulation; Neoplasm Metastasis; Potassium Channels, Tandem Pore Domain; Lactate Dehydrogenase 5; Mice, Nude; Neoplasm Invasiveness; Glycolysis; L-Lactate Dehydrogenase; Mice, Inbred BALB C; Prognosis; Cell Movement
PubMed: 38905316
DOI: 10.1371/journal.pbio.3002666 -
Journal of the American Heart... Jul 2024The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We...
BACKGROUND
The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration.
METHODS AND RESULTS
C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca activated K BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes.
CONCLUSIONS
Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.
Topics: Animals; Mice, Inbred C57BL; Pravastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Oxidative Stress; Time Factors; Vasoconstriction; Vasodilation; Male; NADPH Oxidase 2; Tumor Necrosis Factor-alpha; Transcription Factor RelA; NADPH Oxidases; Mice; Radiation Injuries, Experimental; Drug Administration Schedule; Carotid Arteries; Chronic Disease; Disease Models, Animal; NADPH Oxidase 4
PubMed: 38904226
DOI: 10.1161/JAHA.123.033558 -
Frontiers in Physiology 2024Ion channels play a pivotal role in regulating cellular excitability and signal transduction processes. Among the various ion channels, G-protein-coupled inwardly... (Review)
Review
Ion channels play a pivotal role in regulating cellular excitability and signal transduction processes. Among the various ion channels, G-protein-coupled inwardly rectifying potassium (GIRK) channels serve as key mediators of neurotransmission and cellular responses to extracellular signals. GIRK channels are members of the larger family of inwardly-rectifying potassium (Kir) channels. Typically, GIRK channels are activated via the direct binding of G-protein βγ subunits upon the activation of G-protein-coupled receptors (GPCRs). GIRK channel activation requires the presence of the lipid signaling molecule, phosphatidylinositol 4,5-bisphosphate (PIP). GIRK channels are also modulated by endogenous proteins and other molecules, including RGS proteins, cholesterol, and SNX27 as well as exogenous compounds, such as alcohol. In the last decade or so, several groups have developed novel drugs and small molecules, such as ML297, GAT1508 and GiGA1, that activate GIRK channels in a G-protein independent manner. Here, we aim to provide a comprehensive overview focusing on the direct modulation of GIRK channels by G-proteins, PIP, cholesterol, and novel modulatory compounds. These studies offer valuable insights into the underlying molecular mechanisms of channel function, and have potential implications for both basic research and therapeutic development.
PubMed: 38903913
DOI: 10.3389/fphys.2024.1386645 -
European Journal of Medical Research Jun 2024
PubMed: 38902786
DOI: 10.1186/s40001-024-01905-5 -
Nature Communications Jun 2024DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA...
DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na and K across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.
Topics: Humans; Peptidomimetics; DNA; G-Quadruplexes; Potassium; Cell Line, Tumor; Sodium; Cell Nucleus; Ion Channels; DNA-Binding Proteins
PubMed: 38902227
DOI: 10.1038/s41467-024-49534-0 -
Microvascular Research Jun 2024Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular...
Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I. HO enhanced I and ET-1 production. Enhancing I caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.
PubMed: 38901735
DOI: 10.1016/j.mvr.2024.104699 -
Translational Vision Science &... Jun 2024To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
PURPOSE
To compare gene expression changes following branch retinal vein occlusion (BRVO) in the pig with and without bevacizumab (BEV) and triamcinolone acetonide (TA).
METHODS
Photothrombotic BRVOs were created in both eyes of four groups of nine pigs (2, 6, 10, and 20 days). In each group, six pigs received intravitreal injections of BEV in one eye and TA in the fellow eye, with three pigs serving as untreated BRVO controls. Three untreated pigs served as healthy controls. Expression of mRNA of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), dystrophin (DMD), potassium inwardly rectifying channel subfamily J member 10 protein (Kir4.1, KCNJ10), aquaporin-4 (AQP4), stromal cell-derived factor-1α (CXCL12), interleukin-6 (IL6), interleukin-8 (IL8), monocyte chemoattractant protein-1 (CCL2), intercellular adhesion molecule 1 (ICAM1), and heat shock factor 1 (HSF1) were analyzed by quantitative reverse-transcription polymerase chain reaction. Retinal VEGF protein levels were characterized by immunohistochemistry.
RESULTS
In untreated eyes, BRVO significantly increased expression of GFAP, IL8, CCL2, ICAM1, HSF1, and AQP4. Expression of VEGF, KCNJ10, and CXCL12 was significantly reduced by 6 days post-BRVO, with expression recovering to healthy control levels by day 20. Treatment with BEV or TA significantly increased VEGF, DMD, and IL6 expression compared with untreated BRVO eyes and suppressed BRVO-induced CCL2 and AQP4 upregulation, as well as recovery of KCNJ10 expression, at 10 to 20 days post-BRVO.
CONCLUSIONS
Inflammation and cellular osmohomeostasis rather than VEGF suppression appear to play important roles in BRVO-induced retinal neurodegeneration, enhanced in both BEV- and TA-treated retinas.
TRANSLATIONAL RELEVANCE
Inner retinal neurodegeneration seen in this acute model of BRVO appears to be mediated by inflammation and alterations in osmohomeostasis rather than VEGF inhibition, which may have implications for more specific treatment modalities in the acute phase of BRVO.
Topics: Animals; Bevacizumab; Triamcinolone Acetonide; Retinal Vein Occlusion; Disease Models, Animal; Angiogenesis Inhibitors; Cytokines; Intravitreal Injections; Swine; Vascular Endothelial Growth Factor A; RNA, Messenger; Glucocorticoids; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Potassium Channels, Inwardly Rectifying
PubMed: 38899953
DOI: 10.1167/tvst.13.6.13