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  1. Bhowmik R, Zhu Y, Gao K
    PLoS One, 2021;16(12):e0261270.
    PMID: 34936662 DOI: 10.1371/journal.pone.0261270
    China-ASEAN are the two huge markets in trade world, they can bring out greater dynamism from within their economies and contribute to regional economic development. This study explores the present situation on the trade between the Central region of China and ASEAN through empirical assessment and try to find the potential effects and trade flows between them. Firstly, we analysis the trade integration index, HM index, explicit comparative advantage index, and trade complementarity index. Finally, we use the gravity model of international trade and data on 2006-2018. The bilateral trade relations between the central region and ASEAN are getting closer, but the central region has not yet become the major trade area of ASEAN countries in the Chinese market. The bilateral economic development level plays a positive role in promoting the export trade between the Central region and ASEAN, while the bilateral distance plays a negative role in difficulty. The empirical results show that trade potential between the Central region and Indonesia and the Philippines is huge, and there is still opportunity for the development of the trade potential with Thailand. The trade prospective with Malaysia, Singapore and Vietnam is limited, and new approaches need to be developed to achieve further trade cooperation.
  2. Liu X, Wu Y, Chen Y, Xu F, Halliday N, Gao K, et al.
    Res. Microbiol., 2016 Apr;167(3):168-77.
    PMID: 26671319 DOI: 10.1016/j.resmic.2015.11.003
    The σ(S) subunit RpoS of RNA polymerase functions as a master regulator of the general stress response in Escherichia coli and related bacteria. RpoS has been reported to modulate biocontrol properties in the rhizobacterium Serratia plymuthica IC1270. However, the role of RpoS in the stress response and biofilm formation in S. plymuthica remains largely unknown. Here we studied the role of RpoS from an endophytic S. plymuthica G3 in regulating these phenotypes. Mutational analysis demonstrated that RpoS positively regulates the global stress response to acid or alkaline stresses, oxidative stress, hyperosmolarity, heat shock and carbon starvation, in addition to proteolytic and chitinolytic activities. Interestingly, rpoS mutations resulted in significantly enhanced swimming motility, biofilm formation and production of the plant auxin indole-3-acetic acid (IAA), which may contribute to competitive colonization and environmental fitness for survival. These findings provide further insight into the strain-specific role of RpoS in the endophytic strain G3 of S. plymuthica, where it confers resistance to general stresses encountered within the plant environment. The heterogeneous functionality of RpoS in rhizosphere and endophytic S. plymuthica populations may provide a selective advantage for better adaptation to various physiological and environmental stresses.
  3. Liu X, Yu X, Yang Y, Heeb S, Gao S, Chan KG, et al.
    Appl Microbiol Biotechnol, 2018 Apr;102(8):3711-3721.
    PMID: 29511844 DOI: 10.1007/s00253-018-8857-0
    The antibiotic pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite that plays an important role in the biocontrol of plant diseases due to its broad-spectrum of antimicrobial activities. The PRN biosynthetic gene cluster remains to be characterised in Serratia plymuthica, though it is highly conserved in PRN-producing bacteria. To better understand PRN biosynthesis and its regulation in Serratia, the prnABCD operon from S. plymuthica G3 was cloned, sequenced and expressed in Escherichia coli DH5α. Furthermore, an engineered strain prnind which is a conditional mutant of G3 prnABCD under the control of the Ptac promoter was constructed. This mutant was able to overproduce PRN with isopropylthiogalactoside (IPTG) induction by overexpressing prnABCD, whilst behaving as a conditional mutant of G3 prnABCD in the absence of IPTG. These results confirmed that prnABCD is responsible for PRN biosynthesis in strain G3. Further experiments involving lux-/dsRed-based promoter fusions, combined with site-directed mutagenesis of the putative σS extended -10 region in the prnA promoter, and liquid chromatography-mass spectrometry (LC-MS) analysis extended our previous knowledge about G3, revealing that quorum sensing (QS) regulates PRN biosynthesis through cross talk with RpoS, which may directly activated prnABCD transcription. These findings suggest that PRN in S. plymuthica G3 is produced in a tightly controlled manner, and has diverse functions, such as modulation of cell motility, in addition to antimicrobial activities. Meanwhile, the construction of inducible mutants could be a powerful tool to improve PRN production, beyond its potential use for the investigation of the biological function of PRN.
  4. Feng Y, Xiong Y, Hall-Spencer JM, Liu K, Beardall J, Gao K, et al.
    Glob Chang Biol, 2024 Jan;30(1):e17018.
    PMID: 37937464 DOI: 10.1111/gcb.17018
    Blooms of microalgal red tides and macroalgae (e.g., green and golden tides caused by Ulva and Sargassum) have caused widespread problems around China in recent years, but there is uncertainty around what triggers these blooms and how they interact. Here, we use 30 years of monitoring data to help answer these questions, focusing on the four main species of microalgae Prorocentrum donghaiense, Karenia mikimotoi, Noctiluca scintillans, and Skeletonema costatum) associated with red tides in the region. The frequency of red tides increased from 1991 to 2003 and then decreased until 2020, with S. costatum red tides exhibiting the highest rate of decrease. Green tides started to occur around China in 1999 and the frequency of green tides has since been on the increase. Golden tides were first reported to occur around China in 2012. The frequency of macroalgal blooms has a negative linear relationship with the frequency and coverage of red tides around China, and a positive correlation with total nitrogen and phosphorus loads as well as with atmospheric CO2 and sea surface temperature (SST). Increased outbreaks of macroalgal blooms are very likely due to worsening levels of eutrophication, combined with rising CO2 and SST, which contribute to the reduced frequency of red tides. The increasing grazing rate of microzooplankton also results in the decline in areas affected by red tides. This study shows a clear shift of algal blooms from microalgae to macroalgae around China over the past 30 years driven by the combination of eutrophication, climate change, and grazing stress, indicating a fundamental change in coastal systems in the region.
  5. Gao K, Su Z, Meng J, Yao Y, Li L, Su Y, et al.
    Biol Res Nurs, 2024 Jan;26(1):125-138.
    PMID: 37579279 DOI: 10.1177/10998004231195541
    OBJECTIVE: This study aimed to investigate the effects of aerobic interval training and resistance training on anti-inflammatory adipokines, high sensitivity C-reactive protein, and clinical outcomes in sedentary men with metabolic syndrome.

    METHODS: A total of 33 sedentary men with metabolic syndrome (age: 46.2 ± 4.6 years; body mass index: 35.4 ± 1.9 kg.m2) were randomly assigned to one of 3 groups: aerobic interval training (n = 12), resistance training (n = 10), or control (n = 11). Participants in the exercise groups completed a 12-week training program, 3 sessions per week, while those in the control group maintained their sedentary lifestyle. The levels of high sensitivity C-reactive protein (hs-CRP), omentin-1, adiponectin, lipid profiles, blood pressure, glucose metabolism, body composition, and peak oxygen uptake (VO2peak) were measured at baseline and after the intervention.

    RESULTS: Both aerobic interval training and resistance training significantly improved the levels of omentin-1 and adiponectin, as well as reduced inflammation, as indicated by a decrease in hs-CRP levels. Exercise training also led to significant improvements in lipid profiles, blood pressure, glucose metabolism, and body composition. Specifically, the aerobic interval training group had significantly greater increases in high-density lipoprotein cholesterol and VO2peak, as well as greater reductions in low-density lipoprotein cholesterol, triglycerides, and total cholesterol compared to the resistance training group.

    CONCLUSION: Exercise training, particularly aerobic interval training and resistance training, can be an effective non-pharmacological intervention for managing inflammation and improving cardiovascular health in metabolic syndrome patients.

  6. Schiestl M, Li J, Abas A, Vallin A, Millband J, Gao K, et al.
    Biologicals, 2014 Mar;42(2):128-32.
    PMID: 24373974 DOI: 10.1016/j.biologicals.2013.11.009
    A determination of biosimilarity is based on a thorough characterization and comparison of the quality profiles of a similar biotherapeutic product and its reference biotherapeutic product. Although the general principles on the role of the quality assessment in a biosimilar evaluation are widely understood and agreed, detailed discussions have not been published yet. We try to bridge this gap by presenting a case study exercise based on fictional but realistic data to highlight key principles of an evaluation to determine the degree of similarity at the quality level. The case study comprises three examples for biosimilar monoclonal antibody candidates. The first describes a highly similar quality profile whereas the second and third show greater differences to the reference biotherapeutic product. The aim is to discuss whether the presented examples can be qualified as similar and which additional studies may be helpful in enabling a final assessment. The case study exercise was performed at the WHO implementation workshop for the WHO guidelines on quality assessment of similar biotherapeutic products held in Xiamen, China, in May 2012. The goal was to illustrate the interpretation of the comparative results at the quality level, the role of the quality assessment in the entire biosimilarity exercise and its influence on the clinical evaluation. This paper reflects the outcome of the exercise and discussion from Xiamen.
  7. Kang HN, Thorpe R, Knezevic I, Casas Levano M, Chilufya MB, Chirachanakul P, et al.
    Ann N Y Acad Sci, 2021 05;1491(1):42-59.
    PMID: 33222245 DOI: 10.1111/nyas.14522
    The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019-2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars.
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