Light and gas dual-function detection and mutual enhancement based on hyperdoped black silicon.

We introduce a unique dual-function detector with an asymmetric light illumination based on the black silicon co-hyperdoped with sulfur and nitrogen for light and gas detection, and the properties in NO2 gas sensing and photoelectric detection are studied under various light and gas environments, respectively. Enhanced performance of the device under certain light and gas conditions is observed. When illuminated at the optimal wavelength, the gas sensors' responsivity to NO2 can be enhanced by approximately 5 to 200 times over 730 nm illumination, respectively. The photodetectors' photoresponsivity increases 15 to 200 times in a 300 ppm NO2 gas environment compared to air. Such mutual enhancement achieved through the clever combination of light and gas implies a novel approach to improve the performance of the black silicon detectors in both gas sensing and photoelectric detection.

Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.

BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs. METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts. RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo . CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.

Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.

Perineal ultrasound to assess the urethral spatial movement in stress urinary incontinence in women.

BACKGROUND: Perineal ultrasound as a non-invasive method for the diagnosis of female stress urinary incontinence has attracted more and more attention. However, the criteria for stress urinary incontinence in women using perineal ultrasound have not been fully established. Our study aimed to evaluate characteristics of the urethral spatial movement with perineal ultrasonography. METHODS: A total of 136 female patients with stress urinary incontinence and 44 controls were enrolled. Stress urinary incontinence was diagnosed using the International Consultation on Incontinence Questionnaire Short Form, medical history and physical examination, and severity was assessed using a 1 h pad test. We described the mobility of four equidistant points (A-D) located along the urethra length. The retrovesical and urethral rotation angles were measured using perineal ultrasonography at rest and during the maximal Valsalva maneuver. RESULTS: Patients with stress urinary incontinence showed a more significant vertical movement at Points A, B and C than controls. The mean variations in the retrovesical angle were significantly larger in patients with stress urinary incontinence at rest and during the Valsalva maneuver than in controls (21.0 ± 16.5° vs. 14.7 ± 20.1°, respectively). The cut-off value for the retrovesical angle variation was 10.7° with 72% sensitivity and 54% specificity. There was a receiver-operating characteristic curve area of 0.73 and 0.72 for Points A and B, respectively. A cut-off of 10.8 mm, and 9.4 mm provided 71% sensitivity and 68% specificity and 67% sensitivity and 75% specificity, respectively. CONCLUSIONS: The spatial movement of the bladder neck and proximal urethra, and variations in the retrovesical angle may be correlated with clinical symptoms and facilitate to the assessment of SUI.

Biocytin-Labeling in Whole-Cell Recording: Electrophysiological and Morphological Properties of Pyramidal Neurons in CYLD-Deficient Mice.

Biocytin, a chemical compound that is an amide formed from the vitamin biotin and the amino acid L-lysine, has been used as a histological dye to stain nerve cells. Electrophysiological activity and morphology are two key characteristics of neurons, but revealing both the electrophysiological and morphological properties of the same neuron is challenging. This article introduces a detailed and easy-to-operate procedure for single-cell labeling in combination with whole-cell patch-clamp recording. Using a recording electrode filled with a biocytin-containing internal solution, we demonstrate the electrophysiological and morphological characteristics of pyramidal (PNs), medial spiny (MSNs) and parvalbumin neurons (PVs) in brain slices, where the electrophysiological and morphological properties of the same individual cell are elucidated. We first introduce a protocol for whole-cell patch-clamp recording in various neurons, coupled with the intracellular diffusion of biocytin delivered by the glass capillary of the recording electrode, followed by a post hoc procedure to reveal the architecture and morphology of biocytin-labeled neurons. An analysis of action potentials (APs) and neuronal morphology, including the dendritic length, number of intersections, and spine density of biocytin-labeled neurons, were performed using ClampFit and Fiji Image (ImageJ), respectively. Next, to take advantage of the techniques introduced above, we uncovered defects in the APs and the dendritic spines of PNs in the primary motor cortex (M1) of deubiquitinase cylindromatosis (CYLD) knock-out (Cyld-/-) mice. In summary, this article provides a detailed methodology for revealing the morphology as well as the electrophysiological activity of a single neuron that will have many applications in neurobiology.

Two-Electron Redox Chemistry Enabled High-Performance Iodide-Ion Conversion Battery.

A single-electron transfer mode coupled with the shuttle behavior of organic iodine batteries results in insufficient capacity, a low redox potential, and poor cycle durability. Sluggish kinetics are well known in conventional lithium-iodine (Li-I) batteries, inferior to other conversion congeners. Herein, we demonstrate new two-electron redox chemistry of I- /I+ with inter-halogen cooperation based on a developed haloid cathode. The new iodide-ion conversion battery exhibits a state-of-art capacity of 408 mAh gI-1 with fast redox kinetics and superior cycle stability. Equipped with a newly emerged 3.42 V discharge voltage plateau, a recorded high energy density of 1324 Wh kgI-1 is achieved. Such robust redox chemistry is temperature-insensitive and operates efficiently at -30 °C. With systematic theoretical calculations and experimental characterizations, the formation of Cl-I+ species and their functions are clarified.

Metal-Tuned Acetylene Linkages in Hydrogen Substituted Graphdiyne Boosting the Electrochemical Oxygen Reduction.

Different from graphene with the highly stable sp2 -hybridized carbon atoms, which shows poor controllability for constructing strong interactions between graphene and guest metal, graphdiyne has a great potential to be engineered because its high-reactive acetylene linkages can effectively chelate metal atoms. Herein, a hydrogen-substituted graphdiyne (HsGDY) supported metal catalyst system through in situ growth of Cu3 Pd nanoalloys on HsGDY surface is developed. Benefiting from the strong metal-chelating ability of acetylenic linkages, Cu3 Pd nanoalloys are intimately anchored on HsGDY surface that accordingly creates a strong interaction. The optimal HsGDY-supported Cu3 Pd catalyst (HsGDY/Cu3 Pd-750) exhibits outstanding electrocatalytic activity for the oxygen reduction reaction (ORR) with an admirable half-wave potential (0.870 V), an impressive kinetic current density at 0.75 V (57.7 mA cm-2 ) and long-term stability, far outperforming those of the state-of-the-art Pt/C catalyst (0.859 V and 15.8 mA cm-2 ). This excellent performance is further highlighted by the Zn-air battery using HsGDY/Cu3 Pd-750 as cathode. Density function theory calculations show that such electrocatalytic performance is attributed to the strong interaction between Cu3 Pd and CC bonds of HsGDY, which causes the asymmetric electron distribution on two carbon atoms of CC bond and the strong charge transfer to weaken the shoulder-to-shoulder π conjugation, eventually facilitating the ORR process.

Early versus delayed postoperative oral hydration in children following general anesthesia: a prospective randomized trial.

BACKGROUND: Oral hydration has typically not been administered for between 4 and 6 h postoperative for children's safety in China. But children are more likely to suffer from apnea, crying and agitation, wound bleeding, and other complications during the post-anesthesia recovery period because of thirsty and fear. This Prospective, randomized study sought to assess the compare the early and late oral hydration (EOH and DOH, respectively) in children following general anesthesia, with the goal of assessing relative safety and tolerability and thereby improving patient comfort. METHODS: A total of 2000 children corresponding to the American Society of Anesthesiology (ASA) I-III were randomized into an EOH group (n = 1000) and a DOH group (n = 1000). For the former group, children were administered a small amount of drinking water following recovery of the swallowing reflex, and children's vital signs were monitored for 20 min in a postanesthesia care unit (PACU). DOH group patients received water at 4 h following general anesthesia). All patients underwent monitoring to assess their thirst, satisfaction, oropharyngeal discomfort, nausea, and vomiting. RESULTS: Complete data were collected from a total of 1770 patients (EOH = 832, DOH = 938) and was compared via chi-squared and t-tests as appropriate. There was no hypoxemia in either group, nor did the incidence of nausea and vomiting differ between the two groups (P > 0.05). The thirst score of the EOH group was significantly decreased relative to the DOH group in the children over 5 years old after drinking for 10 to 20 min (P < 0.05). CONCLUSIONS: For children undergoing general anesthesia, a small amount of drinking water in the early stages of recovery will not increase the incidence of nausea, vomiting, or hypoxemia, but will decrease thirst and improve satisfaction. It is important, however, that medical staff carefully monitor the swallowing reflex and vital signs of all children. TRIAL REGISTRATION: This study was registered on the Chinese Clinical Trial Registry (ChiCTR-IOR-16008197) (http://www.chictr.org.cn/index.aspx. On April 2, 2016 the first patients was enrolled and on March 31, 2016 the trial was registered).

[Discovery and functional analysis of a novel ISL1 variant associated with congenital heart defect].

OBJECTIVE: To analyze variation of ISL1 gene and explore its functional characteristics in relation with congenital heart defect (CHD). METHODS: Clinical data and peripheral blood samples of 194 CHD patients and 232 healthy controls were collected for the extraction of genomic DNA. The coding exons and flanking intronic regions of the ISL1 gene were sequenced. Expression plasmid for the wild-type ISL1 gene ISL1-pcDNA3.1 was constructed, and the corresponding variants were obtained by site-specific mutagenesis. The gene expression plasmid was transfected into CHO cells with liposome, and the functional characteristics of ISL1 variant were studied by double luciferase reporter gene analysis. RESULTS: A novel variant of the ISL1 gene c.499C>T (p.Q167X) was detected in a patient with sporadic CHD. Functional study showed that the variant has lost its transcriptional activation function for the MEF2C promoter. CONCLUSION: A novel variant of the ISL1 gene related to CHD has been identified. The defect of ISL1 gene may underlay the pathogenesis for a proportion of CHD.

Liquid-Free All-Solid-State Zinc Batteries and Encapsulation-Free Flexible Batteries Enabled by In†Situ Constructed Polymer Electrolyte.

Zn batteries are usually considered as safe aqueous systems that are promising for flexible batteries. On the other hand, any liquids, including water, being encapsulated in a deformable battery may result in problems. Developing completely liquid-free all-solid-state Zn batteries needs high-quality solid-state electrolytes (SSEs). Herein, we demonstrate in situ polymerized amorphous solid poly(1,3-dioxolane) electrolytes, which show high Zn ion conductivity of 19.6 mS cm-1 at room temperature, low interfacial impedance, highly reversible Zn plating/stripping over 1800 h cycles, uniform and dendrite-free Zn deposition, and non-dry properties. The in-plane interdigital-structure device with the electrolyte completely exposed to the open atmosphere can be operated stably for over 30 days almost without weight loss or electrochemical performance decay. Furthermore, the sandwich-structure device can normally operate over 40 min under exposure to fire. Meanwhile, the interfacial impedance and the capacity using in situ-formed solid polymer electrolytes (SPEs) remain almost unchanged after various bending tests, a key criterion for flexible/wearable devices. Our study demonstrates an approach for SSEs that fulfill the requirement of no liquid and mechanical robustness for practical solid-state Zn batteries.

Dark Matter Results from 54-Ton-Day Exposure of PandaX-II Experiment.

We report a new search for weakly interacting massive particles (WIMPs) using the combined low background data sets acquired in 2016 and 2017 from the PandaX-II experiment in China. The latest data set contains a new exposure of 77.1 live days, with the background reduced to a level of 0.8×10^{-3} evt/kg/day, improved by a factor of 2.5 in comparison to the previous run in 2016. No excess events are found above the expected background. With a total exposure of 5.4×10^{4} kg day, the most stringent upper limit on the spin-independent WIMP-nucleon cross section is set for a WIMP with mass larger than 100 GeV/c^{2}, with the lowest 90% C.L. exclusion at 8.6×10^{-47} cm^{2} at 40 GeV/c^{2}.

Theoretical study on lithium storage performance of V-doped Ti2CO2 MXene.

With the increasing application of lithium-ion batteries, the demand for high energy density, high-rate performance and high stability lithium-ion batteries is becoming more and more urgent. Ti2CO2 MXene, as a two-dimensional material with multilayer atomic structure and multiple active sites, has great advantages in lithium-ion battery electrode materials. However, the original Ti2CO2 MXene has been unable to meet the requirements of lithium-ion batteries due to its semiconductor properties. Doping is an effective means to regulate the conductivity and electrochemical properties of Ti2CO2 and improve the capacity of lithium-ion batteries and other energy storage devices. Hence, we use first-principles calculations to study the effect of V atom doping on the adsorption and diffusion of Li on the MXene surface. The density of states (DOS) and partial density of states (PDOS) of TiVCO2 and Ti2CO2 MXene indicated the transition of their conductive types from semiconductors to conductors. In addition, we observed that TiVCO2 has higher electrical conductivity and ion transport speed than the original Ti2CO2 MXene, and at the same time, Li atoms can be adsorbed well on the surface of MXene and show a lower diffusion energy barrier. Therefore, TiVCO2 is expected to become the anode material for the next generation of lithium-ion batteries and has good lithium storage performance.

Discovery of BMP10 as a new gene underpinning congenital heart defects.

OBJECTIVE: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, BMP10 was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in Bmp10-knockout animals. The objective of this retrospective study was to identify a new BMP10 mutation responsible for CHD and characterize the functional effect of the identified CHD-causing BMP10 mutation. METHODS: Sequencing assay of BMP10 was fulfilled in a cohort of 276 probands with various CHD and a total of 288 non-CHD volunteers. The available family members from the proband harboring an identified BMP10 mutation were also BMP10-genotyped. The effect of the identified CHD-causative BMP10 mutation on the transactivation of TBX20 and NKX2.5 by BMP10 was quantitatively analyzed in maintained HeLa cells utilizing a dual-luciferase reporter assay system. RESULTS: A novel heterozygous BMP10 mutation, NM_014482.3:c.247G>T;p.(Glu83*), was identified in one proband with patent ductus arteriosus (PDA), which was confirmed to co-segregate with the PDA phenotype in the mutation carrier's family. The nonsense mutation was not observed in 288 non-CHD volunteers. Functional analysis unveiled that Glu83*-mutant BMP10 had no transactivation on its two representative target genes TBX20 and NKX2.5, which were both reported to cause CHD. CONCLUSION: These findings provide strong evidence indicating that genetically compromised BMP10 predisposes human beings to CHD, which sheds light on the new molecular mechanism that underlies CHD and allows for antenatal genetic counseling and individualized precise management of CHD.

MXene/graphene oxide heterojunction as a high performance anode material for lithium ion batteries.

MXene/graphene oxide composites with strong interfacial interactions were constructed by ball milling in vacuum. Graphene oxide (GO) acted as a bridge between Ti3C2Tx nanosheets in the composite material, which could buffer the mechanical shear force during the ball milling process, avoid the structural damage of nanosheets and improve the structural stability of the composite material during the lithium process. Partial oxidation of Ti3C2Tx nanosheets is caused by high temperatures during ball milling, which is beneficial to improve the intercalation of lithium ions in the material, reduce the stress and electrostatic repulsion between adjacent layers, and cause the composite to have better lithium storage performance. Under the high current density of 2.5 A g-1, the reversible capacity of the Ti3C2Tx/GO composite material after 2000 cycles was 116.5 mA h g-1, and the capacity retention was as high as 116.6%.

The Study of Crystallization Behavior, Microcellular Structure and Thermal Properties of Glass-Fiber/Polycarbonate Composites.

Polycarbonate (PC) foam is a versatile material with excellent properties, but its low thermal stability limits its application in high-temperature environments. The aim of this study was to improve the thermal stability of PC foam by adding glass fibers (GF) and to investigate the effect of GF on PC crystallization behavior and PC foam cell morphology. This study was motivated by the need to improve the performance of PC foams in various industries, such as construction, automotive, and medical. To achieve this goal, PC/GF composites were prepared by extrusion, and PC/GF composite foams were produced using a batch foaming process with supercritical carbon dioxide (SC-CO2) as the blowing agent. The results showed that the addition of GF accelerated the SC-CO2-induced crystallization stability of PC and significantly increased the cell density to 4.6 cells/cm3. In addition, the thermal stability of PC/GF foam was improved, with a significant increase in the residual carbon rate at 700 °C and a lower weight loss rate than PC matrix. Overall, this study highlights the potential of GF as a PC foam reinforcement and its effect on thermal and structural properties, providing guidance for industrial production and applications.

The Study on the Morphology and Compression Properties of Microcellular TPU/Nanoclay Tissue Scaffolds for Potential Tissue Engineering Applications.

Thermoplastic polyurethane (TPU) materials have shown promise in tissue engineering applications due to their mechanical properties and biocompatibility. However, the addition of nanoclays to TPU can further enhance its properties. In this study, the effects of nanoclays on the microstructure, mechanical behavior, cytocompatibility, and proliferation of TPU/nanoclay (TPUNC) composite scaffolds were comprehensively investigated. The dispersion morphology of nanoclays within the TPU matrix was examined using transmission electron microscopy (TEM). It was found that the nanoclays exhibited a well-dispersed and intercalated structure, which contributed to the improved mechanical properties of the TPUNC scaffolds. Mechanical testing revealed that the addition of nanoclays significantly enhanced the compressive strength and elastic resilience of the TPUNC scaffolds. Cell viability and proliferation assays were conducted using MG63 cells cultured on the TPUNC scaffolds. The incorporation of nanoclays did not adversely affect cell viability, as evidenced by the comparable cell numbers between nanoclay-filled and unfilled TPU scaffolds. The presence of nanoclays within the TPUNC scaffolds did not disrupt cell adhesion or proliferation. The incorporation of nanoclays improved the dispersion morphology, enhanced mechanical performance, and maintained excellent biocompatibility. These findings suggest that TPUNC composites have great potential for tissue engineering applications, providing a versatile and promising scaffold material for regenerative medicine.

Electrochemical Synthesis of Functionalized Graphene/Polyaniline Composite Using Two Electrode Configuration for Supercapacitors.

An effective approach for the large-scale fabrication of conducting polyaniline (PANI) using in situ anodic electrochemical polymerization on nickel foam which had been coated in aryl diazonium salt (ADS)-modified graphene (ADS-G). In the present work, ADS-G was used as a high surface-area support material for the electrochemical polymerization of PANI. The electrochemical performances of the ADS-G/PANI composites exhibited better suitability as supercapacitor electrode materials than those of the PANI. The ADS-G/PANI composites achieved a specific capacitance of 528 F g-1, which was higher than that of PANI (266 F g-1) due to excellent electrode-electrolyte interaction and the synergistic effect of electrical conductivity between ADS-G and PANI in the composites. These findings suggest that the ADS-G/PANI composites are a suitable composite for potential supercapacitor applications.

Distinct chemistry between Zn and Li at varied temperature.

The operating temperature of batteries is an essential consideration in actual applications. Understanding the temperature dependence is conducive to battery design. The experience in lithium-ion batteries (LIBs) indicates that the dendrite issue is exacerbated at lower temperatures and suppressed at higher temperatures. In this study, we revealed the dendrite evolution in aqueous rechargeable zinc-based batteries (RZBs), for which the opposite temperature dependence was observed. Detailed investigations elucidate that the degree of matching of the interface reaction rate and ion diffusivity, together with side reactions, are the key factors that determine the cycling performance. The different properties of organic and aqueous electrolytes result in a reversed temperature dependence. We further conducted a detailed investigation of hybrid electrolytes (organic and aqueous) for balancing the ion diffusivity and side reactions to broaden the working temperature window for RZBs. This work reveals a completely opposite temperature dependence for LIBs and RZBs and discloses the underlying mechanism, reminding one of the differences between LIBs and RZBs in many aspects.

A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1.1.

BACKGROUND: Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown. RESULTS: We identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1W183R in excitatory neurons lacking natural LGI1, and found that this mutation downregulated Kv1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring Kv1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice. CONCLUSIONS: These results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy.

Electro-mechanical coupling directs endothelial activities through intracellular calcium ion deployment.

Conversion between mechanical and electrical cues is usually considered unidirectional in cells with cardiomyocytes being an exception. Here, we discover a material-induced external electric field (Eex) triggers an electro-mechanical coupling feedback loop in cells other than cardiomyocytes, human umbilical vein endothelial cells (HUVECs), by opening their mechanosensitive Piezo1 channels. When HUVECs are cultured on patterned piezoelectric materials, the materials generate Eex (confined at the cellular scale) to polarize intracellular calcium ions ([Ca2+]i), forming a built-in electric field (Ein) opposing Eex. Furthermore, the [Ca2+]i polarization stimulates HUVECs to shrink their cytoskeletons, activating Piezo1 channels to induce influx of extracellular Ca2+ that gradually increases Ein to balance Eex. Such an electro-mechanical coupling feedback loop directs pre-angiogenic activities such as alignment, elongation, and migration of HUVECs. Activated calcium dynamics during the coupling further modulate the downstream angiogenesis-inducing eNOS/NO pathway. These findings lay a foundation for developing new ways of electrical stimulation-based disease treatment.