Analytical Interference in Chemiluminescence Assay-Measured Angiotensin I, Angiotensin II, Aldosterone, and Renin.

BACKGROUND: The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro. METHODS: Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose-response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined. RESULTS: Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays. CONCLUSION: Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.

Development of Binder-Free Pigment Inks for Direct Inkjet Printing on Cotton Fabric without Pretreatment.

Inkjet printing technology is widely used in the textile digital printing application today though the current technology still requires pretreatment and postwashing procedures before and after printing. Additional chemical treatment generates a large amount of wastewater and complicates the process. Among the many potential approaches for reducing chemical waste, pigments with self-dispersing capability were prepared and formulated into binder-free inkjet inks that require no pretreatment or after-washing process when printing cotton fabrics. The new self-dispersing pigment inks were tested and evaluated on cotton fabrics. The distribution of particles was between 122.2 and 188.5 nm, and inks have excellent storage capability. Printed fabrics' light fastness and acid/alkali resistance are about grade 5, and printed cotton's washing and rubbing fastness are above grade 3. The mechanism and performance of ink drops were investigated by LF-NMR and ink-drop observation methods. This work provides a possible solution for reducing wastewater in the textile industry.

New asymptomatic thrombosis caused by carotid web during the acute period of cerebral infarction.

BACKGROUND: At present, the carotid web (CaW) as an important cause of cryptogenic ischemic stroke has gradually received clinical attention. CaW is associated with a high risk of stroke and patient is more likely to have recurrent stroke if the CaW is untreated. We report a patient who developed CaW related thrombosis during the acute period of cerebral infarction. CASE PRESENTATION: A 49-year-old male patient with CaW in the left internal carotid artery was diagnosed by computed tomography angiography (CTA) and had two cerebral infarctions in two years. Within 72 h after thrombolysis for an acute cerebral infarction, acute thrombosis was identified between the web and the posterior wall of the carotid artery on carotid ultrasound. Emergent carotid endarterectomy (CEA) was performed to remove abnormal CaW structures and thrombosis to prevent stroke. The patient recovered well and was asymptomatic at 2 months follow-up. CONCLUSION: Carotid web related thromboembolism is a rare cause of stroke. Carotid ultrasound plays an important role in the diagnosis of asymptomatic thrombosis caused by carotid web. Carotid endarterectomy is effective for stroke prevention in patient with carotid web related thrombosis.

TRIM28 functions as the SUMO E3 ligase for PCNA in prevention of transcription induced DNA breaks.

In human cells, the DNA replication factor proliferating cell nuclear antigen (PCNA) can be conjugated to either the small ubiquitinlike modifier SUMO1 or SUMO2, but only SUMO2-conjugated PCNA is induced by transcription to facilitate resolution of transcription-replication conflict (TRC). To date, the SUMO E3 ligase that provides substrate specificity for SUMO2-PCNA conjugation in response to TRC remains unknown. Using a proteomic approach, we identified TRIM28 as the E3 ligase that catalyzes SUMO2-PCNA conjugation. In vitro, TRIM28, together with the RNA polymerase II (RNAPII)-interacting protein RECQ5, promotes SUMO2-PCNA conjugation but inhibits SUMO1-PCNA formation. This activity requires a PCNA-interacting protein (PIP) motif located within the bromodomain of TRIM28. In cells, TRIM28 interaction with PCNA on human chromatin is dependent on both transcription and RECQ5, and SUMO2-PCNA level correlates with TRIM28 expression. As a consequence, TRIM28 depletion led to RNAPII accumulation at TRC sites, and expression of a TRIM28 PIP mutant failed to suppress TRC-induced DNA breaks.

A signal-switchable fluorescent probe for detection of HPO4 2- based on 5,10,15,20-(4-sulphonatophenyl)porphyrin (TPPS4 ).

In this study, 5,10,15,20-(4-sulphonatophenyl)porphyrin (TPPS4 ) was selected as a fluorescent probe due to its excellent characteristics including high quantum yield, good water solubility, and exceptional biocompatibility. With an excitation wavelength set at 515 nm, the optimal fluorescence emission wavelength for TPPS4 was measured at 642 nm. At this moment, the fluorescence signal of TPPS4 pink solution was in the 'ON' state. The fluorescence intensity of TPPS4 was quenched when ascorbic acid (AA) was introduced, which was due to the electron transfer quenching effect between AA and TPPS4 . The colour of the corresponding solution changed from pink to green, and the fluorescence signal was in the 'OFF' state. When HPO4 2- was further introduced into the TPPS4 -AA system, the quenched fluorescence intensity of TPPS4 was recovered due to the unique interaction between HPO4 2- and AA. At this time, the colour of the corresponding solution changed from green to red, and the fluorescence signal was in the 'ON' state. Therefore, an 'ON-OFF-ON' signal-switchable fluorescent probe was constructed based on TPPS4 to detect HPO4 2- . The results showed that the linear range of HPO4 2- was 4.0 × 10-9 to 1.7 × 10-6  M, and the detection limit was 1.3 × 10-9  M (S/N = 3). The sensing system exhibited high accuracy and sensitivity, and it could be used successfully to detect HPO4 2- in real samples.

Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. OBJECTIVE: This study determines whether baicalin could affect the progression of PCOS. MATERIALS AND METHODS: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 µM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 µM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. CONCLUSIONS: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Development and Validation of a Knowledge Scale About the Behavioral and Psychological Symptoms of Dementia (KS-BPSD) Among Chinese Formal Caregivers.

OBJECTIVES: The current study aimed to develop a scale assessing knowledge about behavioral and psychological symptoms of dementia (KS-BPSD) among Chinese formal caregivers and to investigate its psychometric properties and factorial structure. METHODS: The scale was generated with a systematic development process, and 229 formal caregivers working at nursing homes were recruited to construct and assess the psychometric properties of the scale. The preliminary scale was reviewed by an expert panel and items were selected based on item discrimination, difficulty, and item-total correlation. RESULTS: The final KS-BPSD version consisted of 12 items, loaded into three factors (i.e., Disease Characteristics, Care and Risks, and Treatment Needs) following principal component analysis (PCA). The KS-BPSD showed good test-retest reliability, internal consistency, as well as construct and concurrent validity. CONCLUSIONS: The 12-item KS-BPSD was found to have high reliability and preliminary validity in assessing the level of knowledge about patient's BPSD among formal Chinese caregivers in nursing homes. CLINICAL IMPLICATIONS: KS-BPSD is a reliable tool to address the knowledge discrepancies and support needs among dementia caregivers, helping to develop and evaluate educational programs in the management of patient's BPSD.

Recent advances in nanoplatforms for the treatment of neuropathic pain.

STUDY DESIGN: Narrative review. OBJECTIVES: The objective was to summarize the literature on nanoplatforms in spinal cord injury (SCI) and describe their effect in facilitating experiments for SCI. Currently, the primary clinical treatment for neuropathic pain (NP) is drug therapy, but these traditional drugs have many disadvantages, such as high dose, rapid clearance from the circulatory system, off-target side effects, and cytotoxicity. Moreover, the treatment for NP is complicated by the existence of blood-brain barrier. In recent years, nanomedicine has been receiving increased attention; this novel modality could help deliver drugs to treat NP via nanoplatforms, making it a promising alternative therapy. The use of nanoplatforms can enhance pharmaceutic effectiveness by either avoiding rapid clearance from the blood or ensuring adequate concentration in the lesion. METHODS: A literature review was conducted, with a focus on nanoplatforms that have been described in the experimental studies of neuropathic pain. RESULTS: We provide a brief description of the roles of liposomes, polymeric nanoparticles, metal nanoparticles, micelles, and dendrimers in the treatment of NP and discuss the prospective development of the nanoplatform system for NP. CONCLUSION: The emergence of various nanoplatform drug delivery systems can provide an advantageous resource tool for real-time diagnosis and effective treatment of SCI-related NP.

Developing a leadership and management competency framework for nurse champion: A qualitative study from Shanghai, China.

AIM: To develop a leadership and management competency framework applicable to Chinese nurse champions guided by the competency matrix for clinical nurse leader (CNL). BACKGROUND: As the clinical leaders and future nurse manager candidates in the Chinese clinical setting, nurse champions are in great need of leadership and management competency training, but it is unclear what content should be included in the training curriculum, a guiding framework applicable to Chinese nurse champions was needed to be constructed. METHODS: This study used a qualitative descriptive design to explore nurse champions' competency requirements from clinical nurse managers' perspective. Semi-structure interviews guided by the CNL competency matrix were conducted with 27 clinical nurse managers from six large-scale tertiary grade A hospitals in Shanghai, China. Interview transcripts were analysed using deductive and inductive content analysis. RESULTS: The data analysis yielded three main categories: nursing leadership, clinical outcome management and care environment management, containing 14 subordinate themes, which represent the leadership and management competencies needed for nurse champions. CONCLUSIONS: A leadership and management competency framework for Chinese nurse champion was built in this study, which covering the competencies needed by Chinese nurse champions to lead care teams, improve quality of care for patient outcomes and enhance systems and equipment for the better care environment. This framework will be the direct basis for guiding the development of the nurse leadership curriculum for driving nurse champion to achieve role success. IMPLICATIONS FOR NURSING MANAGEMENT: This framework provides a theoretical foundation for clarifying the role of nurse champion in clinical management. Training curriculum guided by this framework will help nurses in their clinical management role and share the burden of clinical nursing managers, as well as promote the development of a clinical nursing management reserve talents and support the future development of nursing staff in health care organisations.

Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Sequential Functionalization of meta-C-H and ipso-C-O Bonds of Phenols.

The use of a template as a linchpin motif in directed remote C-H functionalization is a versatile yet relatively underexplored strategy. We have developed a template-directed approach to realizing one-pot sequential palladium-catalyzed meta-selective C-H olefination of phenols, and nickel-catalyzed ipso-C-O activation and arylation. Thus, this bifunctional template converts phenols to synthetically useful 1,3-disubstituted arenes.

The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China.

BACKGROUND: To investigate the prevalence and risk factors of premature thelarche (PT) in girls and gynecomastia (GM) in boys in Southern China. METHODS: We conducted a cross-sectional study of preschool children across 9 cities in Zhejiang province. A total of 6273 children in the age-group of 2-7 years were recruited from January 2014 to March 2015. Relevant information was collected from mothers through face-to-face interviews. Logistic regression models were used to examine the correlates of PT and GM. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. RESULTS: The prevalence of PT among girls was 4.8% and that of GM among boys was 0.8%. One hundred girls were diagnosed with PT before the age of 2 years; 69 (69.0%) of these girls experienced spontaneous resolution of PT. Twenty-four boys were diagnosed with GM before the age of 2 years; 10 (41.7%) of these experienced spontaneous resolution of GM. Children borne of mothers with early onset of menarche and those belonging to high-income families were at a higher risk of premature breast development. Greater consumption of eggs was associated with premature breast development in early childhood. CONCLUSIONS: Socioeconomic status of family, early onset of menarche in mother, and consumption of eggs were strongly associated with premature breast development in early childhood.

Silencing the FOLR2 Gene Inhibits Cell Proliferation and Increases Apoptosis in the NCI-H1650 Non-Small Cell Lung Cancer Cell Line via Inhibition of AKT/Mammalian Target of Rapamycin (mTOR)/Ribosomal Protein S6 Kinase 1 (S6K1) Signaling.

BACKGROUND The FOLR2 gene encodes folate receptor-beta (FR-beta), which is expressed by tumor-associated macrophages. The effects of FOLR2 gene expression in non-small cell lung cancer (NSCLC) remains unknown. This study aimed to investigate the effects of FOLR2 gene expression and gene silencing in human NSCLC cell lines and normal human bronchial epithelial (HBE) cells in vitro. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expression of the FOLR2 gene, cell cycle and apoptosis-associated genes in normal HBE cells and the NSCLC cell lines, A549, NCI-H1299, NCI-H1650, and NCI-H460. Using small interfering RNA (siRNA), or silencing RNA, FOLR2 gene silencing was performed for NCI-H1650 cells. Cell counting kit-8 (CCK-8) was used to measure cell viability. Cell cycle and apoptosis were determined using flow cytometry. Western blot evaluated the expression of Akt, mTOR, and S6K1 signaling. RESULTS Expression of the FOLR2 gene was increased in NSCLC cells compared with normal HBE cells. Silencing of the expression of the FOLR2 gene in NCI-H1650 cells reduced cell viability, increased cell apoptosis, and arrested cells in the G1 phase of the cell cycle, decreased the expression of cyclin D1, upregulated expression of cell cycle inhibitors, p21 and p27, upregulated the expression of Bax/Bcl-2, and inhibited phosphorylation of AKT, mTOR, and S6K1. CONCLUSIONS Silencing of the FOLR2 gene inhibited phosphorylation of AKT, mTOR, and S6K1, inhibited cell proliferation and increased apoptosis in the NCI-H1650 human NSCLC cell line.

Methylenetetrahydrofolate Dehydrogenase 1 Silencing Expedites the Apoptosis of Non-Small Cell Lung Cancer Cells via Modulating DNA Methylation.

BACKGROUND Non-small cell lung cancer (NSCLC) accounts for about 85% of all types of lung cancer. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is involved in DNA methylation, and DNA methylation is related to tumorigenesis. The role of MTHFD1 in NSCLC was examined in our study. MATERIAL AND METHODS The correlation between the expression of MTHFD1 and the clinicopathological features of patients diagnosed with lung cancer was investigated using the chi-square test. The viability and apoptosis of NCI-H1299 cells was respectively detected using cell counting kit-8 and flow cytometry assays. The expression levels of MTHFD1, apoptosis-related factors and DNA methyltransferase-related factors were assessed by quantitative real-time PCR (qRT-PCR) and western blot assays. RESULTS We found that MTHFD1 expression in the tumor tissues and cells was higher than that of adjacent normal tissues and cells. The survival time of patients with high MTHFD1 expression was shorter than those with low MTHFD1 expression. The expression level of MTHFD1 was related to tumor size, TNM stage, histologic grade, and metastasis, but not linked to gender and age. Besides, si-MTHFD1 significantly decreased the viability of cells in a time-dependent manner, and increased cell apoptosis. When cells were transfected with MTHFD1-siRNA, the levels of surviving and B-cell lymphoma-2 (Bcl-2) were attenuated, while p53 and Bcl-2 associated X protein (Bax) levels were enhanced. Moreover, si-MTHFD1 markedly downregulated the expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, and DNMT3b. CONCLUSIONS Collectively, our results proved that MTHFD1 silencing obviously reduced the proliferation and enhanced the apoptosis of NSCLC via suppressing DNA methylation.

Disaster Nursing Development in China and Other Countries: A Bibliometric Study.

PURPOSE: China is a country with frequent disasters, and nurses play indispensable roles in the disaster process. The Chinese disaster nursing specialty developed with several deficiencies. This study aimed to identify the limitations in the development of disaster nursing in China and to provide a reference for the future by comparing relevant studies between China and other countries. DESIGN: A systematic literature review was conducted in English and Chinese databases to identify disaster nursing articles published from January 1, 2000, to December 31, 2016. METHODS: This study followed the systematic literature collection tactic and bibliometric method. Basic information such as country, number of publications, and discussed disaster types were described through frequency distributions. Article themes were extracted and divided into the four phases of the International Council of Nurses Framework of Disaster Nursing Competencies. FINDINGS: 1,384 articles were included in the analysis, containing 781 written in Chinese and 603 written in English (with 56 of them written by Chinese researchers). The number of Chinese disaster nursing articles and other publications increased sharply between 2007 and 2009 but dropped significantly afterwards, while the total number of articles in other countries fluctuated, with a general upward trend. Compared to other countries, there were fewer research methods used and less focus on disaster prevention and preparedness in China, an imbalanced focus on disaster types, and a lack of focus on prevention, preparedness, and recovery phases. CONCLUSIONS: In China, there is a lack of stable development of disaster nursing research, a lack of study types, and less focus on disaster prevention, preparedness, and recovery. Varied study methods and an increased focus on disaster prevention and preparedness are required in the future. CLINICAL RELEVANCE: This study analyzed the deficiencies in Chinese disaster nursing, which led to recommendations and proposed directions for future studies and a clinical focus in this field, in compliance with the United Nations guidelines for disaster management.

TIMELESS Suppresses the Accumulation of Aberrant CDC45·MCM2-7·GINS Replicative Helicase Complexes on Human Chromatin.

The replication licensing factor CDC6 recruits the MCM2-7 replicative helicase to the replication origin, where MCM2-7 is activated to initiate DNA replication. MCM2-7 is activated by both the CDC7-Dbf4 kinase and cyclin-dependent kinase and via interactions with CDC45 and go-ichi-ni-san complex (GINS) to form the CDC45·MCM2-7·GINS (CMG) helicase complex. TIMELESS (TIM) is important for the subsequent coupling of CMG activity to DNA polymerases for efficient DNA synthesis. However, the mechanism by which TIM regulates CMG activity for proper replication fork progression remains unclear. Here we show that TIM interacts with MCM2-7 prior to the initiation of DNA replication. TIM depletion in various human cell lines results in the accumulation of aberrant CMG helicase complexes on chromatin. Importantly, the presence of these abnormal CMG helicase complexes is not restricted to cells undergoing DNA synthesis. Furthermore, even though these aberrant CMG complexes interact with the DNA polymerases on human chromatin, these complexes are not phosphorylated properly by cyclin-dependent kinase/CDC7-Dbf4 kinase and exhibit reduced DNA unwinding activity. This phenomenon coincides with a significant accumulation of the p27 and p21 replication inhibitors, reduced chromatin association of CDC6 and cyclin E, and a delay in S phase entry. Our results provide the first evidence that TIM is required for the correct chromatin association of the CMG complex to allow efficient DNA replication.

Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2.

BACKGROUND: Chronic exposure to fine ambient particulate matter (PM2.5) induces insulin resistance. CC-chemokine receptor 2 (CCR2) appears to be essential in diet-induced insulin resistance implicating an important role for systemic cellular inflammation in the process. We have previously suggested that CCR2 is important in PM2.5 exposure-mediated inflammation leading to insulin resistance under high fat diet situation. The present study assessed the importance of CCR2 in PM2.5 exposure-induced insulin resistance in the context of normal diet. METHODS AND RESULTS: C57BL/6 and CCR2-/- mice were subjected to exposure to concentrated ambient PM2.5 or filtered air for 6 months. In C57BL/6 mice, concentrated ambient PM2.5 exposure induced whole-body insulin resistance, macrophage infiltration into the adipose tissue, and upregulation of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. While CCR2 deficiency reduced adipose macrophage content in the PM2.5-exposed animals, it did not improve systemic insulin resistance. This lack of improvement in insulin resistance was paralleled by increased hepatic expression of genes in PEPCK and inflammation. CONCLUSION: CCR2 deletion failed to attenuate PM2.5 exposure-induced insulin resistance in mice fed on normal diet. The present study indicates that PM2.5 may dysregulate glucose metabolism directly without exerting proinflammatory effects.

Algicidal Activity of Bacillamide Alkaloids and Their Analogues against Marine and Freshwater Harmful Algae.

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A-C, alkaloid (1), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue (10d) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa, suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms.

Effect of allelochemical tricin and its related benzothiazine derivative on photosynthetic performance of herbicide-resistant barnyardgrass.

Despite increasing knowledge of allelochemicals as leads for new herbicides, relatively little is known about the mode of action of allelochemical-based herbicides on herbicide-resistant weeds. In this study, herbicidal activities of a series of allelochemical tricin-derived compounds were evaluated. Subsequently, a benzothiazine derivative 3-(2-chloro-4-methanesulfonyl)-benzoyl-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide with 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibiting activity was identified as a target compound on photosynthetic performance of penoxsulam-resistant versus -susceptible barnyardgrass (Echinochloa crus-galli). Regardless of barnyardgrass biotype, the benzothiazine derivative greatly affected chlorophyll fluorescence parameters (Fv/Fm, ETR1min and NPQ1min), reduced the chloroplast fluorescence levels and expression of HPPD gene. In particular, the benzothiazine derivative interfered with photosynthetic performance of resistant barnyardgrass more effectively than the allelochemical tricin itself. These results showed that the benzothiazine derivative effectively inhibited the growth of resistant barnyardgrass and its mode of action on photosynthesis system was similar to HPPD-inhibiting sulcotrione, making it an ideal lead compound for further development of allelochemical-based herbicide discovery.

Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator plays a key role in maintenance of lung fluid homeostasis. Cigarette smoke decreases CFTR expression in the lung but neither the mechanisms leading to CFTR loss, nor potential ways to prevent its loss have been identified to date. METHODS: The molecular mechanisms leading to down-regulation of CFTR by cigarette smoke were determined using pharmacologic inhibitors and silencing ribonucleic acids (RNAs). RESULTS: Using human bronchial epithelial cells, here we show that cigarette smoke induces degradation of CFTR that is attenuated by lysosomal inhibitors, but not proteasome inhibitors. Cigarette smoke can activate multiple signaling pathways in airway epithelial cells, including the MEK/Erk1/2 MAPK (MEK: mitogen-activated protein kinase/ERK kinase Erk1/2: extracellular signal-regulated kinase 1/2 MAPK: Mitogen-activated protein kinase) pathway regulating cell survival. Interestingly, pharmacological inhibition of the MEK/Erk1/2 MAPK pathway prevented the loss of plasma membrane CFTR upon cigarette smoke exposure. Similarly, decreased expression of Erk1/2 using silencing RNAs prevented the suppression of CFTR protein by cigarette smoke. Conversely, specific inhibitors of the c-Jun N-terminal kinase (JNK) or p38 MAPK pathways had no effect on CFTR decrease after cigarette smoke exposure. In addition, inhibition of the MEK/Erk1/2 MAPK pathway prevented the reduction of the airway surface liquid observed upon cigarette smoke exposure of primary human airway epithelial cells. Finally, addition of the antioxidant N-acetylcysteine inhibited activation of Erk1/2 by cigarette smoke and precluded the cigarette smoke-induced decrease of CFTR. CONCLUSIONS: These results show that the MEK/Erk1/2 MAPK pathway regulates plasma membrane CFTR in human airway cells. GENERAL SIGNIFICANCE: The MEK/Erk1/2 MAPK pathway should be considered as a target for strategies to maintain/restore CFTR expression in the lung of smokers.