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The report of the 19th National Congress of the Communist Party of China first proposed the strategy of rural revitalization. This proposal constitutes a major strategic deployment for work related to “agriculture, the countryside and farmers” based on China’s national and agricultural conditions and scientific analysis of the new problems faced by agricultural and rural reform in the new era. China’s agricultural development is facing multiple challenges, such as market competition, resource scarcity, environmental constraints, labor exodus, and technological innovation. Additionally, China’s agricultural production is inefficient, farmers’ income is low, and the hollowing out of the countryside has further intensified. To address these challenges, the Party Central Committee made the major decision to implement the rural revitalization strategy, and governments at all levels have introduced a series of policies to support agriculture. However, with the rapid advancement of industrialization and urbanization, the proportion of agricultural output to the total output of the national economy and the proportion of the agricultural labor force to the social labor force are not decreasing, and the idea of seizing the opportunities offered by agriculture is no longer able to solve the current dilemma faced by agricultural and rural development. Expanding the function of agriculture and actively docking with the industry and the service industry are a major strategic initiative for actively adapting to the new normal of economic development. They also represent major innovative thinking to accelerate the transformation of the agricultural development mode. Only when industries are prosperous can rural revitalization have a strong material foundation. To achieve industrial prosperity, industrial integration is the key. Therefore, the realization of rural industrial revitalization must take the path of industrial integration and development. At present, research on rural industrial integration is limited to the local regions, such as provinces and cities, and analysis at the level of national rural industrial integration is lacking. Accelerating the integrated development of rural industries is key to promoting rural revitalization. This paper scientifically establishes an evaluation index system for the level of rural industrial integration development based on five related aspects: society, the economy, resources, facilities, and the environment. Factor analysis is used to reduce the dimensionality of the evaluation index system, and cluster analysis is used to classify the rural industrial integration development level of each province in China into different tiers. The results show that there are obvious regional differences in the levels of rural industrial integration development in China. The provinces and cities with development levels that are higher than average (i.e., scores ranging from 0.291 to 0.915) are concentrated in the eastern coastal areas and inland riverine areas. In contrast, those with development levels that are lower than average (i.e., scores ranging from −0.504 to −0.750) are concentrated in Northern China, the northeastern noncoastal areas and northwestern areas. In addition, provinces can be divided into five development tiers of rural industrial integration. Based on this information, national, provincial, and municipal improvement strategies are proposed to address the differences in development among and the prospects for each province, and to effectively promote the integration of rural industries in China.

Though dentin hypersensitivity (DHS) is one of the most common complaints from patients in dental clinics, there are no universally accepted guidelines for differential diagnosis as well as selection of reliable treatment modalities for this condition. The neurosensory mechanisms underlying DHS remain unclear, but fluid movements within exposed dentinal tubules, i.e., the hydrodynamic theory, has been a widely accepted explanation for DHS pain. As several dental conditions have symptoms that mimic DHS at different stages of their progression, diagnosis and treatment of DHS are often confusing, especially for inexperienced dental practitioners. In this paper we provide an up-to-date review on risk factors that play a role in the development and chronicity of DHS and summarize the current principles and strategies for differential diagnosis and management of DHS in dental practices. We will outline the etiology, predisposing factors and the underlying putative mechanisms of DHS, and provide principles and indications for its diagnosis and management. Though desensitization remains to be the first choice for DHS for many dental practitioners and most of desensitizing agents reduce the symptoms of DHS by occluding patent dentinal tubules, the long-term outcome of such treatment is uncertain. With improved understanding of the underlying nociceptive mechanisms of DHS, it is expected that promising novel therapies will emerge and provide more effective relief for patients with DHS.

Human dental pulp stem cells (hDPSCs) reside in postnatal dental pulp and exhibit the potential to differentiate into odontoblasts as well as neurons. However, the intercellular signaling niches necessary for hDPSC survival and self-renewal remain largely unknown. The objective of this study is to demonstrate the existence of intercellular purinergic signaling in hDPSCs and to assess the impact of purinergic signaling on hDPSC survival and proliferation. hDPSCs were isolated from extracted third molars and cultured in minimum essential medium. To demonstrate responsiveness to ATP application and inhibitions by purinergic receptor antagonists, whole cell patch-clamp recordings of ATP-induced currents were recorded from cultured hDPSCs. Immunofluorescence and enzymatic histochemistry staining were performed to assess purinergic receptor expression and ectonucleotidase activity in hDPSCs, respectively. To determine the effects of purinergic signaling on hDPSC, purinergic receptor antagonists and an ectonucleotidase inhibitor were applied in culture medium, and hDPSC survival and proliferation were assessed with DAPI staining and Ki67 immunofluorescence staining, respectively. We demonstrated that ATP application induced inward currents in hDPSCs. P2X and P2Y receptors are involved in the generation of ATP-induced inward currents. We also detected expression of NTPDase3 and ectonucleotidase activity in hDPSCs. We further demonstrated that purinergic receptors were tonically activated in hDPSCs and that inhibition of ectonucleotidase activity enhanced ATP-induced inward currents. Furthermore, we found that blocking P2Y and P2X receptors reduced—and inhibition of ecto-ATPase activity enhanced—the survival and proliferation of hDPSCs, while blocking P2X receptors alone affected only hDPSC proliferation. Autocrine/paracrine purinergic signaling is essential for hDPSC survival and proliferation. These results reveal potential targets to manipulate hDPSCs to promote tooth/dental pulp repair and regeneration.

Purinergic signaling is involved in pain generation and modulation in the nociceptive sensory nervous system. Adenosine triphosphate (ATP) induces pain via activation of ionotropic P2X receptors while adenosine mediates analgesia via activation of metabotropic P1 receptors. These purinergic signaling are determined by ecto-nucleotidases that control ATP degradation and adenosine generation. Using enzymatic histochemistry, we detected ecto-AMPase activity in dental pulp, trigeminal ganglia (TG) neurons, and their nerve fibers. Using immunofluorescence staining, we confirmed the expression of ecto-5′-nucleotidase (CD73) in trigeminal nociceptive neurons and their axonal fibers, including the nociceptive nerve fibers projecting into the brainstem. In addition, we detected the existence of CD73 and ecto-AMPase activity in the nociceptive lamina of the trigeminal subnucleus caudalis (TSNC) in the brainstem. Furthermore, we demonstrated that incubation with specific anti-CD73 serum significantly reduced the ecto-AMPase activity in the nociceptive lamina in the brainstem. Our results indicate that CD73 might participate in nociceptive modulation by affecting extracellular adenosine generation in the trigeminal nociceptive pathway. Disruption of TG neuronal ecto-nucleotidase expression and axonal terminal localization under certain circumstances such as chronic inflammation, oxidant stress, local constriction, and injury in trigeminal nerves may contribute to the pathogenesis of orofacial neuropathic pain.

We report a capillary-based surface plasmon resonance sensor that integrates sample collection, injection, and measurement. The sensor reported here can be fabricated at low cost and possesses a small and robust package. The hollow structure of the capillary not only can be used as a fluid channel but also allows light to travel along a spiral and straight line, which is very helpful for reducing the length of the sensing region. The operation wavelength of the sensor can be tuned with a harmless high-index dielectric layer, which makes it possible to generate a reference signal to correct the effect of changes in the bulk refractive index or temperature. Our experiments show that the sensor can operate at room temperature and is capable of performing label-free detection and real-time monitoring through a single sensing device. Furthermore, similar to needles and insertable probes, the sensor could also potentially be used for minimally invasive medical diagnostics and monitoring. As a biosensor, it will be a practical and specific detection device that can be widely used, such as in biological and life sciences research, and rapid diagnostics.

We present a novel multi-point fiber-optic refractive index (RI) sensor based on two different length coreless fibers spliced between single mode fibers (SMFs). The sensing probe operated based on multimode interference. A multi-point interferometer with 25 mm and 30 mm coreless fiber is fabricated and the measurement of RI is realized by measuring the wavelength shift of resonance dips in the transmission spectrum of the multi-point interferometer. Experimental characterization for a multi-point refractometer is presented. In the RI range of 1.3288–1.3666, the corresponding RI sensitivities are 148.60 nm/RIU and 119.27 nm/RIU for each point, respectively. We demonstrate that this multi-point fiber optic interferometer can be used as a simple transducer for RI sensing with comparable sensitivity.

Rationale Tension band wiring is the most widely accepted technique for the treatment of patellar fractures but the technique is associated with common complications like wire migration, prominence, and breakage. To reduce these complications, we developed and propose a modified technique that has a superior biomechanical strength and a potential to reduce such postoperative complications. Patient concerns The patient presented with pain and mild swelling in his left knee after he slipped on the floor and fell on his left knee. He has no significant past medical or surgical history. The patient took the tension band wiring as the first choice because of the wide acceptance. But he worried about the complications. Diagnoses X-ray showed a transverse fracture of the left patella with an inferior pole occult fracture. Interventions The patient was operated with a modified technique of the classic tension band wiring for patellar fractures. In our 4-step procedure, double tension cerclage wires were wrapped under the exposed ends of the Kirschner wires (K-wires) and the tendons in figure-of-8 fashion. The aim was to increase the biomechanical strength so that when one of the tension wires fail, the other one can hold the fragments together. Outcomes The patient recovered very well and without any complications. The patient was followed-up for 1 year and the fracture has united very well, with satisfying knee range of motion. Lessons From this case study, we can detect the biomechanical advantages of our technique which can increase the stability of the fracture and that allows early functional exercise and additionally the micromotion at the fracture site has a beneficial effect of fracture union. Based on the perfect outcomes, our technique is worthy of clinical application.

A fiber optic surface plasmon resonance (SPR) sensor based on light guiding flexible fused silica tubing with its cladding stripped and coated with gold film as SPR sensing area is presented. Theoretical simulate of the proposed sensing structure for different sensing area length and different film thickness of sensors is done to obtain the suitable parameters, and the simulation for different refractive index is carried out. Meanwhile, the experiments for refractive index (RI) measurement have been demonstrated using the developed sensor, 400 μm optical fiber sensor and 125 μm optical fiber sensor. Experimental results have shown the capillary sensor has advantage in terms of sensitivity and resolution. The capillary sensor is also used for detecting and monitoring biochemical binding and dissociation processes of the RNase B and Con A. It is proved that the sensor with chemical modification can be implemented for specific biochemical sensing

An optical fiber displacement sensor with a large measuring range for simultaneous displacement and temperature measurement is presented in this paper. We developed a specific transducer based on the piston and hydraumatic structure to realize a large displacement measurement, which combined the large measuring range and high precision into a single sensor system. The spectrum showed two reflection peaks used to compensate for cross-sensitivity in the displacement detection. This displacement sensor can linearly work in a large measuring displacement range greater than 45 mm with a high sensitivity of 0.036 nm/mm. The sensor we reported can be developed for real-time displacement monitoring in many industrial environments such as the mechanical shape or liquid level monitoring.

Dental procedure induced pain may develop into a chronic condition that accompanied with functional or neuropathy changes in the nerve system. In this case, severe persistent pain gradually developed after repeatedly placing a subgingival amalgam restoration in the right second molar. Hyperalgesia and allodynia were present at the affected region. A provisional diagnosis of chronic orofacial pain with peripheral and central sensitization was considered. After re-contouring, local debridement and occlusal adjustment the pain disappeared. The underlying mechanism in this case is neuronal sensitization and peripheral Aβ-fiber mechanoreceptor activation. Its diagnosis and management depend on identification and treatment of the cause for pain generation and sensitization.

Background We investigated the underlying molecular mechanisms of bone overgrowth after femoral fracture by using high-throughput bioinformatics approaches. Methods The gene expression profile of GSE3298 (accession number) was obtained from the Gene Expression Omnibus database. Sixteen femoral growth plate samples, including nine samples without fracture and seven fracture samples for seven time points, were used for analysis. The Limma package was applied to identify differentially expressed genes (DEGs) between fractured and intact samples. The DAVID online tool was used for Gene ontology functional and pathway enrichment analysis. A protein-protein interaction (PPI) network established by String software was used to identify interactions between significant DEGs, and network modules were detected using plug-in MCODE. Additionally, a transcription regulatory network was constructed based on the ENCODE Project and PPI network. Results A total of 680 DEGs were screened in fractured femoral growth plate samples compared with controls, including 238 up- and 442 down-regulated genes. These DEGs were significantly involved in the calcium signaling pathway and cancer pathway. A PPI network was constructed with 167 nodes and 233 edges, and module analysis demonstrated that CCL2, CSF2, NOS2, and DLC1 may stimulate bone overgrowth after femoral fracture via anti-apoptosis-related functions. A transcription regulatory network was constructed with 387 interacting pairs, and overlapping nodes were significantly enriched in intracellular signaling cascade and regulation of cell proliferation, among others. Conclusions Bone overgrowth was associated with changes in the expression of identified DEGs such as CCL2, NOS2, CSF2, and DLC1 in the femoral head. They may be important in regulating bone overgrowth via the anti-apoptosis of osteoblasts. Electronic supplementary material The online version of this article (doi:10.1186/s13018-017-0510-6) contains supplementary material, which is available to authorized users.

Corrosion of dental alloys is a major concern in dental restorations. Streptococcus mutans reduces the pH in oral cavity and induces demineralization of the enamel as well as corrosion of restorative dental materials. The rough surfaces of dental alloys induced by corrosion enhance the subsequent accumulation of plaque. In this study, the corrosion process of nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) alloys in a nutrient-rich medium containing S. mutans was studied using inductively coupled plasma atomic emission spectrometry (ICP-AES), X-ray photoelectron spectroscopy (XPS) and electrochemical corrosion test. Our results showed that the release of Ni and Co ions increased, particularly after incubation for 3 days. The electrochemical corrosion results showed a significant decrease in the corrosion resistance (Rp) value after the alloys were immersed in the media containing S. mutans for 3 days. Correspondingly, XPS revealed a reduction in the relative dominance of Ni, Co, and Cr in the surface oxides after the alloys were immersed in the S. mutans culture. After removal of the biofilm, the pre-corroded alloys were re-incubated in S. mutans medium, and the expressions of genes associated with the adhesion and acidogenesis of S. mutans, including gtfBCD, gbpB, fif and ldh, were evaluated by detecting the mRNA levels using real-time reverse transcription polymerase chain reaction (RT-PCR). We found that the gtfBCD, gbpB, ftf and Idh expression of S. mutans were noticeably increased after incubation with pre-corroded alloys for 24 h. This study demonstrated that S. mutans enhanced the corrosion behavior of the dental alloys, on the other hand, the presence of corroded alloy surfaces up-regulated the virulent gene expression in S. mutans. Compared with smooth surfaces, the rough corroded surfaces of dental alloys accelerated the bacteria-adhesion and corrosion process by changing the virulence gene expression of S. mutans.

The prospective pyramidal neurons, migrating from the proliferative ventricular zone to the overlaying cortical plate, assume multipolar morphology while passing through the transient subventricular zone. Here, we show that this morphogenetic transformation, from the bipolar to the mutipolar and then back to bipolar again, is associated with expression of connexin 43 (Cx43) and, that knockdown of Cx43 retards, whereas its overexpression enhances, this morphogenetic process. In addition, we have observed that knockdown of Cx43 reduces expression of p27, whereas overexpression of p27 rescues the effect of Cx43 knockdown in the multipolar neurons. Furthermore, functional gap junction/hemichannel domain, and the C-terminal domain of Cx43, independently enhance the expression of p27 and promote the morphological transformation and migration of the multipolar neurons in the SVZ/IZ. Collectively, these results indicate that Cx43 regulates the passage of migrating neurons through their multipolar stage via p27 signaling and that interference with this process, by either genetic and/or environmental factors, may cause cortical malformations.

Neuronal progenitors are continuously generated in the postnatal rodent subventricular zone and migrate along the rostral migratory stream to supply interneurons in the olfactory bulb. Nonsynaptic GABAergic signaling affects the postnatal neurogenesis by depolarizing neuronal progenitors, which depends on an elevated intracellular Cl(-) concentration. However, the molecular mechanism responsible for Cl(-) accumulation in these cells still remains elusive. Using confocal Ca(2+) imaging, we found that GABA depolarization-induced Ca(2+) increase was either abolished by bumetanide, a specific inhibitor of the Na(+) -K(+) -2Cl(-) cotransporter, or reduced by partial replacement of extracellular Na(+) with Li(+) , in the HEPES buffer but not in the CO(2)/HCO₃⁻ buffer. GABA depolarization-induced Ca(2+) increase in CO(2)/HCO₃⁻ buffer was abolished by a combination of bumetanide with the anion exchanger inhibitor DIDS or with the carbonic anhydrase inhibitor acetozalimide. Using gramicidin-perforated patch-clamp recording, we further confirmed that bumetanide, together with DIDS or acetozalimide, reduced the intracellular chloride concentration in the neuronal progenitors. In addition, with BrdU labeling, we demonstrated that blocking of the Na(+) -K(+) -2Cl(-) cotransporter, but not anion exchangers, reduced the proliferation of neuronal progenitors. Our results indicate that both the Na(+) -K(+) -2Cl(-) cotransporter and anion exchangers contribute to the elevated intracellular chloride responsible for the depolarizing action of GABA in the postnatal forebrain neuronal progenitors. However, the Na(+) -K(+) -2Cl(-) cotransporter displays an additional effect on neuronal progenitor proliferation.

Dental pulpal nerve fibers express ionotropic adenosine triphosphate (ATP) receptors, suggesting that ATP signaling participates in the process of dental nociception. In this study, we investigated if the principal enzymes responsible for extracellular ATP hydrolysis, namely, nucleoside triphosphate diphosphohydrolases (NTPDases), are present in human dental pulp. Immunohistochemical and immunofluorescence experiments showed that NTPDase2 was predominantly expressed in pulpal nerve bundles, Raschkow’s nerve plexus, and in the odontoblast layer. NTPDase2 was expressed in pulpal Schwann cells, with processes accompanying the nerve fibers and projecting into the odontoblast layer. Odontoblasts expressed the gap junction protein, connexin43, which can form transmembrane hemichannels for ATP release. NTPDase2 was localized close to connexin43 within the odontoblast layer. These findings provide evidence for the existence of an apparatus for ATP release and degradation in human dental pulp, consistent with the involvement of ATP signaling in the process of dentin sensitivity and dental pain.

Axon-dendrite polarization is crucial for neural network wiring and information processing in the brain. Polarization begins with the transformation of a single neurite into an axon and its subsequent rapid extension, which requires coordination of cellular energy status to allow for transport of building materials to support axon growth. We found that activation of the energy-sensing adenosine 5′-monophosphate (AMP)–activated protein kinase (AMPK) pathway suppressed axon initiation and neuronal polarization. Phosphorylation of the kinesin light chain of the Kif5 motor protein by AMPK disrupted the association of the motor with phosphatidylinositol 3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting polarization and axon growth.

Cortical axons contain a diverse range of voltage-activated ion channels, including Ca2+currents. Interestingly, Ca2+channels are not only located at presynaptic terminals, but also in the axon initial segment (AIS), suggesting a potentially important role in the regulation of action potential generation and neuronal excitability. Here, using two-photon microscopy and whole-cell patch-clamp recording, we examined the properties and role of calcium channels located in the AIS and presynaptic terminals of ferret layer 5 prefrontal cortical pyramidal cellsin vitro. Subthreshold depolarization of the soma resulted in an increase in baseline and spike-triggered calcium concentration in both the AIS and nearby synaptic terminals. The increase in baseline calcium concentration rose with depolarization and fell with hyperpolarization with a time constant of approximately 1 s and was blocked by removal of Ca2+from the bathing medium. The increases in calcium concentration at the AIS evoked by subthreshold or suprathreshold depolarization of the soma were blocked by the P/Q-channel antagonist ω-agatoxin IVA or the N-channel antagonist ω-conotoxin GVIA or both. The presence of these channels in the AIS pyramidal cells was confirmed with immunochemistry. Block of these channels slowed axonal action potential repolarization, apparently from reduction of the activation of a Ca2+-activated K+current, and increased neuronal excitability. These results demonstrate novel mechanisms by which calcium currents may control the electrophysiological properties of axonal spike generation and neurotransmitter release in the neocortex.

During mitotic division in the telencephalic proliferative ventricular zone (VZ), the nuclei of the neural precursors move basally away from the ventricular surface for DNA synthesis, and apically return to the surface for mitotic division; a process known as interkinetic migration or “to-and-fro” nuclear translocation. The cell, which remains attached to the ventricular surface, either continues cycling, or exits the cycle and migrates to the subventricular zone or the developing cortical plate. Although gap junctions/hemichannels are known to modulate DNA synthesis via Ca2+waves, the role of Ca+oscillations and the mechanism of nuclear translocation in the VZ precursors are unclear. Here, we provide evidence that, during apical nuclear migration, VZ precursors display dynamic spontaneous Ca2+transients, which depend on functional gap junctions/hemichannels via ATP release and Ca2+-mobilizing messenger diffusion. Furthermore, we found that blocking gap junctions/hemichannels or short hairpin RNA-mediated knockdown of Cx43 (connexin 43) retards the apically directed interkinetic nuclear migration accompanied with changes in the nuclear length/width ratio. In addition, we demonstrated that blocking functional gap junctions/hemichannels induces phosphorylation of small GTPase cdc42 in the VZ precursors. The basal phase of interkinetic migration is much slower and appears to be mediated passively by mechanical forces after cell division. Our findings indicate that functional interference with gap junctions/hemichannels during embryonic development may lead to abnormal corticogenesis and dysfunction of the cerebral cortex in adult organisms.

Most neurons of the cerebral cortex are generated in the germinal zones near the embryonic cerebral ventricle and migrate radially to the overlying cortical plate. Initially, all dividing cells are attached to the surface of the embryonic ventricle (ventricular zone) until a subset of dividing cells (basal or intermediate neuronal progenitors, INPs), recognized by their immunoreactivity to Tbr2, detach from the ventricular surface and migrate a short distance to establish a secondary proliferative compartment (the subventricular zone). The mechanism that regulates migration of the Tbr2 + INPs from the ventricular to the subventricular zones is unknown. Here, we show that INPs, unlike the postmitotic neurons that tend to lose the ATP response, continue to express the purinergic P2Y1 receptor. Furthermore, blocking ATP signaling by the P2Y1 blockers, MRS2176, suramin, and apyrase, reduces Ca 2+ transients and retards INP migration to the subventricular zone. In addition, genetic knockdown of the P2Y1 receptor by in vivo application of short hairpin RNA selectively impairs the migration of INPs to the subventricular zone. Together, these results suggest that intercellular ATP signaling is essential for the migration of INPs and the proper formation of the subventricular zone. Interference of ATP signaling or abnormal Ca 2+ fluctuations in INPs may play a significant role in variety of genetic or acquired cortical malformations.

Cilia are present on nearly all cell types in mammals and perform remarkably diverse functions. However, the mechanisms underlying ciliogenesis are unclear. Here, we cloned a previously uncharacterized highly conserved gene, stumpy , located on mouse chromosome 7. Stumpy was ubiquitously expressed, and conditional loss in mouse resulted in complete penetrance of perinatal hydrocephalus (HC) and severe polycystic kidney disease (PKD). We found that cilia in stumpy mutant brain and kidney cells were absent or markedly deformed, resulting in defective flow of cerebrospinal fluid. Stumpy colocalized with ciliary basal bodies, physically interacted with γ-tubulin, and was present along ciliary axonemes, suggesting that stumpy plays a role in ciliary axoneme extension. Therefore, stumpy is essential for ciliogenesis and may be involved in the pathogenesis of human congenital malformations such as HC and PKD.

ATP induces pain via activation of purinergic receptors in nociceptive sensory nerves. ATP signaling is terminated by ATP hydrolysis mediated by cell surface-localized ecto-nucleotidases. Using enzymatic histochemical staining, we show that ecto-ATPase activity is present in mouse trigeminal nerves. Using immunofluorescence staining, we found that ecto-NTPDase3 is expressed in trigeminal nociceptive neurons and their projections to the brainstem. In addition, ecto-ATPase activity and ecto-NTPDase3 are also detected in the nociceptive outermost layer of the trigeminal subnucleus caudalis. Furthermore, we demonstrate that incubation with anti-NTPDase3 serum reduces extracellular ATP degradation in the nociceptive lamina of both the trigeminal subnucleus caudalis and the spinal cord dorsal horn. These results are consistent with neuronal NTPDase3 activity modulating pain signal transduction and transmission by affecting extracellular ATP hydrolysis within the trigeminal nociceptive pathway. Thus, disruption of trigeminal neuronal NTPDase3 expression and localization to presynaptic terminals during chronic inflammation, local constriction and injury may contribute to the pathogenesis of orofacial neuropathic pain.

1 The potential cardioprotective effect of ACE inhibitors has been attributed to the inhibition of bradykinin degradation. Recent data in rats documented a kallidin-like peptide, which mimics the cardioprotective effect of ischaemic preconditioning. This study investigates in isolated Langendorff rat heart the effect of the ACE inhibitor captopril, the role of bradykinin, kallidin-like peptide, and nitric oxide (NO). 2 The bradykinin level in the effluent of the control group was 14.6 pg ml−1 and was not affected by captopril in the presence or absence of kinin B2-receptor antagonist, HOE140. 3 The kallidin-like peptide levels were approximately six-fold higher (89.8 pg ml−1) and increased significantly by treatment with captopril (144 pg ml−1), and simultaneous treatment with captopril and HOE140 (197 pg ml−1). 4 Following 30 min ischaemia in the control group, the creatine kinase activity increased from 0.4 to 53.4 U l−1. In the captopril group and in the captopril+L-NAME group, the creatine kinase activity was significantly lower (18.5 and 22.8 U l−1). This beneficial effect of captopril was completely abolished by the kinin B2-receptor antagonist, HOE140, as well as by the kallidin antiserum. 5 Perfusion of the hearts with kallidin before the 30 min ischaemia, but not with bradykinin, yielded an approximately 50% reduction in creatine kinase activity after reperfusion. 6 Pretreatment with L-NAME alone and simultaneously with captopril, and with kallidin, respectively, suggests a kinin-independent action of NO before the 30 min ischaemia on coronary flow and a kinin-dependent action after ischaemia. 7 These data show that captopril increases kallidin-like peptide in the effluent. Kallidin-like peptide via kinin B2 receptor seems to be the physiological mediator of cardioprotective actions of captopril against ischaemic reperfusion injury. HOE140 as well as the kallidin antiserum abolished the cardioprotective effects of captopril. British Journal of Pharmacology (2006) 148, 825–832. doi:10.1038/sj.bjp.0706799

Bradykinin is thought to play a major role among the endogenous cardioprotective candidates of ischaemic preconditioning (IPC). Little attention has been paid to the fact that in the tissue kallidin (KAL), rather than bradykinin might be the physiological mediator of the kallikrein–kinin system. In order to evaluate the importance of one or the other peptide the release and effect of both kinins has been investigated in isolated rat hearts following IPC. Bradykinin- and a KAL-like peptide were measured in the effluent of the rat isolated Langendorff heart with two different specific radioimmunoassays. The creatine kinase activity in the effluent was judged as degree of cardiac injury caused by ischaemia. During IPC, which consists of three 5 min no-flow and 5 min reperfusion cycles prior to the 30 min ischaemia, the bradykinin level in the effluent did not change significantly (15.4–19.4 pg ml−1). In the control group the bradykinin levels were 15.9–16.6 pg ml−1. During IPC KAL-like peptide (Arg1-, instead of Lys1-KAL), which has recently been verified by mass spectrometry, displays 5.8-fold higher levels in the effluent and significantly increases in the same time interval from 90.4 to 189 pg ml−1. After 30 min ischaemia the bradykinin levels in the IPC group were not significantly different to those of the control group (18.7 vs 14.4 pg ml−1). The KAL-like peptide levels in the IPC group vs the control group were 105 vs 86.1 pg ml−1. By the 30 min ischaemia the creatine kinase activity in the IPC group increased from 0.367 to 8.93 U l−1 (before and 10–30 min after ischaemia). In the control group during the same time period the creatine kinase levels increased from 0.277 to 34.9 U l−1. The low increase in creatine kinase activity following IPC was taken as equivalent of the cardioprotective action. A KAL antibody or HOE140 (kinin B2-receptor antagonist) completely abolished this beneficial effect of IPC (36.6 and 53.0 U l−1) when added to the perfusion medium during the reperfusion cycles of IPC prior to the 30 min ischaemia. Our data suggest that in rat hearts KAL-like peptide rather than bradykinin is the physiological compound activated by IPC and acting via the cardiac kinin B2-receptor. Thus, endogenously generated KAL-like peptide seems to play a major role in the cardioprotection of IPC. British Journal of Pharmacology (2005) 146, 952–957. doi:10.1038/sj.bjp.0706402

In the postnatal subventricular zone (SVZ), local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarization of neuroblasts induces nonsynaptic SNARE-independent GABA(A) receptor currents in GFAP-expressing cells, the time course of which depends on GABA uptake in acute mouse slices. We found that GABA(A) receptors are tonically activated in GFAP-expressing cells, consistent with the presence of spontaneous depolarizations in neuroblasts that are sufficient to induce GABA release. These data demonstrate the existence of nonsynaptic GABAergic signaling between neuroblasts and GFAP-expressing cells. Furthermore, we show that GABA(A) receptor activation in GFAP-expressing cells limits their progression through the cell cycle. Thus, as GFAP-expressing cells generate neuroblasts, GABA released from neuroblasts provides a feedback mechanism to control the proliferation of GFAP-expressing progenitors by activating GABA(A) receptors.

Derivatives of somatostatin (SST) represent the most important peptides for receptor targeting in oncological applications. Whereas the pharmacophor in somatostatin receptor-affine substances has been thoroughly investigated, the influence of modifications at the N-terminal has not yet been systematically studied. In order to investigate the influence of hydrophilic versus lipophilic modifications at the N-terminal end, a series of homologous derivatives of Tyr3-octreotate modified with oligomers of ethylene glycol or fatty acids were synthesized. For this purpose, Tyr3-octreotate was assembled using solid phase peptide synthesis and the fatty acids or oligomers of ethylene glycol were conjugated to the N-terminal end. The oligomers of ethylene glycol were activated by 4-nitrophenylchloroformate to obtain carbamate-linked hydrophilic compounds. The receptor affinities of these compounds were determined by competition experiments with [125I]Tyr3-octreotide on rat cortex membranes. The hydrophilic derivatives and the short chain lipophilic derivatives revealed IC50 values between 0.66 +/- 0.02 nM and 2.16 +/- 0.31 nM respectively. After labeling with (125)I the organ distribution of selected derivatives was investigated in Lewis rats bearing the rat pancreatic tumor CA20948. All of the compounds showed high tumor uptake. The peptides conjugated to oligomers of ethylene glycol showed low uptake into the liver and kidneys. Increasing the length of the fatty acids resulted in a remarkable decrease in kidney uptake. In conclusion, the systematic modifications at the N-terminal result in a low effect on the receptor affinity but allow the modulation of the pharmacokinetic properties of octreotide derivatives.

Patients presenting with referred dental orofacial pain are not rare in dental clinics. The most common cause for referred dental craniofacial pain is of odontogenic origin. An accurate diagnosis will depend on a comprehensive clinical exam and dental history review. For differential diagnosis, it is critical to consider both the odontognic and nonodontogenic etiology. Once a correct diagnosis is established, a proper treatment can be administrated by elimination of the etiology. We describe the updated mechanism for referred pain with neuronal plasticity and central sensitization theory. Through clinical cases, we elucidate how the diagnosis of odontogenic referred dental craniofacial pain is achieved, and the etiology is established. Because of its complex nature, odontogenic referred dental craniofacial pain can be misdiagnosed and patients may receive unnecessary procedures. Proper knowledge and strategy would help to achieve success in the diagnosis and treatment of odontogenic referred dental orofacial pain.

We present a wavelength-tunable tapered optics fiber surface Plasmon resonance (SPR) sensor by polishing the end faces of multimode fibers(MMF).Two hard plastic clad optical fibers joint closely and are used as the light input and output channels. Their end faces are polished to produce two oblique planes, which are coated with gold film to be the sensing surface and the front mirror. The presence of the tapered geometry formed by the two oblique planes in the orthogonal directions makes it possible to adjust incident angle through changing the tilt angles of the two end faces, so as to achieve tuning the SPR coupling wavelength-angle pair. Compared with previous researches based a tapered optic fiber probe, we report the approach theoretically increase the signal noise ratio (SNR) by separating incident and emergent light propagating in the different coordinate fiber. Since fabricating the sensing surface and the front mirror on the two fibers to replace one single fiber tip, there is more incident light can reach the sensing surface and satisfy SPR effective. In addition, this improvement in structure has advantages of large grinding and sensing area, which can lead to high sensitivity and simple manufacture process of the sensor. Experimental measurement demonstrates the sensor has a favorable SPR resonanceabsorption and the ability of measuring refractive index (RI) of aqueous solution. This novel tapered SPR sensor has the potential to be applied to the biological sensing field.

A novel fiber-optic SPR sensor with multi-alternating metal layers is presented. Numerical simulation results show that the structure has higher sensitivity than the traditional SPR sensor and a wider detecting range of refractive index.

This paper reports surface plasmon resonance (SPR) sensor based on light guiding flexible fused silica capillary tubing. We demonstrate the feasibility of the sensor experimentally. This sensor can be used in the biochemical sensing with further development.

This chapter argues for the view that intercellular γ-aminobutyric acid (GABA)ergic signaling between neural stem cells and neuronal precursors in the subventricular zone (SVZ), also called subependymal zone (1), is critical for controlling postnatal neurogenesis, and that nonsynaptic communication between SVZ cells displays characteristics of that between cells of neuron-glial networks elsewhere in the brain. GABA plays an important signaling role in developmental processes, such as embryonic cell proliferation (2,3), migration (4, 5, 6, 7, 8), and differentiation (9, 10, 11, 12). The function of GABA on the various developmental stages has been the subject of many reviews (13, 14, 15, 16, 17). This chapter will focus on the signaling function of GABA in postnatal neurogenesis in the SVZ (18, 19, 20). The cellular architecture of the SVZ and the GABAergic system will be described. Although no anatomically defined synaptic contacts have been observed, local GABAergic signaling between SVZ stem cells and neuronal precursors, or between neuronal precursors, exists and is thought to maintain a balance between the production and mobilization of SVZ precursors.

Neural stem cells in the adult subventricular zone (SVZ) derive from radial glia and express the astroglial marker glial fibrillary acidic protein (GFAP). Thus, they have been termed astrocytes. However, it remains unknown whether these GFAP-expressing cells express the functional features common to astrocytes. Using immunostaining and patch clamp recordings in acute slices from transgenic mice expressing green fluorescent protein (GFP) driven by the promoter of human GFAP, we show that GFAP-expressing cells in the postnatal SVZ display typical glial properties shared by astrocytes and prenatal radial glia such as lack of action potentials, hyperpolarized resting potentials, gap junction coupling, connexin 43 expression, hemichannels, a passive current profile, and functional glutamate transporters. GFAP-expressing cells express both GLAST and GLT-1 glutamate transporters but lack AMPA-type glutamate receptors as reported for dye-coupled astrocytes. However, they lack 100 microM Ba2+-sensitive inwardly rectifying K+ (K(IR)) currents expressed by astrocytes, but display delayed rectifying K+ currents and 1 mM Ba2+-sensitive K+ currents. These currents contribute to K+ transport at rest and maintain hyperpolarized resting potentials. GFAP-expressing cells stained positive for both K(IR)2.1 and K(IR)4.1 channels, two major K(IR) channels in astrocytes. Ependymal cells, which also derive from radial glia and express GFAP, display typical glial properties and K(IR) currents consistent with their postmitotic nature. Our results suggest that GFAP-expressing cells in concert with ependymal cells can perform typical astrocytic functions such as K+ and glutamate buffering in the postnatal SVZ but display a unique set of functional characteristics intermediate between astrocytes and radial glia.

Bradykinin is thought to play a major role among the endogenous cardioprotective candidates of ischaemic preconditioning (IPC). Little attention has been paid to the fact that in the tissue kallidin (KAL), rather than bradykinin might be the physiological mediator of the kallikrein-kinin system. In order to evaluate the importance of one or the other peptide the release and effect of both kinins has been investigated in isolated rat hearts following IPC. Bradykinin- and a KAL-like peptide were measured in the effluent of the rat isolated Langendorff heart with two different specific radioimmunoassays. The creatine kinase activity in the effluent was judged as degree of cardiac injury caused by ischaemia. During IPC, which consists of three 5 min no-flow and 5 min reperfusion cycles prior to the 30 min ischaemia, the bradykinin level in the effluent did not change significantly (15.4-19.4 pg ml(-1)). In the control group the bradykinin levels were 15.9-16.6 pg ml(-1). During IPC KAL-like peptide (Arg(1)-, instead of Lys(1)-KAL), which has recently been verified by mass spectrometry, displays 5.8-fold higher levels in the effluent and significantly increases in the same time interval from 90.4 to 189 pg ml(-1). After 30 min ischaemia the bradykinin levels in the IPC group were not significantly different to those of the control group (18.7 vs 14.4 pg ml(-1)). The KAL-like peptide levels in the IPC group vs the control group were 105 vs 86.1 pg ml(-1). By the 30 min ischaemia the creatine kinase activity in the IPC group increased from 0.367 to 8.93 U l(-1) (before and 10-30 min after ischaemia). In the control group during the same time period the creatine kinase levels increased from 0.277 to 34.9 U l(-1). The low increase in creatine kinase activity following IPC was taken as equivalent of the cardioprotective action. A KAL antibody or HOE140 (kinin B(2)-receptor antagonist) completely abolished this beneficial effect of IPC (36.6 and 53.0 U l(-1)) when added to the perfusion medium during the reperfusion cycles of IPC prior to the 30 min ischaemia. Our data suggest that in rat hearts KAL-like peptide rather than bradykinin is the physiological compound activated by IPC and acting via the cardiac kinin B(2)-receptor. Thus, endogenously generated KAL-like peptide seems to play a major role in the cardioprotection of IPC.

Elevated levels of [Formula: see text] in the brain impair neuronal function. We studied the effects of [Formula: see text] on postsynaptic inhibition of cultured rat brain neurons using whole cell recording under nominally [Formula: see text] -free conditions. Application of [Formula: see text] shifted the reversal potentials for spontaneous inhibitory postsynaptic currents and currents elicited by dendritic GABA applications in a positive direction because [Cl–]i increased. The positive shift of the reversal potentials of GABA-induced Cl– currents was equal on equimolar elevation of [Formula: see text] or [K+]o, respectively. The [Formula: see text]-induced increase in [Cl–]i was reversed by an inhibitor of cation-anion cotransport, furosemide (0.1 mM), but not by bumetanide (0.01 mM) or by replacement of [Na+]o by Li+. We conclude that neuron-specific K-Cl cotransporter (KCC2) transports [Formula: see text] similar to K+. Despite this fact, the small increase of [Formula: see text] during metabolic encephalopathies will barely elevate [Cl–]i. However, an impairment of neuronal function may result because KCC2 provides a pathway to accumulate [Formula: see text], and thereby, a continuous acid load to neurons.