Interfacial Dehydration Strategy for Chitosan Film Shape Morphing and Its Application.

Shape morphing of biopolymer materials, such as chitosan (CS) films, has great potential for applications in many fields. Traditionally, their responsive behavior has been induced by the differential water swelling through the preparation of multicomponent composites or cross-linking as deformation is not controllable in the absence of these processes. Here, we report an interfacial dehydration strategy to trigger the shape morphing of the monocomponent CS film without cross-linking. The release of water molecules is achieved by spraying the surface with a NaOH solution or organic solvents, which results in the interfacial shrinkage and deformation of the entire film. On the basis of this strategy, a range of CS actuators were developed, such as soft grippers, joint actuators, and a light switch. Combined with the geometry effect, edited deformation was also achieved from the planar CS film. This shape-morphing strategy is expected to enable the application of more biopolymers in a wide range of fields.

Ultra-Low Loading of Ultra-Small Fe3 O4 Nanoparticles on Nonmodified CNTs to Improve Green EMI Shielding Capability of Rubber Composites.

From a material design perspective, the incorporation of Fe3 O4 @carbon nanotube (Fe3 O4 @CNT) hybrids is an effective approach for reconciling the contradictions of high shielding and low reflection coefficients, enabling the fabrication of green shielding materials and reducing the secondary electromagnetic wave pollution. However, the installation of Fe3 O4 nanoparticles on nonmodified and nondestructive CNT walls remains a formidable challenge. Herein, a novel strategy for fabricating the above-mentioned Fe3 O4 @CNTs and subsequently assembling segregated Fe3 O4 @CNT networks in natural rubber (NR) matrices is proposed. The advanced and unique structure, magnetism, and lossless conductivity endow the as-obtained Fe3 O4 @CNT/NR with a shielding effectiveness (SE) of 63.8 dB and a low reflection coefficient of 0.24, which indicates a prominent green-shielding capability that surpasses those of previously reported green-shielding materials. Moreover, the specific SE reaches 531 dB cm-1 , exceeding that of those of previously reported carbon/polymer composites. Meanwhile, the outstanding conductivity enables the composite to reach a saturation temperature of ≈95 °C at a driving voltage of 1.5 V with long-term stability. Therefore, the as-fabricated Fe3 O4 @CNT/rubber composites represent an important development in green-shielding materials that are applied in cold environment.

Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex.

The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.

Discriminative neural pathways for perception-cognition activity of color and face in the human brain.

Human performance can be examined using a visual lens. The identification of psychophysical colors and emotional faces with perceptual visual pathways may remain invalid for simple detection tasks. In particular, how the visual dorsal and ventral processing streams handle discriminative visual perceptions and subsequent cognition activities are obscure. We explored these issues using stereoelectroencephalography recordings, which were obtained from patients with pharmacologically resistant epilepsy. Delayed match-to-sample paradigms were used for analyzing the processing of simple colors and complex emotional faces in the human brain. We showed that the angular-cuneus gyrus acts as a pioneer in discriminating the 2 features, and dorsal regions, including the middle frontal gyrus (MFG) and postcentral gyrus, as well as ventral regions, such as the middle temporal gyrus (MTG) and posterior superior temporal sulcus (pSTS), were involved in processing incongruent colors and faces. Critically, the beta and gamma band activities between the cuneus and MTG and between the cuneus and pSTS would tune a separate pathway of incongruency processing. In addition, posterior insular gyrus, fusiform, and MFG were found for attentional modulation of the 2 features via alpha band activities. These findings suggest the neural basis of the discriminative pathways of perception-cognition activities in the human brain.

Probiotic-derived amphiphilic exopolysaccharide self-assembling adjuvant delivery platform for enhancing immune responses.

Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

A novel UPLC-ESI-MS assay for fifteen portal estrogens and metabolites detection and application in hepatic fibrosis.

Estrogens and their metabolites (EMs) are involved in chronic liver disease and gut microbiota regulates estrogen metabolism, whereas the role of enterogenous EMs in liver disease is still elusive. Because of the extremely low level of EMs in portal serum and the EMs contain multiple pairs of isomers, an accurate determination of portal serum EMs is urgently needed. This study established a quantitative detection method for portal serum EMs and applied to non-alcoholic fatty liver disease (NAFLD) related hepatic fibrosis mice model. The serum was derived with a novel derivatization reagent 4-acetyl aminobenzene sulfonyl chloride, and a UPLC-ESI-MS system was used for quantification of 15 EMs in 120 min. Compared with normal group, the concentrations of E1, E2 in model group were significantly decreased by 4-8 times, all the C2 and C4 substitution products (2-OHE1, 2-OHE2, 2-MeOE1, 4-OHE1, 4-MeOE1, 4-OHE2, 4-MeOE2, 2-MeOE2) were significantly decreased by 2-22 times. However, the C16 and C17 substitution products (E3, 16-epiE3, 17-epiE3, 16-ketoE2) levels were increased by 3-5 times (P < 0.01). This study elucidated the changes of enterogenous EMs which entered the liver via portal vein in NAFLD - related hepatic fibrosis and provided methodological platform for other related studies on estrogen metabolism.

EEG complexity correlates with residual consciousness level of disorders of consciousness.

BACKGROUND AND OBJECTIVE: Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. METHODS: Resting-state EEG was recorded from twenty-five patients with DOC. Lempel-Ziv complexity (LZC) and permutation Lempel-Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. RESULTS: PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. CONCLUSION: Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

[Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids].

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11ß-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Real-time effects of Cd(II) on the cellular membrane permeability.

Cell membrane permeability is one of the main indicators of cytotoxicity and related to many critical biological pathways. Here, we determined the Cd2+-induced membrane permeability of human MCF-7 cells using ferrocene methanol molecular probes based on scanning electrochemical microscopy (SECM). The cell height and topography were examined with an impermeable Ru(NH3)6Cl3 probe. The membrane permeability exhibited no significant changes when the Cd2+ incubation time was less than 2 h and its concentration was less than 40 µM. The permeability increased when the Cd2+ concentration was greater than 60 µM, or when the incubation time was longer than 3 h. From the combined 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cytoskeleton imaging experiments, it was found that the changes occurred because the cells exhibited a defensive mode and their membranes contracted when treated with a low concentration of Cd2+ for a short time. However, the cell membranes were irreversibly damaged when the cytoskeleton structures were destroyed, and the cell activities decreased at high concentrations over long periods. Interestingly, through the comparison with an x-scan study, it was found that DPV technology shows a higher performance in the detection of changes in the membrane permeability. Using a combination of cytoskeleton fluorescence imaging and cell-viability tests, the effect of the cadmium metal on the cell membrane permeability can be explored deeper and more comprehensively. This study provides a new idea for exploring the changes in the cell membrane permeability and may be helpful for rapid evaluation of cytotoxicity.

Dithienocoronene diimide (DTCDI)-derived triads for high-performance air-stable, solution-processed balanced ambipolar organic field-effect transistors.

Developing ambipolar organic semiconducting materials is essential for use in complementary-like inverters and light-emitting transistors. In this study, three new dithienocoronenediimide (DTCDI)-derived triads, DTCDI-BT, DTCDI-BBT and DTCDI-BNT, were designed and synthesized, in which various sizes of terminal groups, i.e., thiophene (T), benzo[b]thiophene (BT) and naphtha[2,3-b]thiophene (NT) were substituted at the α-positions of the two thiophene rings of DTCDI, respectively. The DFT calculations reveal that the HOMO energy levels of the three triads when compared to that of the parent DTCDI-core (-5.99 eV) are significantly increased to -5.59, -5.59 and -5.45 eV for DTCDI-BT, DTCDI-BBT and DTCDI-BNT, respectively, whereas the LUMO energy levels (-3.07 eV ∼ -3.14 eV) are almost identical with that of the DTCDI-core (-3.10 eV). The results predict that the triads could possess ambipolar transport properties in organic field-effect transistor (OFET) applications. In fact, under an ambient atmosphere, solution-processed bottom-gate top-contact (BGTC) transistors exhibit ambipolar charge transport properties by tuning the HOMOs of the DTCDI-based triads so that they were suitable for hole injection, resulting in balanced maximum electron and hole mobilities of 1.66 × 10-3 and 1.02 × 10-3 cm2 V-1 s-1 for DTCDI-BT, 2.60 × 10-2 and 3.60 × 10-2 cm2 V-1 s-1 for DTCDI-BBT, and 2.43 × 10-3 and 4.15 × 10-3 cm2 V-1 s-1 for DTCDI-BNT, respectively. This is the first time that the DTCDI building block has been used to develop ambipolar small molecular semiconductors, and achieved a device performance comparable to that of the DTCDI-based polymeric semiconductors. In addition, DTCDI-BBT-based complementary-like inverters were made, and the inverter devices operated well in both p-mode and n-mode under ambient conditions. The results show that the DTCDI is a promising π-electron-deficient building block which could be further used to develop ambipolar semiconducting materials for OFET devices.

Anti-Swelling Gradient Polyelectrolyte Hydrogel Membranes as High-Performance Osmotic Energy Generators.

Emerging asymmetric ionic membranes consisting of two different porous membranes show great superiority in harvesting clean and renewable osmotic energy. The main barriers constraining their applications are incompatible interfaces and a low interfacial ionic transport efficiency, which are detrimental to the long-term stability and improvement of the power density. Here, continuous-gradient all-polysaccharide polyelectrolyte hydrogel membranes prepared by ultrafast reaction/diffusion have been demonstrated to enable high-performance osmotic energy conversion. Besides an inherent high ion conductivity and excellent ion selectivity, the anti-swelling polyelectrolyte gradient membranes preserve the ionic diode effect of the asymmetric membranes to facilitate one-way ion diffusion but circumvent adverse interfacial effects. In consequence, they can present ultrahigh power densities of 7.87 W m-2 by mixing seawater and river water, far superior to state-of-the-art membranes.

Cenpj Regulates Cilia Disassembly and Neurogenesis in the Developing Mouse Cortex.

Primary cilia are microtubule-based protuberances that project from the eukaryotic cell body to sense the extracellular environment. Ciliogenesis is closely correlated to the cell cycle and defects of cilia are related to human systemic diseases such as primary ciliary dyskinesia. However, the role of ciliogenesis in cortical development remains unclear. Here, we demonstrate that Cenpj, a protein that is required for centriole biogenesis, plays a role in regulating cilium disassembly in vivo Depletion of Cenpj in neural progenitor cells results in long cilia and abnormal cilia disassembly. Radial glial cells Cenpj depletion exhibit uncompleted cell division, reduced cell proliferation, and increased cell apoptosis in the developing mouse cerebrum cortex, leading to microcephaly. In addition, Cenpj depletion causes long and thin primary cilia and motile cilia in adult neural stem cells and reduced cell proliferation in the subventricular zone. Furthermore, we show that Cenpj regulates cilia disassembly and neurogenesis through Kif2a, a plus-end-directed motor protein. These data collected from mice of both sexes provide insights into how ciliogenesis plays roles in cortical development and how primary microcephaly is induced by Cenpj mutations in humans.SIGNIFICANCE STATEMENT Autosomal recessive primary microcephaly is a neurodevelopmental disorder with the major symptoms of reduction of circumference of the head, brain volume, and cortex thickness with normal brain architecture in birth. We used conditional Cenpj deletion mice and found that neural progenitor cells (NPCs) exhibited long primary cilia and abnormal cilium appendages. The defective cilium disassembly caused by Cenpj depletion might correlate to reduced cell proliferation, uncompleted cell division, cell apoptosis, and microcephaly in mice. Cenpj also regulates the cilium structure of adult neural stem cells and adult neurogenesis in mice. Additionally, our results illustrate that Cenpj regulates cilia disassembly and neurogenesis through Kif2a, indicating that primary cilia dynamics play a crucial role in NPC mitosis and adult neurogenesis.

New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer.

BACKGROUND: Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment. However, there is lack of reports on the association between metabolic variables and intra-tumor immune markers. Herein, we investigate the correlation between metabolic status on 18F-FDG PET/CT and intra-tumor immunomarkers' expression in NSCLC patients. METHODS: From April 2008 to August 2014, 763 patients were enrolled in the analysis to investigate the role of maximum standardized uptake value (SUVmax) in lung cancer. One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells. The correlation between metabolic variables and the expression of tissue immune markers were analyzed. RESULTS: SUVmax values have significant variations in different epidermal growth factor receptor (EGFR) statuses (wild type vs mutant type), high/low neutrophil-to-lymphocyte ratio (NLR) groups, and high/low platelets-to-lymphocyte ratio (PLR) groups (p < 0.001, p < 0.001, p = 0.003, respectively). SUVmax was an independent prognostic factor in lung cancer patients (p = 0.013). IHC demonstrated a statistically significant correlation between SUVmax and the expression of CD8 tumor-infiltrating lymphocytes (p = 0.015), CD163 tumor-associated macrophages (TAMs) (p = 0.003), and Foxp3-regulatory T cells (Tregs) (p = 0.004), as well as PD-1 and PD-L1 (p = 0.003 and p = 0.012, respectively). With respect to patient outcomes, disease stage, BMI, SUVmax, metabolic tumor volume (MTV), TLG (tumor lesion glycolysis), CD163-TAMs, CD11c-dendritic cells (DCs), PD-L1, and Tregs showed a statistically significant correlation with progression-free survival (PFS) (p < 0.001, 0.023, < 0.001, 0.007, 0.005, 0.004, 0.008, 0.048, and 0.014, respectively), and disease stage, SUVmax, MTV, TLG, CD163-TAMs, CD11c-DCs, and PD-L1 showed a statistically significant correlation with overall survival (OS) (p < 0.001, < 0.001, 0.014, 0.012, < 0.001, 0.001, and < 0.001, respectively). CONCLUSION: This study revealed an association between metabolic variable and immune cell expression in the tumor microenvironment and suggests that SUVmax on 18F-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.

Early Excitatory Activity-Dependent Maturation of Somatostatin Interneurons in Cortical Layer 2/3 of Mice.

GABAergic interneurons perform distinct functions during cortical development in the mouse brain. Among the diverse GABAergic neurons present in the brain, early-born somatostatin (SST)-expressing inhibitory interneurons, which are innervated by other interneurons and local pyramidal cells (PCs), act in a neural computational role in circuitry regulation. The synapses between the SST+ interneurons and other cells form gradually during development. Here, we traced the developmental course of the electrophysiological properties of SST+ interneurons at layer 2/3 of the neocortical secondary motor area (M2) in mouse, and the synaptic connectivity between SST+ interneurons and PCs. Also, we used toxin-mediated and genetic method to suppress the activities of PCs, and demonstrate that decreasing excitatory input at early stage (before P1) rather than late stage (after P8) would delay the functional maturation of SST+ interneurons. In conclusion, our results indicate that early functional activity of PCs is crucial for the intrinsic maturation of SST+ interneurons, following which these interneurons participate in local circuitry.

The residue I257 at S4-S5 linker in KCNQ1 determines KCNQ1/KCNE1 channel sensitivity to 1-alkanols.

AIM: KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes, which are important in maintaining a normal heart rhythm. In the present study we investigated the effects of a homologous series of 1-alkanols on KCNQ1/KCNE1 channels expressed in Xenopus oocytes. METHODS: ECG recording was made in rats injected with ethanol-containing solution (0.3 mL, ip). Human KCNQ1 channel and its auxiliary subunit KCNE1 were heterologously coexpressed in Xenopus oocytes, which were superfused with ND96 solution; 1-alkanols (ethanol, 1-butanol and 1-hexanol) were delivered through a gravity-driven perfusion device. The slow-delayed rectifier potassium currents IKs (KCNQ1/KCNE1 currents) were recorded using a two-electrode voltage clamp method. Site-directed mutations (I257A) were made in KCNQ1. RESULTS: In ECG recordings, a low concentration of ethanol (3%, v/v) slightly increased the heart rate of rats, whereas the higher concentrations of ethanol (10%, 50%, v/v) markedly reduced it. In oocytes coexpressing KCNQ1/KCNE1 channels, ethanol, 1-butanol and 1-hexanol dose-dependently inhibited IKs currents with IC50 values of 80, 11 and 2.7 mmol/L, respectively. Furthermore, the 1-alkanols blocked the KCNQ1 channel in both open and closed states, and a four-state model could adequately explain the effects of 1-alkanols on the closed-state channel block. Moreover, the mutation of I257A at the intracellular loop between S4 and S5 in KCNQ1 greatly decreased the sensitivity to 1-alkanols; and the IC50 values of ethanol, 1-butanol and 1-hexanol were increased to 634, 414 and 7.4 mmol/L, respectively. The mutation also caused the ablation of closed-state channel block. CONCLUSION: These findings provide new insight into the intricate mechanisms of the blocking effects of ethanol on the KCNQ1 channel.

Activation of galanin receptor 2 stimulates large conductance Ca(2+)-dependent K(+) (BK) channels through the IP3 pathway in human embryonic kidney (HEK293) cells.

The large conductance Ca(2+)-activated K(+) (BK) channels are widely distributed in the brain, and act as intracellular calcium sensors in neurons. They play an important feedback role in controlling Ca(2+) flux and Ca(2+)-dependent processes, including neurotransmitter release and cellular excitability. In this study, the effects of the neuropeptide galanin on BK channels were examined by determining the whole-cell currents and single-channel activities in human embryonic kidney (HEK293) cells co-expressing GalR2 and the BK alpha subunit. Galanin enhanced the currents of BK channels, in a concentration-dependent and PTX-independent manner, with an ED50 value of 71.8±16.9 nM. This activation was mediated by GalR2, since its agonist AR-M1896 mimicked the effect of galanin, and since galanin did not facilitate BK currents in cells co-expressing cDNAs of BK and GalR1 or GalR3. The galanin-induced BK current persisted after replacement with Ca(2+)-free solution, suggesting that extracellular Ca(2+) is not essential. Chelating intracellular Ca(2+) by either the slow Ca(2+) buffer EGTA or the fast Ca(2+) buffer BAPTA abolished galanin-mediated activation of BK channels, indicating the important role of intracellular Ca(2+). The role of Ca(2+) efflux from the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) was confirmed by application of thapsigargin, an irreversible inhibitor that depletes Ca(2+) from SR/ER. Moreover, the inositol-1,4,5-triphosphate receptor (IP3R) was identified as the mediator responsible for increased intracellular Ca(2+) activating BK channels. Taken together, activation of GalR2 leads to elevation of intracellular Ca(2+) is due to Ca(2+) efflux from ER through IP3R sequentially opening BK channels.

ALA-PDT combined with 2940 nm ablative fractional Er:YAG laser for Darier's disease.

Darier's disease is a rare, genetically determined dyskeratotic skin disorder. Although many conventional treatments have been reported, management of Darier's disease remains challenging. Most patients are at high risk of recurrence during long-term follow-up. Here, we present two patients who were successfully treated with ALA photodynamic therapy (PDT) and ablative 2940 nm Er:YAG fractional laser. Both patients exhibited significant improvements in the affected areas with moderate pain, transient erythema and edema. Remission durations of up to 2 years were observed in both patients after combination treatment. Our findings suggest that the combination of ALA-PDT and 2940 nm fractional Er:YAG laser may be an effective, safe and well-tolerated treatment option for Darier's disease.

Temporal-spatial deciphering mental subtraction in the human brain.

Mental subtraction, involving numerical processing and operation, requires a complex interplay among several brain regions. Diverse studies have utilized scalp electroencephalograph, electrocorticogram, or functional magnetic resonance imaging to resolve the structure pattern and functional activity during subtraction operation. However, a high resolution of the spatial-temporal understanding of the neural mechanisms involved in mental subtraction is unavailable. Thus, this study obtained intracranial stereoelectroencephalography recordings from 20 patients with pharmacologically resistant epilepsy. Specifically, two sample-delayed mismatch paradigms of numeric comparison and subtracting results comparison were used to help reveal the time frame of mental subtraction. The brain sub-regions were chronologically screened using the stereoelectroencephalography recording for mental subtraction. The results indicated that the anterior cortex, containing the frontal, insular, and parahippocampous, worked for preparing for mental subtraction; moreover, the posterior cortex, such as parietal, occipital, limbic, and temporal regions, cooperated during subtraction. Especially, the gamma band activities in core regions within the parietal-cingulate-temporal cortices mediated the critical mental subtraction. Overall, this research is the first to describe the spatiotemporal activities underlying mental subtraction in the human brain. It provides a comprehensive insight into the cognitive control activity underlying mental arithmetic. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09937-z.

An isolated single-particle-based SECM tip interface for single-cell NO sensing.

As a key factor in cellular metabolic processes, nitric oxide (NO) is a challenging target for in situ real-time monitoring due to its transient property and short diffusion distance. Scanning electrochemical microscopy (SECM) has unique advantages in single-cell analysis, which can obtain the electrochemical current by scanning the cell surface with a tip microelectrode. In particular, it can further improved the electrochemical response by enhancing the interface properties of its tip. Here, an interface design strategy based on platinum single nanoparticle (Pt NP) was developed, and fluorinated self-assembled monolayers (SAMs) were used to further improve its performance. This modified tip was used as an SECM probe for NO concentration monitoring and morphological imaging of single MCF-7 cells. It has the high sensitivity (164.7 µA/µM·cm2) and good selectivity for NO detection, which benefits from the efficient catalytic properties of Pt NPs and high mass transport and hydrophobic antifouling properties of the interface. Notably, it shows a superior performance in detecting the fluctuation of NO released by a single MCF-7-cell under the stimulation of cadmium (Cd), which demonstrates a promising method for using a single-particle-based tip in SECM applications.