Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/ß-catenin signalling pathway.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Characterization and stability investigation of rhein encapsulated microcapsules using different enteric biopolymers with pullulan and Jiuzao glutelin conjugates via Maillard reaction.

The poor water solubility and rhein (RH) stability limit its application in the functional food industry. In the present study, the RH-loaded water-in-oil-in-water nano emulsion and microcapsules were prepared using the conjugates of pullulan-Jiuzao glutelin (JG) (m/m, 2:1, PJC-2) obtained by Maillard reaction and enteric-soluble materials (polymethlacrylic acid, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and D-mannitol). The effects of different formulations on the microstructure, physicochemical properties, and storage stability of microcapsules were analyzed. The results showed that microcapsules exhibited stability against different external environments. The encapsulation efficiency of RH in the four enteric-soluble-PJC-2 double-deck microcapsules (70.03 ± 3.24%-91.08 ± 4.78%) was significantly improved than PJC-2 ones (61.84 ± 0.47%). The antioxidant activity and stability of RH in the microcapsules were improved (ABTS, 49.7%-113.93%; DPPH, 40.85%-101.82%; FRA, 62.32%-126.42%; and FCA, 70.58%-147.20%) after in vitro simulated digestion and extreme environmental conditions compared to free RH. This work provides a microcapsule based on PJC-2 with enteric-soluble materials for insoluble functional ingredients to improve solubility, stability, and bioactivity in the food industry.

Hordenine Activated Dermal Papilla Cells and Promoted Hair Regrowth by Activating Wnt Signaling Pathway.

Hordenine is effective in treating hyperpigmentation, fighting diabetes and resisting fibrosis and acute inflammation. However, the role of Hordenine on hair growth has not been elucidated. Here, we found that Hordenine treatments significantly enhance proliferation of primary mouse dermal-papilla cells (DPCs) and increase the activity of DPCs in a dose-dependent manner. Additionally, Hordenine markedly promoted the elongation of the hair shaft in the model of in vitro-cultured mouse vibrissa follicle and accelerated hair regrowth in a mouse model of depilation-induced hair regeneration. Real-time PCR, Western Blot and immunofluorescent assays showed that nuclear ß-catenin and its downstream gene expression such as Lef1, Axin2, Cyclin D1 and ALP were greatly upregulated in DPCs and mouse hair follicles after Hordenine treatments. Moreover, the increased DPCs' proliferation and hair shaft elongation of cultured mouse vibrissa follicles induced by Hordenine treatments were rescued by a Wnt/ß-catenin signaling inhibitor, FH535. These data indicate that Hordenine can effectively enhance DPCs' activity and accelerate hair regrowth through activating the Wnt/ß-catenin signaling pathway. Therefore, these findings suggest Hordenine/its derivatives may be potentially used for preventing and treating alopecia in the future.

Modification of Jiuzao glutelin with pullulan through Maillard reaction: Stability effect in nano-emulsion, in vitro antioxidant properties, and interaction with curcumin.

Pullulan-Jiuzao glutelin (JG) conjugates (PJCs) were prepared via Maillard reaction in this study. PJCs were prepared by optimizing pullulan to JG ratios (0.5:1, 1:1, 2:1, and 4:1, expressed as PJC-0.5, PJC-1, PJC-2, and PJC-4, respectively) and reaction times (0-180 min) at pH 7 and 11. The secondary structure changes of PJC compared to JG, potential conjugation sites between pullulan and JG, PJC emulsifying properties, in vitro antioxidant activities, and interaction with curcumin (CUR) were investigated. Among the four PJCs, PJC-2 obtained after 180 min reaction at pH 11 and 90 °C exhibited the best ability in nano-emulsion stabilization with the lowest particle size (180-200 nm and 290-450 nm against NaCl during storage), PDI (0.2-0.4 and 0.4-0.7 against NaCl during storage), highest zeta-potential (-20.10 mV), and lowest backscattering intensity. The spontaneous conjugation binding sites between pullulan and JG were Arg-39, Arg-54, and Asp-168. In contrast to native JG, PJC-2 exhibited better antioxidant capacities, low toxicity for CCD 841 CON and Caco-2 cells, and enhancement of antioxidant enzyme content (i.e., SOD, GPX, and CAT) after AAPH-induced oxidative stress. In addition, there exists an interaction between CUR and PJC-2 by residues Ala-74, Asp-376, Arg-368 and -374, Val-45, and Ala-44 of JG. The results above exhibit important implications for the fabrication of PJC-stabilize nano-emulsion and even for developing PJC product as a potential carrier of CUR in the functional food industry.

Heavy metal ecological-health risk assessment under wheat-maize rotation system in a high geological background area in eastern China.

A high geological background can increase the ecological and health risks associated with crop production; therefore, it is essential to assess the heavy metals and their impact. In this study, ecological and health risk impacts of heavy metal contamination, in combination with positive matrix factorization was assessed for an area with high geological background with wheat-maize cropping system, to provide a quantitative understanding of the effects of heavy metals, enabling its prevention and control. This study revealed that the comprehensive ecological risk (RIwheat-maize) is 56.21 (low), with industries being the biggest contributors (34.22%). Comprehensive health risk (non-carcinogenic) assessment showed that industrial (40.98-49.30%) and natural (23.96-37.64%) factors were the primary (particularly of Cd and Zn) and secondary (particularly of Cr and Ni) contributors, respectively in eastern China. Comprehensive health risk (HIwheat-maize) for children and adults were 0.74 and 0.42, respectively, indicating that non-carcinogenic risks were at an acceptable level. Soil ingestion was the primary pathway for health risks (62.23-73.00%), especially for children. Based on soil heavy metal sources and crop systems, source-ecological risk assessment and source-health risk assessment were used to provided valuable insights on making strategies to protect human health in high geological background areas.

Preparation of modified Jiuzao glutelin isolate with carboxymethyl chitosan by ultrasound-stirring assisted Maillard reaction and its protective effect of loading resveratrol/quercetin in nano-emulsion.

Jiuzao glutelin isolate (JGI) was reported to possess interface and functional properties. To enhance the stability and properties of JGI, conjugation between JGI and carboxymethyl chitosan (CTS) through ultrasound-stirring assisted Maillard reaction (UTSA-MR) was investigated and optimized. The changes of molecular distribution, secondary structure, morphology, and amino acid composition of JGI were detected after conjugation with CTS. The solubility, foaming property and stability, viscosity, and thermal stability of four conjugates (CTS-JGI, with weight ratios of 0.5:1, 1:1, 2:1, and 4:1) were significantly increased compared to native JGI. Under the optimal glycation, the conjugate (CTS/JGI, 2:1, w/w; CTS-JGI-2) exhibited the best emulsifying ability and stability against NaCl solution, in vitro antioxidant activity, and cholesterol-lowering ability. CTS-JGI-2 stabilized oil-in-water nano-emulsion improved resveratrol (RES) and quercetin (QUE) encapsulation efficiency (80.96% for RES and 93.13% for QUE) and stability during the simulated digestion process (73.23% for RES and 77.94% for QUE) due to the connection through hydrogen bonds, pi-anion, pi-sigma, and donors between CTS-JGI and RES/QUE. Taken together, the modification of JGI by conjugating with CTS through UTSA-MR could be an excellent method to improve the functional properties of JGI. CTS-JGI-2 is a potential conjugate with functions that can be used to encapsulate functional substances in the stabilized nano-emulsion.

3D Quantitative Prediction of the Groundwater Potential Area-A Case Study of a Simple Geological Structure Aquifer.

The Ordos Basin is a sedimentary basin located in Inner Mongolia, China, where coal and uranium coexist. Water inrush disasters have always been one of the main disasters that threaten the safety of coal mine production, and thus, the study and division of groundwater potential regions are of great significance for the prevention of water inrush disasters and in situ leaching of sandstone-type uranium ore. A new method combining truncated Gaussian simulation and sedimentary facies control was established to predict the groundwater potential area. Taking a typical aquifer, the Zhiluo Formation, as an example, based on high-resolution sequence stratigraphy, geophysics, sedimentary geology, and geostatistical theory, the plane distribution of sand bodies was predicted. Furthermore, the relationship between rock porosity and electricity porosity was established to calculate the regional porosity. Combined with truncated Gaussian simulation and facies-controlled modeling methods, a facies-controlled heterogeneous property model was established to analyze the heterogeneous effective porosity of the aquifer in the study area. Groundwater potential areas were quantitatively evaluated by 3D modeling analysis. The results of the evaluated model were verified by actual data and provide a geological guarantee for the accurate mining of deep coal and uranium ore. A 3D distributed model of chemical elements, which is meaningful for in situ leaching uranium mining, is expected in future research.

Infection of Nigrospora nonsegmented RNA Virus 1 Has Important Biological Impacts on a Fungal Host.

Nigrospora nonsegmented RNA virus 1 (NoNRV1) has been reported previously in the fungus Nigrospora oryzae, but its biological effects on its host are unknown. In this work, we isolated a strain 9-1 of N. oryzae from a chrysanthemum leaf and identified NoNRV1 infection in the isolated strain. The genome sequence of NoNRV1 identified here is highly homologous to that of the isolate HN-21 of NoNRV1 previously reported; thus, we tentatively designated the newly identified NoNRV1 as NoNRV1-ZJ. Drug treatment with Ribavirin successfully removed NoNRV1-ZJ from the strain 9-1, which provided us with an ideal control to determine the biological impacts of NoNRV1 infection on host fungi. By comparing the virus-carrying (9-1) and virus-cured (9-1C) strains, our results indicated that infection with NoNRV1 promoted the pigmentation of the host cells, while it had no discernable effects on host growth on potato dextrose agar plates when subjected to osmotic or oxidative stress. Interestingly, we observed inhibitory impacts of virus infection on the thermotolerance of N. oryzae and the pathogenicity of the host fungus in cotton leaves. Collectively, our work provides clear evidence of the biological relevance of NoNRV1 infection in N. oryzae, including pigmentation, hypovirulence, and thermotolerance.

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma.

OBJECTIVE: The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies. METHODS: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95% CI: 5.6%-34.7%). The median PFS and OS were 3.1 months (95% CI: 1.5-4.3) and 6.8 months (95% CI: 4.7-10.1), respectively. A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions (≥ 50%: 25.0% vs. < 50%: 0%, P = 0.140) or TP53 mutation abundance (< 10%: 23.8% vs. ≥ 10%: 0%, P = 0.286). Improved median PFS (3.4 vs. 1.4 months, P = 0.006) and OS (8.0 vs. 4.2 months, P = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-related adverse events of grade 3 or 4 (occurring in ≥ 2 patients) were hypomagnesemia [7 (23.3%)] and rash [2 (6.7%)]. No treatment-related death occurred. CONCLUSIONS: SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.

A coma-free super-high resolution optical spectrometer using 44 high dispersion sub-gratings.

Unlike the single grating Czerny-Turner configuration spectrometers, a super-high spectral resolution optical spectrometer with zero coma aberration is first experimentally demonstrated by using a compound integrated diffraction grating module consisting of 44 high dispersion sub-gratings and a two-dimensional backside-illuminated charge-coupled device array photodetector. The demonstrated super-high resolution spectrometer gives 0.005 nm (5 pm) spectral resolution in ultra-violet range and 0.01 nm spectral resolution in the visible range, as well as a uniform efficiency of diffraction in a broad 200 nm to 1000 nm wavelength region. Our new zero-off-axis spectrometer configuration has the unique merit that enables it to be used for a wide range of spectral sensing and measurement applications.

Distinct Function of Estrogen Receptors in the Rodent Anterior Cingulate Cortex in Pain-related Aversion.

BACKGROUND: Brain-derived estrogen is implicated in pain-related aversion; however, which estrogen receptors mediate this effect remains unclear. This study hypothesized that the different estrogen receptors in the rostral anterior cingulate cortex play distinct roles in pain-related aversion. METHODS: Formalin-induced conditioned place avoidance and place escape/avoidance paradigms were used to evaluate pain-related aversion in rodents. Immunohistochemistry and Western blotting were used to detect estrogen receptor expression. Patch-clamp recordings were used to examine N-methyl-D-aspartate-mediated excitatory postsynaptic currents in rostral anterior cingulate cortex slices. RESULTS: The administration of the estrogen receptor-ß antagonist 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP) or the G protein-coupled estrogen receptor-1 antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15) but not the estrogen receptor-α antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) into the rostral anterior cingulate cortex blocked pain-related aversion in rats (avoidance score, mean ± SD: 1,3-bis [4-hydroxyphenyl]-4-methyl-5-(4-[2-piperidinylethoxy] phenol)-1H-pyrazole dihydrochloride (MPP): 47.0 ± 18.9%, 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP): -7.4 ± 20.6%, and [3aS*,4R*,9bR*]-4-[6-bromo-1,3-benzodioxol-5-yl]-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15): -4.6 ± 17.0% vs. vehicle: 46.5 ± 12.2%; n = 7 to 9; P < 0.0001). Consistently, estrogen receptor-ß knockdown but not estrogen receptor-α knockdown by short-hairpin RNA also inhibited pain-related aversion in mice (avoidance score, mean ± SD: estrogen receptor-α-short-hairpin RNA: 26.0 ± 7.1% and estrogen receptor-ß-short-hairpin RNA: 6.3 ± 13.4% vs. control short-hairpin RNA: 29.1 ± 9.1%; n = 7 to 10; P < 0.0001). Furthermore, the direct administration of the estrogen receptor-ß agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) or the G protein-coupled estrogen receptor-1 agonist (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1) into the rostral anterior cingulate cortex resulted in conditioned place avoidance (avoidance score, mean ± SD: 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN): 35.3 ± 9.5% and (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1): 43.5 ± 22.8% vs. vehicle: 0.3 ± 14.9%; n = 8; P < 0.0001) but did not affect mechanical or thermal sensitivity. The activation of the estrogen receptor-ß/protein kinase A or G protein-coupled estrogen receptor-1/protein kinase B pathway elicited the long-term potentiation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. CONCLUSIONS: These findings indicate that estrogen receptor-ß and G protein-coupled estrogen receptor-1 but not estrogen receptor-α in the rostral anterior cingulate cortex contribute to pain-related aversion by modulating N-methyl-D-aspartate receptor-mediated excitatory synaptic transmission.

Enterochromaffin cell hyperplasia in the gut: Factors, mechanism and therapeutic clues.

Enterochromaffin (EC) cell is the main cell type that responsible for 5-hydroxytryptamine (5-HT) synthesis, storage and release of the gut. Intestinal 5-HT play a key role in visceral sensation, intestinal motility and permeability, EC cell hyperplasia and increased 5-HT bioavailability in the gut have been found to be involved in the symptoms generation of irritable bowel syndrome and inflammatory bowel disease. EC cells originate from intestinal stem cells, the interaction between proliferation and differentiation signals on intestinal stem cells enable EC cell number to be regulated in a normal level. This review focuses on the impact factors, pathogenesis mechanisms, and therapeutic clues for intestinal EC cells hyperplasia, and showed that EC cell hyperplasia was observed under the condition of physiological stress, intestinal infection or intestinal inflammation, the disordered proliferation and/or differentiation of intestinal stem cells as well as their progenitor cells all contribute to the pathogenesis of intestinal EC cell hyperplasia. The altered intestinal niche, i.e. increased corticotrophin releasing factor (CRF) signal, elevated nerve growth factor (NGF) signal, and Th2-dominant cytokines production, has been found to have close correlation with intestinal EC cell hyperplasia. Currently, CRF receptor antagonist, nuclear factor-κB inhibitor, and NGF receptor neutralizing antibody have been proved useful to attenuate intestinal EC cell hyperplasia, which may provide a promising clue for the therapeutic strategy in EC cell hyperplasia related diseases.

Strong optical absorption of a metallic film to induce a lensing effect in the visible region.

In this work, the two-dimensional profile of the light transmission through a prism-like metallic film sample of Au was measured at a wavelength of 632.8 nm in the visible intraband transition region to verify that, beyond the possible mechanisms of overcoming the diffraction limit, a strongly nonuniform optical absorption path length of the light traveling in the metal could induce a lensing effect, thereby narrowing the image of an object. A set of prism-like Au samples with different angles was prepared and experimentally investigated. Due to the nonuniform paths of the light traveling in the Au samples, lens-effect-like phenomena were clearly observed that reduced the imaged size of the beam spot with decreasing light intensity. The experimental measurements presented in the work may provide new insight to better understand the light propagation behavior at a metal/dielectric interface.

Activation of Kir2.3 Channels by Tenidap Suppresses Epileptiform Burst Discharges in Cultured Hippocampal Neurons.

BACKGROUND & OBJECTIVE: Tenidap, a selective human inwardly rectifying potassium (Kir) 2.3 channel opener, has been reported to have antiepileptic effect in the pilocarpine temporal lobe epilepsy rat model in our previous study. However, the effect of tenidap on neurons and its relationship with the epileptiform bursting charges in neuron is still required to be explored. METHODS: In this study, cyclothiazide (CTZ) induced cultured hippocampal neuron epileptic model was used to study the antiepileptic effect of tenidap and the relationship between Kir2.3 channel and the neuronal epileptiform burst. RESULTS: Patch clamp recording showed that both acute (2h) and chronic (48h) CTZ pre-treatment all significantly induced robust epileptiform burst activities in cultured hippocampal neurons, and tenidap acutely application inhibited this highly synchronized abnormal activities. The effect of tenidap is likely due to increased activity of Kir2.3 channels, since tenidap significantly enhanced kir current recorded from those neurons. In addition, neurons overexpressing Kir2.3 channels, by transfection with Kir2.3 plasmid, showed a significant large increase of the Kir current, prevented CTZ treatment to induce epileptiform burst discharge. CONCLUSION: Our current study demonstrated that over activation of Kir2.3 channel in hippocampal neurons could positively interference with epileptiform burst activities, and tenidap, as a selective Kir2.3 channel opener, could be a potential candidate for seizure therapy.

Ultrahigh-resolution spectrometer based on 19 integrated gratings.

Optical spectrometers play a key role in acquiring rich photonic information in both scientific research and a wide variety of applications. In this work, we present a new spectrometer with an ultrahigh resolution of better than 0.012 nm/pixel in the 170-600 nm spectral region using a grating-integrated module that consists of 19 subgratings without any moving parts. By using two-dimensional (2D) backsideilluminated complementary metal-oxide-semiconductor (BSI-CMOS) array detector technology with 2048 × 2048 pixels, a high data acquisition speed of approximately 25 spectra per second is achieved. The physical photon-sensing size of the detector along the one-dimensional wavelength direction is enhanced by a factor of 19 to approximately 428 mm, or 38912 pixels, to satisfy the requirement of seamless connection between two neighboring subspectral regions without any missing wavelengths throughout the entire spectral region. As tested with a mercury lamp, the system has advanced performance capabilities characterized by the highest k parameter reported to date, being approximately 3.58 × 104, where k = (working wavelength region)/(pixel resolution). Data calibration and analysis as well as a method of reducing background noise more efficiently are also discussed. The results presented in this work will stimulate further research on precision spectrometers based on advanced BSI-CMOS array detectors in the future.

Improving characterization capabilities in new single-photon avalanche diode research.

Many novel and promising single-photon avalanche diodes (SPADs) emerged in recent years. However, some of them may demonstrate a very high dark count rate, even tens of megahertz, especially during the development phase or at room temperature, posing new challenges to device characterization. Gating operation with a width of 10 ns can be used to suppress the dark counts not coincident with the photon arriving time. However, as a side effect of the fast-gating operation, the gating response could be much higher than the avalanche signal and is usually removed by various circuit-based cancellation techniques. Here, we present an alternative method. A high-speed digital storage oscilloscope (DSO) is used to extract the weak avalanche signals from the large gating response background by waveform subtraction in software. Consequently, no complex circuit and precise tuning for each SPAD are needed. The avalanche detection threshold can be reduced to 5% of the full vertical scale of the DSO or 5 mV, whichever is greater. The timing resolution can be better than 2 ps for typical avalanche signals. Optical alignment and calibration are easy. The feasibility of on-wafer test with an RF probe station is discussed. All the advantages and features listed above make this method very useful in new SPAD research.

Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon.

Intestinal enterochromaffin (EC) cell hyperplasia and increased 5-hydroxytryptamine (5-HT) availability play key roles in the pathogenesis of abdominal hypersensitivity of irritable bowel syndrome (IBS). This study aims to study the effect of quercetin on visceral pain and 5-HT availability in postinflammatory IBS (PI-IBS) rats. PI-IBS model rats were administered quercetin by gavage at doses of 5, 10, and 20 mg/kg for 14 days. Compared with normal rats, the visceral pain threshold of PI-IBS rats was markedly decreased and the abdominal motor response to colon distension was markedly increased. The EC cell count and 5-HT level, as well as tryptophan hydroxylase (TPH) protein, were all significantly elevated in PI-IBS rats, while the 5-HT reuptake transporter (serotonin transporter) was reduced. Genes that are responsible for enteroendocrine cell differentiation, that is, Ngn3 and pdx1, were significantly increased in the PI-IBS group. Quercetin treatment markedly elevated the pain threshold pressure and decreased the visceral motor response of PI-IBS animals; and EC cell density and 5-HT level, as well as TPH expression, in the PI-IBS group were all reduced by quercetin. Quercetin treatment also significantly reduced colonic expression of Ngn3 and pdx1 of PI-IBS. Findings from the present study indicated that the analgesic effect of quercetin on PI-IBS may result from reduction of 5-HT availability in the colon, and the regulatory role of quercetin in endocrine progenitors may contribute to reduced EC cells.

A High-Performance Spectrometer with Two Spectral Channels Sharing the Same BSI-CMOS Detector.

Optical spectrometers play an important role in modern scientific research. In this work, we present a two-channel spectrometer with a pixel resolution of better than 0.1 nm/pixel in the wavelength range of 200 to 950 nm and an acquisition speed of approximately 25 spectra per second. The spectrometer reaches a high k factor which characterizes the spectral performance of the spectrometer as k = (working wavelength region)/(pixel resolution) = 7500. Instead of using mechanical moving parts in traditional designs, the spectrometer consists of 8 integrated sub-gratings for diffracting and imaging two sets of 4-folded spectra on the upper and lower parts, respectively, of the focal plane of a two-dimensional backside-illuminated complementary metal-oxide-semiconductor (BSI-CMOS) array detector, which shows a high peak quantum efficiency of approximately 90% at 400 nm. In addition to the advantage of being cost-effective, the compact design of the spectrometer makes it advantageous for applications in which it is desirable to use the same two-dimensional array detector to simultaneously measure multiple spectra under precisely the same working conditions to reduce environmental effects. The performance of the finished spectrometer is tested and confirmed with an Hg-Ar lamp.

The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy.

BACKGROUND & OBJECTIVE: The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. Moreover, after-hyperpolarization induced by BK channels closes Cav channels and thus precludes excessive Ca2+ influx. Considering this negative feedback effect, BK channel seemly acts to decrease membrane excitability in order to prevent hyperexcitation which is a typical characteristic of epilepsy. Therefore, one may reasonably suppose that membrane excitability would increase when the BK channel activity decreases. However, the membrane excitability displays elevation when the function of BK channel is under either upregulated or down-regulated status. Factors altering the activity of BK channels, such as gene mutations, polymorphism, channel openers or blockers that lead to loss- or gain-of-function, have all been linked to epilepsy onset. CONCLUSION: The aim of this review is to summarize existing knowledge and recent findings on the molecular properties, signaling complex and channel dysfunction of the BK channels with a particular attention to the possible relevance to the pathophysiology of epilepsy.

GIRK1-mediated inwardly rectifying potassium current suppresses the epileptiform burst activities and the potential antiepileptic effect of ML297.

G protein-gated inwardly rectifying potassium (GIRK) channels are important inhibitory regulators of neuronal excitability in central nervous system, and the impairment of GIRK channel function has been reported to be associated with the susceptibility of epilepsy. However, the dynamics of GIRK channels in the pathogenesis of epilepsy are still unclear. In this study, our results showed that cyclothiazide, a potent convulsant, dose dependently increased the epileptiform bursting activities and suppressed the baclofen induced GIRK currents. In addition, TPQ, a selective GIRK antagonist, significantly decreased the total inwardly rectifying potassium (Kir) current, and increased the neuronal epileptiform activities. In contrast, ML297, a potent and selective GIRK channel agonist, reversed the cyclothiazide induced decrease of GIRK currents and the increase of neuronal excitability in cultured hippocampal neurons. Further investigation revealed that GIRK1, but not GIRK2, played a key role in suppressing epileptic activities. Finally, in pilocarpine mice seizure model, we demonstrated that ML297 significantly suppressed the seizure behavior. In summary, our current results indicate that GIRK channels, especially GIRK1-containing channels, are involved in epileptic activities and ML297 has a potential antiepileptic effect.