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A photocatalyzed, efficient, and mild approach for the synthesis of various substituted isothiocyanates from amine and carbon disulfide was reported in this work. This approach expands the scope of photocatalytic applications and provides a new method for the preparation of aliphatic and aromatic isothiocyanates, which are significant organic building blocks and biological diagnostic markers.

A tremendous amount of proteomic and phosphoproteomic data has been produced over the years with the development of mass spectrometry techniques, providing us with new opportunities to explore and understand the proteome and phosphoproteome as well as the function of proteins and protein phosphorylation sites. However, a lack of powerful tools that we can utilize to explore these valuable data limits our understanding of the proteome and phosphoproteome, particularly in diseases such as cancer. To address these unmet needs, we established CPPA (Cancer Proteome and Phosphoproteome Atlas), a web tool to mine abnormalities of the proteome and phosphoproteome in cancer based on published data sets. All analysis results are presented in CPPA with a flexible web interface to provide key customization utilities, including general analysis, differential expression profiling, statistical analysis of protein phosphorylation sites, correlation analysis, similarity analysis, survival analysis, pathological stage analysis, etc. CPPA greatly facilitates the process of data mining and therapeutic target discovery by providing a comprehensive analysis of proteomic and phosphoproteomic data in normal and tumor tissues with a simple click, which helps to unlock the precious value of mass spectrometry data by bridging the gap between raw data and experimental biologists. CPPA is currently available at https://cppa.site/cppa.

Thermoresponsive aggregation-induced emission (AIE) luminogens, especially in the solid state, have attracted extensive attention due to their potential applications as smart materials. Herein, we report an AIE-active tetraphenylethene (TPE)-based Schiff base derivative (TPENOMe-I) that exhibits rapid and reversible thermochromism along with luminescence in the solid state. The excited-state intramolecular proton transfer-induced AIE and efficient thermochromism (rather than photochromism) are facilitated by the relatively compact crystal packing and polymorphism of TPENOMe-I, which effectively suppress cis-to-transisomerization. Theoretical calculations demonstrated that the two-step isomerization process between the enol isomer and the cis- and twisted cis-keto isomers is responsible for the thermochromic behavior of solid-state TPENOMe-I. The chromic transitions may result from the reversible interconversion between various twisted cis-keto forms during the thermal isomerization process. Three composites containing TPENOMe-I that were simply prepared with low cost excited reversible thermochromism and were successfully demonstrated in thermochromic patterns. The findings suggest that these TPENOMe-I composites have promising applications for use in warning labels, thermochromic textiles, and thermal printing.

ABSTRACTThere is no clear treatment guideline or individualized treatment plan for triple-negative breast cancer (TNBC). The aim of this study was to investigate more effective targets for TNBC-targeted therapy. MDA-MB-231 and BT549 cell lines were used to explore the function of LINC00649 on the proliferation, invasion, and migration of TNBC cells. A mice subcutaneous tumor model and a pulmonary metastasis model was established to identify the role of LINC00649 on the growth and metastasis of TNBC in vivo. LINC00649 was found to be a key molecule involved in the occurrence and development of TNBC by screening of public databases and detection of TNBC clinical samples. LINC00649 increased hypoxia-inducible factor 1α (HIF-1α) mRNA stability and protein expression by interacting with the nuclear factor 90 (NF90)/NF45 complex. In vitro, interference with LINC00649 inhibits MDA-MB-231 and BT549 cell proliferation, migration, and invasion, and the addition of HIF-1α revised this effect. In vivoexperiments showed that LINC00649 promoted the growth and metastasis of TNBC. We demonstrated that LINC00649 interacts with the NF90/NF45 complex to increase the mRNA stability of HIF-1α and up-regulate HIF-1α expression, thereby inducing the proliferation, invasion, and migration of TNBC cells as well as tumor growth and metastasis.

Electrophysiology is a powerful tool to examine cellular functions, but the use of the techniques remains challenging outside of physiology and neuroscience fields. We aim to provide a practical methods guide for electrophysiological recordings to nonexperts in the field to help with the utility of these important research tools. We focus on two techniques that are critical in the context of tissue engineering, whole-cell patch clamp recording for assessing cellular functions and extracellular field potential recording for evaluating network activities. Specific examples are presented to demonstrate how the techniques were applied to tissue engineering studies.

Emerging evidence suggests that circular RNAs (circRNAs) are linked to the development and progression of human cancers. Nevertheless, their contribution to breast cancer (BC) is still largely unknown. In the current study, we screened and identified a novel circRNA, circ-UBE2D2, which was highly expressed in BC cell lines and tissues and was closely related to aggressive clinical features and dismal prognosis. Small interfering RNA (siRNA)–mediated circ-UBE2D2 silencing notably inhibited the proliferation, migration and invasion of BC cells, whereas circ-UBE2D2 overexpression displayed opposite effects. Mechanistically, circ-UBE2D2 was able to simultaneously function as molecular sponges of miR-1236 and miR-1287 to regulate the expression of their respective target genes. Moreover, circ-UBE2D2–induced tumor-promoting effects could be effectively blocked by miR-1236 or miR-1287 in BC cells. More importantly, therapeutic delivery of cholesterol-conjugated si-circ-UBE2D2 oligonucleotides significantly delayed tumor growth in vivo. Overall, our findings indicate that circ-UBE2D2 plays an essential oncogenic role in BC, and targeting circ-UBE2D2 may be a feasible treatment for BC patients.

The substantia nigra pars compacta (SNpc) is a discrete region of the brain that exhibits a dark pigment, neuromelanin (NM), a biomaterial with unique properties and the subject of ongoing research pertaining to neurodegenerative conditions like Parkinson’s disease (PD). Obtaining human tissue to isolate this pigment is costly and labor intensive, making it necessary to find alternatives to model the biochemical interaction of NM and its implications on PD. To address this limitation, we modified our established silk 3D brain tissue model to emulate key characteristics of the SNpc by using a structural analogue of NM to examine the effects of the material on dopaminergic neurons using Lund’s human mesencephalon (LUHMES) cells. We utilized a sepia-melanin, squid ink, derived NM analogue (NM-sim) to chelate ferric iron, and this iron-neuromelanin precipitate (Fe-NM) was purified and characterized. We then exposed LUHMES dopaminergic cells to the NM-sim, Fe-NM-sim, and control vehicle within 3D silk protein scaffolds. The presence of both NM-sim and Fe-NM-sim in the scaffolds negatively impacted spontaneous electrical activity from the LUMES networks, as evidenced by changes in local field potential (LFP) electrophysiological recordings. Furthermore, the Fe-NM-sim precipitate generated peroxides, depleted nutrients/antioxidants, and increased protein oxidation by carbonylation in sustained (>2 weeks) 3D cultures, thereby contributing to cell dysfunction. The results suggest that this 3D tissue engineered brain-like model may provide useful readouts related to PD neuro-toxicology research.

Three-dimensional (3D) in vitrocell and tissue culture models, particularly for the central nervous system, allow for the exploration of mechanisms of organ development, cellular interactions, and disease progression within defined environments. Here, we describe the development and characterization of human 3D tissue models that promote the differentiation and long-term survival of functional neural networks. This work builds upon previous work where primary rodent neurons were successfully grown in a similar 3D system.(1) The model was adapted to human induced pluripotent stem cells, allowing for a more direct exploration of the human condition. These tissue cultures show diverse cell populations, including neurons and astroglial cells, interacting in 3D and exhibit spontaneous neural activity confirmed through electrophysiological recordings and calcium imaging over at least nine months. This approach allows for the direct integration of pluripotent stem cells into the 3D construct, bypassing early neural differentiation steps (embryoid bodies and neural rosettes). The streamlined process, in combination with the longevity of the cultures, provides a system that can be manipulated to support a variety of experimental applications, including the study of network development, maturation, plasticity, and/or degeneration. This tissue model was tested with stem cells derived from healthy individuals as well as Alzheimer’s and Parkinson’s disease patients. We observed similar growth and gene expression, which indicates the feasibility of generating patient-derived brain tissue models. These could be used to uncover early stage biomarkers of the disease state, in turn supporting earlier diagnosis and improving understanding of disease progression. With additional model development, this approach would have potential use for investigating drug targets in neurodegenerative diseases.

The cerebral cortex is essential for integration and processing of information that is required for most behaviors. The exquisitely precise laminar organization of the cerebral cortex arises during embryonic development when neurons migrate successively from ventricular zones to coalesce into specific cortical layers. While radial glia act as guide rails for projection neuron migration, pre-formed vascular networks provide support and guidance cues for GABAergic interneuron migration. This study provides novel conceptual and mechanistic insights into this paradigm of vascular-neuronal interactions, revealing new mechanisms of GABA and its receptor-mediated signaling via embryonic forebrain endothelial cells. With the use of two new endothelial cell specific conditional mouse models of the GABA pathway (Gabrb3ΔTie2-Creand VgatΔTie2-Cre), we show that partial or complete loss of GABA release from endothelial cells during embryogenesis results in vascular defects and impairs long-distance migration and positioning of cortical interneurons. The downstream effects of perturbed endothelial cell-derived GABA signaling are critical, leading to lasting changes to cortical circuits and persistent behavioral deficits. Furthermore, we illustrate new mechanisms of activation of GABA signaling in forebrain endothelial cells that promotes their migration, angiogenesis and acquisition of blood-brain barrier properties. Our findings uncover and elucidate a novel endothelial GABA signaling pathway in the CNS that is distinct from the classical neuronal GABA signaling pathway and shed new light on the etiology and pathophysiology of neuropsychiatric diseases, such as autism spectrum disorders, epilepsy, anxiety, depression and schizophrenia.

The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity, and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Because fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling, and electrophysiology. Both adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single-component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling, and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

The risk of steel sheet pile cofferdam construction is very high, and the collapse often results in heavy casualties. This paper discusses the calculation model of single wall steel sheet pile cofferdam system in detail during construction. Take for instance the R38# pier construction process of Haihe Bridge, the construction monitoring system of the steel sheet pile cofferdam is established to get the deformation and stress ofsteel sheet pile and supporting system. Comparative analysis between measurable results and 3D FEM results is done, and both are basically consistent.

In this paper, in order to simulate the corrosion of seawater, the drying-wetting cycling test was used. The mechanical properties of carbon fiber-reinforced concrete beam under salt damage were studied and the reinforcement effect of the CFRP was analyzed. At the same time, the bearing capacity of cross section of CFRP strengthened PC beam under corroded was analyzed.

Based on the pseudo-static tests among three different types of joints (traditional planted-bar joint, the CFRP strengthening joint and the transformed-connection joint) between concrete frame and adding light steel storey, the research was carried out to contrast the seismic performance of these joints. The results showed that: three joints’ destruction was due to the plastic hinge and the maximum crack appearing at the end of beams, the seismic performance of the two new types of joints were better than the traditional planted-bar joint; Among the three joints, the hysteresis curve envelope area of CFRP strengthening joint was the biggest and the energy consumption was the most powerful; The stiffness of transformed-connection joint was improved significant, and its manufacture technology of joint was simple and convenient.

The aging of asphalt pavement gets serious in the course of service due to the large number of vehicles and high pavement temperature. A survey was conducted on urban road’s asphalt pavement in the city of Tianjin. By analyzing the extracted asphalt sample from asphalt pavement built in different years, it shows that asphalt’s softening point and viscosity increase but its penetration and ductility attenuate with the extension of service period. Of which, the ductility changes dramatically with its ductility attenuating fast in the early years of service and the attenuation of ductility tending to slow down later. The vertical difference of aging in different depth of pavement is marked and degree of aging tends to attenuate from the surface to the center.

In this paper, a composite pavement stress absorbing layer is researched. Through the creation of the finite element analysis model of the composite pavement, the paper analyzed the shear stress and influencing factors such as a different level of force, the contact between the different layer, shear stress conditions, the surface layer modulus and thickness, base thickness, soil base resilient modulus. At last, the optimum thickness of the composite pavement structure layers is put forward.

According to the principle of minimum potential energy and energy differential methods and assuming the shear lag warp displacement function with consideration of prestressed steel, a set of differential equations are deduced with different boundary conditions in considering moment, torsion, shear lag coupling. And the numerical solution of the differential equations is gained by Galerlein method. In addition, explores the influence on shear lag with prestressed force or not, dead loading, live loading and prestressed forces of the prestessed steels the areas of them basing on the model experiment and finite element model. Comparisons of results for typical numerical examples are given to verify the accuracy and applicability of the present method.

This paper presents comparison of calculation methods on bi-directional shearing capacity of RC framed columns, mainly analyzing on the characteristics of the different method. It is demonstrated that the code method, the minimum volume of steel method,the simplified tri-linear analytical method are all derived from over-strength factor method.The difference among them is only different over-strength factor.Their three over-strength factors are to reduce all bearing capacity item,while the proposed method is only the parts of reduction to bearing capacity item. From the veiw of designing for security, all methods can meet the requirement of safety.

Based on the numerical calculation and the theoretical formula for crack width,a new semi-numerical and semi-theoretical calculation formula for crack width of beam was given. By using this new formula,finite element method and theoretical method is combined. The method has been validated with the beam, it is indicated that the proposed method can be used to calculate the crack width of beam accurately and efficiently.

Six specimens, including 4 ceramsite concrete beams(one of beams mixed into the polypropylene fiber ) and 2 normal concrete beams, were tested to investigate the flexural behavior. The test results show that cracking load of ceramsite concrete beams is slightly smaller than the ordinary concrete beam and cracking load of ceramsite concrete beams has significantly improved after mixing into the polypropylene fibers. The ultimate load of ceramsite concrete beams are no less than ordinary concrete beam,and fibers have not effects on the increase of ultimate load. Load-deflection curves were compared,and the results show that stiffness of ceramsite concrete beam is less than ordinary concrete beam. Ductility of ceramsite concrete beam is poorer than ordinary concrete beam. Fibers improve the stiffness of ceramsite concrete beam. Cover thickness of concrete beam has little effect on the performance of ceramsite concrete beam.

According to the confined characteristic of square concrete–filled steel tubular(CFST) column, core concrete zone was divided into the weak confined zone and the strong confined zone.A formula is derived for estimating the bearing capacity of square CFST column by analogy RC column with spiral stirrup. The proposed formula was used to calculate the existing experiments,the results showed that the computing values agreed well with the experimental values. The paper can be seen as a valuable guide for computing the bearing capacity of square CFST column.

The finite element models of biaxial shear capacity of RC frame columns are investigated.The calculation results and experimental results are compared using the different models.It is shown that different finite element models are effectively used to simulate the RC frame column. However, the simplified model may save computer time and be more convenient for the numerical simulation. Finally, the bilateral shear correlation of RC frame column is investigated using the simplified model. The results indicate that the bilateral shear correlation of the RC frame columns with different quantity of stirrups in two directions accords with the ellipse law and the fitting formula is presented.

In this paper, a comprehensive numerical investigation is presented on the behaviour of ceramsite light aggregate concrete(CLAC) beam by the non-linear finite element method. The investigation includes the entire process of the beam from loading to failure. Numerical analysis results show that the flexural behavior of CLAC beam is obtained by numerical simulation,including load-deflection curve, cross section stress and crack development ect. Numerical simulation may replace the actual experiment for study on flexural behavior of CLAC beam.

In order to study the performance of asphalt pavement with function layer under temperature-load coupling action, the thickness of surface layer, the module of surface layer and was analyzed to abtain their influence on the function layer stress using the finite element method. The results clearly indicated that it is very effective to prevent the reflection crack by increasing the thickness of asphalt surface layer and it is not obvious to reduce the reflection crack through enhancing the module of asphalt surface layer.

In this paper, a comparative investigation into the behavior of concrete-filled steel tube column and reinforced concrete column with the same quantity of material and cross-section sizes under axial load have been undertaken using the finite element method. Both is analyzed to compare the axial compression performance,including bearing capacity, ductility and their mechanism. The results of the analyses clearly exhibit that bearing capacity of concrete-filled steel tube column is higher about 25% than that of reinforced concrete column. Under the same conditions, ductility of concrete-filled steel tube column is better than reinforced concrete column, its application is recommended in construction practice.

Based on the shear performance of existing reinforced concrete beam oblique section and referring to the slipping theory of bending crack of the beam, a formula of the diagonal crack width is proposed through the equilibrium condition, the geometric condition and the concrete failure criteria. This formula has explicitly and clearly the physical concept.So,it can be used to check the maximum diagonal crack width of RC beam in the design.

A nonlinear finite element model is developed to study the behavior of square concrete-filled steel tubular(CFST) column and reinforced concrete (RC) column with the same quantity of material and cross-section sizes under eccentric load using ANSYS software.The results indicate that the bearing capacity of CFST column is about 30% greater than RC column and the ductility of CFST column is much greater than RC column under the same conditions. Eccentricity and slenderness ratio have same effect on the bearing capacity of both, which are drop.

The hexagonalphase NaYF4:Yb3+, Er3+hollow nanospheres HNS have been successfully prepared for the first time by means of a hydrothermal route with the aid of polyethylenimine PEI as a surfactant. The nitrogen adsorptiondesorption isotherms demonstrated the porous nature of the NaYF4HNS. The formation mechanism was explored based on the effects of the reaction parameters. The NaYF4solid spheres underwent a dissolutionrecrystallisation transformation and a hollowing process when the hydrothermal reaction time was prolonged. The localised Ostwald ripening mechanism was proposed to account for the formation of NaYF4HNS, in which loose aggregations were found to be crucial. The upconversion luminescence of NaYF4:Yb3+, Er3+HNS was also investigated. It is expected that these NaYF4HNS might have potential in applications as building blocks for biolabels and drugdelivery.

The diversity of neuronal nicotinic acetylcholine receptors (nAChRs) is likely an important factor in the modulation of synaptic transmission by acetylcholine and nicotine. We have tested whether postsynaptic nAChRs are modulated in a subtype-specific manner by prostaglandin E2(PGE2), a regulator of neuronal excitability in both the central and peripheral nervous systems, and examined the effects of PGE2on nicotinic transmission. Somatodendritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtypes distinguished on the basis of conductance and kinetic profile. Nanomolar PGE2applied to the extrapatch membrane differentially regulates opening probability (Po), frequency and the opening duration of each nAChR channel subtype in cell-attached patches. PGE2decreases the Po of the predominant nAChR subtype (36 pS) and significantly increases Po and open duration of the 23 pS subtype. The 23 pS subtype is gated by the α7-selective agonist choline, and choline-gated currents are inhibited by α-bungarotoxin. To examine whether PGE2modulates nAChRs at synaptic sites, we studied the effects of PGE2on amplitude and decay of synaptic currents in visceral motoneuron-sympathetic neuron co-cultures. PGE2significantly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), consistent with the predominant inhibition by PGE2of all but the 23 pS subtype. The time constant of mEPSCs at PGE2-treated synapses is prolonged, which is also consistent with an increased contribution of the longer open duration of the 23 pS nAChR subtype with PGE2treatment. To examine the presynaptic effect of PGE2, nanomolar nicotine was used. Nicotine induces facilitation of synaptic transmission by increasing mEPSC frequency, an action thought to involve presynaptic, α7-containing nAChRs. In the presence of PGE2, nicotine-induced synaptic facilitation persists. Thus the net effect of PGE2is to alter the profile of nAChRs contributing to synaptic transmission from larger conductance, briefer opening channels to smaller conductance, longer opening events. This subtype-specific modulation of nAChRs by PGE2may provide a mechanism for selective activation and suppression of synaptic pathways mediated by different nAChR subtype(s) at both pre- and postsynaptic sites.

Partial obstruction of the opossum esophagus leads to thickening of the circular muscle, hypertrophy of smooth muscle cells, and diminution of the extracellular space. The pharmacological and electrophysiological properties of this hypertrophied muscle were studied. Carbachol produced phasic and tonic contractions of the circular muscle. The EC50for tonic contractions was greater for hypertrophied than for normal muscle (21.1 ± 3.9 μmol/L vs. 4.8 ± 2.2 μmol/L; P< 0.05). The resting membrane potential difference of hypertrophied muscle (−50.8 ± 0.2 mV) was similar to that of normal muscle (−50.0 ± 0.2 mV). Electrical stimulation of intrinsic nerves in the normal muscle produced a hyperpolarization followed by a depolarization of smooth muscle membrane potential. Hypertrophied muscle responded either with an attenuated hyperpolarization or no hyperpolarization, both of which were followed by a depolarization. The space constant in the long axes of the hypertrophied circular muscle cells was greater than normal (4.4 ± 0.2 mm vs. 3.4 ± 0.1 mm; P< 0.001). The threshold potential for initiation of action potentials was more negative for hypertrophied (−43.2 ± 0.4 mV) than for normal circular muscle (−41.6 ± 0.2 mV; P< 0.005). These data indicate that alterations in neuromuscular function accompany the hypertrophy of esophageal smooth muscle.

Tan, Wen, Chuang Du, Steven A. Siegelbaum, and Lorna W. Role.Modulation of nicotinic AChR channels by prostaglandin E2in chick sympathetic ganglion neurons. J. Neurophysiol.79: 870–879, 1998. The effects of prostaglandin E2(PGE2), an important metabolite of arachidonic acid, were studied on the activity of nicotinic AChR channels in cultured chick sympathetic ganglion neurons. In whole cell recordings, PGE2(25 nM) inhibited significantly the ACh-evoked macroscopic current. In cell-attached patch recordings, PGE2significantly inhibited single AChR channel currents as a result of a decrease in the frequency of channel opening, with no change in open time and conductance. PGE2did not alter the extent or rate of agonist-induced desensitization of the AChR channels. These effects are specific since the related compound PGD2had no effect on AChR channel function. Because there is an abundant endogenous production of PGE2within sympathetic ganglia in response to certain stimuli, the inhibition of AChR channel function by PGE2could serve an important role to modulate synaptic transmission in the sympathetic nervous system.

These studies test the hypothesis that the generation of colonic slow waves can be modulated by stimulation of intrinsic enteric nerves and attempt to identify a neurotransmitter that may be responsible for this change in slow-wave activity. Isolated segments from the mid-colon of the cat generated regular, continuous slow waves at 6.5±1.1 cpm. Activation of the intrinsic nerves by electrical field stimulation transiently reduced the rate of slow-wave generation to 4.7±0.7 cpm (P<0.001). The response to electrical stimulation was blocked by tetrodotoxin and a-chymotrypsin. The following antagonists were not effective in blocking the response: atropine, hexamethonium, phenoxybenzamine, propranolol, methysergide, naloxone, or imidazole. Vasoactive intestinal polypeptide (5×10-7 M) decreased slow wave frequency to 4.5±0.4 cpm. Vasoactive intestinal polypeptide (VIP) fragment 10-28 inhibited the effect of electrical field stimulation but also decreased the slow-wave frequency. VIP-immunoreactive nerves were much more abundant in the plexus submucosus extremus than in the circular muscle of the muscularis externa. Thus, pacemakers for colonic slow waves may be modulated by intrinsic colonic nerves, and vasoactive intestinal polypeptide may be the neurotransmitter responsible for this modulation.

Background:Nitric oxide and an apamin-sensitive transmitter may both contribute to neural inhibition in the human colon. The present study investigated the role of NO in regulating spontaneous rhythmic contractions and examined NO-dependent and independent components of neurally evoked hyperpolarization in the human colon. Methods:Mechanical and electrical activity were recorded from isolated circular muscle strips. Results:Rhythmic contractions were inhibited by nerve stimulation. This response was reduced by apamin, oxyhemoglobin, and l-NG-nitro arginine methyl ester (l-NAME). Electrical recording revealed two components of neurally evoked hyperpolarization: a fast hyperpolarization resulting from a single stimulus and a sustained hyperpolarization that developed with repetitive stimulation. Fast hyperpolarization was not affected by l-NAME or oxyhemoglobin but was significantly reduced by apamin. The sustained hyperpolarization was reduced by l-NAME or apamin. Exogenous NO and the P2yreceptor agonist 2-methylthio adenosine 5′-triphosphate (2-MATP) inhibited spontaneous contractions and produced hyperpolarization. Apamin reduced the effects of 2-MATP but not those of NO. Conclusions:The results support the concept that the inhibitory neurotransmission in the human colon involves two transmitters. A single stimulus results in an apamin-sensitive response. With multiple stimuli, a NO-dependent response develops and sums with the apamin-sensitive mechanism, producing sustained hyperpolarization and inhibition of contractions.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

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