Publications by authors named "Li-Wei Liu"

88 Publications

Fabrication of Isopropanolamine-Decorated Coumarin Derivatives as Novel Quorum Sensing Inhibitors to Suppress Plant Bacterial Disease.

J Agric Food Chem 2022 May 17;70(20):6037-6049. Epub 2022 May 17.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, Guizhou 550025, China.

Emerging pesticide-resistant phytopathogenic bacteria have become a stumbling block in the development and use of pesticides. Quorum sensing (QS) blockers, which interfere with bacterial virulence gene expression, are a compelling way to manage plant bacterial disease without resistance. Herein, a series of isopropanolamine-decorated coumarin derivatives were designed and synthesized, and their potency in interfering with QS was investigated. Notably, compound exhibited a better bioactivity with median effective concentration (EC) values of 6.75 mg L against pv. () than bismerthiazol (EC = 21.9 mg L). Further biochemical studies revealed that compound disturbed biofilm formation and suppressed bacterial virulence factors and so forth. Moreover, compound decreased the expression of QS-related genes. Interestingly, compound had the acceptable control effect (53.2%) toward . Overall, this study identifies a novel lead compound for the development of bactericide candidates to control plant bacterial diseases by interfering with QS.
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http://dx.doi.org/10.1021/acs.jafc.2c01141DOI Listing
May 2022

Design, Synthesis, and Biological Profiles of Novel 1,3,4-Oxadiazole-2-carbohydrazides with Molecular Diversity.

J Agric Food Chem 2022 Mar 24;70(9):2825-2838. Epub 2022 Feb 24.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including -CH-, -OCH-, and -SCH-) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC) against , , , and could reach 1.29 (), 0.63 (), 1.50 (), and 2.09 () μg/mL, respectively, which were slightly lower than those of carbendazim (EC were 0.69, 0.13, 0.55, and 0.80 μg/mL, respectively). Especially, compound was extremely bioactive against () with an EC value of 0.45 μg/mL. This outcome was better than that of fluopyram (3.76 μg/mL) and was similar to prochloraz (0.47 μg/mL). trials against the corn scab (infected by ) showed that compound had control activity of 86.8% at 200 μg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound could inhibit the enzymatic activity of SDH in the strain with an IC value of 3.67 μM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward afforded a minimal EC value of 3.22 μg/mL (); compound could strongly suppress the growth of bacterial strains pv. and pv. with EC values of 3.79 and 11.4 μg/mL, respectively; and compound displayed some insecticidal activity toward . Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.
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http://dx.doi.org/10.1021/acs.jafc.1c07190DOI Listing
March 2022

Synthesis and Biological Evaluation of 1,2,4-Triazole Thioethers as Both Potential Virulence Factor Inhibitors against Plant Bacterial Diseases and Agricultural Antiviral Agents against Tobacco Mosaic Virus Infections.

J Agric Food Chem 2021 Dec 14;69(50):15108-15122. Epub 2021 Dec 14.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

Targeting the virulence factors of phytopathogenic bacteria is an innovative strategy for alleviating or eliminating the pathogenicity and rapid outbreak of plant microbial diseases. Therefore, several types of 1,2,4-triazole thioethers bearing an amide linkage were prepared and screened to develop virulence factor inhibitors. Besides, the 1,2,4-triazole scaffold was exchanged by a versatile 1,3,4-oxadiazole core to expand molecular diversity. Bioassay results revealed that a 1,2,4-triazole thioether bearing a privileged -(3-nitrophenyl)acetamide fragment was extremely bioactive against (Xoo) with an EC value of 5.01 μg/mL. Label-free quantitative proteomics found that compound could significantly downregulate the expression of Xoo's type III secretion system (T3SS) and transcription activator-like effector (TALE) correlative proteins. Meanwhile, qRT-PCR detection revealed that the corresponding gene transcription levels of these virulence factor-associated proteins were substantially inhibited after being triggered by compound . As a result, the hypersensitive response and pathogenicity were strongly depressed, indicating that a novel virulence factor inhibitor () was probably discovered. In vivo anti-Xoo trials displayed that compound yielded practicable control efficiency (54.2-59.6%), which was superior to thiadiazole-copper and bismerthiazol (38.1-44.9%). Additionally, compound showed an appreciable antiviral activity toward tobacco mosaic virus (TMV) with the curative and protective activities of 54.6 and 76.4%, respectively, which were comparable to ningnanmycin (55.2 and 60.9%). This effect was further validated and visualized by the inoculation test using GFP-labeled TMV, thereby leading to the reduced biosynthesis of green-fluorescent TMV on . Given the outstanding features of compound , it should be deeply developed as a versatile agricultural chemical.
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http://dx.doi.org/10.1021/acs.jafc.1c05202DOI Listing
December 2021

Metabolomics and Transcriptomics Analysis on Metabolic Characteristics of Oral Lichen Planus.

Front Oncol 2021 19;11:769163. Epub 2021 Oct 19.

Department of Oral Emergency, The First Affiliated Hospital of Zhengzhou University· Stomatological Hospital of Henan Province, Zhengzhou, China.

Objective: To explore metabolic biomarkers related to erosive and reticulated oral lichen planus (OLP) by non-targeted metabolomics methods and correlate metabolites with gene expression, and to investigate the pathological network pathways of OLP from the perspective of metabolism.

Methods: A total of 153 individuals were enrolled in this study, including 50 patients with erosive oral lichen planus (EOLP), 51 patients with reticulated oral lichen planus (ROLP), and 52 healthy controls (HC). The ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS) was used to analyze the metabolites of 40 EOLP, 40 ROLP, and 40 HC samples, and the differential metabolic biomarkers were screened and identified. The regulatory genes were further screened through the shared metabolites between EOLP and ROLP, and cross-correlated with the OLP-related differential genes in the network database. A "gene-metabolite" network was constructed after finding the key differential genes. Finally, the diagnostic efficiency of the biomarkers was verified in the validation set and a diagnostic model was constructed.

Result: Compared with HC group, a total of 19 and 25 differential metabolites were identified in the EOLP group and the ROLP group, respectively. A total of 14 different metabolites were identified between EOLP and ROLP. Two diagnostic models were constructed based on these differential metabolites. There are 14 differential metabolites shared by EOLP and ROLP. The transcriptomics data showed 756 differentially expressed genes, and the final crossover network showed that 19 differential genes were associated with 12 metabolites. Enrichment analysis showed that alanine, aspartate and glutamate metabolism were closely associated with the pathogenesis of OLP.

Conclusion: The metabolic change of different types of OLP were clarified. The potential gene perturbation of OLP was provided. This study provided a strong support for further exploration of the pathogenic mechanism of OLP.
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http://dx.doi.org/10.3389/fonc.2021.769163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560742PMC
October 2021

A modified theory of planned behavioral: A case of tourist intention to visit a destination post pandemic Covid-19 in Indonesia.

Heliyon 2021 Oct 21;7(10):e08230. Epub 2021 Oct 21.

Department of Leisure and Service Management, Chaoyang University of Technology, Taiwan.

The Pandemic covid-19 spread globally has been given impact in the tourism industry, especially in the tourism destination. This study investigated to build the concept and theoretical framework that explains the decision of local tourist intention to visit a local destination in Indonesia post-pandemic covid-19. This study was considered the perception of Covid-19, non-pharmaceutical intervention and health consciousness by implying of Theory of Planned Behavior constructs. This study, health consciousness is the moderator variable to predict the decision of tourist to visit a destination. Structural Equation Model-Partial Least Square (SEM-PLS) was used to analyze the construct of study. The model found that the Theory of Planned Behavior was successfully broadened in making the decision of tourist to visit a destination post-covid-19 with considering non-pharmaceutical intervention and health consciousness. The results showed that generally the constructs of Theory Planned Behavior are significantly impacted in intention to visit a local destination in Indonesia, except Hypothesis of subjective norm and intention to visit was rejected. The variable health consciousness through intention to visit also was rejected. The framework also used moderating variable health consciousness between subjective norm and intention to visit was rejected. This study was given insight an issue of covid-19 in the tourism sector, and the implication was providing government, stakeholders, tourism marketers and policy-making with considering non-pharmaceutical and health consciousness during and post-pandemic covid-19.
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http://dx.doi.org/10.1016/j.heliyon.2021.e08230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529901PMC
October 2021

Long-Term Clinical Outcomes of New-Generation Drug-Eluting Stents in Coronary Artery Disease: A Real-World Observational Study.

Acta Cardiol Sin 2021 Sep;37(5):484-495

Department of Cardiology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan.

Background: Treating vessels with a very small reference vessel diameter (RVD) in coronary artery disease is challenging.

Objective: Long-term evaluation of new-generation drug-eluting stents (DESs) for the treatment of coronary lesions with different RVDs.

Methods: From April 2009 to March 2019, 780 patients who underwent single coronary stenting were divided into ≤ 2.25 (very small), 2.5-3.0 (small), and ≥ 3.5 mm (large) DES groups after 1:2:2 propensity score matching. The primary endpoint was target lesion failure (TLF), and the secondary endpoints were major adverse cardiac events (MACEs) and stent thrombosis (ST).

Results: During 3 years after new-generation DES implantation, TLF and MACE rates were significantly lower in the very small DES group. The risk of TLF was significantly lower in the very small DES group compared to the small DES group [very small vs. small: TLF, adjusted hazard ratio (HR) = 0.282, p = 0.040]. The risks of MACEs and all-cause mortality were significantly lower in the very small DES group compared to the small DES group (very small vs. small: MACEs, adjusted HR = 0.215, p = 0.001; all-cause mortality, adjusted HR = 0.181, p = 0.005). The cumulative incidence rates of TLF-free (log-rank test p = 0.001) and MACE-free (log-rank test p < 0.001) survival were significantly different among the groups, and the very small DES group had a high event-free survival rate. No cases of ST occurred in any group.

Conclusions: Our results indicate that the use of new-generation DESs for treating coronary lesions in very small vessels is safe and effective.
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http://dx.doi.org/10.6515/ACS.202109_37(5).20210426ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414071PMC
September 2021

Relationship between chromatin configuration and in vitro maturation ability in guinea pig oocytes.

Vet Med Sci 2021 11 19;7(6):2410-2417. Epub 2021 Aug 19.

Department of Histology and Embryology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong Province, China.

Background: Germinal vesicle (GV) chromatin configurations of oocytes are proposed to be related to oocyte competence and may reflect the quality of oocyte. Currently, a limited number of published studies investigated the GV chromatin configurations of guinea pig oocytes.

Objective: In this study on the in vitro maturation (IVM) of guinea pig oocytes, we examined the changes in their GV chromatin configurations during meiotic progression.

Methods: Based on the degree of chromatin compaction, the GV chromatin configurations of guinea pig oocytes could be divided into three categories depending on whether the nucleolus-like body (NLB) was surrounded or partly surrounded by compacted chromatin, namely the uncondensed (NSN), the intermediate type (SN-1) and the compacted type (SN-2).

Results: The percentage of cells displaying the SN-2 configuration increased with the growth of guinea pig oocytes, suggesting that this configuration presents the potential for maturation in oocytes. Oocytes derived from larger follicle exhibited increased meiotic potential. Serum starvation affected the GV chromatin configurations of guinea pig oocytes.

Conclusions: Collectively, these results suggest that the SN-2 type might be a more mature form of configuration in guinea pig oocyte, whose proportion was associated with the follicle size and susceptible to the environment (e.g. serum concentration).
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http://dx.doi.org/10.1002/vms3.596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604138PMC
November 2021

Fabrication of Versatile Pyrazole Hydrazide Derivatives Bearing a 1,3,4-Oxadiazole Core as Multipurpose Agricultural Chemicals against Plant Fungal, Oomycete, and Bacterial Diseases.

J Agric Food Chem 2021 Aug 23;69(30):8380-8393. Epub 2021 Jul 23.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds -, -, , , , and . For the antifungal activity, the minimal EC values could afford 0.47 (), 1.05 (), 0.65 (), and 1.32 μg/mL () against the corresponding fungi (), , , and . In vivo pot experiments against corn scab (caused by ) revealed that the compound was effective with protective and curative activities of 90.2 and 86.3% at 200 μg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC = 3.21 μM, ) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds and yielded superior anti-oomycete and antibacterial activities toward and with EC values of 2.92 and 8.43 μg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% () at 200 μg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.
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http://dx.doi.org/10.1021/acs.jafc.1c02460DOI Listing
August 2021

Combined cesarean delivery and repair of acute aortic dissection at 34 weeks of pregnancy during COVID-19 outbreak: A case report.

World J Clin Cases 2021 May;9(15):3644-3648

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the exclusion of a patient from COVID-19 should be performed before surgery. However, patients with type A acute aortic dissection (AAD) during pregnancy can seriously endanger the health of either the mother or fetus that requires emergency surgical treatment without the test for COVID-19.

Case Summary: A 38-year-old woman without Marfan syndrome was admitted to the hospital because of chest pain in the 34 week of gestation. She has diagnosed as having a Stanford type-A AAD involving an aortic arch and descending aorta aortic computed tomographic angiography. The patient was transferred to the isolated negative pressure operating room in one hour and underwent cesarean delivery and ascending aorta replacement. All medical staff adopted third-level medical protection measures throughout the patient transfer and surgical procedure. After surgery, the patient was transferred to the isolated negative pressure intensive care unit ward. The nucleic acid test and anti-COVID-19 immunoglobulin (Ig) G and IgM were performed and were negative. The patient and infant were discharged without complication nine days later and recovered uneventfully.

Conclusion: The results indicated that the procedure that we used is feasible in patients with a combined cesarean delivery and surgery for Stanford type-A AAD during the COVID-19 outbreak, which was mainly attributed to rapid multidisciplinary consultation, collaboration, and quick decision-making.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130093PMC
May 2021

Rational Optimization of 1,2,3-Triazole-Tailored Carbazoles As Prospective Antibacterial Alternatives with Significant In Vivo Control Efficiency and Unique Mode of Action.

J Agric Food Chem 2021 Apr 15;69(16):4615-4627. Epub 2021 Apr 15.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, P. R. China.

Plant bacterial diseases can potentially damage agricultural products around the world, and few effective bactericides can manage these infections. Herein, to sequentially explore highly effective antibacterial alternatives, 1,2,3-triazole-tailored carbazoles were rationally fabricated. These compounds could suppress the growth of three main intractable pathogens including pv (), pv (), and pv () with lower EC values of 3.36 (), 2.87 (), and 4.57 μg/mL (), respectively. Pot experiments revealed that compound could control the rice bacterial blight with protective and curative efficiencies of 53.23% and 50.78% at 200 μg/mL, respectively. Interestingly, the addition of 0.1% auxiliaries such as organic silicon and orange oil could significantly enhance the surface wettability of compound toward rice leaves, resulting in improved control effectiveness of 65.50% and 61.38%, respectively. Meanwhile, compound could clearly reduce the white pyogenic exudates triggered by infection and afforded excellent control efficiencies of 79.42% (protective activity) and 78.74% (curative activity) at 200 μg/mL, which were quite better than those of commercial pesticide thiodiazole copper. Additionally, a plausible apoptosis mechanism for the antibacterial behavior of target compounds was proposed by flow cytometry, reactive oxygen species detection, and defensive enzyme (e.g., catalase and superoxide dismutase) activity assays. The current work can promote the development of 1,2,3-triazole-tailored carbazoles as prospective antibacterial alternatives bearing an intriguing mode of action.
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http://dx.doi.org/10.1021/acs.jafc.1c00707DOI Listing
April 2021

Fuzheng Yiliu Formula Regulates Tumor Invasion and Metastasis through Inhibition of WAVE3 Expression.

Evid Based Complement Alternat Med 2021 27;2021:8898668. Epub 2021 Mar 27.

Department of Diagnostics of Chinese Medicine, School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.

Objective: To explore the mechanism of action of Fuzheng Yiliu formula (FZYLF) in regulation of the invasion and metastasis of MDA-MB-231/Adr human breast cancer cells through WAVE3.

Methods: The MDA-MB-231/Adr cells with high invasive ability were screened by Transwell, and the plasmid with high WAVE3 expression was made for transfection. Plasmid transfection efficiency and protein expression level were verified by polymerase chain reaction (PCR) and western blotting (WB). The effect of FZYLF on cell proliferation and invasion was investigated before and after WAVE3 silencing by flow cytometry. A nude mouse model of tumor metastasis was established to study the antitumor activity of FZYLF.

Results: The expression levels of mRNA and proteins of intracellular WAVE3 increased significantly after plasmid transfection, mRNA from 1.37± 0.41 to 9.88 ± 1.31 and protein from 1 ± 0.08 to 5.09 ± 0.03 ( < 0.01). Intervention with FZYLF could significantly affect the activity of MDA-MB-231/Adr cells and inhibit invasion and metastasis, IC from 71.04 to 46.41 mg/mL and from 162 ± 14.82 to 81.4 ± 12.05 ( < 0.05 or  < 0.01), and significantly reduce the expression levels of WAVE3 (from 1 ± 0.02 to 0.63 ± 0.04), MMP-9 (from 1 ± 0.05 to 0.63 ± 0.03), NF-B (p65) (from 1 ± 0.02 to 0.62 ± 0.02), and p-IB (from 1 ± 0.03 to 0.68 ± 0.02) ( < 0.05 or  < 0.01). The T/C (%) of FZYLF (13 g crude drug/kg) was 62.06% for MDA-MB-231/Adr tumor xenografted in nude mice, with a tumor inhibition rate of 39.64%.

Conclusion: FZYLF can inhibit the invasion and proliferation of the MDA-MB-231/Adr human breast cancer cells, and the mechanism of action may be related to the regulation of WAVE3 expression.
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http://dx.doi.org/10.1155/2021/8898668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019629PMC
March 2021

Cardiac-specific microRNA-125b deficiency induces perinatal death and cardiac hypertrophy.

Sci Rep 2021 01 27;11(1):2377. Epub 2021 Jan 27.

Cardiovascular Division, Institute of Biomedical Science, Academia Sinica, National Taiwan University College of Medicine, 128 Academia Road, Sec. 2, Nankang, Taipei, 115, Taiwan.

MicroRNA-125b, the first microRNA to be identified, is known to promote cardiomyocyte maturation from embryonic stem cells; however, its physiological role remains unclear. To investigate the role of miR-125b in cardiovascular biology, cardiac-specific miR-125b-1 knockout mice were generated. We found that cardiac-specific miR-125b-1 knockout mice displayed half the miR-125b expression of control mice resulting in a 60% perinatal death rate. However, the surviving mice developed hearts with cardiac hypertrophy. The cardiomyocytes in both neonatal and adult mice displayed abnormal mitochondrial morphology. In the deficient neonatal hearts, there was an increase in mitochondrial DNA, but total ATP production was reduced. In addition, both the respiratory complex proteins in mitochondria and mitochondrial transcription machinery were impaired. Mechanistically, using transcriptome and proteome analysis, we found that many proteins involved in fatty acid metabolism were significantly downregulated in miR-125b knockout mice which resulted in reduced fatty acid metabolism. Importantly, many of these proteins are expressed in the mitochondria. We conclude that miR-125b deficiency causes a high mortality rate in neonates and cardiac hypertrophy in adult mice. The dysregulation of fatty acid metabolism may be responsible for the cardiac defect in the miR-125b deficient mice.
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http://dx.doi.org/10.1038/s41598-021-81700-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840921PMC
January 2021

Rational design of an oxygen-enriching nanoemulsion for enhanced near-infrared laser activatable photodynamic therapy against hypoxic tumors.

Colloids Surf B Biointerfaces 2021 Feb 1;198:111500. Epub 2020 Dec 1.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address:

Photodynamic therapy (PDT) has emerged as one of the most promising modalities to treat cancers. However, the hypoxic microenvironment in tumors severely limits the efficiency of PDT. IR780 is a near-infrared light activatable photosensitizer for PDT. It has attracted intensive attention owing to its intriguing properties such as mitochondria-targeting ability and fluorescence imaging capability. Nevertheless, its application in tumor treatment is hampered by its low aqueous solubility and poor stability. To address these obstacles, here we designed a novel hierarchical nanoplatform containing a uniquely stable high loading capacity oxygen carrier (perfluoropolyether, in short, PFPE) and IR780. This nanoplatform (IR780-P/W NE, in abbreviation for IR780-PFPE-in-water nanoemulsion) has no detectable dark cytotoxicity. It not only improves the aqueous solubility and stability of IR780, but also transports oxygen to relieve hypoxia and boosts the efficiency of near-infrared light triggered PDT via augmentation of reactive oxygen species generation. Particularly, the innovative nanosized oxygen carrier developed in this research, P/W NE, is a potential universal platform for loading hydrophobic photosensitizers (including but not limited to IR780), sonosensitizers, or radiosensitizers, and simultaneously improving the therapeutic efficacy. Our results highlight the intriguing potential of the developed nanoemulsions for mitigating tumor hypoxia and enhancing the efficiencies of oxygen-dependent therapies including PDT, sonodynamic therapy, radiotherapy, and so on.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111500DOI Listing
February 2021

Potential Metabolic Biomarkers for Early Detection of Oral Lichen Planus, a Precancerous Lesion.

Front Pharmacol 2020 6;11:603899. Epub 2020 Nov 6.

Stomatological Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disorder and precancerous oral lesion with high incidence. The current diagnostic method of OLP is very limited and metabolomics may provide a new approach for quantitative evaluation. The Ultra-Performance Liquid Chromatography-Quadrupole/Orbitrap High Resolution Mass Spectrometry (UHPLC-Q-Orbitrap HRMS) was applied to analyze the change of metabolites in serum of patients with OLP. A total of 115 OLP patients and 124 healthy controls were assigned to either a training set ( = 160) or a test set ( = 79). The potential biomarkers and the change of serum metabolites were profiled and evaluated by multivariate analysis. Totally, 23 differential metabolites were identified in the training set between OLP group and healthy group. Three prominent metabolites in receiver operating characteristic (ROC) were selected as a panel to distinguish OLP or healthy individuals in the test set, and the diagnostic accuracy was 86.1%. This study established a new method for the early detection of OLP by analyzing serum metabolomics using UHPLC-Q-Orbitrap HRMS, which will help in understanding the pathological processes of OLP and identifying precancerous lesions in oral cavity.
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http://dx.doi.org/10.3389/fphar.2020.603899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677577PMC
November 2020

Correction: Gut microbiota patterns associated with somatostatin in patients undergoing pancreaticoduodenectomy: a prospective study.

Cell Death Discov 2020 15;6:105. Epub 2020 Oct 15.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang China.

[This corrects the article DOI: 10.1038/s41420-020-00329-4.].
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http://dx.doi.org/10.1038/s41420-020-00339-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562950PMC
October 2020

Gut microbiota patterns associated with somatostatin in patients undergoing pancreaticoduodenectomy: a prospective study.

Cell Death Discov 2020 28;6(1):94. Epub 2020 Sep 28.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang China.

Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The gut microbiota has been considered as an crucial mediator of postoperative complications, however, the precise roles of gut microbiota in POPF are unclear. A prospective study was developed to explore the effects of somatostatin on gut microbiota and we aim to identify the microbial alterations in the process of POPF. A total of 45 patients were randomly divided into PD group or additional somatostatin therapy group. The fecal sample of each patient was collected preoperatively and postoperatively and the gut microbiota was analyzed by 16S rRNA sequencing. Our study found that somatostatin therapy was independent risk factor for the occurrence of POPF, and it reduced the microbial diversity and richness in patients. At genus level, somatostatin therapy led to a decreased abundance in Bifidobacterium, Subdoligranulum and Dubosiella, whereas the abundance of Akkermansia, Enterococcus and Enterobacter were increased. The abundance levels of certain bacteria in the gut microbiota have significantly shifted in patients with POPF. The LEfSe analysis revealed that Ruminococcaceae could be used as microbial markers for distinguishing patients with high risk of POPF. Furthermore, Verrucomicrobia and Akkermansia could be used as preoperative biomarkers for identifying patients without POPF. Our prospective study highlights the specific communities related with somatostatin therapy and discovers POPF-associated microbial marker, which suggests that gut microbiota may become a diagnostic biomarker and potential therapeutic target for POPF.
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http://dx.doi.org/10.1038/s41420-020-00329-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522245PMC
September 2020

Bioinformatics Data Mining Repurposes the JAK2 (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal Adenocarcinoma by Reversing the (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog)-Driven Gene Signature.

J Pers Med 2020 Sep 16;10(3). Epub 2020 Sep 16.

Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive and lethal cancer types due to the late diagnosis, high metastatic potential, and drug resistance. The development of novel therapeutic strategies is urgently needed. (Kirsten rat sarcoma 2 viral oncogene homolog) is the major driver mutation gene for PDAC tumorigenesis. In this study, we mined cancer genomics data and identified a common -driven gene signature in PDAC, which is related to cell-cell and cell-extracellular matrix (ECM) interactions. Higher expression of this gene signature was associated with poorer overall survival of PDAC patients. Connectivity Map (CMap) analysis and drug sensitivity profiling predicted that a clinically approved JAK2 (Janus kinase 2)-selective inhibitor, fedratinib (also known as TG-101348), could reverse the -driven gene signature and exhibit -dependent anticancer activity in PDAC cells. As an approved treatment for myelofibrosis, the pharmacological and toxicological profiles of fedratinib have been well characterized. It may be repurposed for treating -driven PDAC in the future.
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http://dx.doi.org/10.3390/jpm10030130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563462PMC
September 2020

Synthesis and Docking Study of -(Cinnamoyl)-'-(substituted)acryloyl Hydrazide Derivatives Containing Pyridinium Moieties as a Novel Class of Filamentous Temperature-Sensitive Protein Z Inhibitors against the Intractable pv. Infections in Rice.

J Agric Food Chem 2020 Aug 22;68(31):8132-8142. Epub 2020 Jul 22.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

pv. () is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate -induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from may lead to the discovery of highly efficient and innovative anti- agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting FtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of . As such, a series of novel -(cinnamoyl)-'-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti- activity was determined. The bioassay results showed that compound had excellent anti- activity (EC = 0.99 mg L) in vitro and distinct curative activity (63.2% at 200 mg L) in vivo. Further studies revealed that these designed compounds were FtsZ inhibitors, validating by the reduced GTPase activity of recombinant FtsZ, the nonfilamentous FtsZ assembly observed in the TEM images, and the prolonged cells from the fluorescence patterns. Computational docking studies showed that compound had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of FtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control -induced infections.
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http://dx.doi.org/10.1021/acs.jafc.0c01565DOI Listing
August 2020

Impact of DNA Demethylases on the DNA Methylation and Transcription of Genes.

Front Genet 2020 26;11:460. Epub 2020 May 26.

College of Life Sciences, Nanjing Agricultural University, Nanjing, China.

Active DNA demethylation is an important epigenetic process that plays a key role in maintaining normal gene expression. In plants, active DNA demethylation is mediated by DNA demethylases, including ROS1, DME, DML2, and DML3. In this study, the available bisulfite sequencing and mRNA sequencing data from and mutants were analyzed to reveal how the active DNA demethylation process shapes the DNA methylation patterns of nucleotide-binding leucine-rich repeat () genes, a class of important plant disease resistance genes. We demonstrate that the CG methylation levels of three genes (, , and ) are increased in the mutants relative to the wild-type plants, whereas the CG methylation level of is decreased. We also observed increased CG methylation levels of and and decreased CG methylation levels of in mutants. We further found that the expression of three genes (, , and ) was activated in both and mutants, whereas the expression of another three genes (, and ) was repressed in these two mutants. Quantitative reverse transcriptase-polymerase chain reaction detection showed that the expression levels of AT1G58602.1, AT4G19520.3, AT4G19520.4, and AT4G19520.5 were decreased in the mutant; AT3G50950.1 and AT3G50950.2 in the mutant were also decreased in expression compared to Col-0, whereas AT1G57630.1, AT1G58602.2, and AT5G45510.1 were upregulated in the mutant relative to Col-0. These results indicate that some genes are regulated by DNA demethylases. Our study demonstrates that each DNA demethylase (ROS1, DML2, and DML3) exerts a specific effect on the DNA methylation of the genes, and active DNA demethylation is part of the regulation of DNA methylation and transcriptional activity of some genes.
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http://dx.doi.org/10.3389/fgene.2020.00460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264425PMC
May 2020

Universal mechanical exfoliation of large-area 2D crystals.

Nat Commun 2020 May 15;11(1):2453. Epub 2020 May 15.

Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, China.

Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
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http://dx.doi.org/10.1038/s41467-020-16266-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228924PMC
May 2020

Metabolomic Insights Into the Synergistic Effect of Biapenem in Combination With Xuebijing Injection Against Sepsis.

Front Pharmacol 2020 22;11:502. Epub 2020 Apr 22.

Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The drug combination of biapenem (BIPM) and xuebijing injection (XBJ) is commonly applied for the treatment of sepsis in China. However, the potential synergistic mechanism is still enigmatic. There have been no studies focused on the plasma metabolome alterations in sepsis after the intervention of this combination. In this work, an untargeted metabolomics approach was performed by liquid chromatography-mass spectrometry coupled with multivariate statistical analysis to provide new insights into the synergistic effect of BIPM in combination with XBJ. We characterized the metabolic phenotype of sepsis and described metabolic footprint changes in septic rats responding to XBJ and BIPM individually and in combination, in addition to histopathological and survival evaluation. A total of 91 potential biomarkers of sepsis were identified and 32 disturbed metabolic pathways were constructed. Among these biomarkers, 36 metabolites were reversely regulated by XBJ, mainly including glycerophospholipids, sphingolipids, free fatty acids (FFAs), bile acids and acylcarnitines; 42 metabolites were regulated by BIPM, mainly including amino acids, glycerophospholipids, and acylcarnitines; 72 metabolites were regulated after XBJ-BIPM combination treatment, including most of the 91 potential biomarkers. The results showed that the interaction between XBJ and BIPM indeed exhibited a synergistic effect by affecting some key endogenous metabolites, 15 metabolites of which could not be regulated when XBJ or BIPM was used alone. Compared with Model group, 13, 22, and 27 metabolic pathways were regulated by XBJ, BIPM, and XBJ-BIPM combination, respectively. It suggested that many more endogenous metabolites and metabolic pathways were significantly regulated after combination treatment compared with XBJ or BIPM monotherapy. Metabolisms of lipids, amino acids, acylcarnitines, and bile acids were common pathways involved in the synergistic action of XBJ and BIPM. This study was the first to employ metabolomics to elucidate the synergistic effect and decipher the underlying mechanisms of BIPM in combination with XBJ against sepsis. The results provide some support for clinical application of antibiotics in combination with traditional Chinese medicines and have important implications for the treatment of sepsis in clinic.
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http://dx.doi.org/10.3389/fphar.2020.00502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189733PMC
April 2020

Assembling Anthracene-Tailored Amphiphiles: Charge-Transfer Interactions Directed Hierarchical Nanofibers with Ameliorative Antibacterial Activity toward Plant Pathogens.

J Agric Food Chem 2020 May 5;68(20):5579-5585. Epub 2020 May 5.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

The effective prevention of plant bacterial infections has been complicated and challenged by unceasing bacterial resistance. The application of traditional bactericides has achieved certain effects to alleviate this situation. However, these chemicals also have limitations, such as short half-life in reality, limited bioavailability, and pollutant emission from their formulations. These disadvantages drive the demand for promoting antibacterial therapeutics. Self-assembled nanostructures based on amphiphiles have inherently versatile characteristics, including high durability, good bioavailability, sustained release, and regenerability. As such, they have garnered wide interest because of these advantages that may serve as a feasible platform for the management of pathogenic infections. Flexible tuning of the shapes of these nanostructures by manipulating noncovalent driving forces consequently results in different levels of antibacterial activity. Herein, an antibacterial amphiphile, 1-[11-(9-anthracenylmethoxy)-11-oxoundecyl]pyridinium bromide (AP), was assembled into microfilms in screening medium. Hierarchical nanofibers were constructed by introducing an electron-deficient trinitrofluorenone (TNF) molecule into the assembling system directed by charge-transfer (CT) interactions to further investigate the contribution of aggregate shape to bioactivity. Biological evaluation revealed that antibacterial efficacy improved after CT complex formation. This study provides an innovative platform for developing versatile assembled structures for restraining the propagation of plant pathogens and an improved understanding of the actual interplay between the self-assembly and antibacterial ability of bactericides at the supramolecular level.
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http://dx.doi.org/10.1021/acs.jafc.0c01991DOI Listing
May 2020

Development of efficient on-bead protein elution process coupled to ultra-high performance liquid chromatography-tandem mass spectrometry to determine immunoglobulin G subclass and glycosylation for discovery of bio-signatures in pancreatic disease.

J Chromatogr A 2020 Jun 14;1621:461039. Epub 2020 Mar 14.

Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address:

Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4-related disease in which higher IgG4 and total IgG levels have been found in patient serum. Due to the similar imaging features and laboratory parameters between AIP and pancreatic ductal adenocarcinoma (PDAC), a differential diagnosis is still challenging. Since IgG profiles can be potential bio-signatures for disease, we developed and validated a method which coupled on-bead enzymatic protein elution process to an efficient UHPLC-MS/MS method to determine IgG subclass and glycosylation. A stable-isotope labeled IgG was incorporated as internal standard to achieve accurate quantification. For calibration curves, the correlation coefficients for total IgG and the four IgG subclasses were higher than 0.995. Intraday (n = 5) and interday (n = 3) precisions of the peak area ratios of LLOQ, low, medium, and high QC samples were all less than 6.6% relative standard deviation (% RSD), and the accuracies were between 93.5 and 114.9%. Calibration curves, precision, and accuracy were also evaluated for 26 IgG glycopeptides. The method was applied to samples from healthy controls and patients with AIP and PDAC. Distinct IgG patterns were discovered among the groups, and 7 glycopeptides showed high potential in differentiating AIP and PDAC. The results demonstrated that the developed method is suitable for multi-feature analysis of human IgG, and the discovered IgG profiles can be used as bio-signatures for AIP and PDAC.
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http://dx.doi.org/10.1016/j.chroma.2020.461039DOI Listing
June 2020

Synthesis of novel 18β-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases.

Pest Manag Sci 2020 Sep 27;76(9):2959-2971. Epub 2020 Apr 27.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China.

Background: The limited amount of agrochemicals targeting plant bacterial diseases has motivated us to study innovative antibacterial surrogates with fresh modes of action. Notably, fabrication of violent apoptosis inducers to control the reproduction of pathogenic bacteria should be a feasible way to control plant bacterial diseases. To achieve this aim, we constructed a series of novel 18β-glycyrrhetinic piperazine amides based on the natural bioactive ingredient 18β-glycyrrhetinic acid to evaluate the in vitro and in vivo antibacterial activity and induced apoptosis behaviors on tested pathogens.

Results: Screening results suggested that these designed compounds were extremely bioactive against two notorious pathogens, Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. This conclusion was highlighted by the biological effects of compounds A and B , affording the related EC values of 2.28 and 0.93 μg mL . In vivo trials confirmed the prospective application for managing rice bacterial blight disease with control efficiency within 50.57-53.70% at 200 μg mL . In particular, target compounds could induce the generation of excessive reactive oxygen species (ROS) in tested pathogens, subsequently leading to a strong apoptotic effect at a very low drug concentration (≤ 10 μg mL ). This finding was consistent with the observed ROS-enhanced fluorescent images and morphological changes of pathogens from scanning electron microscopy patterns.

Conclusion: Given these features, we anticipate that these novel piperazine-tailored 18β-glycyrrhetinic hybrids can provide an perceptible insight for fighting bacterial infections by activation of the apoptosis mechanism. Novel 18β-glycyrrhetinic piperazine amides were reported to have excellent antibacterial efficacy toward phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. A possible apoptosis mechanism was proposed from the remarkable apoptotic behaviors triggered by target compounds. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5841DOI Listing
September 2020

A Multilevel Analysis of Organizational Support on the Relationship between Person-Environment Fit and Performance of University Physical Education Teachers.

Int J Environ Res Public Health 2020 03 19;17(6). Epub 2020 Mar 19.

Office of Physical Education Academic Affairs, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.

Limited research has evaluated the performance of physical education (PE) teachers. This study aimed to use person-environment fit and organizational support to evaluate PE teachers' work performance using multilevel analysis. The relationship between person-environment fit and performance of university physical education teachers (at the person-level) and a cross-level effect on performance of university physical education teachers of perceived organizational support (at the school-level) and a moderator effect of organizational support were examined. A total of 447 PE teachers recruited from 55 universities in Taiwan were invited to participate in this survey, with a return rate of 65.74%. Using hierarchical linear modeling, the study found that person-job fit, person-organization fit, and person-supervisor fit at individual level have positive impacts on the performance of university PE teachers. As for cross-level effect, organizational support has positive impacts on the performance of university physical education teachers. However, organizational support at school level had no significant moderating effects on the relationship between person-environment fit and the performance of university physical education teachers. The implications of the findings for both university PE teachers and administrators and suggestions for future research are discussed.
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http://dx.doi.org/10.3390/ijerph17062041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143768PMC
March 2020

Sacubitril/Valsartan Improves Left Ventricular Ejection Fraction and Reverses Cardiac Remodeling in Taiwanese Patients with Heart Failure and Reduced Ejection Fraction.

Acta Cardiol Sin 2020 Mar;36(2):125-132

Tainan Municipal Hospital (Managed by Show Chwan Medical Care Coporation).

Background: The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan is known to improve outcomes of cardiac death and hospitalization due to heart failure in patients with heart failure and reduced ejection fraction (HFrEF). However, data on improvements in ejection fraction after using sacubitril/valsartan are still lacking in Taiwan.

Methods: We conducted this prospective, single armed, observation cohort study to evaluate changes in left ventricular ejection fraction (LVEF) in patients with heart failure and reduced LVEF treated with sacubitril/valsartan. This was an all-comer study. We prescribed sacubitril/valsartan as both first-line and second-line therapy to every eligible patient regardless of whether they were already on standard therapy or newly-diagnosed with HFrEF. The primary outcome was improvements in LVEF. We also collected data about changes in left ventricular chamber size, blood pressure, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and renal function according to serum creatinine level.

Results: During March 2016 to April 2018, 93 patients were enrolled. The mean LVEF improved from 35 ± 6.1% to 50 ± 8.8% at 6 months use of sacubitril/valsartan (p < 0.001). The left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial diameter all decreased. The average NT-proBNP level decreased from 6379 pg/mL to 1661 pg/dL.

Conclusions: Sacubitril/valsartan demonstrated a significant effect in improving LVEF, left ventricular reverse remodeling, and reduction of NT-proBNP in this Taiwanese cohort.
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http://dx.doi.org/10.6515/ACS.202003_36(2).20190812ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062818PMC
March 2020

Novel piperazine-tailored ursolic acid hybrids as significant antibacterial agents targeting phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri probably directed by activation of apoptosis.

Pest Manag Sci 2020 Aug 17;76(8):2746-2754. Epub 2020 Apr 17.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China.

Background: Induced apoptosis is an effective technique that can reprogram cellular physiological and pathological processes to eradicate undesirable cells using their innate systems. Inspired by this, numerous apoptosis inducers have been developed to treat animal diseases, especially in the anticancer field. However, few studies have reported on the development of inductive agents that attack plant pathogens by activation of apoptosis. With the aim of exploring and discovering apoptosis inducers that target phytopathogens, a cluster of piperazine-tailored ursolic acid (UA) hybrids was systematically fabricated.

Results: In vitro testing showed that the title molecules could inhibit the growth of two intractable bacterial strains, defined as Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri. The corresponding lowest EC values were 0.37 and 1.08 μg mL , which exceed those of UA (>400 μg mL ) and positive controls. Moreover, compounds 5u and 5v could manage bacterial blight in vivo using pot experiments. Flow cytometer analysis indicted that the title compounds could induce distinct apoptotic behaviors on tested bacteria. In-depth study revealed that the introduction of designed compounds could reduce the enzyme activities of catalase and superoxide dismutase, subsequently leading to the accumulation of reactive oxygen species.

Conclusion: This study promoted the development of apoptosis initiators for managing bacterial infections in agriculture by an innovative mode of action. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5822DOI Listing
August 2020

Design, synthesis, and antimicrobial behavior of novel oxadiazoles containing various N-containing heterocyclic pendants.

Pest Manag Sci 2020 Aug 4;76(8):2681-2692. Epub 2020 Apr 4.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, China.

Background: The gradually elevated outbreak of plant bacterial diseases severely limits agricultural products and small amounts of pesticides can manage them. Our group has previously synthesized and screened the antimicrobial activity of diverse 1,3,4-oxadiazole thioether/sulfone compounds bridged by a sulfur atom at the 2-position of 1,3,4-oxadiazole. However, few studies have evaluated the effect of eliminating the sulfur atom on bioactivity. Herein, a novel type of N-containing heterocyclic pendants-tagged 1,3,4-oxadiazoles bridged by alkyl chains only was systematically synthesized and evaluated for their antimicrobial activities.

Results: Bioassay results revealed that antibacterial efficacy increased by 551- and 314-fold against the corresponding phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri compared to commercial agents bismerthiazol and thiodiazole copper. In vivo trials showed that C exerted remarkable curative activity against rice bacterial blight with a control effectiveness of 52.9% at 200 μg mL . Antibacterial mechanism research found that C could reduce the hypersensitive response behavior and pathogenicity of Xoo through targeting the type III secretion system (T3SS) at a lower drug dose. This outcome was verified by observing the significantly down-regulated proteins and representative genes from the related quantitative proteomics and qRT-PCR assays.

Conclusion: This study can inspire the design of innovative molecular frameworks targeting the T3SS of phytopathogens for controlling bacterial infections. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5814DOI Listing
August 2020

Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway.

Biomed Res Int 2020 10;2020:1874387. Epub 2020 Feb 10.

School of Basic Sciences of Shanxi University of Chinese Medicine, Taiyuan, China.

Objective: To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway.

Methods: The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid.

Results: Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice ( < 0.05).

Conclusions: Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1155/2020/1874387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035546PMC
November 2020
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