ABSTRACT
Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.
Subject(s)
Hyperalgesia , Pain , Mice , Animals , Pain/metabolism , Hyperalgesia/metabolism , Gyrus Cinguli/metabolism , Anxiety , ThalamusABSTRACT
To improve the utilization efficiency of nutrients and water and determine the best drip irrigation frequency for long-season tomato cultivation in solar greenhouses, we cultivated tomato grafted seedlings in soil using an integrated water and fertilizer technology: drip irrigation under mulch. Seedlings drip-irrigated with balanced fertilizer (containing 20% N, 20% P2O5, and 20% K2O) and high-K fertilizer (containing 17% N, 8% P2O5, and 30% K2O) once every 12 days were set as control (CK) and that with water once every 12 days as CK1, while other seedling groups, drip-irrigated with a nutrient solution of Yamazaki (1978) formula for tomato, were set as treatments (T1-T4). There were four drip-irrigation frequencies, i.e., once every 2 days (T1), 4 days (T2), 6 days (T3), or 12 days (T4), who received the same total amounts of fertilizer and water over the 12 experimental days. The results showed that, with the decreases of drip irrigation frequency, tomato yield, the accumulation of N, P and K in plant dry matter, the fertilizer partial productivity, and the nutrient utilization rate first increased and then decreased, peaking at the T2 treatment. Compared with CK, under the T2 treatment, plant dry matter accumulation and the accumulation of N, P and K increased by 4.9%, 8.0%, 8.0%, 16.8%, the partial productivity of fertilizer and the utilization efficiency of water increased by 142.8% and 12.2%, the use efficiency of N, P and K was better than CK by 241.4%, 466.6% and 235.9%, respectively, and the tomato yield increased by 12.2%. Under the experimental conditions, drip irrigation with the Yamazaki nutrient solution at a frequency of 4 days could increase the tomato yield, as well as the use efficiency of nutrients and water. Under long-season cultivation, these trends would result in considerable saving of water and fertilizer. Overall, our findings provided a basis for improving the scientific management of water and fertilizers under long-season tomato cultivation in protected facilities.
Subject(s)
Solanum lycopersicum , Fertilizers/analysis , Seasons , Nitrogen/analysis , Soil , Water , Nutrients , Agricultural Irrigation/methodsABSTRACT
Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.
Subject(s)
Intralaminar Thalamic Nuclei , Mice , Male , Animals , Sensation , Prefrontal Cortex/physiology , Interneurons , AnxietyABSTRACT
Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+-PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.
ABSTRACT
Benzo[1,2-b:6,5-b']dithiophene (BDT) entity with rigid skeleton is introduced into the conjugated spacer of organic dyes, with triphenylamine as the electron donor and 2-cyanoacrylic acid as the acceptor, have been prepared for dye-sensitized solar cells. Inserting an aromatic entity between BDT and the anchor extends the absorption wavelength of the dyes and improves the dark current suppression efficiency, and consequently leads to better cell performance. Addition of chenodeoxycholic acid coadsorbent alleviates dye aggregation and results in better cell efficiency. The dye inserted with 4H-cyclopenta[2,1-b:3,4-b']dithiophene entity achieves the best efficiency (9.11%) when I-/I3- was used as the electrolyte. When Co(phen)32+/3+ was used as the electrolyte, the efficiency further boosts to 9.88%.
ABSTRACT
Metal-free dyes (EO1 to EO4) containing the hydrophilic triethylene oxide methyl ether (TEOME) unit in the spacer have been synthesized and used in dye-sensitized solar cells (DSSCs). Efficient lithium-ion trapping by TEOME results in improved open-circuit voltage (VOC ), leading to excellent conversion efficiency of the cells, ranging from 9.02 to 9.98 % with I(-) /I3 (-) electrolyte in acetonitrile under AMâ 1.5 illumination. The TEOME unit also enhances the wettability of the dye molecules for application in aqueous-based DSSCs. Aqueous-based DSSCs with a dual TEMPO/iodide electrolyte exhibit high VOC values (0.80-0.88â V) and very promising cell performances of up to 5.97 %.
Subject(s)
Coloring Agents/chemistry , Electric Power Supplies , Ethylene Oxide/analogs & derivatives , Methyl Ethers/chemistry , Phenothiazines/chemistry , Solar Energy , Electrochemistry , Ethylene Oxide/chemistryABSTRACT
Metal-free dyes (MD1 to MD5) containing an anthracene/phenothiazine unit in the spacer have been synthesized. The conversion efficiency (7.13 %) of the dye-sensitized solar cell using MD3 as the sensitizer reached approximately 85 % of the N719-based standard cell (8.47 %). The cell efficiency (8.42 %) of MD3-based dye-sensitized solar cells (DSSCs) with addition of chenodeoxycholic acid is comparable with that of N719-based standard cell. The MD3 water-based DSSCs using a dual-TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl)/iodide electrolyte exhibited very promising cell performance of 4.96 % with an excellent Voc of 0.77â V.
Subject(s)
Anthracenes/chemistry , Coloring Agents/chemistry , Electric Power Supplies , Phenothiazines/chemistry , Solvents/chemistry , Water/chemistry , Adsorption , Cyclic N-Oxides/chemistry , Electrochemistry , Models, Molecular , Molecular Conformation , Optical Phenomena , Oxidation-Reduction , Solar EnergyABSTRACT
BACKGROUND: Reversine, a small synthetic purine analogue, has been reported to be effective in tumor suppression. In the present study, we demonstrated an antitumor activity of reversine that could suppress cellular proliferation and induce cell cycle arrest and apoptosis in human breast cancer cell lines. METHODS: To evaluate whether reversine could suppress cell growth of MCF-7 and MDA-MB-231 cells and induce cell death, the cell viability, cell cycle, and apoptosis were determined in this study. RESULTS: Reversine treatment in human breast cancer cells reduced cell viability in a dose-dependent manner. Cell cycle accumulation at the G2/M phase in reversine-treated cells was also determined. Moreover, polyploidy was also found in reversine-treated cells. Apoptosis in reversine-treated cells was exhibited with PARP cleavage and caspase-3 and caspase-8 activation, but not caspase-9 activation, indicating that caspase-dependent apoptosis mediated by an extrinsic pathway took place in reversine-treated cells. Furthermore, reversine attenuated cell death in cells pretreated with a pan-caspase inhibitor before reversine treatment. CONCLUSIONS: In the present study, we demonstrated that reversine contributes to growth inhibition in human breast cancer cells through cell cycle arrest, polyploidy, and/or apoptosis induction. The apoptosis mediated by reversine was induced by the mitochondria-independent pathway. Therefore, the potential role of reversine as a novel therapeutic agent for the treatment of breast cancer is worthy of further investigation.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Morpholines/pharmacology , Purines/pharmacology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor/drug effects , Drug Screening Assays, Antitumor , Female , Humans , MCF-7 Cells/drug effects , Mitochondria/drug effects , PolyploidyABSTRACT
In 2006, an outbreak of aseptic meningitis was noted in Taiwan. From January to October 2006, a total of 3283 specimens collected from patients with viral infection, including 173 cerebrospinal fluid (CSF) samples, were examined for virus isolation and identification. Overall, 339 enterovirus (EV)-positive cases were identified by virus culture: echovirus 18 (E18) formed the majority (27.4â%, 93 cases), followed by coxsackievirus B2 (13.8â%, 47 cases) and coxsackievirus A2 (10.8â%, 37 cases). The manifestations of the 93 E18 cases were aseptic meningitis (44.1â%), viral exanthema (23.6â%), acute tonsillitis (15.1â%), acute pharyngitis (14.0â%), acute gastritis (11.8â%), herpangina (7.5â%) and bronchopneumonia (5.3â%). Of 107 E18 isolates identified, 100, 62.5 and 19â% were obtained following culture in RD, MRC-5 and A549 cells, respectively. E18 was identified most frequently from throat swabs (67.2â%) and less frequently from stool samples (15.9â%) and CSF (16.8â%). The detection rate of E18 was 78.2â% from CSF, 50â% from stool samples and 22.9â% from throat swabs. Phylogenetic relationships among the E18 strains were examined. Analysis of the partial VP1 gene showed 3.7-23.8â% variation in sequence compared with sequences from GenBank and, notably, the amino acid change V152S was detected in a protruding loop within the VP1 protein. These results indicate that a genetic variant of E18 was circulating and caused an outbreak of aseptic meningitis in Taiwan in 2006.
Subject(s)
Disease Outbreaks , Echovirus Infections/epidemiology , Enterovirus B, Human/isolation & purification , Meningitis, Aseptic/epidemiology , Meningitis, Aseptic/virology , Adolescent , Adult , Aged , Amino Acid Substitution , Capsid Proteins/genetics , Cell Line , Cerebrospinal Fluid/virology , Child , Child, Preschool , Cluster Analysis , Echovirus Infections/pathology , Echovirus Infections/virology , Feces/virology , Female , Humans , Infant , Male , Meningitis, Aseptic/pathology , Middle Aged , Molecular Sequence Data , Mutation, Missense , Pharynx/virology , Phylogeny , RNA, Viral/genetics , Sequence Analysis, DNA , Taiwan/epidemiology , Virus Cultivation/methods , Young AdultABSTRACT
In the title compound, C(11)H(11)N(3)O(2), prepared by the [3+2] cycloaddition reaction of benzyl azide with methyl propiolate, the dihedral angle between the ring planes is 67.87â (11)°.
ABSTRACT
Morusin is a pure compound isolated from root bark of Morusaustralis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G(1) phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-alpha, IKK-beta and IkappaB-alpha, increased expression of IkappaB-alpha, and suppressed nuclear translocation of NF-kappaB and its DNA binding activity. Dephosphorylation of NF-kappaB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-kappaB.