Publications by authors named "Dandan Xu"

195 Publications

Physalin B inhibits cell proliferation and induces apoptosis in undifferentiated human gastric cancer HGC-27 cells.

Asia Pac J Clin Oncol 2021 Jun 23. Epub 2021 Jun 23.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.

Background: Physalin B (PB) from Physalis angulata L. (Solanaceae) is a naturally occurring secosteroid with multiple biological activities, including anti-inflammatory and anticancer activity. However, PB's effects and mechanisms in human gastric cancer (GC) cells are not well characterized.

Methods: The undifferentiated GC cell line HGC-27 and semi-differentiated GC cell line SGC-7901 were treated with PB. Cell counting kit-8 (CCK-8) and colony formation assays were performed to evaluate cell viability. Apoptosis and the cell cycle were assessed by Annexin V/PI and PI/RNase DNA staining assays, respectively, and Western blotting was used to evaluate the expression of a protein.

Results: PB significantly inhibited the proliferation of HGC-27 cells in a dose- and time-dependent manner. Moreover, PB induced G0/G1 cycle arrest and caspase-dependent apoptosis of HGC-27 cells. Cleaved caspases 8, 3, and 7, poly(ADP)-ribose polymerase (PARP), and the cyclin-dependent kinase (CDK) inhibitor p-Chk2 was induced by PB in HGC-27 cells, while the cell cycle-related proteins cyclin D1, cyclin D3, CDK4, CDK6, cyclin E, and phosphorylated retinoblastoma tumor suppressor protein (p-Rb) were downregulated in a dose-dependent manner.

Conclusions: PB inhibits proliferation via cyclin-dependent kinase and induces caspase-dependent apoptosis in HGC-27 cells, suggesting that PB might be a novel and effective agent for undifferentiated GC therapy.
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http://dx.doi.org/10.1111/ajco.13593DOI Listing
June 2021

The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response.

NPJ Precis Oncol 2021 Jun 22;5(1):56. Epub 2021 Jun 22.

Department of Gastrointestinal Medical oncology, Harbin Medical University Cancer Hospital, Harbin, PR China.

An emerging body of evidence has recently recognized the coexistence of epithelial-mesenchymal transition (EMT) and immune response. However, a systems-level view and survey of the interplay between EMT and immune escape program, and their impact on tumor behavior and clinical outcome across various types of cancer is lacking. Here, we performed comprehensive multi-omics analyses to characterize the landscape of crosstalk between EMT and immune evasion and their clinical relevance across 17 types of solid cancer. Our study showed the presence of complex and dynamic immunomodulatory crosstalk between EMT and immune evasion shared by pan-cancer, and the crosstalk was significantly associated with cancer prognosis and immunotherapy response. Integrative quantitative analyses of genomics and immunogenomics revealed that cellular composition of immune infiltrates, non-synonymous mutation burden, chromosomal instability and oncogenic gene alterations are associated with the balance between EMT and immune evasion. Finally, we proposed a scoring model termed EMT-CYT Index (ECI) to quantify the EMT-immunity axis, which was a superior predictor of prognosis and immunotherapy response across different malignancies. By providing a systematic overview of crosstalk between EMT and immune evasion, our study highlights the potential of pan-cancer EMT-immunity crosstalk as a paradigm for dissecting molecular mechanisms underlying cancer progression and guiding more effective and generalized immunotherapy strategies.
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http://dx.doi.org/10.1038/s41698-021-00200-4DOI Listing
June 2021

Highly Sensitive Pseudocapacitive Iontronic Pressure Sensor with Broad Sensing Range.

Nanomicro Lett 2021 Jun 11;13(1):140. Epub 2021 Jun 11.

State Key Laboratory for Mechanical Behavior of Materials, Xian Jiaotong University, No. 28, Xianning West Road, Xian, 710049, Shaanxi, P. R. China.

Highlights: The iontronic pressure sensor achieved an ultrahigh sensitivity (S > 200 kPa, S > 45,000 kPa). The iontronic pressure sensor exhibited a broad sensing range of over 1.4 MPa. Pseudocapacitive iontronic pressure sensor using MXene was proposed. Flexible pressure sensors are unprecedentedly studied on monitoring human physical activities and robotics. Simultaneously, improving the response sensitivity and sensing range of flexible pressure sensors is a great challenge, which hinders the devices' practical application. Targeting this obstacle, we developed a TiCT-derived iontronic pressure sensor (TIPS) by taking the advantages of the high intercalation pseudocapacitance under high pressure and rationally designed structural configuration. TIPS achieved an ultrahigh sensitivity (S > 200 kPa, S > 45,000 kPa) in a broad sensing range of over 1.4 MPa and low limit of detection of 20 Pa as well as stable long-term working durability for 10,000 cycles. The practical application of TIPS in physical activity monitoring and flexible robot manifested its versatile potential. This study provides a demonstration for exploring pseudocapacitive materials for building flexible iontronic sensors with ultrahigh sensitivity and sensing range to advance the development of high-performance wearable electronics.
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http://dx.doi.org/10.1007/s40820-021-00664-wDOI Listing
June 2021

Multi-omics analysis of brain tissue metabolome and proteome reveals the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat.

J Ethnopharmacol 2021 Jun 1;278:114280. Epub 2021 Jun 1.

Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, 130021, China. Electronic address:

Ethnopharmacological Relevance: Gross Saponins of Tribulus terrestris L. Fruit (GSTTF) has been reported to have a protective effect against ischemic stroke, but the related mechanism is complex and still not fully investigated.

Aim Of The Study: The combination of metabolomics and proteomics approach was applied to reveal the mechanisms of GSTTF in treating ischemic stroke.

Materials And Methods: The metabolite and protein changes in brain tissue were analyzed by the LC-MS-based untargeted metabolomics method and tandem mass tags (TMT)-based quantitative proteomics technology. The multivariate statistical analysis and protein-protein interaction (PPI) analysis were conducted to screen out the biomarkers, and their related pathway was further investigated by the joint pathway analysis.

Results: A total of 110 metabolites and 359 differential proteins, which were mainly associated with complement and coagulation cascades, sphingolipid metabolism, glycerophospholipid metabolism, glutathione metabolism, and platelet activation, etc. were screened out from the rat brain tissue. The PPI network exhibited that the protein F2, Fga, Fgb, Fgg, Plg, and C3, which are greatly involved in the complement and coagulation cascades, have a relatively high connectivity degree, indicating their importance in the process of middle cerebral artery occlusion (MCAO). The GSTTF exerted a protective effect against MCAO via modulating multiple proteins on this pathway. Moreover, F2 played a key role during the protective process and worth to be further investigated due to it has been reported as one of the therapeutic targets of ischemic stroke.

Conclusion: The present study could improve the understanding of the potential therapeutic mechanism of GSTTF against ischemic stroke.
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http://dx.doi.org/10.1016/j.jep.2021.114280DOI Listing
June 2021

Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2-EED Interaction.

J Med Chem 2021 Jun 2. Epub 2021 Jun 2.

School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023 Jiangsu, China.

Disruption of EZH2-embryonic ectoderm development (EED) protein-protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery of astemizole, a small-molecule inhibitor targeting the EZH2-EED PPI. Herein, we report the cocrystal structure of EED in complex with astemizole at 2.15 Å. The structure elucidates the detailed binding mode of astemizole to EED and provides a structure-guided design for the discovery of a novel EZH2-EED interaction inhibitor, DC-PRC2in-01, with an affinity of 4.56 μM. DC-PRC2in-01 destabilizes the PRC2 complex, thereby leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. The proliferation of PRC2-driven lymphomas cells is effectively inhibited, and the cell cycle is arrested in the G0/G1 phase. Together, these data demonstrate that DC-PRC2in-01 could be an effective chemical probe for investigating the PRC2-related physiology and pathology and providing a promising chemical scaffold for further development.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02261DOI Listing
June 2021

Analysis of the effects of prepared porcelain veneers and unprepared porcelain veneers on gingival crevicular flora based on high-throughput sequencing.

Exp Ther Med 2021 Jul 18;22(1):777. Epub 2021 May 18.

Department of Stomatology, The First Hospital of Qiqihar, Qiqihar, Heilongjiang 161006, P.R. China.

The effect of tooth preparation on the gingival crevicular flora of abutment teeth during porcelain veneer treatment is not clear. The purpose of the present study was to analyze the difference between prepared porcelain veneers and unprepared porcelain veneers on gingival crevicular flora. High-throughput sequencing was used in the present study. A total of 20 patients (40 anterior teeth) with veneer restoration of anterior teeth were enrolled. They were divided into two groups: The prepared porcelain veneer group (group P, 11 cases, 19 anterior teeth) and unprepared porcelain veneer group (group U, 9 cases, 21 anterior teeth). After 2 years of follow-up, the restoration and healthy natural gingival crevicular fluid were collected to extract bacterial DNA. 16S ribosomal DNA high-throughput sequencing technique was used to compare the diversity of gingival sulcus flora structure between the prepared porcelain veneer and unprepared porcelain veneer groups. In addition, a healthy control group (group H) was also used for comparison. The Shannon index of the group U was lower than that of group H and group P. The abundance of Proteus in group U was higher than that in group H and group P at the phylum level (P<0.05). At the genus level, the abundance of , and Actinomycetes in group U was significantly higher than that in group H and group P (P<0.05). Compared with the group P, the bacterial diversity of the group U was lower, and the proportion of gingival sulcus pathogenic bacteria was higher. The unprepared porcelain veneer had a certain adverse effect on the periodontal tissue.
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http://dx.doi.org/10.3892/etm.2021.10209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145799PMC
July 2021

Phenacyl Phenothiazinium Salt as A New Broad-wavelength-absorbing Photoinitiator for Cationic and Free Radical Polymerizations.

Angew Chem Int Ed Engl 2021 May 28. Epub 2021 May 28.

Jiangnan University, school of chemical and material engineering, CHINA.

A novel broad-wavelength-absorbing photoinitiator based on phenacyl phenothiazinium hexafluroantimonate (P-PTh) possessing both phenacyl and phenothiazine chromophoric groups was reported. P-PTh absorbs light at UV, Visible and Near-IR region. Photophysical, photochemical, and computational investigations revealed that P-PTh in solution decomposes at all wavelengths by homolytic and heterolytic cleavages and generates cationic and radical species, which could efficiently initiate cationic and free radical polymerizations. It is anticipated that the photoinitiator with such wavelength flexibility may open up new pathways in curing applications of formulations of pigment systems.
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http://dx.doi.org/10.1002/anie.202104531DOI Listing
May 2021

Increasing mortality caused by chronic obstructive pulmonary disease (COPD) in relation with exposure to ambient fine particulate matters: an analysis in Southeastern China.

Environ Sci Pollut Res Int 2021 May 25. Epub 2021 May 25.

Zhejiang Ecological and Environmental Monitoring Center, Xueyuan Road 117#, Hangzhou, 310012, Zhejiang Province, China.

The objective of this study was to investigate the association between ambient particulate matters (PMs) and chronic obstructive pulmonary disease (COPD) mortality. generalized additive mixed model was employed to investigate the effects of ambient fine and coarse PMs on COPD mortality using 13,066 deaths from 2014 to 2016 among six cities in Zhejiang Province in Southeastern China. The daily average death count due to COPD was 3, varying from 1 to 7 among six cities. The daily 24-h mean concentrations were diverse among cities, from 29.7 to 56.8 μg/m for PM, 16.7 to 30.3 μg/m for PM, and 50.3 to 87.1 μg/m for PM, respectively. The analysis showed that daily exposure to PM and PM was associated with increased mortality due to COPD and that weak effects were observed between PM and COPD mortality. Our results provided solid evidence that the fine particles in air pollution have stronger functions on adverse health effects other than coarser particles in Southeastern China, which may be considered as a potential clinic target in PM-associated COPD.
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http://dx.doi.org/10.1007/s11356-021-14009-yDOI Listing
May 2021

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation.

Eur J Med Chem 2021 Aug 25;220:113497. Epub 2021 Apr 25.

Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 555 Zu Chong Zhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China. Electronic address:

Axl has emerged as an attractive target for cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery.
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http://dx.doi.org/10.1016/j.ejmech.2021.113497DOI Listing
August 2021

Long-term PM exposure and survival among cardiovascular disease patients in Beijing, China.

Environ Sci Pollut Res Int 2021 Apr 23. Epub 2021 Apr 23.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, No.7 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.

Previous studies have proved that particulate air pollution was related to adverse cardiovascular effects. However, most studies focused on the acute effects of short-term fine particulate matter (PM) exposure and the general population. Evidence from long-term cohort studies based on the cardiovascular disease (CVD) patients was scarce. Our study aimed to explore the impact of long-term exposure to PM on the mortality among post-CVD patients. This is a cohort study that involved 5143 post-CVD patients in Beijing, China. We collected records of CVD patients from hospitals in Beijing, China from 1 January 2012 to 31 December 2012 and followed up these patients from hospital admission until December 31, 2016. The vital status of the patients was determined using the National Death Surveillance Point System (DSPs). The PM concentrations were obtained from the Atmospheric Composition Analysis Group. The Cox regression models were used for data analyses. Our findings suggested that increased mortality of CVD patients with an HR of 1.43 (95% CI: 1.24, 1.63) was related to long-term exposure to PM. The association was stronger for cardiovascular-related mortality, especially for mortality from myocardial infarction (MI). The HR for any CVD mortality was 1.57 (95% CI: 1.27, 1.94), HR for MI mortality was 1.82 (95% CI: 1.16, 2.83). Long-term PM exposure may significantly affect the survival of CVD patients. Compared with the general population, patients with CVD are more susceptible to PM exposure. Increased attention to the management of CVD patients is warranted.
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http://dx.doi.org/10.1007/s11356-021-14043-wDOI Listing
April 2021

The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.

Front Cell Dev Biol 2021 18;9:648808. Epub 2021 Feb 18.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University of New Jersey, New Brunswick, NJ, United States.

Hypoxia is a hallmark of solid tumors and plays a critical role in different steps of tumor progression, including proliferation, survival, angiogenesis, metastasis, metabolic reprogramming, and stemness of cancer cells. Activation of the hypoxia-inducible factor (HIF) signaling plays a critical role in regulating hypoxic responses in tumors. As a key tumor suppressor and transcription factor, p53 responds to a wide variety of stress signals, including hypoxia, and selectively transcribes its target genes to regulate various cellular responses to exert its function in tumor suppression. Studies have demonstrated a close but complex interplay between hypoxia and p53 signaling pathways. The p53 levels and activities can be regulated by the hypoxia and HIF signaling differently depending on the cell/tissue type and the severity and duration of hypoxia. On the other hand, p53 regulates the hypoxia and HIF signaling at multiple levels. Many tumor-associated mutant p53 proteins display gain-of-function (GOF) oncogenic activities to promote cancer progression. Emerging evidence has also shown that GOF mutant p53 can promote cancer progression through its interplay with the hypoxia and HIF signaling pathway. In this review, we summarize our current understanding of the interplay between the hypoxia and p53 signaling pathways, its impact upon cancer progression, and its potential application in cancer therapy.
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http://dx.doi.org/10.3389/fcell.2021.648808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930565PMC
February 2021

The Early Perioperative Outcomes of Subxiphoid Approach Versus Lateral Intercostal Approach Thoracoscopic Thymectomy for Thymic Tumors: A Meta-Analysis.

J Laparoendosc Adv Surg Tech A 2021 Mar 4. Epub 2021 Mar 4.

Department of Oncology, The Second People's Hospital of Lianyungang, Lianyungang, China.

To systematically evaluate the early perioperative outcomes regarding the safety and efficacy of subxiphoid thoracoscopic thymectomy (STT) versus lateral intercostal thoracoscopic thymectomy (LITT) for patients with thymic tumors. A thorough literature search of the following online databases was performed: Web of Science, PubMed, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.gov. Original research articles published before December 30, 2020, that compared STT with LITT were included. Meta-analysis was performed for early perioperative outcomes, including blood loss, pain score, duration of hospital stay, operative time, chest tube drainage time, and incidence of postoperative complications. Six studies that included 604 patients were finally selected for our analysis, with 296 cases of STT and 308 cases of LITT. Our results showed that compared with LITT, STT was associated with less blood loss (standardized mean difference = -0.81, 95% confidence interval [CI] = -1.49 to -0.14,  = .02), a lower pain score (weighted mean difference [WMD] = -2.55, 95% CI = -3.52 to -1.59;  < .00001), and a shorter hospital stay (WMD = -1.37, 95% CI = -2.37 to -0.36;  = .008), whereas there were no significant differences with regard to the operative time (WMD = -10.04, 95% CI = -22.29 to 2.21,  = .11), chest tube drainage time (WMD = -0.58, 95% CI = -1.17 to 0.02,  = .06), and the incidence of postoperative complications (odds ratio = 0.75, 95% CI = 0.39 to 1.44,  = .38). The current analysis suggests that STT is superior to LITT with respect to the early perioperative outcomes, and STT is a safe and effective surgical method for patients with thymic tumors.
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http://dx.doi.org/10.1089/lap.2021.0036DOI Listing
March 2021

Elevated cadmium and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in residents living near electroplating industries.

Environ Sci Pollut Res Int 2021 Mar 2. Epub 2021 Mar 2.

Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou, 310051, China.

This study aims to evaluate the body burdens of cadmium (Cd) associated with potential health impairment in residents living near electroplating industries. A total of 269 residents from exposure area and 106 from control area were recruited. We measured the blood and urinary Cd levels using an inductively coupled plasma mass spectrometer (ICP-MS); performed physical examinations; determined the urinary levels of β-microglobulin (β-MG), Nacetyl-β--glucosaminidase (NAG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and evaluated the associations between Cd and these biomarkers. Blood and urinary Cd levels in exposure group were statistically higher than in control group (1.712 vs. 1.159 μg/L; 1.980 vs. 1.740 μg/L, respectively, p < 0.05). Urinary β-MG and 8-OHdG levels in exposure group were also statistically higher (0.448 vs. 0.090 mg/L; 12.759 vs. 12.115 μg/L, respectively, p < 0.05), but urinary NAG levels showed no significant difference between the two groups (13.614 vs. 8.246 IU/L, p > 0.05). The proportion of abnormal nasal symptoms occurring in exposed subjects (88.8%) was much higher than in control subjects (78.2%, p < 0.05). Urinary Cd levels were positively correlated with blood Cd levels, urinary 8-OHdG, and NAG levels (r = 0.307, r = 0.185, r = 0.150, p < 0.05), but not correlated with urinary β-MG levels (p > 0.05). In conclusion, our study revealed that residents living in close proximity to electroplating industries had elevated body burdens of Cd levels, as well as slight renal dysfunction and DNA oxidation damage.
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http://dx.doi.org/10.1007/s11356-021-13209-wDOI Listing
March 2021

Specification of complex-PAHs in coal fire sponges (CFS) by high-resolution mass spectrometry with electrospray ionization.

Environ Sci Pollut Res Int 2021 Feb 25. Epub 2021 Feb 25.

State Key Laboratory of Coal Resources and Safe Mining, Beijing, 100083, China.

Underground coal fires are considered an ecological disaster. While underground coal fires are prevalent in coal-producing areas throughout the world, they are most problematic in northern China. Previous studies have shown that underground coal fires stimulate the formation of cracks or gas outlets on the surface, as well as coal fire sponges (CFS) on the soil layer surface, which collect coal-fired pollutants. Herein, ultra-high-performance liquid chromatography (UHPLC) was used in conjunction with electrospray ionization (ESI) high-resolution mass spectrometry to analyze CFS samples collected from the No. 8 fire zone, located in Wuda coalfield, Inner Mongolia, China. The results show that CFS contain 233 oxy-substituted polycyclic aromatic hydrocarbons (O-PAHs), e.g., naphthaldehyde; 40 oxapolycyclic aromatic hydrocarbons (OPAHs), e.g., dibenzofuran; 40 alkyl-substituted polycyclic aromatic hydrocarbons (R-PAHs); and 11 parent polycyclic aromatic hydrocarbons (PPAHs). Thus, CFS are primarily composed of O-PAHs, which are 25 times and 5 times more prevalent than PPAHs and R-PAHs, respectively. As such, a high relative abundance of varied O-PAHs are discharged from underground coal fires, which is significantly different from what is released during industrial coal burning. Owing to their water solubility and condensability, the new facts disclosed in this paper may provide a new perspective for understanding complex organic pollutants from underground coal fires and their environmental impacts.
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http://dx.doi.org/10.1007/s11356-021-12929-3DOI Listing
February 2021

Apelin-36 Protects HT22 Cells Against Oxygen-Glucose Deprivation/Reperfusion-Induced Oxidative Stress and Mitochondrial Dysfunction by Promoting SIRT1-Mediated PINK1/Parkin-Dependent Mitophagy.

Neurotox Res 2021 Jun 13;39(3):740-753. Epub 2021 Feb 13.

Neurobiology Institute, Jining Medical University, Jining, 272067, China.

Oxidative stress and mitochondrial dysfunction are involved in cerebral ischemia/reperfusion injury-induced neuronal apoptosis. Mitophagy is the main method to eliminate dysfunctional mitochondria. Apelin-36, a type of neuropeptide, has been reported to exert protective effects in cerebral I/R (I/R) injury, but its precise mechanisms remain to be elucidated. To study the effects of Apelin-36 on oxidative stress and mitochondrial dysfunction in cerebral I/R injury, the oxygen-glucose deprivation/reperfusion (OGD/R) model with 6 h of ischemia and 6 h of reperfusion was established in HT22 cells. Results demonstrated that Apelin-36 protected against OGD/R injury by improving cell viability, decreasing the apoptotic cells ratio and increasing the ratio of Bcl-2/Bax. In addition, Apelin-36 treatment inhibited oxidative stress by downregulating the level of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as the expression of inducible nitric oxide synthase (iNOS). And Apelin-36 also activated the level of superoxide dismutase (SOD) and glutathione (GSH). Mitochondrial apoptosis was also alleviated with Apelin-36 treatment detected by the mitochondrial membrane potential (MMP) and the expression of Cytochrome c (Cyt c), Cleaved caspase-9, and Cleaved caspase-3. Furthermore, the SIRT1-mediated PINK1/Parkin-dependent mitophagy was activated by Apelin-36 treatment with the downregulation of p62 and upregulation of LC3B-II and Beclin1. Both EX527 and Cyclosporine A (CsA), which are inhibitors of SIRT1 and mitophagy, markedly alleviated the inhibition of oxidative stress and mitochondrial dysfunction caused by Apelin-36. These findings suggest that SIRT1-mediated PINK1/Parkin-dependent mitophagy is involved in the neuroprotective effects of Apelin-36 on OGD/R-induced oxidative stress and mitochondrial dysfunction.
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http://dx.doi.org/10.1007/s12640-021-00338-wDOI Listing
June 2021

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis.

Mol Med Rep 2021 04 12;23(4). Epub 2021 Feb 12.

Neurobiology Key Laboratory of Jining Medical University in Colleges of Shandong, Jining, Shandong 272067, P.R. China.

Orexin‑A (OXA) protects neurons against cerebral ischemia‑reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase‑12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS‑induced neuronal apoptosis. A model of CIRI was established, in which rats were subjected to middle cerebral artery occlusion with ischemic intervention for 2 h, followed by reperfusion for 24 h. Neurological deficit examination and 2,3,5‑triphenyltetrazolium chloride staining were performed to assess the level of CIRI and neuroprotection by OXA. Expression levels of ERS‑related proteins and cleaved caspase‑3 were measured via western blotting, while the rate of neuronal apoptosis in the cortex was determined using a TUNEL assay. OXA treatment decreased the infarct volume of rats after CIRI and attenuated neuron apoptosis. Furthermore, administration of OXA decreased the expression levels of GRP78, phosphorylated (p)‑PERK, p‑eukaryotic initiation factor‑2α, p‑inositol requiring enzyme 1α, p‑JNK, cleaved caspase‑12, CHOP and cleaved caspase‑3, all of which were induced by CIRI. Collectively, these findings suggested that OXA attenuated CIRI by inhibiting ERS‑mediated apoptosis, thus clarifying the mechanism underlying its neuroprotective effect and providing a novel therapeutic direction for the treatment of CIRI.
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http://dx.doi.org/10.3892/mmr.2021.11905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893697PMC
April 2021

HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas.

Genes (Basel) 2021 Jan 19;12(1). Epub 2021 Jan 19.

Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remains obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from The Cancer Genome Atlas (TCGA) database using the correlation analysis of gene expression and gene set enrichment analysis (GSEA), which revealed that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited the Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected using RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2, and BUB1, was involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with the shorter overall survival of LSCC patients. Taken together, our results indicate that GLI1/2 mediates the expression of the PRR11-SKA2-centric gene set that serves as an unfavorable prognostic indicator for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC.
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http://dx.doi.org/10.3390/genes12010120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833434PMC
January 2021

Correction: Cepharanthine hydrochloride reverses the mdr1 (P-glycoprotein)-mediated esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53 signals.

Oncotarget 2021 Jan 5;12(1):61-62. Epub 2021 Jan 5.

Guangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, P. R. China.

[This corrects the article DOI: 10.18632/oncotarget.22676.].
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http://dx.doi.org/10.18632/oncotarget.27638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800775PMC
January 2021

In Situ Synthesis of α-FeO/FeO Heterojunction Photoanode via Fast Flame Annealing for Enhanced Charge Separation and Water Oxidation.

ACS Appl Mater Interfaces 2021 Jan 12;13(3):4785-4795. Epub 2021 Jan 12.

Key Laboratory of Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin 150025, China.

Hematite (α-FeO) is a promising photoanode material in photoelectrochemical (PEC) water splitting. To further improve the catalytic activity, a reasonable construction of heterojunction and surface engineering can effectively improve the photoanode PEC water-splitting performance via improving bulk carrier transport and interfacial charge-transfer efficiency. As FeO has an excellent conductivity and a suitable energy band position, α-FeO/FeO heterojunction can be an ideal structure to improve the activity of α-FeO. However, only few studies have been reported on α-FeO/FeO heterojunctions as photoanodes. In this work, a holey nanorod FeO/FeO heterojunction photoanode with oxygen vacancies was fabricated using a rapid and facile flame reduction treatment. Compared with pure FeO, the water oxidation performance of the FeO/FeO photoanode is improved by ninefold at 1.23 V. Our study revealed that the porous nanorod structure providing more active sites and oxygen vacancies as the hole transfer medium, together improve the interface charge transfer performance of the photoanode. At the same time, FeO can form a FeO/FeO heterojunction to improve the carrier separation efficiency. More importantly, FeO can serve as active sites, solving the slow water oxidation kinetic problem of hematite to enhance the catalytic activity. Our work shows that when flame acts on precursors containing oxygen or hydroxide, it is easy to form compounds with different microstructures or compositions in situ.
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http://dx.doi.org/10.1021/acsami.0c19927DOI Listing
January 2021

Magnetically steerable iron oxides-manganese dioxide core-shell micromotors for organic and microplastic removals.

J Colloid Interface Sci 2021 Apr 29;588:510-521. Epub 2020 Dec 29.

State Key Laboratory of Advanced Welding and Joining, Flexible Printed Electronic Technology Center, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China; Shenzhen Bay Laboratory, No. 9 Duxue Road, Shenzhen 518050, China. Electronic address:

Because of micro/nanoscale manipulation and task-performing capability, micro/nanomotors (MNMs) have attracted lots of research interests for potential applications in biomedical and environmental applications. Owing to the low-cost, good motion behavior, and environmental friendliness, various low-cost metal oxides based MNMs become promising alternatives to the precious metal based MNMs, in particular for environmental remediation applications. Hereby, we demonstrate the facile and scalable fabrication of two types of bubble-propelled iron oxides-MnO core-shell micromotors (FeO-MnO and FeO-MnO) for pollutant removal. The FeO-MnO micromotor exhibits efficient removals of both aqueous organics and suspended microplastics via the synergy of catalytic degradation, surface adsorption, and adsorptive bubbles separations mechanisms. The adsorptive bubbles separation achieved more than 10% removal of the suspended microplastics from the polluted water in 2 h. We clarified the major contributions of different remediation mechanisms in pollutants removals, and the findings may be beneficial to a wide range of environmental applications of MNMs.
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http://dx.doi.org/10.1016/j.jcis.2020.12.097DOI Listing
April 2021

The Role of Mitophagy in Ischemic Stroke.

Front Neurol 2020 23;11:608610. Epub 2020 Dec 23.

Neurobiology Institute, Jining Medical University, Jining, China.

Mitochondria are important places for eukaryotes to carry out energy metabolism and participate in the processes of cell differentiation, cell information transmission, and cell apoptosis. Autophagy is a programmed intracellular degradation process. Mitophagy, as a selective autophagy, is an evolutionarily conserved cellular process to eliminate dysfunctional or redundant mitochondria, thereby fine-tuning the number of mitochondria and maintaining energy metabolism. Many stimuli could activate mitophagy to regulate related physiological processes, which could ultimately reduce or aggravate the damage caused by stimulation. Stroke is a common disease that seriously affects the health and lives of people around the world, and ischemic stroke, which is caused by cerebral vascular stenosis or obstruction, accounts for the vast majority of stroke. Abnormal mitophagy is closely related to the occurrence, development and pathological mechanism of ischemic stroke. However, the exact mechanism of mitophagy involved in ischemic stroke has not been fully elucidated. In this review, we discuss the process and signal pathways of mitophagy, the potential role of mitophagy in ischemic stroke and the possible signal transduction pathways. It will help deepen the understanding of mitophagy and provide new ideas for the treatment of ischemic stroke.
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http://dx.doi.org/10.3389/fneur.2020.608610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793663PMC
December 2020

Discussion on "Correct and logical causal inference for binary and time-to-event outcomes in randomized controlled trials" by Yi Liu, Bushi Wang, Miao Yang, Jianan Hui, Heng Xu, Siyoen Kil, and Jason C. Hsu.

Biom J 2020 Dec 30. Epub 2020 Dec 30.

Division of Biostatistics, Office of Clinical Evidence and Analysis, Office of Product Evaluation and Quality, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, USA.

In their paper, Liu et al. (2020) pointed out illogical discrepancies between subgroup and overall causal effects for some efficacy measures, in particular the odds and hazard ratios. As the authors show, the culprit is subgroups having prognostic effects within treatment arms. In response to their provocative findings, we found that the odds and hazard ratios are logic respecting when the subgroups are purely predictive, that is, the distribution of the potential outcome for the control treatment is homogeneous across subgroups. We also found that when we redefined the odds and hazards ratio causal estimands in terms of the joint distribution of the potential outcomes, the discrepancies are resolved under specific models in which the potential outcomes are conditionally independent. In response to other discussion points in the paper, we also provide remarks on association versus causation, confounding, statistical computing software, and dichotomania.
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http://dx.doi.org/10.1002/bimj.202000320DOI Listing
December 2020

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1.

Cell Discov 2020 Dec 11;6(1):93. Epub 2020 Dec 11.

Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.
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http://dx.doi.org/10.1038/s41421-020-00215-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733455PMC
December 2020

A Semi-Automated Method to Extract Green and Non-Photosynthetic Vegetation Cover from RGB Images in Mixed Grasslands.

Sensors (Basel) 2020 Dec 1;20(23). Epub 2020 Dec 1.

Department of Geography and Planning, University of Saskatchewan, 117 Science Place, Saskatoon, SK S7N5C8, Canada.

Green (GV) and non-photosynthetic vegetation (NPV) cover are both important biophysical parameters for grassland research. The current methodology for cover estimation, including subjective visual estimation and digital image analysis, requires human intervention, lacks automation, batch processing capabilities and extraction accuracy. Therefore, this study proposed to develop a method to quantify both GV and standing dead matter (SDM) fraction cover from field-taken digital RGB images with semi-automated batch processing capabilities (i.e., written as a python script) for mixed grasslands with more complex background information including litter, moss, lichen, rocks and soil. The results show that the GV cover extracted by the method developed in this study is superior to that by subjective visual estimation based on the linear relation with normalized vegetation index (NDVI) calculated from field measured hyper-spectra (R = 0.846, < 0.001 for GV cover estimated from RGB images; R = 0.711, < 0.001 for subjective visual estimated GV cover). The results also show that the developed method has great potential to estimate SDM cover with limited effects of light colored understory components including litter, soil crust and bare soil. In addition, the results of this study indicate that subjective visual estimation tends to estimate higher cover for both GV and SDM compared to that estimated from RGB images.
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http://dx.doi.org/10.3390/s20236870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731437PMC
December 2020

Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK/ERK/mTOR pathway.

Cell Signal 2021 Mar 16;79:109839. Epub 2020 Nov 16.

Neurobiology Key Laboratory of Jining Medical University, Jining 272067, PR China. Electronic address:

Orexin A (OXA) is a neuroprotective peptide that exerts protective effects on multiple physiological and pathological processes. Activation of autophagy is linked to the occurrence of cerebral ischemia-reperfusion injury (CIRI); however, its function remains incompletely understood. In this study, OXA was sought to exert its neuroprotective role by regulating autophagy in oxygen and glucose deprivation and reoxygenation (OGD/R) model and middle cerebral artery occlusion (MCAO) model of rats, and to elucidate the underlying molecular mechanisms. Acridine orange (AO) staining was used to evaluate autophagic vacuoles. Cell viability was measured by CCK8. The levels of p-ERK, t-ERK, p-mTOR, LC3B, Beclin 1, and p62 were evaluated by western blotting. Apoptosis rate was detected by Hoechst 33342 staining and Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL). OXA treatment alleviated neuronal apoptosis and significantly inhibited autophagy activity. Mechanistically, OXA exerted its neuroprotective effects in vivo and in vitro by suppressing over-activated autophagy by modulating OX1R-mediated MAPK/ERK/mTOR pathway. The results of this study elucidate the roles of autophagy in CIRI and the mechanisms underlying the neuroprotective action of OXA. Our findings could facilitate the development of novel therapeutics for ischemic stroke.
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http://dx.doi.org/10.1016/j.cellsig.2020.109839DOI Listing
March 2021

Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1.

J Biol Chem 2020 Nov 18. Epub 2020 Nov 18.

Northwestern University Feinberg School of Medicine, United States.

The TP53 gene is the most frequently mutated gene in human cancers, and the majority of TP53 mutations are missense mutations. As a result, these mutant p53 (mutp53) either directly lose wild-type p53 (wtp53) tumor suppressor function or exhibit a dominant negative effect over wtp53. In addition, some mutp53 have acquired new oncogenic function (gain of function). Therefore, targeting mutp53 for its degradation, may serve as a promising strategy for cancer prevention and therapy. Based on our previous finding that farnesylated DNAJA1 is a crucial chaperone in maintaining mutp53 stabilization, and by using an in silico approach, we built 3-D homology models of human DNAJA1 and mutp53R175H proteins, identified the interacting pocket in the DNAJA1-mutp53R175H complex, and found one critical druggable small molecule binding  site in the DNAJA1 glycine/phenylalanine rich region. We confirmed that the interacting pocket in the DNAJA1-mutp53R175H complex was crucial for stabilizing mutp53R175H using a site-directed mutagenesis approach. We further screened a drug-like library to identify a promising small molecule hit (GY1-22) against the interacting pocket in DNAJA1-mutp53R175H complex. The GY1-22 compound displayed an effective activity against DNAJA1-mutp53R175H complex. Treatment with GY1-22 significantly reduced mutp53 protein levels, enhanced Waf1p21 expression, suppressed cyclin D1 expression, and inhibited mutp53-driven pancreatic cancer growth both in vitro and in vivo. Together, our results indicate that the interacting pocket in the DNAJA1-mutp53R175H complex is critical for mutp53's stability and oncogenic function, and DNAJA1 is a robust therapeutic target for developing the efficient small molecule inhibitors against oncogenic mutp53.
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http://dx.doi.org/10.1074/jbc.RA120.014749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948449PMC
November 2020

Downregulation of lncRNA ZFAS1 inhibits the hallmarks of thyroid carcinoma via the regulation of miR‑302‑3p on cyclin D1.

Mol Med Rep 2021 01 12;23(1). Epub 2020 Nov 12.

Department of Thyroid Surgery, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University, Qiqihar, Heilongjiang 161000, P.R. China.

At present, treatment options for thyroid carcinoma remain limited. The present study aimed to investigate the role of ZFAS1 in various major hallmarks of cancer and the underlying mechanisms in thyroid carcinoma cells. The interactions between long non‑coding RNAs (lncRNAs), microRNAs (miRs) and target genes were predicted by bioinformatics and confirmed by performing dual‑luciferase assays. The mRNA and protein expressions were determined by reverse transcription‑quantitative PCR and western blotting. Cell invasion, migration, and viability were evaluated via Transwell, wound‑healing and Cell Counting Kit‑8 assays, respectively. The results demonstrated that lncRNA ZFAS1 expression was upregulated in thyroid carcinoma tissues, TT and SW579 cells, and was associated with the proliferation of these two cell lines. Notably, downregulation ZFAS1 reduced migration and invasion, and reversed the promotive effects of miR‑302a‑3p inhibitor on the proliferation, migration and invasion of TT and SW579 cells. Moreover, cyclin D1 (CCND1) is targeted by miR‑302a‑3p, and was regulated by ZFAS1. In addition, the downregulation of ZFAS1 not only reversed the promotive effects of miR‑302a‑3p inhibitor on CCND1 expression and the epithelial‑mesenchymal transition (EMT) of TT and SW579 cells, but also targeted and increased the expression of miR‑302a‑3p, and further reduced the expression of CCND1, resulting in suppression of the proliferation, migration, invasion and EMT of thyroid carcinoma cells.
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http://dx.doi.org/10.3892/mmr.2020.11640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673324PMC
January 2021

First report of powdery mildew of crape jasmine () caused by in China.

Plant Dis 2020 Oct 13. Epub 2020 Oct 13.

Shenzhen Polytechnic, 47891, Shenzhen, Guangdong, China;

Crape jasmine (Tabernaemontana divaricata) is a popular flowering shrub widely grown in southern China. Its leaves and roots are used in Chinese traditional medicine. In December, 2019, powdery mildew symptoms were observed on five crape jasmine shrubs on the campus of Shenzhen Polytechnic (22°35'N; 113°56'E), in Guangdong province. Approximately 45% of leaves were infected. Symptoms initially appeared as circular to irregular white patches on the leaf petiole, and subsequently coalesced to develop into abundant hyphal growth on both sides of the leaves, which soon wilted. Hyphae were septate, branched, with simple kidney-shaped to moderately lobed appressoria. Conidia formed singly, ellipsoid-ovoid to subcylindrical, 27-37 × 14-20 μm (mean 32±2.5 × 17±1.6 μm), with a length/width ratio varying from 1.3 to 2.4. Conidiophores were erect, unbranched, consisted of two cells, 60 to 84 μm long (mean 73±4 μm), and with straight to severely kinked cylindrical foot-cells at the base, 29-35 × 3-7 μm (mean 32±3 × 6±2 μm). Chasmothecia were not observed on sampled plants. These morphological characteristics were typical to the conidial stage of the genus Erysiphe (Braun and Cook, 2012). For molecular identification, genomic DNA was extracted from conidia washed from infected leaves and using Fungal DNA Kit (Omega Bio-tek Inc., Guangzhou, China). Semi-nested PCR amplification of the internal transcribed spacer (ITS) region of rDNA was conducted by using primer sets P3 (Kusaba et al., 1995)/ITS5 and ITS5/ITS4 (White et al., 1990) for the first and second reactions, respectively. BLASTn analysis of the obtained 719 bp sequence (GenBank Accession No. MT802112) showed 99.7% identity with those of E. elevata (KY660910, MH985631, MK253282). On the basis of morphological and molecular analyses, the fungus was identified as Erysiphe elevata. To confirm pathogenicity, infected leaves were gently pressed onto healthy leaves of three healthy plants in separate pots, and three noninoculated plants were used as controls. All plants were maintained in a greenhouse at 25 ℃, and relative humidity of 50 to 65%. After 11 days, similar disease symptoms were observed on the inoculated plants while no symptoms developed on control plants. The fungus observed on the inoculated shrubs was identical morphologically to that o the original infected leaves. E. elevata is a common powdery mildew species infecting Catalpa spp. (Cook et al., 2006), Plumeria rubra (Wu et al., 2019; Yeh et al., 2019) and Eucalyptus camaldulensis (Meeboon and Takamatsu, 2017). However, no powdery mildew were found on P. rubra nearby. To our knowledge, this is the first report of this fungus infecting T. divaricata.
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http://dx.doi.org/10.1094/PDIS-08-20-1717-PDNDOI Listing
October 2020

Transcriptome profiling and functional analysis suggest that the constitutive overexpression of four cytochrome P450s confers resistance to abamectin in Tetranychus urticae from China.

Pest Manag Sci 2021 Mar 4;77(3):1204-1213. Epub 2020 Nov 4.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

Background: The two-spotted spider mite Tetranychus urticae is a polyphagous and cosmopolitan pest that has developed high resistance to abamectin, making it difficult to control. Although 'target resistance' related to glutamate-gated chloride channel mutations was found in T. urticae field populations in China, other resistance mechanisms appear to be involved. Here, we conducted genome-wide transcriptome profiling using RNA-sequencing of two abamectin-resistant populations (NB-ZJ and SY-BJ) and one susceptible strain (Lab-SS) to identify differentially expressed genes that might contribute to the resistance of T. urticae to abamectin in China.

Results: Our experiments showed that abamectin resistance was synergized by piperonyl butoxide (PBO) and triphenyl phosphate (TPP), with synergistic ratios (SR) of 2.95-fold and 2.21-fold for PBO and 3.55-fold and 2.84-fold for TPP in NB-ZJ and SY-BJ populations, respectively. Transcriptome data and quantitative real-time PCR (qRT-PCR) revealed that seven detoxification enzyme genes were overexpressed in the two resistant populations. Furthermore, functional analysis by RNA interference (RNAi) indicated that the mortality caused by abamectin was significantly increased by the separate silencing of the P450 genes CYP389C10, CYP392D8, CYP392A11, and CYP392A12.

Conclusion: qRT-PCR expression and RNAi data suggest that the overexpression of P450 genes CYP389C10, CYP392D8, CYP392A11, and CYP392A12 may be involved in the abamectin-resistance of field populations of T. urticae in China. This knowledge could facilitate the elucidation of resistance mechanisms and the development of resistance management of T. urticae field populations. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6130DOI Listing
March 2021

Separation in genetic pathogenesis of mutations in FBN1-TB5 region between autosomal dominant acromelic dysplasia and Marfan syndrome.

Birth Defects Res 2020 12 8;112(20):1834-1842. Epub 2020 Oct 8.

Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Mutations in the transforming growth factor β-binding protein-like domain 5 (TB5) region of FBN1 can lead to autosomal acromelic dysplasia and Marfan syndrome, which are two diseases with apparently opposite phenotypes. We identified six patients with acromelic dysplasia carrying either the previously reported mutations c.5284G > A (p.Gly1762Ser) and c.5096A > G (p.Tyr1699Cys) or the novel mutation c.5260G > A (p.Gly1754Ser). A systematic review of patients with mutations in the FBN1-TB5 region showed that acromelic dysplasia is caused only by in-frame amino acid substitutions. In contrast, truncating mutations in the FBN1-TB5 have been reported only in Marfan syndrome. Acromelic dysplasia subtypes that share symptoms with Marfan syndrome are associated with FBN1-TB5 disulfide disruptions, which are also commonly found in Marfan syndrome. These results suggest that the type and location of mutations in the FBN1-TB5 region determine the clinical spectrum of fibrillinopathy.
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http://dx.doi.org/10.1002/bdr2.1814DOI Listing
December 2020