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During neuropathic pain, glial cells (mainly astrocytes and microglia) become activated and initiate a series of signaling cascades that modulate pain processing at both spinal and supraspinal levels. It has been generally accepted that glial cell activation contributes to neuropathic pain because glia release proinflammatory cytokines, chemokines, and factors such as calcitonin gene-related peptide, substance P, and glutamate, which are known to facilitate pain signaling. However, recent research has shown that activation of glia also leads to some beneficial outcomes. Glia release anti-inflammatory factors that protect against neurotoxicity and restore normal pain. Accordingly, use of glial inhibitors might compromise the protective functions of glia in addition to suppressing their detrimental effects. With a better understanding of how different conditions affect glial cell activation, we may be able to promote the protective function of glia and pave the way for future development of novel, safe, and effective treatments of neuropathic pain. [ABSTRACT FROM AUTHOR]

Amplified fragment length polymorphism (AFLP) was employed to analyze the population genetics of relict tree fern Sphaeropteris brunoniana. A total of 132 individuals from ten natural populations in China and Laos were collected for this study. Using two selective primers, 234 reliable bands were generated, of which 221 (94.4%) were polymorphic. Genetic analysis indicated an unexpectedly high level of genetic diversity in S. brunoniana (Ht= 0.333, Hsp= 0.499), but a low level of genetic differentiation among populations (Gst= 0.16, φST= 0.12 and (Hsp-Hpop)/Hsp= 0.16). This result may be due to its life traits, evolutionary history and gene flow. Two major genetic groups, one from Yunnan and the other from Hainan-Laos, were detected among the ten investigated populations. The Mantel test correlated this differentiation with geographic distance. However, the different population origins may also have an effect on this differentiation. Based on these findings, implications for conservation strategies of this species in China are discussed. [ABSTRACT FROM AUTHOR]

Here the distance dependence of metal-enhanced quantum dots (QDs) fluorescence in solution is studied systematically by capillary electrophoresis (CE). Complementary DNA oligonucleotides-modified CdSe/ZnS QDs and gold nanoparticles (Au NPs) were connected together in solution by the hybridization of complementary oligonucleotides, and a model system (QD-Au) for the study of metal-enhanced QDs fluorescence was constructed, in which the distance between the QDs and Au NPs was controlled by adjusting the base number of the oligonucleotide. In our CE experiments, the metal-enhanced fluorescence of the QDs solution was only observed when the distance between the QDs and Au NPs ranged from 6.8 to 18.7 nm, and the maximum enhancement by a factor of 2.3 was achieved at 11.9 nm. Furthermore, a minimum of 19.6 pg of target DNA was identified in CE based on its specific competition with the QD-DNA in the QD-Au system. This work provides an important reference for future study of metal-enhanced QDs fluorescence in solution and exhibits potential capability in nucleic acid hybridization analysis and high-sensitivity DNA detection. [ABSTRACT FROM AUTHOR]

The interaction between parasitic plants and their hosts is an important topic in both agriculture and ecology. Little, however, is known about that of the hemiparasite Pedicularis. It is essential to understand the host dependence and preference of Pedicularis for successful cultivation of plants in this genus and for understanding the roles they play in natural communities. We tested the effects of two herbaceous host species ( Trifolium repens and Polypogon monspeliensis) on the survival and growth performance of Pedicularis cephalantha. Five P. cephalantha seedlings and two host plants were planted in each pot. In the control, no host plants were planted (treatment 1). Host plants were planted in three combinations: only T. repens (treatment 2) or P. monspeliensis (treatment 3) or a mixture of both (treatment 4). The results showed that P. cephalantha performed better in the presence of host plants, and host plants are more essential to P. cephalantha for proper development than for survival. The grass host P. monspeliensis proved to be a better host plant for P. cephalantha than the legume host T. repens. The high dependence of P. cephalantha on host plants and its host preference were demonstrated in this study. This is the first report of the performance of Chinese Pedicularis species in cultivation throughout all life stages (from seeds to seeds). [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the effect of bipolar electrical-conditioning stimulation of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rates after L5 spinal nerve injury. The researchers observed significant reduction in the spontaneous activity rate of WDR neurons in nerve-injured rats within 15 minutes of the dorsal column or root conditioning stimulation. Results suggested a potential cellular mechanism underlying spinal cord stimulation-induced pain relief.

An important objective of pain research is to identify novel drug targets for the treatment of pathological persistent pain states, such as inflammatory and neuropathic pain. Mas-related G-protein-coupled receptors (Mrgprs) represent a large family of orphan receptors specifically expressed in small-diameter nociceptive primary sensory neurons. To determine the roles of Mrgprs in persistent pathological pain states, we exploited a mouse line in which a chromosomal locus spanning 12 Mrgpr genes was deleted (KO). Initial studies indicated that these KO mice show prolonged mechanical- and thermal-pain hypersensitivity after hind-paw inflammation compared with wild- type littermates. Here, we show that this mutation also enhances the windup response of dorsal-horn wide dynamic-range neurons, an electrophysiological model for the triggering of central pain sensitization. Deletion of the Mrgpr cluster also blocked the analgesic effect of intrathecally applied bovine adrenal medulla peptide 8-22 (BAM 8- 22), an Mrgprc11 agonist, on both inflammatory heat hyperalgesia and neuropathic mechanical allodynia. Spinal application of bovine adrenal medulla peptide 8-22 also significantly attenuated windup in wild-type mice, an effect eliminated in KO mice. These data suggest that members of the Mrgpr family, in particular MrgprC11, may constitute an endogenous inhibitory mechanism for regulating persistent pain in mice. Agonists for these receptors may. therefore, represent a class of antihyperalgesics for treating persistent pain with minimal side effects because of the highly specific expression of their targets. [ABSTRACT FROM AUTHOR]

LiEu1−x(W2−yMoy)O8:xBi3+ series red-emitting phosphors were synthesized by solid state reaction. The structure, morphology, and photoluminescent properties of phosphors were studied by X-ray powder diffraction, scanning electron microscopy, and photoluminescence spectrum, respectively. X-ray powder diffraction analysis showed that the as-obtained phosphors belong to the scheelite structure. The average particle size of the investigated phosphor was about 8 μm. The excitation spectrum exhibits a charge-transfer broad band along with some sharp peaks from the typical 4f–4f transitions of Eu3+. Under excitation of UV, near-UV, or blue light, these phosphors showed strong red emission at 615 nm due to 5D0–7F2 transition of Eu3+. The incorporation of Mo6+ into LiEuW2O8:Bi3+ could induce red-shift of the charge-transfer broad band and a remarkable increase of photoluminescence. The highest red-emission intensity was observed with LiEu0.80Mo2O8:0.20Bi3+. Compared with the commercial red-emitting phosphor, Y2O2S:Eu3+, the emission intensity of LiEu0.80Mo2O8:0.20Bi3+ phosphor is much stronger than that of Y2O2S:Eu3+ and its chromaticity coordinates are closer to the standard values than that of the commercial phosphor. The optical properties of LiEu0.80Mo2O8:0.20Bi3+ phosphor make it attractive for the application in white-light-emitting diodes (LEDs), in particular for near-UV InGaN-based white-LEDs. [ABSTRACT FROM AUTHOR]

Abstract: Rice-duck mutualism is one form of ecological engineering which makes use of the symbiotic relationship between rice and ducks to more effectively utilize materials, reduce chemical fertilizer and pesticide inputs, increase product safety and overall productivity and decrease the pollutants discharged from rice-fields. This is becoming a popular mode for organic rice production in China and it can be used as one measure taken in the drainage area to assist in the ecological rehabilitation of lakes. This study applied the emergy evaluation method to analyze the resource use and environmental impact of organic rice-duck mutualism (mode 1) compared with the conventional wheat/rice rotation system (mode 2) in the same farm to evaluate its sustainability and ecological and economic benefits and provide suggestions for optimizing this system. The results showed that mode 1 produced greater emergy benefits, and had higher self-organization, lower environmental pressure and higher product safety. The net emergy yield ratio (EYR), feedback ratio of yield emergy (FYE) and emergy sustainable index (ESI) of mode 1 were 1.57 times, 14.10 times and 8.71 times those of mode 2, respectively, and the emergy index of product safety (PSI) was 0 in mode 1 and −0.66 in mode 2. The emergy investment ratio (EIR) and environmental loading ratio (ELR) were 40.1 and 18.3% of those of mode 2. The economic benefit of mode 1 was lower than mode 2. The economic output, gross income and net income of mode 1 were 15.7, 10.8 and 35.4% less than those of mode 2, respectively, but using Em$, the output, gross income and net income of mode 1 were 47.4, 161.2, 87.3% higher than mode 2. With the development of markets for organic foods, mode 1 has the potential to achieve better economic benefits. [Copyright &y& Elsevier]

Abstract: The rational input of materials is one of the key techniques to realize the comprehensive benefits of an agro-ecological engineering mode and is an important element of the hardware of an ecological engineering. The calculation of fertilizer application rate is the common difficulty for farmers in planting organic rice, for which the model of an optimum fertilizer application was applied and the corresponding field verification experiment was also carried out. The results showed that the calculated yields were quite close to the actual ones by the selected model, although the actual yields were all higher. So adding a constant K adjusting N supply to the model was set forth in order to improve the accuracy of forecasting yields. The field experiment showed that if the green manure grew well, no application, the occurrence of diseases and pests (except rice leaf rollers) did not become heavier with more organic N input, and the resistance to white-backed plant hoppers became higher with more organic N input. The test of the rice quality showed that the organic rice quality was quite stable and rarely impacted by different N input levels. [Copyright &y& Elsevier]

Seeds of most Pedicularis species do not germinate easily and uniformly, which hinders the process of seeking solutions for successful cultivation of these taxa. In an attempt to determine optimal conditions and effective methods for uniform, rapid, and high-percent germination, the effects of light, scarification, and gibberellic acid (GA3) were tested on seed germination of eight Pedicularis species from nine sites in the northwestern Yunnan Province of China. There were some differences in germination characteristics among the tested species. Seed germination of some species was promoted by light, but not in others. Wet-habitat species generally had positive photoblastic responses. For many species, scarification was effective to promote seed germination, but neither 100 nor 500 mg·L-1 GA3 had consistent promoting effects. [ABSTRACT FROM AUTHOR]

Neuronal nitric oxide synthase (nNOS) is a key enzyme for nitric oxide production in neuronal tissues and contributes to the spinal central sensitization in inflammatory pain. However, the role of nNOS in neuropathic pain remains unclear. The present study combined a genetic strategy with a pharmacologic approach to examine the effects of genetic knockout and pharmacologic inhibition of nNOS on neuropathic pain induced by unilateral fifth lumbar spinal nerve injury in mice. In contrast to wildtype mice, nNOS knockout mice failed to display nerve injury-induced mechanical hypersensitivity. Furthermore, either intraperitoneal (100 mg/kg) or intrathecal (30 µg/5 µl) administration of L-NG-nitro-arginine methyl ester, a nonspecific NOS inhibitor, significantly reversed nerve injury-induced mechanical hypersensitivity on day 7 post-nerve injury in wildtype mice. Intrathecal injection of 7-nitroindazole (8.15 µg/5 µl), a selective nNOS inhibitor, also dramatically attenuated nerve injury-induced mechanical hypersensitivity. Western blot analysis showed that the expression of nNOS protein was significantly increased in ipsilateral L5 dorsal root ganglion but not in ipsilateral L5 lumbar spinal cord on day 7 post-nerve injury. The expression of inducible NOS and endothelial NOS proteins was not markedly altered after nerve injury in either the dorsal root ganglion or spinal cord. Our findings suggest that nNOS, especially in the dorsal root ganglion, may participate in the development and/or maintenance of mechanical hypersensitivity after nerve injury. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) are porous organic materials with well‐defined and uniform structure. The material is an excellent candidate as a solid adsorbent for iodine adsorption. In the present study, we report the synthesis of COF with porphyrin moiety, TF‐TA‐COF, by solvothermal reaction, which was characterized by XRD, solid‐state 13C NMR, IR, TGA, and nitrogen adsorption‐desorption analysis. TF‐TA‐COF showed a high specific surface area of 443 m2 g−1, and exhibited good adsorption performance for iodine vapor, with an adsorption capacity of 2.74 g g−1. XPS and Raman spectrum indicated that a hybrid of physisorption and chemisorption took place between host COF and iodine molecules. The electric properties of iodine‐loaded TF‐TA‐COF were also studied. After doped with iodine, the conductivity of the material increased by more than 5 orders of magnitude. The photoconductivity of I2‐doped COF was also studied and TF‐TA‐COF showed doping‐enhanced photocurrent generation. [ABSTRACT FROM AUTHOR]

Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration. [ABSTRACT FROM AUTHOR]

Cyclogramma costularisora Ching ex K.H. Shing, described as a new species in 1999, was not validly published because the herbarium in which the types were conserved was not indicated. Here the name is validated by indicating that the holotype is deposited in PE. [ABSTRACT FROM AUTHOR]

Solvent retention capacity (SRC) is an important tool for assessing wheat quality by estimating the biochemical characteristics of flour components. Although it has been widely used in wheat breeding programs, its genetic architecture is still poorly understood. Hence, the objective of this study was to find quantitative trait loci (QTLs) associated with four SRC traits, namely sucrose SRC, sodium carbonate SRC, water SRC and lactic acid SRC, in a recombinant inbred line population consisting of 173 lines descended from Shannong 01–35/Gaocheng 9411 and an association panel of 205 wheat varieties. The 90K single nucleotide polymorphism array was used to genotype both populations. SRC was primarily influenced by genotype, with broad‐sense heritability (H2) ranging from 59.72% to 80.76%. Linkage mapping revealed seven major QTLs on chromosomes 1B, 4B, 5B, and 6B. Among them, QSc1B.6‐27 was repeatedly identified in two different environments, with a 14.7% phenotypic variance explained value. Additionally, 24 significant QTLs, consisting of 57 marker‐trait associations, were identified using association mapping across four environments. Nineteen of them explained more than 10.0% of the phenotypic variance, with QSU6A.141 explaining the most (20.1%). Two common chromosomal regions were discovered when combining the two mapping populations. These regions were located between IACX5803 and BS00067000_51 on chromosome 1B and between IACX557 and CAP11_c3631_75 on chromosome 4B, respectively. In addition, four candidate genes associated with wheat SRC were identified. These findings shed light on the complex genetic mechanisms underlying wheat SRC and may help to genetically enhance wheat quality. Core Ideas: Two common genomic regions responsible for wheat solvent retention capacity (SRC) were identified in both linkage and association mapping.For wheat SRC, several new loci were found by combined quantitative trait locus mapping and genome‐wide association study.Four candidate genes may be related to solvent retention capacity were searched. [ABSTRACT FROM AUTHOR]

Pr3+-activated barium tungsto-molybdate solid solution phosphor Ba(Mo1−zWz)O4:Pr3+ is successfully fabricated via a facile molten-salt approach. The as-synthesized microcrystal is of truncated octahedron and exhibits deep-red-emitting upon blue light excitation. Powder x-ray diffraction and Raman spectroscopy techniques are utilized to investigate the formation of solid solution phosphor. The luminescence behaviors depend on the resulting composition of the microcrystals with fixed Pr3+-doping concentration, while the host lattices remain in a scheelite structure. The forming solid solution via the substitution of [WO4] for [MoO4] can significantly enhance its luminescence, which may be due to the fact that Ba(Mo1−zWz)O4:Pr3+ owns well-defined facets and uniform morphologies. Owing to its properties of high phase purity, well-defined facets, highly uniform morphologies, exceptional chemical and thermal stabilities, and stronger emission intensity, the resulting solid solution phosphor is expected to find potential applications in phosphor-converted white light-emitting diodes (LEDs). [ABSTRACT FROM AUTHOR]

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects. [ABSTRACT FROM AUTHOR]

The article presents a study which showed that volume-regulated anion channel (VRAC) is an adenosine 5'-triphosphate (ATP)-releasing channel and is activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Topics discussed include the importance of Swell1 or VRAC activity in microglia and in ATP release, alleviation of CCI-induced neuropathic pain-like behaviors in microglia-specific Swell1 cKO mice, and RNAscope in situ hybridization.

With increasing numbers of young female cancer survivors following chemotherapy, chemotherapy-induced fertility loss must be considered. Menstrual disorder and infertility are of particular concern in female cancer patients. We showed that treatment with the alkylating agent cyclophosphamide (CTX) could cause severe primordial follicle loss and growing follicle apoptosis, resulting in loss of ovarian reserve. SPF C57BL/6 female mice were treated with a single dose of 120 mg/kg of CTX or saline as a control, and both sides of ovaries were collected three or seven days after injection. Following CTX treatment, the ovaries were mostly composed of collapsed oocytes and presented marked cortical fibrosis and a reduced number of follicles, especially primordial follicles. The loss of primordial follicles was confirmed by primordial follicle counting, immunohistochemistry and Western blot detection of DDx4/MVH. Follicle apoptosis was tested by a TUNEL assay and the number of TUNEL-positive follicle cells increased, as expected, in CTX-treated mice. Furthermore, expression of APAF-1 and cleaved caspase-3 was also increased after CTX treatment. Analysis of the PI3K/Akt/mTOR signaling pathway showed that CTX increased phosphorylation of Akt, mTOR and downstream proteins without affecting total levels. These results demonstrated that the CTX treatment led to the hyperactivation of the PI3K/Akt/mTOR signaling pathway in ovaries which may be related to primordial follicle loss and growing follicle apoptosis. [ABSTRACT FROM AUTHOR]

Thesolubilities of 1,3,2-dioxaphosphorinane-2-methanol-α,α-5,5-tetramethyl2-oxide (DMTO) were measured in different solvents including ethylacetate, methanol, ethanol, chloroform, acetonitrile, acetone, 1,2-dichloroethane,and water at temperature ranging from 278.15 K to 343.15 K by thegravimetrical method. The structure of DMTO was characterized by nuclearmagnetic resonance (1H NMR and 13P NMR), infraredspectroscopy (IR), and mass spectroscopy (MS). The thermal stabilityof DMTO was characterized by thermogravimetric analysis (TGA). Themodified Apelblat was used to correlate the measured solubility data.The results showed that the calculated solubilities were in good agreementwith experimental values in all selected solvents. The root-mean-squaredeviation was less than 0.091 %, and the average relative error wasless than 0.22 % in all of the experiments. [ABSTRACT FROM AUTHOR]

The article focuses on astrocytes contribute to pain gating in the spinal cord. Topics include the various pain therapies have been developed on the basis of the gate control theory of pain, and the postulates that nonpainful sensory inputs mediated by large-diameter afferent fibers can attenuate noxious signals relayed to the brain.

TRP vanilloid 2 (TRPV2) is a nonselective cation channel expressed prominently in medium- to large-diameter sensory neurons that can be activated by extreme heat (>52°C). These features suggest that TRPV2 might be a transducer of noxious heat in vivo. TRPV2 can also be activated by hypoosmolarity or cell stretch, suggesting potential roles in mechanotransduction. To address the physiological functions of TRPV2 in somatosensation, we generated TRPV2 knock-out mice and examined their behavioral and electrophysiological responses to heat and mechanical stimuli. TRPV2 knock-out mice showed reduced embryonic weight and perinatal viability. As adults, surviving knock-out mice also exhibited a slightly reduced body weight. TRPV2 knock-out mice showed normal behavioral responses to noxious heat over a broad range of temperatures and normal responses to punctate mechanical stimuli, both in the basal state and under hyperalgesic conditions such as peripheral inflammation and L5 spinal nerve ligation. Moreover, behavioral assays of TRPV1/TRPV2 double knock-out mice or of TRPV2 knock-out mice treated with resiniferatoxin to desensitize TRPV1-expressing afferents revealed no thermosensory consequences of TRPV2 absence. In line with behavioral findings, electrophysiological recordings from skin afferents showed that C-fiber responses to heat and C- and Aδ-fiber responses to noxious mechanical stimuli were unimpaired in the absence of TRPV2. The prevalence of thermosensitive Aδ-fibers was too low to permit comparison between genotypes. Thus, TRPV2 is important for perinatal viability but is not essential for heat or mechanical nociception or hypersensitivity in the adult mouse. [ABSTRACT FROM AUTHOR]

Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistent mechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate, a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury. Because the different VGLUT isoforms generally have a non-redundant pattern of expression, we used Vglut3 knockout mice to assess the role of VGLUT3+ primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3+ neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs). The analysis of Vglut3-/- mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury. [ABSTRACT FROM AUTHOR]

Nanoplates, flower-like nanostructure of ZnO were successfully synthesized by employing ZnSO4·7H2O, NaOH as the starting materials at 120°C under hydrothermal condition. Keeping the same parameters, ZnO urchin shape was obtained by addition of vitamin C at 190°C. Characterizations were carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) at room temperature. Selected area electron diffraction (SAED) pattern confirms that the product is single crystalline nature. The possible formation mechanisms for synthesized ZnO nanosturcture with various morphologies have also been proposed. PL spectrum from the ZnO flower-like structures reveals weak UV emission and strong green emission. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to the still sparse literature in China, the investigation of hyperoxemia management is required. Thus, we aim to conduct a retrospective study to provide more information about hyperoxemia management in intensive care unit (ICU) patients. METHODS: We retrospectively screened the medical records of adult patients (age ≥18 years) who required mechanical ventilation (MV) ≥24 hours from January 1, 2018, to December 31, 2018. All arterial blood gas (ABG) tested during MV was retrieved, and MV settings were recorded. The median arterial partial pressure of oxygen (PaO2) >120 mmHg (1 mmHg=0.133 kPa) was defined as mild to moderate hyperoxemia, and PaO2 >300 mmHg as extreme hyperoxemia. Intensivists' response to hyperoxemia was assessed based on the reduction of fraction of inspired oxygen (FiO2) within one hour after hyperoxemia was recorded. Multivariable logistic regression analysis was performed to determine the independent factors associated with the intensivists' response to hyperoxemia. RESULTS: A total of 592 patients were finally analyzed. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 21 (15-26). The PaO2, arterial oxygen saturation (SaO2), FiO2, and positive end expiratory pressure (PEEP) were 96.4 (74.0-126.0) mmHg, 97.8% (95.2%-99.1%), 0.4 (0.4-0.5), and 5 (3-6) cmH2O, respectively. Totally 174 (29.39%) patients had PaO2 >120 mmHg, and 19 (3.21%) patients had extreme hyperoxemia at PaO2 >300 mmHg. In cases of mild to moderate hyperoxemia with FiO2 ≤0.4, only 13 (2.20%) patients had a decrease in FiO2 within one hour. The multivariable logistic regression analysis showed that a positive response was independently associated with FiO2 (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.06-1.12, P<0.001), PaO2 (OR 1.01, 95% CI 1.00-1.01, P=0.002), and working shifts (OR 5.09, 95% CI 1.87-13.80, P=0.001). CONCLUSIONS: Hyperoxemia occurs frequently and is neglected in most cases, particularly when mild to moderate hyperoxemia, hyperoxemia with lower FiO2, hyperoxemia during night and middle-night shifts, or FiO2 less likely to be decreased. Patients may be at a risk of oxygen toxicity because of the liberal oxygen strategy. Therefore, further research is needed to improve oxygen management for patients with MV in the ICUs. [ABSTRACT FROM AUTHOR]

Mini: This study defined different anatomic zones within the cervical spinal canal and provides detailed anatomical quantitative data for an accurate diagnosis of cervical spondylosis and a safe and effective anterior decompression surgery. [ABSTRACT FROM AUTHOR]

Abstract: Agonists to subtype C of the Mas-related G-protein-coupled receptors (MrgC) induce pain inhibition after intrathecal (i.t.) administration in rodent models of nerve injury. Here, we investigated whether tolerance develops after repeated MrgC agonist treatments and examined the underlying mechanisms. In animal behavior studies conducted in male rats at 4 to 5 weeks after an L5 spinal nerve ligation (SNL), the ability of dipeptide MrgC agonist JHU58 (0.1 mM, 10 μL, i.t.) to inhibit mechanical and heat hypersensitivity decreased after 3 days of treatment with a tolerance-inducing dose (0.5 mM, 10 μL, i.t., twice/day). In HEK293T cells, acute treatment with JHU58 or BAM8-22 (a large peptide MrgC agonist) led to MrgC endocytosis from the cell membrane and later sorting to the membrane for reinsertion. However, chronic exposure to JHU58 increased the coupling of MrgC to β-arrestin-2 and led to the ubiquitination and degradation of MrgC. Importantly, pretreatment with TAK-243 (0.2 mM, 5 μL, i.t.), a small-molecule inhibitor of the ubiquitin-activating enzyme, during tolerance induction attenuated the development of tolerance to JHU58-induced inhibition of mechanical and heat hypersensitivity in SNL rats. Interestingly, morphine analgesia was also decreased in SNL rats that had become tolerant to JHU58, suggesting a cross-tolerance. Furthermore, i.t. pretreatment with TAK-243, which reduced JHU58 tolerance, also attenuated the cross-tolerance to morphine analgesia. These findings suggest that tolerance can develop to MrgC agonist-induced pain inhibition after repeated i.t. administrations. This tolerance development to JHU58 may involve increased coupling of MrgC to β-arrestin-2 and ubiquitin-mediated receptor degradation. [ABSTRACT FROM AUTHOR]

Abstract: Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. Colorectal distension did not activate L4 DRG neurons. TNBS-treated mice exhibited more Evans blue extravasation than did control mice and developed mechanical hypersensitivity in low-back skin and hind paws, which are innervated by L6 and L4 DRG neurons, respectively, suggesting that colonic inflammation induced mechanical hypersensitivity in both homosegmental and heterosegmental somatic regions. Importantly, the percentage of L4 DRG neurons activated by hind paw pinch and brush stimulation and calcium responses of L6 DRG neurons to low-back brush stimulation were higher at day 7 after TNBS than those in control mice. Visceral irritation from intracolonic capsaicin instillation also increased Evans blue extravasation in hind paws and low-back skin and acutely increased the percentage of L4 DRG neurons responding to hind paw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity. [ABSTRACT FROM AUTHOR]

Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis progression and decrease joint pain effectively. Here, we show that intermittent parathyroid hormone (iPTH) attenuates osteoarthritis pain by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration in a destabilized medial meniscus (DMM) mouse model. We found that subchondral sensory innervation for osteoarthritis pain was significantly decreased in PTH-treated DMM mice compared with vehicle-treated DMM mice. In parallel, deterioration of subchondral bone microarchitecture in DMM mice was attenuated by iPTH treatment. Increased level of prostaglandin E2 in subchondral bone of DMM mice was reduced by iPTH treatment. Furthermore, uncoupled subchondral bone remodeling caused by increased transforming growth factor b signaling was regulated by PTH-induced endocytosis of the PTH type 1 receptor– transforming growth factor b type 2 receptor complex. Notably, iPTH improved subchondral bone microarchitecture and decreased level of prostaglandin E2 and sensory innervation of subchondral bone in DMM mice by acting specifically through PTH type 1 receptor in Nestin+ mesenchymal stromal cells. Thus, iPTH could be a potential disease-modifying therapy for osteoarthritis. [ABSTRACT FROM AUTHOR]

We recently found that adolescent cocaine exposure (ACE) resulted in an enhancement of the γ-aminobutyric acid (GABA) neurotransmitter system in the prelimbic cortex (PrL) of adult mice. Here, we aim to further investigate the role of GABAergic transmission, especially parvalbumin (PV) interneurons within PrL in the development of ACE-induced anxiety-like behavior, and to assess whether and how electro-acupuncture (EA) therapeutically manage the ACE-induced abnormal behaviors in adulthood. ACE mice exhibited the enhanced anxiety-like behaviors in their adulthood, accompanied by increased GABAergic transmission and PV interneurons in PrL. Chemogenetic blocking PV interneurons in PrL alleviated ACE-enhanced anxiety-like behaviors in mice. Importantly, 37-day EA treatments (mixture of 2 Hz/100 Hz, 1 mA, 30 minutes once a day) at the acupoints of Yintang (GV29) and Baihui (GV20) also alleviated ACE-induced anxiety-like behaviors, and rescued ACE-impaired GABAergic neurotransmitter system and PV interneurons in PrL. In parallel, EA treatments further suppressed the activities of pyramidal neurons in PrL, suggesting that EA treatments seem to perform it beneficial effects on the ACE-induced abnormal emotional behaviors by "calming down" the whole PrL. Collectively, these findings revealed that hyper-function of GABAergic transmission, especially mediating by PV interneurons in PrL may be key etiology underlying ACE-induced anxiety-like behaviors. At least by normalizing the function of GABAergic and PV interneurons, EA may represent a promising therapeutic strategy for managing adolescent substance use-related emotional disorders. [ABSTRACT FROM AUTHOR]

Several reports support the idea that µ- and δ-opioid receptors (ORs) may exist as heterodimers in brain regions involved in pain signaling. The unique pharmacology of these heteromers may present a novel analgesic target. However, the role of µ-δ heteromers in sensory neurons involved in pain and opioid analgesia remains unclear, particularly during neuropathic pain. We examined the effects of spinal nerve injury on µ-δ heteromer expression in dorsal root ganglion (DRG) neurons and the effects of a µ-δ heteromer-targeting agonist, CYM51010, on neuropathic pain behavior in rats and mice. An L5 spinal nerve ligation (SNL) in rats significantly decreased µ-δ heteromer expression in L5 DRG but increased heteromer levels in uninjured L4 DRG. Importantly, in SNL rats, subcutaneous injection of CYM51010 inhibited mechanical hypersensitivity in a dose-related manner (EC50: 1.09 mg/kg) and also reversed heat hyperalgesia and attenuated ongoing pain (2 mg/kg, subcutaneously). HEK-293T cell surface-labeled with µ- and δ-ORs internalized both receptors after exposure to CYM51010. By contrast, in cells transfected with µ-OR alone, CYM51010 was significantly less effective at inducing receptor internalization. Electrophysiologic studies showed that CYM51010 inhibited the C-component and windup phenomenon in spinal wide dynamic range neurons of SNL rats. The pain inhibitory effects of CYM51010 persisted in morphine-tolerant rats but was markedly attenuated in µ-OR knockout mice. Our studies show that spinal nerve injury may increase µ-δ heterodimerization in uninjured DRG neurons, and that µ-δ heteromers may be a potential therapeutic target for relieving neuropathic pain, even under conditions of morphine tolerance. [ABSTRACT FROM AUTHOR]

Opioid use for chronic pain is limited by severe central adverse effects. We examined whether activating mu-opioid receptors (MORs) in the peripheral nervous system attenuates spinal cord injury (SCI) pain-like behavior in mice. We produced a contusive SCI at the T10 vertebral level and examined motor and sensory dysfunction for 6 weeks. At 6 weeks, we tested the effect of subcutaneous (s.c.) injection of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripherally acting MOR-preferring agonist, on mechanical and heat hypersensitivity. Basso mouse scale score was significantly decreased after SCI, and mice showed hypersensitivity to mechanical and heat stimulation at the hind paw beginning at 2 weeks, as indicated by increased paw withdrawal frequency to mechanical stimulation and decreased paw withdrawal latency to heat stimulation. In wild-type SCI mice, DALDA (1 mg/kg, s.c.) attenuated heat but not mechanical hypersensitivity. The effect was blocked by pretreatment with an intraperitoneal injection of methylnaltrexone (5 mg/kg), a peripherally restricted opioid receptor antagonist, and was also diminished in Pirt-MOR conditional knockout mice. DALDA did not adversely affect exploratory activity or induced preference to drug treatment in SCI mice. In vivo calcium imaging showed that DALDA (1, 10 mg/kg, s.c.) inhibited responses of small dorsal root ganglion neurons to noxious heat stimulation in Pirt-GCaMP6s mice after SCI. Western blot analysis showed upregulation of MOR in the lumbar spinal cord and sciatic nerves at 6 weeks after SCI. Our findings suggest that peripherally acting MOR agonist may inhibit heat hypersensitivity below the injury level with minimal adverse effects. [ABSTRACT FROM AUTHOR]

The field of spinal cord stimulation is expanding rapidly, with new waveform paradigms asserting supraspinal sites of action. The scope of treatment applications is also broadening from chronic pain to include cerebral ischemia, dystonia, tremor, multiple sclerosis, Parkinson disease, neuropsychiatric disorders, memory, addiction, cognitive function, and other neurologic diseases. The role of neurostimulation as an alternative strategy to opioids for chronic pain treatment is under robust discussion in both scientific and public forums. An understanding of the supraspinal mechanisms underlying the beneficial effects of spinal cord stimulation will aid in the appropriate application and development of optimal stimulation strategies for modulating pain signaling pathways. In this review, the authors focus on clinical and preclinical studies that indicate the role of supraspinal mechanisms in spinal cord stimulation-induced pain inhibition, and explore directions for future investigations. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is a non-mineral macronutrient essential for plant growth and development. Oilseed rape (AnAnCnCn, 2n = 4x = 38) has a high requirement for N nutrients whereas showing the lowest N use efficiency (NUE) among crops. The mechanisms underlying NUE regulation in Brassica napus remain unclear because of genome complexity. In this study, we performed high-depth and -coverage wholegenome re-sequencing (WGS) of an N-efficient (higher NUE) genotype "XY15" and an N-inefficient (lower NUE) genotype "814" of rapeseed. More than 687 million 150-bp paired-end reads were generated, which provided about 93% coverage and 503 depth of the rapeseed genome. Applying stringent parameters, we identified a total of 1,449,157 single-nucleotide polymorphisms (SNPs), 335,228 InDels, 175,602 structure variations (SVs) and 86,280 copy number variations (CNVs) between the N-efficient and -inefficient genotypes. The largest proportion of various DNA polymorphisms occurred in the inter-genic regions. Unlike CNVs, the SNP/InDel and SV polymorphisms showed variation bias of the An and Cn subgenomes, respectively. Gene ontology analysis showed the genetic variants were mapped onto the genes involving N compound transport and ATPase complex metabolism, but not including N assimilation-related genes. On basis of identification of N-starvation responsive genes through high-throughput expression profiling, we also mapped these variants onto some key NUE-regulating genes, and validated their significantly differential expression between the N-efficient and -inefficient genotypes through qRT-PCR assays. Our data provide genome-wide high resolution DNA variants underlying NUE divergence in allotetraploid rapeseed genotypes, which would expedite the effective identification and functional validation of key NUE-regulating genes through genomics-assisted improvement of crop nutrient efficiency. [ABSTRACT FROM AUTHOR]

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder, characterized by loss of algesthesis and inability to sweat. CIPA is known to be caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). However, the details of NTRK1 mutations in Chinese CIPA patients remain unclear. In the present study, we recruited 36 CIPA patients from 34 unrelated families in mainland China. Blood samples from these patients and their available familial members were collected and subjected to genetic analysis. We identified 27 mutations in NTRK1 from this cohort, including 15 novel mutations. Interestingly, we discovered two forms of novel recurrent mutations: the first was a large intragenic deletion c.429-374_717th485del mediated by recombination between Alu elements, and the second was a deep intronic substitutions c.[851-798C>T;851-794C>G]. All probands were homozygotes or compound heterozygotes of these mutations. Current findings expand our knowledge about the mutation spectrum of NTRK1 in Chinese CIPA patients and provide more evidence for precise diagnosis of the clinically suspected patients with CIPA. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding expression of voltage-gated sodium channels in afferent neurons renders selective neural block by ionic direct current. Topic discussed include electrical stimulation held in a nearly axiomatic regard in the field of neuromodulation, transmission of information from the periphery to the central nervous system (CNS) and role of direct current (DC) in blocking the propagation of action potentials (Aps).

Neuroligin1 is an important synaptic cell adhesion molecule that modulates the function of synapses through protein-protein interactions. Yet, it remains unclear whether the regulation of synaptic transmission in the spinal cord by neruoligin1 contributes to the development of postoperative pain. In a rat model of postoperative pain induced by plantar incision, we conducted Western blot study to examine changes in the expression of postsynaptic membrane of neuroligin1, postsynaptic density 95 (PSD-95), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluA1 and GluA2 subunits in the spinal cord dorsal horn after injury. The interaction between neuroligin1 and PSD-95 was further determined by using coimmunoprecipitation. Protein levels of neuroligin1 and GluA1, but not GluA2 and PSD-95, were significantly increased in the postsynaptic membrane of the ipsilateral dorsal horn at 3 h and 1 day after incision, as compared to that in control group (naïve). A greater amount of PSD-95 was coimmunoprecipitated with neuroligin1 at 3 h after incision than that in the control group. Intrathecal administration of small interfering RNAs (siRNAs) targeting neuroligin1 suppressed the expression of neuroligin1 in the spinal cord. Importantly, pretreatment with intrathecal neuroligin1 siRNA2497, but not scrambled siRNA or vehicle, prevented the upregulation of GluA1 expression at 3 h after incision, inhibited the enhanced neuroligin1/PSD-95 interaction, and attenuated postoperative pain. Together, current findings suggest that downregulation of spinal neuroligin1 expression may ameliorate postoperative pain through inhibiting neuroligin1/PSD-95 interaction and synaptic targeting of GluA1 subunit. Accordingly, spinal neuroligin1 may be a potential new target for postoperative pain treatment. [ABSTRACT FROM AUTHOR]

TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen Salmonella typhimurium. The results indicated that TLR9- deficient mice were more susceptible to S. typhimurium infection compared with wild-type and TLR2- or TLR4-deficient mice, as indicated by more severe intestinal damage and the highest bacterial load. TLR9 deficiency in intestinal epithelial cells (IECs) augmented the activation of NF-κB and NLRP3 inflammasomes significantly, resulting in increased secretion of IL-1β. IL-1β increased the expression of NKG2D on intestinal intraepithelial lymphocytes and NKG2D ligands on IECs, resulting in higher susceptibility of IECs to cytotoxicity of intestinal intraepithelial lymphocytes and damage to the epithelial barrier. We proposed that TLR9 regulates the NF-κB-NLRP3-IL-1β pathway negatively in Salmonella-induced NKG2D-mediated intestinal inflammation and plays a critical role in defense against S. typhimurium infection and in the protection of intestinal integrity. [ABSTRACT FROM AUTHOR]

Activation of Aβ-fibers is an intrinsic feature of spinal cord stimulation (SCS) pain therapy. Cannabinoid receptor type 1 (CB1) is important to neuronal plasticity and pain modulation, but its role in SCS-induced pain inhibition remains unclear. In this study, we showed that CB1 receptors are expressed in both excitatory and inhibitory interneurons in substantia gelatinosa (SG). Patch-clamp recording of the evoked excitatory postsynaptic currents (eEPSCs) in mice after spinal nerve ligation (SNL) showed that electrical stimulation of Aβ-fibers (Aβ-ES) using clinical SCS-like parameters (50 Hz, 0.2 millisecond, 10 μA) induced prolonged depression of eEPSCs to C-fiber inputs in SG neurons. Pretreatment with CB1 receptor antagonist AM251 (2 μM) reduced the inhibition of C-eEPSCs by Aβ-ES in both excitatory and inhibitory SG neurons. We further determined the net effect of Aβ-ES on spinal nociceptive transmission in vivo by recording spinal local field potential in SNL rats. Epidural SCS (50 Hz, Aβ-plateau, 5 minutes) attenuated C-fiber-evoked local field potential. This effect of SCS was partially reduced by spinal topical application of AM251 (25 μg, 50 μL), but not CB2 receptor antagonist AM630 (100 μg). Finally, intrathecal pretreatment with AM251 (50 μg, 15 μL) in SNL rats blocked the inhibition of behavioral mechanical hypersensitivity by SCS (50 Hz, 0.2 millisecond; 80% of motor threshold, 60 minutes). Our findings suggest that activation of spinal CB1 receptors may contribute to synaptic depression to high-threshold afferent inputs in SG neurons after Aβ-ES and may be involved in SCS-induced inhibition of spinal nociceptive transmission after nerve injury. [ABSTRACT FROM AUTHOR]

Helicia falcata C. Y. Wu was not validly published in 1977 because two gatherings, one flowering and one fruiting, were simultaneously designated as types in the protologue. This name is validated here by designating the flowering specimen as the holotype. [ABSTRACT FROM AUTHOR]

Amomum tsaoko is a flexistylous ginger. Flexistyly is a unique floral mechanism promoting outcrossing, which is known only in some species of Zingiberaceae till date. This is a pioneer report on flexistyly in A. tsaoko from the aspect of fructification percentage to clarify its influence on reproduction. We observed in 2007 and 2008 that the fructification percentage of the anaflexistyled and the cataflexistyled inflorescence were 14.89 ± 10.35% and 11.31 ± 7.91% respectively, with significant difference (d.f. = 141.920, t = 2.518, P = 0.013 < 0.05). The greatly significant difference between 2007 and 2008 were present in both the flower number (d.f. = 93, t = -2.819, P = 0.006 < 0.01) and the fructification percentage (d.f. = 93, t = -2.894, P = 0.005 < 0.01) of the cataflexistylous inflorescence. Although the two morphs were similar in morphological characteristics, there was some gender differentiation between them, showing a possibility that the anaflexistylous morph might function more as females and the cataflexistylous morph more as males. Reproduction of the cataflexistylous morph was significantly sensitive to change of environmental factors, in contrast to the anaflexistylous morph, thus the yield varied between the abundant year (2008) and the off year (2007). [ABSTRACT FROM AUTHOR]

Enhancing nitrogen use efficiency (NUE) in crop plants is an important breeding target to reduce excessive use of chemical fertilizers, with substantial benefits to farmers and the environment. In Arabidopsis (Arabidopsis thaliana), allocation of more NO3- to shoots was associated with higher NUE; however, the commonality of this process across plant species have not been sufficiently studied. Two Brassica napus genotypes were identified with high and low NUE. We found that activities of V-ATPase and V-PPase, the two tonoplast proton-pumps, were significantly lower in roots of the high-NUE genotype (Xiangyou15) than in the low-NUE genotype (814); and consequently, less vacuolar NO3- was retained in roots of Xiangyou15. Moreover, NO3- concentration in xylem sap, [15N] shoot:root (S:R) and [NO3-] S:R ratios were significantly higher in Xiangyou15. BnNRT1.5 expression was higher in roots of Xiangyou15 compared with 814, while BnNRT1.8 expression was lower. In both B. napus treated with proton pump inhibitors or Arabidopsis mutants impaired in proton pump activity, vacuolar sequestration capacity (VSC) of NO3- in roots substantially decreased. Expression of NRT1.5 was up-regulated, but NRT1.8 was down-regulated, driving greater NO3- long-distance transport from roots to shoots. NUE in Arabidopsis mutants impaired in proton pumps was also significantly higher than in the wild type col-0. Taken together, these data suggest that decrease in VSC of NO3- in roots will enhance transport to shoot and essentially contribute to higher NUE by promoting NO3- allocation to aerial parts, likely through coordinated regulation of NRT1.5 and NRT1.8. [ABSTRACT FROM AUTHOR]

Background: Opioids have long been regarded as the most effective drugs for the treatment of severe acute and chronic pain. Unfortunately, their therapeutic efficacy and clinical utility have been limited because of central and peripheral side effects.Methods: To determine the therapeutic value of peripheral μ-opioid receptors as a target for neuropathic pain treatment, the authors examined the effects of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a hydrophilic, peripherally acting μ-opioid receptor agonist, in male and female rats with spinal nerve ligation-induced neuropathic pain. The authors also utilized behavioral, pharmacologic, electrophysiologic, and molecular biologic tools to characterize DALDA's possible mechanisms of action in male rats.Results: DALDA, administered subcutaneously, had 70 times greater efficacy for inhibiting thermal (n = 8 to 11/group) than mechanical hypersensitivity (n = 6 to 8/group) in male rats. The pain inhibitory effects of DALDA on mechanical and heat hypersensitivity were abolished in animals pretreated with systemic methylnaltrexone (n = 7 to 9/group), a peripheral μ-opioid receptor antagonist. In the spinal wide-dynamic range neurons, systemic DALDA inhibited C-fiber-mediated, but not A-fiber-mediated, response in neuropathic male rats (n = 13). In primary sensory neurons, DALDA inhibited the capsaicin-induced [Ca2+] increase more than the β-alanine-induced [Ca] increase (n = 300); capsaicin and β-alanine activate subpopulations of neurons involved in the signaling of heat and mechanical pain, respectively. DALDA-treated rats (n = 5 to 8/group) did not exhibit motor deficits and locomotor impairment suggesting that it does not induce central side effects.Conclusions: These findings suggest that DALDA may represent a potential alternative to current opioid therapy for the treatment of neuropathic pain and is likely to be associated with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin intofemale mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt+/+ and Pirt-/- mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt-/- mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt+/+ and Pirt-/- mice. We found that the writhing responses were less intensive in Pirt-/- mice than in Pirt+/+ mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrogradelabeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt-/- mice. Taken together, we speculate that Pirt plays an important role in mice uterine contractioninduced pain. [ABSTRACT FROM AUTHOR]

Purpose: To examine the anticancer effect of salvianolic acid-A against human small cell lung cancer (SCLC) cells (H-69). Methods: In vitro antiproliferative effect of salvianolic acid against SCLC cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis induction by salvianolic acid-A in these cells was measured by videomicroscopy along with fluorescence microscopy using Hoechst 33258 staining. The effect of the compound on mitochondrial membrane potential loss was detected by flow cytometry using rhodamine-123 as fluorescent probe. Gel electrophoresis was used to analyze DNA fragmentation after salvianolic acid treatment. Results: The results revealed that salvianolic acid-A induces dose-dependent as well as timedependent growth inhibitory effects against SCLC cancer cells. Videomicroscopy analysis revealed that SCLC cells became rounded (dead) and refringent after drug treatment which increased with increase in salvianolic acid-A dose. Fluorescence microscopy demonstrated that salvianolic acid-A induced dosedependent chromatin condensation in SCLC cells which is characteristic of apoptosis. DNA fragmentation was induced by various doses of the compound again hinting at apoptosis. Flow cytometry analysis using rhodamine-123 showed that salvianolic acid-A also caused substantial loss of mitochondrial membrane potential. Conclusion: The results suggest that salvianolic acid-A is a potential anticancer and apoptotic agent against drug-resistant small cell lung cancer. [ABSTRACT FROM AUTHOR]

The skin epidermis is densely innervated by peripheral sensory nerve endings. Nociceptive neurons, whose terminals are in close contact with epidermal keratinocytes, can be activated directly by noxious physical and chemical stimuli to trigger pain. However, whether keratinocytes can signal acutely to sensory nerve terminals to initiate pain in vivo remains unclear. Here, using the keratin 5 promoter to selectively express the capsaicin receptor TRPV1 in keratinocytes of TRPV1-knockout mice, we achieved specific stimulation of keratinocytes with capsaicin. Using this approach, we found that keratinocyte stimulation was sufficient to induce strong expression of the neuronal activation marker, c-fos, in laminae I and II of the ipsilateral spinal cord dorsal horn and to evoke acute paw-licking nocifensive behavior and conditioned place aversion. These data provide direct evidence that keratinocyte stimulation is sufficient to evoke acute nociception-related responses. [ABSTRACT FROM AUTHOR]

Background: Spinal cord stimulation (SCS) is a useful neuromodulatory technique for treatment of certain neuropathic pain conditions. However, the optimal stimulation parameters remain unclear. Methods: In rats after L5 spinal nerve ligation, the authors compared the inhibitory effects on mechanical hypersensitivity from bipolar SCS of different intensities (20, 40, and 80% motor threshold) and frequencies (50, 1 kHz, and 10 kHz). The authors then compared the effects of 1 and 50 Hz dorsal column stimulation at high- and low-stimulus intensities on conduction properties of afferent Aα/β-fibers and spinal wide-dynamic-range neuronal excitability. Results: Three consecutive daily SCS at different frequencies progressively inhibited mechanical hypersensitivity in an intensity-dependent manner. At 80% motor threshold, the ipsilateral paw withdrawal threshold (% preinjury) increased significantly from pre-SCS measures, beginning with the first day of SCS at the frequencies of 1 kHz (50.2 ± 5.7% from 23.9 ± 2.6%, n = 19, mean ± SEM) and 10 kHz (50.8 ± 4.4% from 27.9 ± 2.3%, n = 17), whereas it was significantly increased beginning on the second day in the 50 Hz group (38.9 ± 4.6% from 23.8 ± 2.1%, n = 17). At high intensity, both 1 and 50 Hz dorsal column stimulation reduced Aα/β-compound action potential size recorded at the sciatic nerve, but only 1 kHz stimulation was partially effective at the lower intensity. The number of actions potentials in C-fiber component of wide-dynamic-range neuronal response to windup-inducing stimulation was significantly decreased after 50 Hz (147.4 ± 23.6 from 228.1 ± 39.0, n = 13), but not 1 kHz (n = 15), dorsal column stimulation. Conclusions: Kilohertz SCS attenuated mechanical hypersensitivity in a time course and amplitude that differed from conventional 50 Hz SCS, and may involve different peripheral and spinal segmental mechanisms. [ABSTRACT FROM AUTHOR]