Site-recognition boosted the sensing performance of terbium-based organic frameworks for UO22+ detection.

A unique fluorescent sensing probe for UO22+ detection was fabricated with terbium-based metal organic frameworks via introducing specific recognition sites (denoted as Tb-TDPAT). The newly formed Tb-TDPAT presented remarkable detection sensitivity and selectivity towards UO22+, surpassing the need for complex post-modification methods.

Acoustic characteristics of infant- and foreigner-directed speech with Mandarin as the target language.

The quality of speech input influences the efficiency of L1 and L2 acquisition. This study examined modifications in infant-directed speech (IDS) and foreigner-directed speech (FDS) in Standard Mandarin-a tonal language-and explored how IDS and FDS features were manifested in disyllabic words and a longer discourse. The study aimed to determine which characteristics of IDS and FDS were enhanced in comparison with adult-directed speech (ADS), and how IDS and FDS differed when measured in a common set of acoustic parameters. For words, it was found that tone-bearing vowel duration, mean and range of fundamental frequency (F0), and the lexical tone contours were enhanced in IDS and FDS relative to ADS, except for the dipping Tone 3 that exhibited an unexpected lowering in FDS, but no modification in IDS when compared with ADS. For the discourse, different aspects of temporal and F0 enhancements were emphasized in IDS and FDS: the mean F0 was higher in IDS whereas the total discourse duration was greater in FDS. These findings add to the growing literature on L1 and L2 speech input characteristics and their role in language acquisition.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization.

Objectives: Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] and tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess the causal relationship between 41 inflammatory cytokines and KOA using Mendelian randomization (MR). Methods: Two-sample bidirectional MR was performed using genetic variation data for 41 inflammatory cytokines that were obtained from European Genome-Wide Association Study (GWAS) data (n=8293). KOA-related genetic association data were also obtained from European GWAS data (n=40,3124). Inverse variance weighting (IVW), MR, heterogeneity, sensitivity, and multiple validation analyses were performed. Results: Granulocyte colony-stimulating factor (G-CSF) or colony-stimulating factor 3 (CSF-3) levels were negatively associated with the risk of developing KOA (OR: 0.93, 95%CI:0.89-0.99, P=0.015). Additionally, macrophage inflammatory protein-1 alpha (MIP-1A/CCL3) was a consequence of KOA (OR: 0.72, 95%CI:0.54-0.97, P=0.032). No causal relationship was evident between other inflammatory cytokines and KOA development. Conclusion: This study suggests that certain inflammatory cytokines may be associated with KOA etiology. G-CSF exerts an upstream influence on KOA development, whereas MIP-1A (CCL-3) acts as a downstream factor.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Research progress of SWI/SNF complex in breast cancer.

In the past decade, numerous epigenetic mechanisms have been discovered to be associated with cancer. The mammalian SWI/SNF complex is an ATP-dependent chromatin remodeling complex whose mutations are associated with various malignancies including breast cancer. As the SWI/SNF complex has become one of the most commonly mutated complexes in cancer, targeting epigenetic mutations acquired during breast cancer progress is a potential means of improving clinical efficacy in treatment strategies. This article reviews the composition of the SWI/SNF complex, its main roles and research progress in breast cancer, and links these findings to the latest discoveries in cancer epigenomics to discuss the potential mechanisms and therapeutic potential of SWI/SNF in breast cancer.

Short-and long-term outcomes of one-stage versus two-stage gastrectomy for perforated gastric cancer: a multicenter retrospective propensity score-matched study.

OBJECTIVE: There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. METHODS: All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. RESULTS: Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P < 0.001], required less blood transfusion [0 (0, 100) vs 200 (0, 800), P = 0.034], had a shorter ICU stay [0 (0, 1.5) vs 3 (0, 3), P = 0.009], and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy [17 (12, 24) vs 29 (21, 37), P < 0.001] and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients. CONCLUSIONS: For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.

Organoboron flank-substituted donor-acceptor polymer anode with ultra-long cycling stability for lithium ion batteries.

The tunable structure and other properties of organic materials suggest that they can potentially solve the shortcomings of traditional anodes such as graphite. We successfully introduced an organoboron unit into the thiophene-based polymer PBT-2 to construct a donor-acceptor polymer anode. The charge delocalization and LUMO energy level resulting from the unique structure of this material enabled good redox activity and a very stable electrochemical performance in electrochemical tests, with a reversible capacity of 262 mA h g-1 at 0.5 A g-1 and >10 000 cycles at 1 A g-1 with a decay of 0.056‰ per cycle. Accordingly, targeted structural design to overcome the shortcomings of active units such as thiophene can effectively regulate their electrochemical performance, providing a solution for the development of high-performance anode materials for use in lithium ion batteries.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study.

BACKGROUND: We aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy. METHODS: This study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect. RESULTS: A total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54-72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282-3.660, P = 0.004; HR 1.583, 95% CI 0.985-2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725). CONCLUSIONS: Perineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Cercospora leaf spot disease of sugar beet.

Leaf spot disease caused by Cercospora beticola Sacc. is the most damaging foliar disease threatening sugar beet production worldwide. The wide spread of disease incurs a reduction of yield and economic losses. The in-depth knowledge of disease epidemiology and virulence factor of pathogen is crucial and basic for preventing fungal disease. The integrated control strategies are needed for an efficient and sustainable disease management. The rotation of fungicides and crop could reduce the initial inoculum and delay the emergence of resistant pathogens. Spraying fungicides under the guide of forecasting models and molecular detecting techniques may hinder the onset of disease prevalence. The resistant varieties of sugar beet to cercospora leaf spot could be obtained by combining classical and molecular breeding methods. More effective approaches are supposed to develop for prevention and control for fungal disease of sugar beet.

Surgical site infection after intracorporeal and extracorporeal anastomosis in laparoscopic left colectomy for colon cancer: a multicenter propensity score-matched cohort study.

BACKGROUND: Intracorporeal anastomosis (IA) is associated with reduced surgical site infection (SSI) and other postoperative complications in laparoscopic right colectomy (LRC). However, evidence is inadequate for IA in laparoscopic left colectomy (LLC). This study aimed to determine the effect of IA and extracorporeal anastomosis (EA) on SSI and other short-term postoperative complications in LLC. METHODS: In this retrospective multicenter propensity score-matched (PSM) cohort study, we enrolled consecutive patients who underwent LLC with IA (TLLC/IA) and laparoscopic-assisted left colectomy with EA (LALC/EA) at two medical centers between January 2015 and September 2021. Propensity score matching with a 1:2 ratio was employed. The primary outcome was SSI occurrence. Secondary outcomes were operating time, intraoperative hemorrhage, other postoperative complications, and pathological outcomes. RESULTS: Overall, 574 and 99 patients received LALC/EA and TLLC/IA, respectively. After PSM, 84 patients with TLLC/IA were matched with 141 patients with LALC/EA. Thirty patients (13.3%) patients experienced SSI (17.0% in LALC/EA vs 7.1% in TLLC/IA). IA was associated with a reduced risk of overall SSI and superficial/deep SSI compared with EA after PSM, with OR of 0.375 (95% CI, 0.147-0.959, P = 0.041). and 0.148 (95% CI, 0.034-0.648, P = 0.011), respectively. Multivariate analysis of unmatched patients indicated similar results. In the analysis of secondary outcomes, LALC/EA may have a shorter operating time (absolute mean difference - 13.41 [95% CI, - 23.76 to - 3.06], P = 0.002) and a higher risk of intraoperative hemorrhage (absolute risk difference 4.96 [95% CI, - 0.09 to 9.89], P = 0.048). CONCLUSIONS: IA in LLC is associated with a reduced risk of overall SSI and superficial/deep SSI. However, it may require a longer operating time.

Establishment of Surgical Difficulty Grading System and Application of MRI-Based Artificial Intelligence to Stratify Difficulty in Laparoscopic Rectal Surgery.

(1) Background: The difficulty of pelvic operation is greatly affected by anatomical constraints. Defining this difficulty and assessing it based on conventional methods has some limitations. Artificial intelligence (AI) has enabled rapid advances in surgery, but its role in assessing the difficulty of laparoscopic rectal surgery is unclear. This study aimed to establish a difficulty grading system to assess the difficulty of laparoscopic rectal surgery, as well as utilize this system to evaluate the reliability of pelvis-induced difficulties described by MRI-based AI. (2) Methods: Patients who underwent laparoscopic rectal surgery from March 2019 to October 2022 were included, and were divided into a non-difficult group and difficult group. This study was divided into two stages. In the first stage, a difficulty grading system was developed and proposed to assess the surgical difficulty caused by the pelvis. In the second stage, AI was used to build a model, and the ability of the model to stratify the difficulty of surgery was evaluated at this stage, based on the results of the first stage; (3) Results: Among the 108 enrolled patients, 53 patients (49.1%) were in the difficult group. Compared to the non-difficult group, there were longer operation times, more blood loss, higher rates of anastomotic leaks, and poorer specimen quality in the difficult group. In the second stage, after training and testing, the average accuracy of the four-fold cross validation models on the test set was 0.830, and the accuracy of the merged AI model was 0.800, the precision was 0.786, the specificity was 0.750, the recall was 0.846, the F1-score was 0.815, the area under the receiver operating curve was 0.78 and the average precision was 0.69; (4) Conclusions: This study successfully proposed a feasible grading system for surgery difficulty and developed a predictive model with reasonable accuracy using AI, which can assist surgeons in determining surgical difficulty and in choosing the optimal surgical approach for rectal cancer patients with a structurally difficult pelvis.

Knockout of cyclase-associated protein CAP1 confers tolerance towards salt and osmotic stress in Arabidopsis.

As a regulator of actin filament turnover, Arabidopsis thaliana CAP1 plays an important role in plant growth and development. Here, we analyzed the phenotypes of two Arabidopsis cap1 mutants: cap1-1 (a T-DNA insertion mutant) and Cas9-CAP1 (generated by CRISPR-Cas9 gene editing). Phenotypic analysis demonstrated that loss of CAP1 results in defects in seed germination and seedling morphology, with some seedlings exhibiting one or three cotyledons. The cap1-1 mutant took longer than the wild type to complete its life cycle, but its flowering time was normal, indicating that loss of CAP1 prolongs reproductive but not vegetative growth. Moreover, loss of CAP1 severely reduces seed production in self-pollinated plants, due to disruption of pollen tube elongation. RNA-seq and qRT-PCR analyses demonstrated that CAP1 may be involved in osmotic stress responses. Indeed, the cap1-1 mutant showed increased tolerance of salt and mannitol treatment, indicating that CAP1 plays a negative role in osmotic stress tolerance in Arabidopsis. Taken together, our results demonstrate that CAP1 functions not only in plant growth and development, but also in Arabidopsis responses to osmotic stress.

Efficient elimination of phenazone by an electro-assisted Fe3+-EDDS/PS process at neutral pH: Kinetics, mechanistic insights and toxicity evaluation.

The feasibility of the degradation of phenazone (PNZ), a common anti-inflammatory drug used for reducing pain and fever, in water at neutral pH by an electrochemically assisted Fe3+-ethylenediamine disuccinate-activated persulfate process (EC/Fe3+-EDDS/PS) was investigated. The efficient removal of PNZ at neutral pH condition was mainly attributed to the continuous activation of PS via electrochemically driven regenerated Fe2+ from a Fe3+-EDDS complex at the cathode. The influence of several critical parameters, including current density, Fe3+ concentration, EDDS to Fe3+ molar ratio, and PS dosage, on PNZ degradation was evaluated and optimized. Both hydroxyl radicals (•OH) and sulfate radicals (SO4●-) were considered major reactive species responsible for PNZ degradation. To understand the mechanistic model of action at the molecular level, the thermodynamic and kinetic behaviors of the reactions between PNZ with •OH and SO4●- were theoretically calculated using a density functional theory (DFT) method. The results revealed that radical adduct formation (RAF) is the most favorable pathway for the •OH-driven oxidation of PNZ, while single electron transfer (SET) appears to be the dominant pathway for the reaction of SO4●- with PNZ. In total, thirteen oxidation intermediates were identified, and hydroxylation, pyrazole ring opening, dephenylization, and demethylation were speculated to be the major degradation pathways. Furthermore, predicted toxicity to aquatic organisms indicated that PNZ degradation resulted in products that were less harmful. However, the developmental toxicity of PNZ and its intermediate products should be further investigated in the environment. The findings of this work demonstrate the viability of effectively removing organic contaminants in water at near-neutral pH by using EDDS chelation combined with electrochemistry in a Fe3+/persulfate system.

Risk Factors of Isolated Microtia: A Systematic Review and Meta-Analysis.

BACKGROUND: Isolated microtia is a congenital facial anomaly, and its cause is unclear. This study systematically investigated related suspicious factors. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Four databases were searched for eligible case-control and cohort studies. Odds ratios and 95% confidence intervals were calculated for each exposure variable if data from at least two eligible studies were provided. If not, narrative syntheses were performed. RESULTS: Twenty-eight articles were included. Meta-analyses were conducted with 22 articles, and 25 factors were identified to have significant association with isolated microtia. Moderate evidence showed that parental low education level, low birth weight (<2500 g), parity greater than or equal to 2, and family history of malformation (especially microtia); maternal intake of antibiotics, benzodiazepines, nonsteroidal antiinflammatory drugs, progesterone, and traditional Chinese medicine; in addition to maternal nongestational diabetes, upper respiratory infection, and radiation exposure increased the risk of microtia in offspring. Limited evidence showed that maternal Hispanic race, pesticide exposure, threatened abortion, history of spontaneous abortion, pet contact, and male gender were associated with increased risk. Maternal race of black or non-Hispanic, and living in an urban area were two protective factors found with moderate and limited evidence, respectively. CONCLUSION: This study has provided an initial investigation of potential factors associated with isolated microtia and evidence-based conclusion supporting prevention of modifiable factors.

A green-inspired method to prepare non-split high-density lipoprotein (HDL) carrier with anti-dysfunctional activities superior to reconstituted HDL.

Numerous studies have demonstrated that dysfunctional high-density lipoprotein (HDL), especially oxidized HDL (OxHDL), could generate multifaceted in vivo proatherogenic effects that run counter to the antiatherogenic activities of HDL. It thereby reminded us that the in vitro reconstituted HDL (rHDL) might encountered with oxidation-induced dysfunction. Accordingly, a green-inspired method was employed to recycle non-split HDL from human plasma fraction IV. Then it was compared with rHDL formulated by an ethanol-injection method in terms of physicochemical properties and anti-dysfunctional activities. Results exhibited that rHDL oxidation extent exceeded that of non-split HDL evidenced by higher malondialdehy content, weaker inhibition on low-density lipoprotein (LDL) oxidation and more superoxide anion. The reserved paraoxonase-1 activity on non-split HDL could partially explain for above experimental results. In the targeted transport mechanism experiment, upon SR-BI receptor inhibition and/or CD36 receptor blockage, the almost unchanged non-split HDL uptake in lipid-laden macrophage indicated its negligible oxidation modification profile with regard to rHDL again. Furthermore, compared to rHDL, better macrophage biofunctions were observed for non-split HDL as illustrated by accelerated cholesterol efflux, inhibited oxidized LDL uptake and lessened cellular lipid accumulation. Along with decreased ROS secretion, obviously weakened oxidative stress damage was also detected under treatment with non-split HDL. More importantly, foam cells with non-split HDL-intervention inspired an enhanced inflammation repression and apoptosis inhibition effect. Collectively, the anti-dysfunctional activities of non-split HDL make it suitable as a potential nanocarrier platform for cardiovascular drug payload and delivery.

Evidence Summary for Nonpharmacological Management of Chemotherapy-Induced Nausea and Vomiting.

Objective: To evaluate and summarize the best evidence for nonpharmacological management of chemotherapy induced nausea and vomiting (CINV). This article aims at serving as a reference for nursing staff to prevent and manage CINV. Methods: We systematically searched for evidence on CINV in databases such as Cnki and Wanfang, guide websites such as GIN and NZGG, and professional websites such as UICC and ACS. Only articles published between November 2012 and November 2021 were considered for inclusion in the summary. Two researchers evaluated the quality of the literature and extracted the data. Results: A total of 22 articles were included in this study, including 3 clinical decisions, 2 guidelines, 1 evidence summary, 2 recommended practices, 13 systematic reviews, and 1 expert consensus. Finally, 15 pieces of evidence were summarized from 3 perspectives: risk factor assessment, nursing process specification, and nonpharmacological interventions. Conclusion: Our research summarizes the best evidence on nonpharmacological management of CINV. During actual clinical application, it is necessary to fully consider the clinical situation, combine professional judgment with patients' wishes, follow the principle of individualization, analyze the obstacles and facilitating factors of the application of evidence, and prudently apply the evidence to the clinical practice.

Timing of MeCP2 Expression Determines Midbrain Dopamine Neuron Phenotype Specification.

Midbrain dopamine (DA) neurons are associated with locomotor and psychiatric disorders. DA phenotype is specified in ancestral neural precursor cells (NPCs) and maintained throughout neuronal differentiation. Here we show that endogenous expression of MeCP2 coincides with DA phenotype specification in mouse mesencephalon, and premature expression of MeCP2 prevents in vitro cultured NPCs from acquiring DA phenotype through interfering NURR1 transactivation of DA phenotype genes. By contrast, ectopic MeCP2 expression does not disturb DA phenotype in the DA neurons. By analyzing the dynamic change of DNA methylation along DA neuronal differentiation at the promoter of DA phenotype gene tyrosine hydroxylase (Th), we show that Th expression is determined by TET1-mediated de-methylation of NURR1 binding sites within Th promoter. Chromatin immunoprecipitation assays demonstrate that premature MeCP2 dominates the DNA binding of the corresponding sites thereby blocking TET1 function in DA NPCs, whereas TET1-mediated de-methylation prevents excessive MeCP2 binding in DA neurons. The significance of temporal DNA methylation status is further confirmed by targeted methylation/demethylation experiments showing that targeted de-methylation in DA NPCs protects DA phenotype specification from ectopic MeCP2 expression, whereas targeted methylation disturbs phenotype maintenance in MeCP2-overexpressed DA neurons. These findings suggest the appropriate timing of MeCP2 expression as a novel determining factor for guiding NPCs into DA lineage.

Binding of 14-3-3κ to ADF4 is involved in the regulation of hypocotyl growth and response to osmotic stress in Arabidopsis.

14-3-3 proteins, a family of conserved molecules in eukaryotes, target a number of protein clients through their ability to recognize well-defined phosphorylated motifs. ADF4, as one of Actin-Depolymerizing Factor (ADF) family of proteins, is involved in plant development, and response to biotic and abiotic stresses. Here, we show that 14-3-3κ specially interacted with ADF4 in vitro and in vivo. The 14-3-3κ×adf4 double mutant displayed less F-actin bundle and shorter hypocotyl compared with adf4 mutant, indicating that 14-3-3κ acts upstream of ADF4 to mediate the hypocotyl growth in the dark-grown seedlings. Under the osmotic stress, 14-3-3κ mutants displayed less survival rate than wild-type plants. The adf4 mutants exhibited markedly enhanced survival rate under osmotic treatment, while ADF4-overexpressing plants displayed the opposite results, indicating that ADF4 plays a negative role in response to osmotic stress in Arabidopsis. The interaction between ADF4 and 14-3-3κ inhibited the association of ADF4 with actin filament. Moreover, the in vitro phosphorylation assay demonstrates that the phosphorylation of ADF4 by CASEIN KINASE1-LIKE PROTEIN2 (CKL2) was enhanced by binding 14-3-3κ. Collectively, our data infer a fundamental role for the interaction between 14-3-3κ and ADF4 in regulating hypocotyl growth and osmotic tolerance of plants.

Monomerization of abscisic acid receptors through CARKs-mediated phosphorylation.

Cytosolic ABA Receptor Kinases (CARKs) play a pivotal role in abscisic acid (ABA)-dependent pathway in response to dehydration, but their regulatory mechanism in ABA signaling remains unexplored. In this study, we showed that CARK4/5 of CARK family physically interacted with ABA receptors (RCARs/PYR1/PYLs), including RCAR3, RCAR11-RCAR14, while CARK2/7/11 only interacted with RCAR11-RCAR14, but not RCAR3. It indicates that the members in CARK family function redundantly and differentially in ABA signaling. RCAR12 can form heterodimer with RCAR3 in vitro and in vivo. Moreover, the members of CARK family can form homodimer or heterodimer in a kinase activity dependent manner. ITC (isothermal titration calorimetry) analysis demonstrated that the phosphorylation of RCAR12 by CARK1 enhanced the ABA binding affinity. The phosphor-mimic RCAR12T105D significantly displayed ABA-induced inhibition of the phosphatase ABI1 (ABA insensitive 1) activity, leading to upregulation of ABA-responsive genes RD29A and RD29B in cark157:RCAR12T105D transgenic plants, which exhibited ABA hypersensitive phenotype. The transcription factor ABI5 (ABA insensitive 5) activates the transcriptions of CARK1 and CARK3 by binding to ABA-response elements (ABREs) of their promoters. Collectively, our data imply that the dimeric CARKs phosphorylate homodimer or heterodimer ABA receptors, leading to monomerization for triggering ABA responses in Arabidopsis.