AGC kinases OXI1 and AGC2-2 regulate camalexin secretion and disease resistance by phosphorylating transporter PDR6.

Plant transporters regulating the distribution of secondary metabolites play critical roles in defending against pathogens, insects, and interacting with beneficial microbes. The phosphorylation of these transporters can alter their activity, stability, and intracellular protein trafficking. However, the regulatory mechanism underlying this modification remains elusive. In this study, we discovered two Orthologs of mammalian PKA, PKG, and PKC (AGC) kinases, Oxidative signal-inducible 1 (OXI1) and its closest homologue, AGC subclass 2 member 2 (AGC2-2; 75% amino acid sequence identity with OXI1), associated with the extracellular secretion of camalexin and Arabidopsis (Arabidopsis thaliana) resistance to Pseudomonas syringae and Botrytis cinerea. These kinases can undergo in vitro kinase reactions with three Pleiotropic drug resistance (PDR) transporters: PDR6, PDR8, and PDR12. Moreover, our investigation confirmed PDR6 interaction with OXI1 and AGC2-2. By performing LC-MS/MS and parallel reaction monitoring, we identified the phosphorylation sites on PDR6 targeted by these kinases. Notably, chitin induced PDR6 phosphorylation at specific residues, namely S31, S33, S827, and T832. Additional insights emerged by expressing dephosphorylated PDR6 variants in a pdr6 mutant background, revealing that the target residues S31, S33, and S827 promote PDR6 efflux activity, while T832 potentially contributes to PDR6 stability within the plasma membrane. The findings of this study elucidate partial mechanisms involved in the activity regulation of PDR-type transporters, providing valuable insights for their potential application in future plant breeding endeavors.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism.

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

[Two new isoquinoline alkaloids from Corydalis hendersonii].

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(ß-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 µmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 µmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

[Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia].

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

[Network pharmacology study of Tibetan medicine Corydalis Herba against acute myocardial ischemia].

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.

[Research progress on terpenes and pharmacological effects of Saussurea lappa].

Saussurea lappa originates in India, and now mainly grow in Yunnan, Sichuan and other places in China. It is one of the commonly used traditional herbal medicines in Tibet and other minority regions, with effects in regulating qi to relieve pain and invigo-rating spleen to promote food. It has been used in clinic for gastrointestinal diseases, such as Qi stagnation syndrome of spleen and stomach, diarrhea and tenesmus. More than 200 compounds have been identified from S. lappa. Among them, sesquiterpenoids attracted much attention. In terms of the number of compounds, eudesmanetype is dominant, guaiane and germacranetypes have also been reported frequently. Pharmacological studies have involved extracts, volatile oils and monomeric components represented by dehydrocostus lactone. Anti-tumor, anti-inflammatory and anti-bacterial effects on digestive system have attracted great attention. However, due to the complex sources of S. lappa and widely used in clinical practice, there is few research progress on relevant chemical constituents and pharmacological activities. This paper systematically summarizes terpenes and the pharmacological effects of S. lappa, in order to provide basis for further studies and clinical applications.

[Comparison Analysis of Economic and Engineering Control of Industrial VOCs].

Volatile organic compounds (VOCs) pollutant has become China's major air pollutant in key urban areas like sulfur dioxide, nitrogen oxides and particulate matter. It is mainly produced from industry sectors, and engineering control is one of the most important reduction measures. During the 12th Five-Year Plan, China decides to invest 40 billion RMB to build pollution control projects in key industry sectors with annual emission reduction of 605 000 t x a(-1). It shows that China attaches a great importance to emission reduction by engineering projects and highlights the awareness of engineering reduction technologies. In this paper, a macroeconomic model, namely computable general equilibrium model, (CGE model) was employed to simulate engineering control and economic control (imposing environmental tax). We aim to compare the pros and cons of the two reduction policies. Considering the economic loss of the whole country, the environmental tax has more impacts on the economy system than engineering reduction measures. We suggest that the central government provides 7 500 RMB x t(-1) as subsidy for enterprises in industry sectors to encourage engineering reduction.

[Effect of electroacupunctu-e intervention on serum IL-17 and IL-23 contents in rheumatoid arthritis rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) stimulation of "Zusanli" (ST 36) and "Kunlun" (BL 60) on serum and knee-joint IL-17 and IL-23 contents in rheumatoid arthritis (RA) rats so as to study its underlying mechanism in improving RA. METHODS: Male Wistar rats were randomly allocated to normal control, RA model, EA and Prednisolone groups (n = 8 in each group). The RA model was established by intra-planta injection of incomplete Freund's adjuvant and type II collagen. EA (2 Hz/100 Hz,1-2 mA)was applied to bilateral "Zusanli"(ST 36) and "Kunlun"(BL 60) for 30 min, once daily for 10 days. The rats' ankle diameter was measured, and IL-17 and IL-23 contents in the serum and the knee-joint cavity were assayed by ELISA and Western blot, respectively. RESULTS: In comparison with the normal control group, the rats' ankle diameter, serum IL-17 and IL-23 contents and knee-joint IL-17 and IL-23 protein expression levels were significantly increased in the model group (P < 0.05). After EA and Prednisolone treatment, compared with the model group, all the rats' ankle diameter, serum IL-17 and IL-23 contents and knee-joint IL-17 and IL-23 protein expression levels were decreased remarkably (P < 0.05). No obvious differences were found between the EA and Prednisolone groups in the aforementioned indexes (P > 0.05), except IL-17 protein expression level (being markedly lower in the Prednisolone group than in the EA group). CONCLUSION: EA intervention can reduce inflammatory reaction of the ankle-joint in RA rats, which may be related to its effects in down-regulating serum and knee-joint IL-17 and IL-23 levels.

[Study of VOCs emission prediction and control based on dynamic CGE].

Researches on controlling volatile organic compounds (VOCs) through macroeconomic policy from the view of cost-benefit analysis are very important for our country to improve the air environment. Based on our previous study, this paper predicted future VOCs emissions until 2020 under current policies with 2007 as reference year by using dynamic CGE model. Meanwhile, environmental tax was imposed in ten industries with high emission and the impacts of emissions and economic system were discussed. Finally, policy implementations for VOCs emission control were suggested for policy-makers. The results showed that environment tax could mitigate VOCs emission, but it also resulted in high cost. Owing to the highly related relationship between different sectors, although transport sector was not taxed, it also suffered a great economic influence. Thus, when using the tax policy for reducing VOCs, subsidy for special sector is necessary.

[Calculation of regional carbon emission: a case of Guangdong Province].

By using IPCC carbon emission calculation formula (2006 edition), economy-carbon emission dynamic model, and cement carbon emission model, a regional carbon emission calculation framework was established, and, taking Guangdong Province as a case, its energy consumption carbon emission, cement production CO2 emission, and forest carbon sink values in 2008-2050 were predicted, based on the socio-economic statistical data, energy consumption data, cement production data, and forest carbon sink data of the Province. In 2008-2050, the cement production CO2 emission in the Province would be basically stable, with an annual carbon emission being 10-15 Mt C, the energy consumption carbon emission and the total carbon emission would be in inverse U-shape, with the peaks occurred in 2035 and 2036, respectively, and the carbon emission intensity would be decreased constantly while the forest carbon sink would have a fluctuated decline. It was feasible and reasonable to use the regional carbon emission calculation framework established in this paper to calculate the carbon emission in Guangdong Province.

[VOCs tax policy on China's economy development].

In this paper, environmental tax was designed to control volatile organic compounds (VOCs) emissions. Computable general equilibrium (CGE) model was used to explore the impacts of environmental tax (in forms of indirect tax) on the macro-economy development at both national and sector levels. Different levels of tax were simulated to find out the proper tax rate. It is found out that imposing environmental tax on high emission sectors can cause the emission decreased immediately and can lead to negative impacts on macro-economy indicators, such as GDP (gross domestic products), total investment, total product and the whole consumption etc. However, only the government income increased. In addition, the higher the tax rate is, the more pollutants can be reduced and the worse economic effects can be caused. Consequently, it is suggested that, the main controlling policies of VOCs abatement should be mandatory orders, and low environmental tax can be implemented as a supplementary.