Dendritic cell mineralocorticoid receptor controls blood pressure by regulating T helper 17 differentiation: role of the Plcß1/4-Stat5-NF-κB pathway.

BACKGROUND AND AIMS: Dendritic cells (DCs) are closely related to blood pressure (BP) regulation. Mineralocorticoid receptor (MR) is an important drug target for antihypertensive treatment. However, the role of DC MR in the pathogenesis of hypertension has not been fully elucidated. This study aimed to determine the role of DC MR in BP regulation and to explore the mechanism. METHODS: Renal biopsy and peripheral blood samples were collected from hypertensive patients (HTN) for immunostaining and flow cytometry. Dendritic cell MR knockout (DCMRKO) mice, DC MR overexpressing (DCMROV) mice, DCMROV/IL-17A knockout (DCMROV/IL-17AKO) mice and finerenone-treated C57BL/6 mice were infused with angiotensin II (Ang II) to establish hypertensive models. Western blotting, chromatin immunoprecipitation, co-immunoprecipitation, and in vivo DC depletion or adoptive transfer were used to delineate the functional importance of DC MR in hypertension development. RESULTS: Mineralocorticoid receptor antagonists (spironolactone and finerenone) suppressed DC aggregation and activation, as well as hypertension in HTN and mice. Compared with littermate control (LC) mice, dendritic cell MR knockout mice had strikingly decreased BPs and attenuated target organ damage after Ang II infusion. Flow cytometry showed that DC MR deficiency mitigated Ang II-induced DC activation and T helper 17 (Th17) cell differentiation. RNA sequencing revealed that MR-deficient DCs had elevated expression of Plcß1 and Plcß4, knockdown of which reversed the inhibitory effect of MR deficiency on DC activation and Th17 differentiation. Adoptive transfer of MR-deficient DCs protected Ang II-induced hypertension, whereas knockdown of Plcß1/4 eliminated the protective effects. At the molecular level, MR negatively regulated Plcß1/4, which recruited SHP-1 to inactivate of Stat5 activity, resulting in enhanced NF-κB activation and Th17 polarization. Furthermore, DCMROV mice manifested more elevated BPs and target organ damage than control mice after Ang II infusion, and these differences were abolished in DCMROV/IL-17AKO mice. Finally, MR antagonists decreased the aggregation of Th17 in HTN and mice. CONCLUSIONS: Dendritic cell MR plays important roles in the pathogenesis of hypertension by regulating Th17 through Plcß1/4-Stat5-NF-κB signalling, and blockade of DC MR is beneficial for treating hypertension.

Regulation of Fuzheng Huayu capsule on inhibiting the fibrosis-associated hepatocellular carcinogenesis.

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3.

Does tourism development contribute to the green water-use efficiency of the Yellow River Basin in China?

The coordination between economic development as well as water resources conservation in ecologically fragile areas is the basis for achieving sustainable development in developing countries. Nonetheless, the existing literature pays little attention to such an issue. The purpose of this quantitative study is to explore the causal relationship between tourism development and green water-use efficiency in the Yellow River Basin (YRB) of China. The findings are as follows: (1) Tourism development can significantly enhance the green water-use efficiency in the YRB; For every 1% increase in tourism revenue, the green water-use efficiency will increase by 4.38%. (2) Tourism affects the green water-use efficiency by increasing the intensity of water pollution and decreasing the intensity of water use; For every 1% increase in tourism revenue, the green water-use efficiency will decrease by 0.2% and increase by 0.9% respectively by increasing the intensity of water pollution and decreasing the intensity of water use. (3) Strengthening environmental regulation and improving service facilities will further enhance the positive impact of tourism development; An increase of one standard deviation in the intensity of environmental regulation or one standard deviation in the level of service facilities will increase the impact of tourism on green water-use efficiency by 1.1% or 1.7%, respectively. The aforementioned findings provide enlightenment for effectively promoting the coordination between economic development and water resources protection in ecologically fragile areas of developing countries.

Sanguinarine, similar to the MICs of spectinomycin, exhibits good anti-Neisseria gonorrhoeae activity in vitro.

The increasing antibiotic resistance of Neisseria gonorrhoeae (NG) is an urgent need to explore new and effective drugs. The antibacterial activities of spectinomycin and sanguinarine against 117 clinical NG isolates and time-kill curve of sanguinarine were evaluated. Almost all isolates were resistant to penicillin (91.5%) and ciprofloxacin (96.5%), 8.5% showed resistance to azithromycin, 10.3% and 10.3% had decreased susceptibility/resistance to ceftriaxone and cefixime, respectively, whereas 100% were susceptible to spectinomycin. The minimum inhibitory concentration (MIC) ranges, MIC50, MIC90 and MICmean values of sanguinarine were 2-64 µg/ml, 16 µg/ml, 32 µg/ml and 16.9 µg/ml, respectively, and time-kill curve showed killing of bacteria in a dose-dependent manner during the assay time of 6h, very similar to spectinomycin. Sanguinarine has great potential as an effective and novel anti-NG agent.

Psychological Inoculation for Credibility Assessment, Sharing Intention, and Discernment of Misinformation: Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of misinformation poses a substantial threat to individuals' daily lives, necessitating the deployment of effective remedial approaches. One promising strategy is psychological inoculation, which pre-emptively immunizes individuals against misinformation attacks. However, uncertainties remain regarding the extent to which psychological inoculation effectively enhances the capacity to differentiate between misinformation and real information. OBJECTIVE: To reduce the potential risk of misinformation about digital health, this study aims to examine the effectiveness of psychological inoculation in countering misinformation with a focus on several factors, including misinformation credibility assessment, real information credibility assessment, credibility discernment, misinformation sharing intention, real information sharing intention, and sharing discernment. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a meta-analysis by searching 4 databases (Web of Science, APA PsycINFO, Proquest, and PubMed) for empirical studies based on inoculation theory and outcome measure-related misinformation published in the English language. Moderator analyses were used to examine the differences in intervention strategy, intervention type, theme, measurement time, team, and intervention design. RESULTS: Based on 42 independent studies with 42,530 subjects, we found that psychological inoculation effectively reduces misinformation credibility assessment (d=-0.36, 95% CI -0.50 to -0.23; P<.001) and improves real information credibility assessment (d=0.20, 95% CI 0.06-0.33; P=.005) and real information sharing intention (d=0.09, 95% CI 0.03-0.16; P=.003). However, psychological inoculation does not significantly influence misinformation sharing intention (d=-0.35, 95% CI -0.79 to 0.09; P=.12). Additionally, we find that psychological inoculation effectively enhances credibility discernment (d=0.20, 95% CI 0.13-0.28; P<.001) and sharing discernment (d=0.18, 95% CI 0.12-0.24; P<.001). Regarding health misinformation, psychological inoculation effectively decreases misinformation credibility assessment and misinformation sharing intention. The results of the moderator analyses showed that content-based, passive inoculation was more effective in increasing credibility and sharing intention. The theme of climate change demonstrates a stronger effect on real information credibility. Comparing intervention types showed that pre-post interventions are more effective for misinformation credibility assessment, while post-only interventions are better for credibility discernment. CONCLUSIONS: This study indicated that psychological inoculation enhanced individuals' ability to discern real information from misinformation and share real information. Incorporating psychological inoculation to cultivate an informed public is crucial for societal resilience against misinformation threats in an age of information proliferation. As a scalable and cost-effective intervention strategy, institutions can apply psychological inoculation to mitigate potential misinformation crises.

Hypoxia is fine-tuned by Hif-1α and regulates mesendoderm differentiation through the Wnt/ß-Catenin pathway.

BACKGROUND: Hypoxia naturally happens in embryogenesis and thus serves as an important environmental factor affecting embryo development. Hif-1α, an essential hypoxia response factor, was mostly considered to mediate or synergistically regulate the effect of hypoxia on stem cells. However, the function and relationship of hypoxia and Hif-1α in regulating mesendoderm differentiation remains controversial. RESULTS: We here discovered that hypoxia dramatically suppressed the mesendoderm differentiation and promoted the ectoderm differentiation of mouse embryonic stem cells (mESCs). However, hypoxia treatment after mesendoderm was established promoted the downstream differentiation of mesendoderm-derived lineages. These effects of hypoxia were mediated by the repression of the Wnt/ß-Catenin pathway and the Wnt/ß-Catenin pathway was at least partially regulated by the Akt/Gsk3ß axis. Blocking the Wnt/ß-Catenin pathway under normoxia using IWP2 mimicked the effects of hypoxia while activating the Wnt/ß-Catenin pathway with CHIR99021 fully rescued the mesendoderm differentiation suppression caused by hypoxia. Unexpectedly, Hif-1α overexpression, in contrast to hypoxia, promoted mesendoderm differentiation and suppressed ectoderm differentiation. Knockdown of Hif-1α under normoxia and hypoxia both inhibited the mesendoderm differentiation. Moreover, hypoxia even suppressed the mesendoderm differentiation of Hif-1α knockdown mESCs, further implying that the effects of hypoxia on the mesendoderm differentiation were Hif-1α independent. Consistently, the Wnt/ß-Catenin pathway was enhanced by Hif-1α overexpression and inhibited by Hif-1α knockdown. As shown by RNA-seq, unlike hypoxia, the effect of Hif-1α was relatively mild and selectively regulated part of hypoxia response genes, which fine-tuned the effect of hypoxia on mESC differentiation. CONCLUSIONS: This study revealed that hypoxia is fine-tuned by Hif-1α and regulates the mesendoderm and ectoderm differentiation by manipulating the Wnt/ß-Catenin pathway, which contributed to the understanding of hypoxia-mediated regulation of development.

Periodontitis aggravates renal inflammatory response in a mouse model of renal fibrosis.

OBJECTIVES: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. MATERIALS AND METHODS: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. RESULTS: Expression of tumour necrosis factor-α, interleukin-1ß, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. CONCLUSIONS: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.

Optimization of Three-Phase Hybrid Stepper Motors for Noise Reduction.

For the optimization of three-phase hybrid stepper motors with complex electromagnetic structures, an optimization method is presented in this paper. The method is a combination of 3D-FEM and the Taguchi optimization method intended to reduce the dependence on FEM results during the optimization calculation. In this paper, the optimization method is used in the optimization of the tooth shape of the three-phase hybrid stepper motor, and the objective is to reduce the noise caused by harmonics in the "torque-angle characteristic" of the motor. It is clear that traditional optimization methods make it very difficult to carry out such an optimization calculation as a large number of finite element calculations have to be used in the optimization process, and the required computation time is extremely long. Using the optimization method presented in the paper, the optimization becomes feasible because the number of finite element calculations is greatly reduced and the computation time is thus greatly reduced. In order to check the effectiveness of the optimization, the waterfall diagram for noise analysis and its application to check torque ripple are also presented in the paper. Both simulation and test results show that the optimized structure can significantly reduce the motor noise caused by torque ripple. Therefore, the optimization method proposed in this paper can be an effective tool for the optimal design of high-performance motors, including stepper motors.

Arabidopsis exoribonuclease USB1 interacts with the PPR-domain protein SOAR1 to negatively regulate abscisic acid signaling.

Signaling by the phytohormone abscisic acid (ABA) involves pre-mRNA splicing, a key process of post-transcriptional regulation of gene expression. However, the regulatory mechanism of alternative pre-mRNA splicing in ABA signaling remains largely unknown. We previously identified a pentatricopeptide repeat protein SOAR1 (suppressor of the ABAR-overexpressor 1) as a crucial player downstream of ABAR (putative ABA receptor) in ABA signaling. In this study, we identified a SOAR1 interaction partner USB1, which is an exoribonuclease catalyzing U6 production for spliceosome assembly. We reveal that together USB1 and SOAR1 negatively regulate ABA signaling in early seedling development. USB1 and SOAR1 are both required for the splicing of transcripts of numerous genes, including those involved in ABA signaling pathways, suggesting that USB1 and SOAR1 collaborate to regulate ABA signaling by affecting spliceosome assembly. These findings provide important new insights into the mechanistic control of alternative pre-mRNA splicing in the regulation of ABA-mediated plant responses to environmental cues.

Arabidopsis translation initiation factors eIFiso4G1/2 link repression of mRNA cap-binding complex eIFiso4F assembly with RNA-binding protein SOAR1-mediated ABA signaling.

The translation initiation factor eIF4E-binding protein-mediated regulation of protein translation by interfering with assembly of mRNA cap-binding complex eIF4F is well described in mammalian and yeast cells. However, it remains unknown whether a signaling regulator or pathway interacts directly with any translation initiation factor to modulate assembly of eIF4F in plant cells. Here, we report that the two isoforms of Arabidopsis eIF4G, eIFiso4G1 and eIFiso4G2, interact with a cytoplasmic-nuclear dual-localized pentatricopeptide repeat protein SOAR1 to regulate abscisic acid (ABA) signaling. SOAR1 inhibits interactions of eIFiso4E, eIF4Es, eIF4A1, eIF4B2 and poly(A)-binding protein PAB6 with eIFiso4G1 and eIFiso4G2, thereby inhibiting eIFiso4F/mixed eIF4F assembly and repressing translation initiation. SOAR1 binds mRNA of a key ABA-responsive gene ABI5 and cooperates with eIFiso4G1/2 to repress translation of ABI5. The binding of SOAR1 to ABI5 mRNA is likely to inhibit the interaction of SOAR1 with eIFiso4G1/2, suggesting a regulatory loop. Our findings identify a novel translation initiation repressor interfering with cap-binding complex assembly, and establish a link between cap-binding complex assembly and ABA signaling.

High Beclin-1 and ARID1A expression corelates with poor survival and high recurrence in intrahepatic cholangiocarcinoma: a histopathological retrospective study.

BACKGROUND: Although surgical resection provides a cure for patients with intrahepatic cholangiocarcinoma (ICC), the risk of mortality and recurrence remains high. Several biomarkers are reported to be associated with the prognosis of ICC, including Beclin-1, ARID1A, carbonic anhydrase IX (CA9) and isocitrate dehydrogenase 1 (IDH1), but results are inconsistent. Therefore, a histopathological retrospective study was performed to simultaneously investigate the relationship of these four potential biomarkers with clinicopathological parameters and their prognostic values in patients with ICC. METHODS: A total of 113 patients with ICC were enrolled from Cancer Hospital of Chinese Academy of Medical Sciences between January 1999 and June 2015. The expression of Beclin-1, ARID1A, IDH1 and CA9 were determined by immunohistochemical staining. The prognostic values of the four biomarkers were analyzed by Cox regression and the Kaplan-Meier method. RESULTS: Beclin-1, ARID1A, CA9 and IDH1 were highly expressed in ICC tumor tissues. Higher mortality was positively associated with Beclin-1 expression (HR = 2.39, 95% CI = 1.09-5.24) and higher recurrence was positively associated with ARID1A expression (HR = 1.71, 95% CI = 1.06-2.78). Neither CA9 nor IDH1 expression was significantly associated with mortality or disease recurrence. Kaplan-Meier survival curves showed that ICC patients with higher Beclin-1 and ARID1A expression had a lower survival rate and a worse recurrence rate than patients with low Beclin-1 and ARID1A expression (p < 0.05). CONCLUSIONS: High Beclin-1 and ARIDIA expression are strongly associated with poor prognosis in ICC patients, and thus Beclin-1 and ARID1A should be simultaneously considered as potential prognostic biomarkers for ICC patients.

Platelet Surface CD62p and Serum Vitamin D Levels are Associated with Clopidogrel Resistance in Chinese Patients with Ischemic Stroke.

BACKGROUND: To explore the association of platelet activation markers, vitamin D, and antiplatelet drugs resistance in ischemic stroke patients. METHODS: A total of 230 patients with ischemic stroke were enrolled in this study. Platelet aggregation, platelet activation marker (CD62p), and vitamin D were measured after 7-14 days of dual antiplatelet treatment (aspirin + clopidogrel). All individuals were divided into a drug resistance group and a drug sensitive group according to the platelet maximum aggregation rate induced by antagonist adenosine diphosphate or arachidonic acid. RESULTS: In this study, the prevalence of aspirin resistance was low (1.2%), while the prevalence of clopidogrel resistance (CR) was 24.8%, so we focused on CR. The percentage of CD62p on activated platelet [(25.74 ± 4.61) versus (12.41 ± 3.93), P < .001] and the prevalence of hypertension [93.0% (53) versus 79.8% (138), P = .021] in CR group were significantly higher than those in clopidogrel sensitive (CS) group, while the vitamin D concentration [(8.96 ± 4.41) versus (13.9 ± 4.84) ng/mL, P = .003] in CR group was significantly lower compared with the CS group. No significant difference was found in soluble P-selectin between these 2 groups [(56.2 ± 16.13) versus (54.2 ± 14.87) ng/mL, P = .258], neither in calcium [(2.29 ± .12) versus (2.33 ± .13) mmol/L, P = .821]. Logistic regression analysis showed that hypertension (odds ratio [OR] = 5.348, 95% confidence intervals [CI] 1.184-23.350, P = .026), expression of platelet CD62p (OR = 1.095, 95% CI 1.052-1.201, P = .018) and vitamin D level (OR = .832, 95% CI .763-.934, P = .005) were associated with CR in ischemic stroke patients. CONCLUSIONS: CR in ischemic stroke patients is associated with several independent predictors, including increased platelet activation marker CD62p, decreased vitamin D level, and hypertension.

Analysis on the characteristic of the optical axis perturbation in a total reflection prismring resonator.

The deduction of the augmented 5×5 matrix describing all the possible angular and decentration misalignment perturbation sources on a spherical prism plane during the refraction is presented in detail for the first time. Combining the augmented matrices and the condition of eigenmode self-consistency, the optical axis perturbation properties (described with the optical axis perturbation sensitivity factor SD1, ST1, SD2, and ST2) in a total reflection prism ring resonator are also analyzed. The singular points of the optical axis perturbation sensitivity factor are found at L/R=0.417 for the cases where the misalignments may originate from distinguished type of prisms P1 and P4 in the resonator, respectively. It is shown that the small errors of the prism can cause large optical axis disturbance in the position of the perturbed singular point and its nearby area, and the disturbance for the case where the misalignments originate from prism P1 is more violent than that of prism P4. With some upgrades to find and avoid the singularity of the optical axis in the total reflection prism ring resonator structure successfully, we expect this work will have great potential for designing and optimizing the structure of super-high-precision ring laser gyroscopes.

Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.

Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.

Arabidopsis ABI5 plays a role in regulating ROS homeostasis by activating CATALASE 1 transcription in seed germination.

It has been known that ABA INSENSITIVE 5 (ABI5) plays a vital role in regulating seed germination. In the present study, we showed that inhibition of the catalase activity with 3-amino-1,2,4-triazole (3-AT) inhibits seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines. Compared with Col-0, the seeds of abi5 mutants showed more sensitive to 3-AT during seed germination, while the seeds of ABI5-overexpression transgenic lines showed more insensitive. H2O2 showed the same effect on seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines as 3-AT. These results suggest that ROS is involved in the seed germination mediated by ABI5. Further, we observed that T-DNA insertion mutants of the three catalase members in Arabidopsis displayed 3-AT-insensitive or -hypersensitive phenotypes during seed germination, suggesting that these catalase members regulate ROS homeostasis in a highly complex way. ABI5 affects reactive oxygen species (ROS) homeostasis by affecting CATALASE expression and catalase activity. Furthermore, we showed that ABI5 directly binds to the CAT1 promoter and activates CAT1 expression. Genetic evidence supports the idea that CAT1 functions downstream of ABI5 in ROS signaling during seed germination. RNA-sequencing analysis indicates that the transcription of the genes involved in ROS metabolic process or genes responsive to ROS stress is impaired in abi5-1 seeds. Additionally, expression changes in some genes correlative to seed germination were showed due to the change in ABI5 expression under 3-AT treatment. Together, all the findings suggest that ABI5 regulates seed germination at least partly by affecting ROS homeostasis.

Particle size effect of curcumin nanosuspensions on cytotoxicity, cellular internalization, in vivo pharmacokinetics and biodistribution.

This study aimed to investigate the particle size effect on bioactivity, cellular internalization and bioavailability of curcumin (CUR) nanosuspension (CUR-NS). CUR-NSs of different particle sizes were prepared by two different anti-solvent precipitation methods. CUR-NS with the smallest size showed similar in vitro anticancer activity and bioavailability to the CUR solution, whereas nanosuspensions of larger particle sizes displayed higher in vitro cellular internalization and cytotoxicity, as well as higher in vivo AUC and slower clearance rate after i.v. administration in rats. CUR solution and different sized CUR-NSs reached the highest concentrations in the lung, followed by liver and spleen while the lowest concentration was observed in the brain after i.v. administration in mice. Specifically, CUR-NS of 70nm accumulated more in the brain, whereas CUR-NS of 200nm accrued more in liver and spleen. CUR-NS of 20nm displayed no significant biodistribution difference compared with CUR solution in all tissues.

Overexpression of the MYB37 transcription factor enhances abscisic acid sensitivity, and improves both drought tolerance and seed productivity in Arabidopsis thaliana.

Although a lot of genes have been revealed to participate in abscisic acid (ABA) signaling, many of the additional components involved in ABA signaling remain to be discovered. Here we report that overexpression of MYB37, a R2R3 MYB subgroup 14 transcription factor in Arabidopsis thaliana, confers hypersensitive phenotypes to exogenous ABA in all the major ABA responses, including ABA-induced inhibition of seed germination, cotyledon greening and early seedling growth, and ABA-induced stomatal closure and inhibition of stomatal opening. Interestingly and importantly, MYB37-overexpression improves plant tolerance to drought, enhances growth of mature plants and seed productivity, thought it delays flowering, which suggests that this gene may be used for improving crop adaptability to drought environment and productivity. However, a myb37-1 knockout mutant displays wild-type ABA responses most likely due to a functional redundancy of the multiple MYB members. Real-time PCR analysis shows that upregulation of the MYB37 expression changes expression of a subset of ABA-responsive genes. Together, these findings suggest that the MYB37 transcription factor plays an important, positive role in plant response to ABA and drought stress, and meanwhile, it plays a positive role in the regulation of seed production.

Overexpression of an Arabidopsis cysteine-rich receptor-like protein kinase, CRK5, enhances abscisic acid sensitivity and confers drought tolerance.

Receptor-like kinases (RLKs) have been reported to regulate many developmental and defense process, but only a few members have been functionally characterized. In the present study, our observations suggest that one of the RLKs, a membrane-localized cysteine-rich receptor-like protein kinase, CRK5, is involved in abscisic acid (ABA) signaling in Arabidopsis thaliana Overexpression of CRK5 increases ABA sensitivity in ABA-induced early seedling growth arrest and promotion of stomatal closure and inhibition of stomatal opening. Interestingly, and importantly, overexpression of CRK5 enhances plant drought tolerance without affecting plant growth at the mature stages and plant productivity. Transgenic lines overexpressing a mutated form of CRK5, CRK5 (K372E) with the change of the 372nd conserved amino acid residue from lysine to glutamic acid in its kinase domain, result in wild-type ABA and drought responses, supporting the role of CRK5 in ABA signaling. The loss-of-function mutation of the CRK5 gene does not affect the ABA response, while overexpression of two homologs of CRK5, CRK4 and CRK19, confers ABA responses, suggesting that these CRK members function redundantly. We further showed that WRKY18, WRKY40 and WRKY60 transcription factors repress the expression of CRK5, and that CRK5 likely functions upstream of ABI2 in ABA signaling. These findings help in understanding the complex ABA signaling network.

Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009-2013): coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics.

BACKGROUND: The recent emergence of azithromycin-resistant (AZM-R) N. gonorrhoeae isolates that have coevolved decreased susceptibility to extended-spectrum cephalosporins has caused great concern. Here we investigated the prevalence of decreased susceptibility to ceftriaxone (CRO(D)) in AZM-R isolates and genetically characterized AZM-R isolates in Guangzhou, China from 2009 to 2013. METHODS: The minimum inhibitory concentration (MIC) of AZM and ceftriaxone was determined using an agar-dilution method. All AZM-R isolates were screened for mutations in 23S rRNA, mtrR and penA genes and genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: Of the 485 identified N. gonorrhoeae isolates, 445 (91.8%) were isolated from male urethritis subjects, and 77 (15.9%) were AZM-R (MIC ≥ 1 mg/L), including 33 (6.8%) with AZM low-level resistant (AZM-LLR, MIC = 1 mg/L) and 44 (9.1%) with AZM middle-level resistant (AZM-MLR, MIC ≥ 2 mg/L). Significantly more CRO(D) (MIC ≥ 0.125 mg/L) showed in AZM-MLR isolates (43.2%, 19/44) as compared with that in AZM-LLR isolates (18.2%, 6/33) (p < 0.05). For the 23S rRNA, mtrR, penA or combined 23S rRNA/MtrR/penA mutations, no significant difference was found between AZM-LLR isolates and AZM-MLR isolates (P > 0.05); similar results were detected between combined AZM-LLR/CRO(D) isolates and combined AZM-MLR/CRO(D) isolates (P > 0.05). No mutation A2059G or AZM high-level resistant (AZM-HLR, MIC ≥ 256 mg/L) isolate was detected. Among 77 AZM-R isolates, 67 sequence types (STs) were identified by NG-MAST, of which 30 were novel. Most STs were represented by a single isolate. CONCLUSIONS: The AZM-R together CRO(D) isolates are now present in Guangzhou, China, which deserve continuous surveillance and the mechanism of concurrent resistance needs further study.

Characterization of the eigenmode frequency spectrum influenced by the polarization states and light field distribution in a nonplanar ring resonator.

We present the evolution of the eigenmode frequency spectrum in a nonplanar ring resonator based on the Jones matrix and the Fresnel-Kirchhoff diffraction integral. Taking the modes TEM(q+1)01 and TEMq10 with different polarization states as examples, we numerically derive the frequency difference between them versus the folding angles of the resonator by considering the polarization and the light field distribution of the eigenmodes synchronously. It can be found that the extreme values of frequency difference between TEM(q+1)01 and TEMq10 are particularly affected by the polarization states of the eigenmode, and the locations of these consecutive extreme values correspond to the total image rotation angle with values of the integer multiple of 90°. Moreover, the influence of the resonator structure on the frequency difference of eigenmodes with the identical polarization state is also analyzed. The results prove that the frequency difference between the fundamental mode and higher order modes declines with the increase of the spherical mirrors' radius of curvature but increases with the augmentation of the resonator's total length. These interesting findings are important for the mode selection in high-accuracy ring laser gyroscopes with nonplanar structure by modulating the polarization states and the light field distribution of the eigenmodes to control the frequency difference between them.