Identification of mitogen-activated protein kinases substrates in Arabidopsis using kinase client assay.

Mitogen-activated protein kinase (MPK) cascades are essential signal transduction components that control a variety of cellular responses in all eukaryotes. MPKs convert extracellular stimuli into cellular responses by the phosphorylation of downstream substrates. Although MPK cascades are predicted to be very complex, only limited numbers of MPK substrates have been identified in plants. Here, we used the kinase client (KiC) assay to identify novel substrates of MPK3 and MPK6. Recombinant MPK3 or MPK6 were tested against a large synthetic peptide library representing in vivo phosphorylation sites, and phosphorylated peptides were identified by high-resolution tandem mass spectrometry. From this screen, we identified 23 and 21 putative client peptides of MPK3 and MPK6, respectively. To verify the phosphorylation of putative client peptides, we performed in vitro kinase assay with recombinant fusion proteins of isolated client peptides. We found that 13 and 9 recombinant proteins were phosphorylated by MPK3 and MPK6. Among them, 11 proteins were proven to be the novel substrates of two MPKs. This study suggests that the KiC assay is a useful method to identify new substrates of MPKs.

Evaluation of the Ejection Pressure for Tracking Internal Cracks during Compaction in Bilayer Tablet Formulations Using Experimental and Finite Element Methods.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

Functional Sulfate Additive-Derived Interfacial Layer for Enhanced Electrochemical Stability of PEO-Based Polymer Electrolytes.

Solid-state electrolyte batteries have attracted significant interest as promising next-generation batteries due to their achievable high energy densities and nonflammability. In particular, curable polymer network gel electrolytes exhibit superior ion conductivity and interfacial adhesion with electrodes compared to oxide or sulfide solid electrolytes, bringing them closer to commercialization. However, the limited electrochemical stability of matrix polymers, particularly those based on poly (ethylene oxide) (PEO), presents challenges in achieving stable electrochemical performance in high-voltage lithium metal batteries. Here, these studies report a sulfate additive-incorporated thermally crosslinked gel-type polymer electrolyte (SA-TGPE) composed of a PEO-based polymer matrix and a functional sulfate additive, 1,3-propanediolcyclic sulfate (PCS), which forms stable interfacial layers on electrodes. The electrode-electrolyte interface modified by the PCS enhances the electrochemical stability of the polymer electrolyte, effectively alleviating decomposition of the PEO-based polymer matrix on the cathode. Moreover, it also mitigates side reactions of the Ni-rich NCM cathode and dendrites of lithium metal anode. These studies provide a novel perspective by utilizing interfacial modification through electrolyte additives to resolve the electrochemical instability of PEO-based polymer electrolytes in high-voltage lithium metal batteries.

The Effect of Compression Pressure on the First Layer Surface Roughness and Delamination of Metformin and Evogliptin Bilayer and Trilayer Tablets.

The objectives of this study were to evaluate the delamination of convex-shaped metformin HCl (MF) and evogliptin tartrate (EG) multi-layer tablets depending on the pre-compression and main compression pressures and simultaneously correlate these results with those of a surface roughness analysis. Free-flowing MF and EG (median diameters of 38.3 and 44.7 µm, respectively) granules prepared using the wet granulation method were pre-compressed and subsequently compressed into bilayer and trilayer tablets using a universal testing machine. The compaction force required to break the tablets increased linearly as the main compression pressure increased (30-150 MPa). Conversely, the interfacial strength and compaction breaking force decreased as the pre-compression pressure increased (10-110 MPa). A surface roughness analysis employing a profilometer revealed that the first layer (MF) roughness drastically decreased from 5.89 to 0.51 µm (Ra, arithmetic average of profile height deviations from the mean line) as the pre-compression pressure increased from 10 to 150 MPa in the bilayer tablet. Accordingly, the decrease in the roughness of the first layer reduced the inter-penetration at the interface, as observed via energy dispersive spectrometer (EDS)-equipped scanning electron microscopy, decreasing the interfacial bonding strength and causing delamination of the MF/EG multi-layer tablets. These findings indicate the significance of roughness control in the actual preparation of multi-layer tablets and the usefulness of profilometer- and EDS-based surface analyses for interpreting the delamination of multi-layer tablets.

Quercetin induces pathogen resistance through the increase of salicylic acid biosynthesis in Arabidopsis.

Quercetin is a flavonol belonging to the flavonoid group of polyphenols. Quercetin is reported to have a variety of biological functions, including antioxidant, pigment, auxin transport inhibitor and root nodulation factor. Additionally, quercetin is known to be involved in bacterial pathogen resistance in Arabidopsis through the transcriptional increase of pathogenesis-related (PR) genes. However, the molecular mechanisms underlying how quercetin promotes pathogen resistance remain elusive. In this study, we showed that the transcriptional increases of PR genes were achieved by the monomerization and nuclear translocation of nonexpressor of pathogenesis-related proteins 1 (NPR1). Interestingly, salicylic acid (SA) was approximately 2-fold accumulated by the treatment with quercetin. Furthermore, we showed that the increase of SA biosynthesis by quercetin was induced by the transcriptional increases of typical SA biosynthesis-related genes. In conclusion, this study strongly suggests that quercetin induces bacterial pathogen resistance through the increase of SA biosynthesis in Arabidopsis.

Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors.

BACKGROUND: 18Fluorine-Fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of 18F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve 18F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing's disease (CD). METHODS: We included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET. RESULTS: Twenty-two patients were included (age at diagnosis: 37 [13-56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006*), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010*; gray matter, 6.25 vs. 7.95, P = 0.010*). CONCLUSION: DEX suppression did not improve 18F-FDG PET/CT localization in patients with CD.

Role of Immediate Postoperative Prolactin Measurement in Female Prolactinoma Patients: Predicting Long-Term Remission After Complete Tumor Removal.

BACKGROUND: Transsphenoidal surgery is one of the important treatment options in the management of prolactinomas; however, complete resection of the tumor does not always lead to endocrinological remission. While many studies have investigated preoperative factors associated with surgical outcome, little has been known about the relationship between postoperative factors and long-term surgical outcomes; moreover, there is no consistency in results. The aim of this study was to demonstrate the reliability of immediate postoperative prolactin levels as predictors of long-term outcomes. METHODS: A total of 105 female patients who underwent complete removal of their histologically confirmed prolactinomas were included, and their medical records were retrospectively reviewed. To evaluate the predictability of immediate postoperative prolactin levels for long-term remission, prolactin levels were measured at 2, 6, 12, 18, 24, 48, and 72 h after surgery. RESULTS: From the 105 included patients, 95 (90.5%) and 10 (9.5%) belonged to the remission and non-remission groups, respectively. A significant difference was observed in the prolactin level measured 6 h after surgery between the remission and non-remission groups, and this difference stayed apparent until 72 h after surgery. We derived a cut-off value for every postoperative time point that showed a significant relationship with disease remission. CONCLUSION: Our study suggests that immediate postoperative measurement of prolactin levels is a reliable predictor of long-term remission and can contribute to early identification of patients who require adjuvant treatment after surgery.

Surgical Treatment of Prolactinomas: Potential Role as a First-Line Treatment Modality.

PURPOSE: Treatment with dopamine agonists (DAs) has been the first-line standard treatment for prolactinoma, and surgery has been reserved for drug intolerance and resistance for several decades. We evaluated whether surgery plays a primary role in prolactinoma management. MATERIALS AND METHODS: We conducted a retrospective study of 210 prolactinoma patients who had received surgical treatment at our institution. We analyzed the treatment outcomes according to tumor extent, sex, and preoperative DA medication. RESULTS: Overall hormonal remission was achieved in 164 patients (78.1%), and complete removal was achieved in 194 patients (92.4%). When the tumors were completely removed, the remission rate increased to 84.5%. Anterior pituitary function was normalized or improved in 94.6% of patients, whereas only 4.1% of patients showed worsening of hormone control. Hormonal remission was higher in patients who had not received DA preoperatively than in those who had received preoperative DA treatment. Smaller tumor size (<1 cm), no invasion into the cavernous sinus, and female sex were predictors of good surgical outcomes. CONCLUSION: Although DAs remain the first-line standard treatment for prolactinomas, surgery can be an excellent option and should be considered as an alternative primary treatment modality when patients are predicted to achieve a good surgical outcome.

MRI-Based Classification of Rathke's Cleft Cyst and Its Clinical Implication.

BACKGROUND: Rathke's cleft cysts (RCCs) are benign tumors of the pituitary gland. Small, asymptomatic RCCs do not require surgical treatment, whereas surgical treatment is required for symptomatic RCCs. METHODS: We retrospectively reviewed medical records of patients with an RCC who were diagnosed and managed in our institution between April 2004 and April 2020 and generated two different cohorts: the observation (n=114) and the surgical group (n=99). Their initial MRI signal characteristics were analyzed. The natural course focusing on cyst size was observed in the observation group and postoperative visual and endocrine outcomes were evaluated in the surgical group. RESULTS: The characterization of MRI signals of cyst contents in both T1-weighted (T1W) and T2-weighted (T2W) images revealed nine combinations for our 213 patients. Among 115 patients with a high T2W signal, the cysts showed hypo-, iso-, and hyper-intensity on T1W images in 72, 39, and 44 patients, respectively; Type S-low, Type S-iso, and Type S-high. One more major group of 35 patients showed RCCs with hyperintensity on the T1W images and hypointensity on the T2W images named as Type M. In the comparison between observation and surgical groups, we identified only two major groups in which the number of patients in the surgical and observation groups was statistically different: more Type S-low in a surgical group (p<0.001) and more Type M in an observation group (p=0.007). In subgroup analysis, the range of change in the cyst size was the highest in Type S-high in the observation group (p=0.028), and intergroup differences in visual and endocrine outcomes were not evident in the surgical group. CONCLUSION: MRI characteristics help to predict the natural course of RCCs. We identified subgroups of RCCs which are more or less likely to require surgical intervention.

Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

Asian-specific 3'UTR variant in CDKN2B associated with risk of pituitary adenoma.

BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.

Phosphorylation of the auxin signaling transcriptional repressor IAA15 by MPKs is required for the suppression of root development under drought stress in Arabidopsis.

Since plants are sessile organisms, developmental plasticity in response to environmental stresses is essential for their survival. Upon exposure to drought, lateral root development is suppressed to induce drought tolerance. However, the molecular mechanism by which the development of lateral roots is inhibited by drought is largely unknown. In this study, the auxin signaling repressor IAA15 was identified as a novel substrate of mitogen-activated protein kinases (MPKs) and was shown to suppress lateral root development in response to drought through stabilization by phosphorylation. Both MPK3 and MPK6 directly phosphorylated IAA15 at the Ser-2 and Thr-28 residues. Transgenic plants overexpressing a phospho-mimicking mutant of IAA15 (IAA15DD OX) showed reduced lateral root development due to a higher accumulation of IAA15. In addition, MPK-mediated phosphorylation strongly increased the stability of IAA15 through the inhibition of polyubiquitination. Furthermore, IAA15DD OX plants showed the transcriptional downregulation of two key transcription factors LBD16 and LBD29, responsible for lateral root development. Overall, this study provides the molecular mechanism that explains the significance of the MPK-Aux/IAA module in suppressing lateral root development in response to drought.

Arachnoid Remodeling by Clipping Technique Facilitates Surgical Maneuverability during Transsphenoidal Surgery for Pituitary Macroadenoma.

OBJECTIVE: Pituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS. METHODS: Total 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients. RESULTS: Our technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism. CONCLUSION: During TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.

Clinical Relevance of New World Health Organization Classification System for Pituitary Adenomas: A Validation Study With 2-Year Experience.

BACKGROUND: The new World Health Organization (WHO) classification system proposed a cell lineage-based classification scheme for pituitary adenomas in which transcription factors (TFs) play a major role as key classifiers. We aimed to evaluate clinical relevance of the new classification system in a clinical setting. METHODS: TF staining was retrospectively performed for 153 clinically and histologically well characterized pituitary adenomas. Then, 484 pituitary adenomas were prospectively stained for TFs and then for relevant pituitary hormones. TF and hormone stain-based diagnoses were compared, and differences in clinical manifestations were evaluated. RESULTS: The accuracies of antibodies for three TFs were successfully validated and had an overall matching rate was 89.6%. We identified 50 (10.4%) cases with discrepancies between TF and pituitary hormone stains. Gonadotroph adenomas lacking follicle-stimulating hormone and luteinizing hormone stains account for most discrepancies. Null cell adenomas may be more prevalent than reported and may be clinically more aggressive than gonadotroph adenomas. CONCLUSION: The new WHO classification is mostly well matched with the traditional classification. However, until the new classification is further validated and interpreted in the context of long-term clinical outcomes, routine histological examination should include full slate of immunostains for pituitary hormones as well as TFs.

ATBS1-INTERACTING FACTOR 2 Negatively Modulates Pollen Production and Seed Formation in Arabidopsis.

ATBS1-INTERACTING FACTOR 2 (AIF2) is a non-DNA-binding basic-helix-loop-helix (bHLH) transcription factor. Here, we demonstrate that AIF2 negatively modulates brassinosteroid (BR)-induced, BRASSINAZOLE RESISTANT 1 (BZR1)-mediated pollen and seed formation. AIF2-overexpressing Arabidopsis plants (AIF2ox) showed defective pollen grains and seed production while two AIF2 knockout mutants, aif2-1 and aif2-1/aif4-1, displayed opposite phenotypes. Genes encoding BZR1-regulated positive factors of seed size determination (SHB1, IKU1, MINI3) were suppressed in AIF2ox and genes for negative factors (AP2 and ARF2) were enhanced. Surprisingly, BZR1-regulated pollen genes such as SPL, MS1, and TDF1 were aberrantly up-regulated in AIF2ox plants. This stage-independent abnormal expression may lead to a retarded and defective progression of microsporogenesis, producing abnormal tetrad microspores and pollen grains with less-effective pollen tube germination. Auxin plays important roles in proper development of flower and seeds: genes for auxin biosynthesis such as TCPs and YUCCAs as well as for positive auxin signalling such as ARFs were suppressed in AIF2ox flowers. Moreover, lipid biosynthesis- and sucrose transport-related genes were repressed, resulting in impaired starch accumulation. Contrarily, sucrose and BR repressed ectopic accumulation of AIF2, thereby increasing silique length and the number of seeds. Taken together, we propose that AIF2 is negatively involved in pollen development and seed formation, and that sucrose- and BR-induced repression of AIF2 positively promotes pollen production and seed formation in Arabidopsis.

Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant.

We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

Effects of Dual Transcranial Direct Current Stimulation and Modified Constraint-Induced Movement Therapy to Improve Upper-Limb Function after Stroke: A Double-Blinded, Pilot Randomized Controlled Trial.

BACKGROUND: Dual transcranial direct current stimulation (dual tDCS) can be combined with stroke rehabilitation interventions to promote excitatory changes in the cerebral cortex. OBJECTIVE: To investigate how the combined intervention of dual tDCS and modified constraint-induced movement therapy (mCIMT) using both anodal and cathodal stimulation affects on the recovery of upper limb function in chronic stroke patients. METHODS: This study was a double-blind randomized controlled trial. A total of 30 patients were randomly assigned to the experimental group (dual tDCS and mCIMT) or control group (sham dual tDCS and mCIMT). The experimental and control group performed mCIMT immediately after applying dual tDCS for 20 min, but the control group also performed mCIMT after applying sham tDCS for 20 min in a state where no current flows. The total intervention period was performed 5 times a week for 4 weeks. The outcome was assessed using Fugle-Meyer Assessment (FMA) Motor Activity Log (MAL) Accelerometer. RESULTS: There was a significant improvement in AOU of MAL and usage of unaffected side in the experimental group compared to the control group, and the experimental group showed more than a small effect difference compared to the control group in the effect size of all evaluations. CONCLUSIONS: This study has clinical significance in that it presents the possibility of convergence intervention that considers the therapeutic efficiency in clinical practice.

Naringenin Induces Pathogen Resistance Against Pseudomonas syringae Through the Activation of NPR1 in Arabidopsis.

Flavonoids are well known for the coloration of plant organs to protect UV and ROS and to attract pollinators as well. Flavonoids also play roles in many aspects of physiological processes including pathogen resistance. However, the molecular mechanism to explain how flavonoids play roles in pathogen resistance was not extensively studied. In this study, we investigated how naringenin, the first intermediate molecule of the flavonoid biosynthesis, functions as an activator of pathogen resistances. The transcript levels of two pathogenesis-related (PR) genes were increased by the treatment with naringenin in Arabidopsis. Interestingly, we found that naringenin triggers the monomerization and nuclear translocation of non-expressor of pathogenesis-related genes 1 (NPR1) that is a transcriptional coactivator of PR gene expression. Naringenin can induce the accumulation of salicylic acid (SA) that is required for the monomerization of NPR1. Furthermore, naringenin activates MPK6 and MPK3 in ROS-dependent, but SA-independent manners. By using a MEK inhibitor, we showed that the activation of a MAPK cascade by naringenin is also required for the monomerization of NPR1. These results suggest that the pathogen resistance by naringenin is mediated by the MAPK- and SA-dependent activation of NPR1 in Arabidopsis.

Embedded Reverse-Offset Printing of Silver Nanowires and Its Application to Double-Stacked Transparent Electrodes with Microscale Patterns.

We propose an embedded reverse-offset printing (EROP) method, which generates silver nanowire (AgNW) transparent electrodes for display applications. The proposed EROP method can solve the two critical issues of microscale pattern formation and surface planarization. The AgNW electrode had a transmittance of 82% at 550 nm, a sheet resistance of 12.2 Ω/sq, and a 3.27 nm smooth surface. We realized the roll-based pattern formation of AgNW on a plastic substrate as small as 10 µm with negligible step differences to facilitate the proposed method. The proposed EROP method also produced a double-stacked AgNW electrode, enabling the simultaneous operation of separately micropatterned devices. To verify the usefulness of EROP, we fabricated an organic light-emitting diode (OLED) device to demonstrate leakage current reduction and efficiency improvement compared with a conventional indium tin oxide (ITO)-based OLED device. The EROP-based OLED showed 38 and 25% higher current efficiencies than an insulator-patterned AgNW OLED and a conventional ITO-based OLED, respectively.

Delayed Hyponatremia after Transsphenoidal Surgery for Pituitary Adenomas: A Single Institutional Experience.

BACKGROUND: Hyponatremia is a common complication after transsphenoidal surgery (TSS) for pituitary adenomas. This study retrospectively reviewed various clinical factors of pituitary adenoma patients who underwent TSS and aimed to identify possible risk factors of postoperative hyponatremia. METHODS: Total 1,343 patients who underwent TSS for their pituitary adenomas in a single institution were enrolled to this study. We identified and analyzed 93 patients (6.9%) with postoperative hyponatremia and compared them with other 1,250 patients in a control group. Patients' age, sex, tumor extent based on the modified Hardy classification, tumor size and hormonal type of the tumors were analyzed in comparison between two groups. The results of pre- and post-operative combined pituitary function test and their comparison were analyzed to elucidate a possible association between postoperative hyponatremia and hypopituitarism. RESULTS: The onset of postoperative hyponatremia was 7.8 days after surgery (range: postoperative day 3-13). The initial level of serum sodium (Na) level at the start of treatment was 123.5 mmol/L (range: 114-131 mmol/L) and the duration of treatment was 2.7 days (range: 1-9 days). Female predominance was evident in the hyponatremia group (77.4% vs. 61.4%, p=0.02). Preoperative hypopituitarism (58.5% vs. 71.5%, p=0.007) and postoperative hypocortisolism (33.7% vs. 23.4%, p=0.029) were related to postoperative hyponatremia. Other pre- and post-operative clinical factors were not associated with postoperative hyponatremia. CONCLUSION: Postoperative hyponatremia is a common complication after TSS and is potentially fatal. Female patients were more likely to develop delayed hyponatremia. We demonstrated possible associations of delayed postoperative hyponatremia with preoperative and postoperative pituitary functions, but the mechanism behind it should be further investigated.