Chronic pain is a common neurological disease involving lasting, multifaceted maladaptations from gene modulations to synaptic malfunctions and to emotional disorders. Sustained pathological stimuli in many diseases alter output activities of certain genes through epigenetic modifications, but it is unclear how epigenetic mechanisms operate in the development of chronic pain. We demonstrate here that, in the rat brainstem nucleus raphe magnus, which is important for central mechanisms of chronic pain, persistent inflammatory and neuropathic pain epigenetically suppresses gad65 activities through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in impaired GABA synaptic inhibition. gad65 knockout mice display similar sensitized pain behavior and impaired GABA synaptic function in the brainstem neurons. HDAC inhibitors overwhelmingly increase gad65 activities, restore GABA synaptic function and relieve the sensitized pain behavior, but not in gad65 knockout mice. These findings suggest GAD65 and HDACs as potential therapeutic targets in an epigenetic approach to the treatment of chronic pain.

Cytokinins are a major group of phytohormones regulating plant growth, development and stress responses. However, in contrast to the well-defined polar transport of auxins, the molecular basis of cytokinin transport is poorly understood. Here we show that an ATP-binding cassette transporter in Arabidopsis, AtABCG14, is essential for the acropetal (root to shoot) translocation of the root-synthesized cytokinins. AtABCG14 is expressed primarily in the pericycle and stelar cells of roots. Knocking out AtABCG14 strongly impairs the translocation of trans-zeatin (tZ)-type cytokinins from roots to shoots, thereby affecting the plant's growth and development. AtABCG14 localizes to the plasma membrane of transformed cells. In planta feeding of C 14 or C 13 -labelled tZ suggests that it acts as an efflux pump and its presence in the cells directly correlates with the transport of the fed cytokinin. Therefore, AtABCG14 is a transporter likely involved in the long-distance translocation of cytokinins in planta.

Abnormal hyperexcitability of primary sensory neurons plays an important role in neuropathic pain. Voltage-gated potassium (Kv) channels regulate neuronal excitability by affecting the resting membrane potential and influencing the repolarization and frequency of the action potential. In this study, we determined changes in Kv channels in dorsal root ganglion (DRG) neurons in a rat model of diabetic neuropathic pain. The densities of total Kv, A-type (IA) and sustained delayed (IK) currents were markedly reduced in medium-and large-, but not in small-, diameter DRG neurons in diabetic rats. Quantitative RT-PCR analysis revealed that the mRNA levels of IA subunits, including Kv1.4, Kv3.4, Kv4.2, and Kv4.3, in the DRG were reduced 50% in diabetic rats compared with those in control rats. However, there were no significant differences in the mRNA levels of IK subunits (Kv1.1, Kv1.2, Kv2.1, and Kv2.2) in the DRG between the two groups.Incubation with brain-derived neurotrophic factor (BDNF) caused a large reduction in Kv currents, especially IA currents, in medium and large DRG neurons from control rats. Furthermore, the reductions in Kv currents and mRNA levels of IA subunits in diabetic rats were normalized by pre-treatment with anti-BDNF antibody or K252a, a TrkB tyrosine kinase inhibitor. In addition, the number of medium and large DRG neurons with BDNF immunoreactivity was greater in diabetic than control rats. Collectively, our findings suggest that diabetes primarily reduces Kv channel activity in medium and large DRG neurons. Increased BDNF activity in these neurons likely contributes to the reduction in Kv channel function through TrkB receptor stimulation in painful diabetic neuropathy.

Suberin, a lipophilic polymer deposited in the outer integument of the Arabidopsis (Arabidopsis thaliana) seed coat, represents an essential sealing component controlling water and solute movement and protecting seed from pathogenic infection. Although many genes responsible for suberin synthesis are identified, the regulatory components controlling its biosynthesis have not been definitively determined. Here, we show that the Arabidopsis MYB107 transcription factor acts as a positive regulator controlling suberin biosynthetic gene expression in the seed coat. MYB107 coexpresses with suberin biosynthetic genes in a temporal manner during seed development. Disrupting MYB107 particularly suppresses the expression of genes involved in suberin but not cutin biosynthesis, lowers seed coat suberin accumulation, alters suberin lamellar structure, and consequently renders higher seed coat permeability and susceptibility to abiotic stresses. Furthermore, MYB107 directly binds to the promoters of suberin biosynthetic genes, verifying its primary role in regulating their expression. Identifying MYB107 as a positive regulator for seed coat suberin synthesis offers a basis for discovering the potential transcriptional network behind one of the most abundant lipid-based polymers in nature.

The use of gold nanoparticles as radiosensitizers is an effective way to boost the killing efficacy of radiotherapy while drastically limiting the received dose and reducing the possible damage to normal tissues. Herein, we designed aggregation‐induced emission gold clustoluminogens (AIE‐Au) to achieve efficient low‐dose X‐ray‐induced photodynamic therapy (X‐PDT) with negligible side effects. The aggregates of glutathione‐protected gold clusters (GCs) assembled through a cationic polymer enhanced the X‐ray‐excited luminescence by 5.2‐fold. Under low‐dose X‐ray irradiation, AIE‐Au strongly absorbed X‐rays and efficiently generated hydroxyl radicals, which enhanced the radiotherapy effect. Additionally, X‐ray‐induced luminescence excited the conjugated photosensitizers, resulting in a PDT effect. The in vitro and in vivo experiments demonstrated that AIE‐Au effectively triggered the generation of reactive oxygen species with an order‐of‐magnitude reduction in the X‐ray dose, enabling highly effective cancer treatment.

g-Aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1 À/À ) mice using several depressionand anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the openfield test, the dark-light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1 À/À mice showed a lower level of depression-and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1 À/À mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1 À/À mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.

Large‐conductance Ca2+‐activated K+ (BKCa, MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BKCa channels in the dorsal root ganglion (DRG) and spinal dorsal horn and their role in the control of nociception in neuropathic pain. Here we show that L5 and L6 spinal nerve ligation in rats resulted in a substantial reduction in both the mRNA and protein levels of BKCa channels in the DRG but not in the spinal cord. Nerve injury primarily reduced the BKCa channel immunoreactivity in small‐ and medium‐sized DRG neurons. Furthermore, although the BKCa channel immunoreactivity was decreased in the lateral dorsal horn, there was an increase in the BKCa channel immunoreactivity present on dorsal horn neurons near the dorsal root entry zone. Blocking the BKCa channel with iberiotoxin at the spinal level significantly reduced the mechanical nociceptive withdrawal threshold in control and nerve‐injured rats. Intrathecal injection of the BKCa channel opener [1,3‐dihydro‐1‐[2‐hydroxy‐5‐(trifluoromethyl)phenyl]‐5‐(trifluoromethyl)‐2H‐benzimidazol‐2‐one] dose dependently reversed allodynia and hyperalgesia in nerve‐ligated rats but it had no significant effect on nociception in control rats. Our study provides novel information that nerve injury suppresses BKCa channel expression in the DRG and induces a redistribution of BKCa channels in the spinal dorsal horn. BKCa channels are increasingly involved in the control of sensory input in neuropathic pain and may represent a new target for neuropathic pain treatment.

Herein, we report highly bright and stable CsPbI 3 (CPI) perovskite quantum dots (PQDs) synthesized with trimethylsilyl iodine (TMSI) under a reaction circumstance with the I/Pb molar ratio of ∼4.2. The obtained CPI (TMSI-CPI) PQDs show near-unity photoluminescence quantum yields (PLQYs) in solution and high stability (only 9% loss in PLQY after 105 day storage) under ambient and dark conditions. The thermal stability of TMSI-CPI PQDs is also improved: the degradation temperature is higher than that of traditional hot-injection-synthesized CPI (Tra-CPI) PQDs. X-ray photoelectron spectroscopy results show that the TMSI-CPI PQDs have a highly iodine-rich surface (the I/Pb atomic ratio is up to 4.4), which is believed to be responsible for such high stability and PLQYs. Further, the size and surface properties of CPI PQDs can be easily adjusted by changing the amount of TMSI. Finally, we fabricated QDs-based light-emitting diodes (QLEDs) utilizing TMSI-CPI PQDs as an emissive layer showing a maximum luminance of 365 cd m −2 and external quantum efficiency of 1.8%. During a working period of 2 h, no shift and broadening of the electroluminescence spectra happen for TMSI-CPI-based QLEDs with an initial luminance of 100 cd m −2 ; the device lifetime for which the luminance drops to half of its initial value (100 cd m −2 ) reaches 3.11 h, which is nearly 7 times longer than that of Tra-CPI-based QLEDs.