Publications by authors named "Ling Guo"

589 Publications

Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy.

Genes (Basel) 2021 Nov 19;12(11). Epub 2021 Nov 19.

Department of Neurology and Neurosurgery, Anderson Moores Veterinary Specialists, Winchester SO21 2LL, Hampshire, UK.

A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. Electrodiagnostic testing supported a myopathy. Histopathology of muscle biopsies confirmed a dystrophic phenotype with excessive variability in myofiber size, degenerating fibers, and endomysial fibrosis. A heritable form of congenital muscular dystrophy (CMD) was suspected, and a genetic analysis initiated. We sequenced the genome of the affected dog and compared the data to that of 795 control genomes. This search revealed a private homozygous nonsense variant in , XM_022419950.1:c.3285G>A, predicted to truncate 65% of the open reading frame of the wild type laminin α2 protein, XP_022275658.1:p.(Trp1095*). Immunofluorescent staining performed on muscle cryosections from the affected dog confirmed the complete absence of laminin α2 in skeletal muscle. loss of function variants were shown to cause severe laminin α2-related CMD in humans, mouse models, and in one previously described dog. Our data together with current knowledge on other species suggest the nonsense variant as cause for the CMD phenotype in the investigated dog.
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http://dx.doi.org/10.3390/genes12111823DOI Listing
November 2021

[Advances on Collection and Analysis of Volatile Organic Compounds 
in the Diagnosis of Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Nov;24(11):796-803

Medical School of Chinese PLA, Beijing 100853, China.

Lung cancer is a leading cause of cancer-related morbidity and mortality globally, which is the biggest menace to the health and life of the population. Screening and early detection of lung cancer are effective in reducing its mortality, and the measurement of volatile organic compounds (VOCs) has become a promising clinical means for early detection, course detection and prognosis management of lung cancer, with advantages of rapid speed, non-invasiveness and convenience. Now, a variety of VOCs collection ways and analysis methods have emerged at home and abroad. This report summarized three aspects, including VOCs collection, multiple methods of analysis and progress in the diagnosis and treatment of lung cancer. At last, we discussed the limitations and prospects of VOCs analysis.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.41DOI Listing
November 2021

Analysis of clinical characteristics and drug resistance of staphylococcus aureus nosocomial infection.

Minerva Surg 2021 Nov 17. Epub 2021 Nov 17.

Infection Control Division, Hengshui People's Hospital, Hengshui, China -

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http://dx.doi.org/10.23736/S2724-5691.21.09199-1DOI Listing
November 2021

[Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration].

Zhongguo Zhong Yao Za Zhi 2021 Oct;46(20):5278-5283

Guizhou University of Traditional Chinese Medicine Guiyang 550025, China Guizhou Engineering Research Center for Traditional Chinese Medicine and Ethnic Medicine Processing and Preparation Guiyang 550025, China.

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210330.303DOI Listing
October 2021

Corrigendum to "TIMELESS confers cisplatin resistance in nasopharyngeal carcinoma by activating the Wnt/β-catenin signaling pathway and promoting the epithelial mesenchymal transition" [2017 Aug 28;402:117-130].

Cancer Lett 2022 Jan 25;524:284-285. Epub 2021 Oct 25.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2021.10.025DOI Listing
January 2022

Muscular dystrophy-dystroglycanopathy in a family of Labrador retrievers with a LARGE1 mutation.

Neuromuscul Disord 2021 Jul 28. Epub 2021 Jul 28.

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108 United States.

Alpha-dystroglycan (αDG) is a highly glycosylated cell surface protein with a significant role in cell-to-extracellular matrix interactions in muscle. αDG interaction with extracellular ligands relies on the activity of the LARGE1 glycosyltransferase that synthesizes and extends the heteropolysaccharide matriglycan. Abnormalities in αDG glycosylation and formation of matriglycan are the pathogenic mechanisms for the dystroglycanopathies, a group of congenital muscular dystrophies. Muscle biopsies were evaluated from related 6-week-old Labrador retriever puppies with poor suckling, small stature compared to normal litter mates, bow-legged stance and markedly elevated creatine kinase activities. A dystrophic phenotype with marked degeneration and regeneration, multifocal mononuclear cell infiltration and endomysial fibrosis was identified on muscle cryosections. Single nucleotide polymorphism (SNP) array genotyping data on the family members identified three regions of homozygosity in 4 cases relative to 8 controls. Analysis of whole genome sequence data from one of the cases identified a stop codon mutation in the LARGE1 gene that truncates 40% of the protein. Immunofluorescent staining and western blotting demonstrated the absence of matriglycan in skeletal muscle and heart from affected dogs. Compared to control, LARGE enzyme activity was not detected. This is the first report of a dystroglycanopathy in dogs.
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http://dx.doi.org/10.1016/j.nmd.2021.07.016DOI Listing
July 2021

Once-monthly hemin suppresses inflammatory and autoreactive CD4 T cell responses to robustly ameliorate experimental rheumatoid arthritis.

iScience 2021 Oct 10;24(10):103101. Epub 2021 Sep 10.

School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, P. R. China.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that would permanently damage the affected joints. Unfortunately, a large proportion of RA patients fail to respond adequately to current treatments. Here, repurposing hemin and its ultra-long-acting formulation were explored for the effective treatment of RA in animal models. We provided evidence that hemin prevented the onset and ameliorated the clinical course of RA. Notably, hemin treatment rescued the dysregulated gene expression in animal models of RA, resulting in attenuation of Th1/Th17 cell-mediated responses and proinflammatory cytokines. Moreover, we further formulated hemin into the forming implant, and a single injection of the ultra-long-acting hemin exerted potent disease-modifying effects for at least six weeks with a remarkable dose reduction. Taken together, given the potent anti-inflammatory and immunosuppressive effects, the once-monthly hemin injection holds promise for rapid clinical translation, and represents a potential strategy to treat RA and possibly other autoimmune diseases.
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http://dx.doi.org/10.1016/j.isci.2021.103101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479697PMC
October 2021

Targeting the Nod-like receptor protein 3 Inflammasome with inhibitor MCC950 rescues lipopolysaccharide-induced inhibition of osteogenesis in Human periodontal ligament cells.

Arch Oral Biol 2021 Nov 30;131:105269. Epub 2021 Sep 30.

Department of prosthodontics, Hospital of Stomatology Affiliated to Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

Objective: We aim to investigate whether lipopolysaccharide-stimulated activition of Nod-like receptor protein 3 (NLRP3) Inflammasome inhibits osteogenesis in Human periodontal ligament cells (HPDLCs). Futhermore, to study whether MCC950 (a inhibitor of NLRP3 Inflammasome) rescues lipopolysaccharide-induced inhibition of osteogenesis in HPDLCs as well as the underlying mechanisms.

Methods: HPDLCs were isolated from periodontal ligament of healthy orthodontic teeth from teenagers, and cells surface marker protein were detected by flow cytometry. Cells viability were determined by Cell Counting kit 8 assay. Enzyme-linked immunosorbent assay was used to analyze the secretion of proinflammatory factors. Western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were measured assessing the expression of NLRP3 and Caspase-1. RT-qPCR, Alizarin red staining and Alkaline phosphatase staining were tested to determine the osteogenic differentiation capacity of HPDLCs.

Results: It was found that lipopolysaccharide in the range of concentrations from 10 to 100 μg/ml significantly inhibited HPDLCs viability at 24 h and significantly improved proinflammatory cytokine expressions at 8 h and 24 h. MCC950 reversed lipopolysaccharide-stimulated proinflammatory cytokine expressions including interleukin-1β and interleukin-18, but not tumor necrosis factor-α. In addition, MCC950 rescued the lipopolysaccharide-inhibited osteogenic gene (Alkaline phosphatase, Runt-related transcription factor 2, and Osteocalcin). Moreover, MCC950 downregulated lipopolysaccharide-induced relative protein of NLRP3 Inflammasome signaling pathway, such as NLRP3 and Caspase-1.

Conclusion: MCC950 rescues lipopolysaccharide-induced inhibition of osteogenesis in HPDLCs via blocking NLRP3 Inflammasome signaling pathway, and it may be used as a promising therapeutic agent for periodontitis or periondontal regenerative related disease.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105269DOI Listing
November 2021

Recent progress in nanotechnology-based drug carriers for celastrol delivery.

Biomater Sci 2021 Sep 28;9(19):6355-6380. Epub 2021 Sep 28.

Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.

Celastrol (CLT) is an active ingredient that was initially discovered and extracted from the root of The potential pharmacological activities of CLT in cancer, obesity, and inflammatory, auto-immune, and neurodegenerative diseases have been demonstrated in recent years. However, CLT's clinical application is extremely restricted by its low solubility/permeability, poor bioavailability, and potential off-target toxicity. The advent of nanotechnology provides a solution to improve the oral bioavailability, therapeutic effects or tissue-targeting ability of CLT. This review focuses on the most recent advances, improvements, inventions, and updated literature of various nanocarrier systems for CLT.
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http://dx.doi.org/10.1039/d1bm00639hDOI Listing
September 2021

1.5T magnetic resonance imaging in evaluating fetal head and abdomen malformations: a preliminary study.

Am J Transl Res 2021 15;13(8):9063-9069. Epub 2021 Aug 15.

Internal Medicine-Cardiovascular Department, Shijiazhuang No. 3 Hospital Shijiazhuang 050000, Hebei, China.

Objective: Magnetic resonance imaging (MRI) is increasingly used in the diagnosis of fetal malformations. The purpose of this study was to determine the diagnostic value of 1.5T MRI in fetal head and abdominal malformations.

Methods: A total of 132 pregnant women admitted to Shijiazhuang NO.4 Hospital were included and divided into a control group (CG; n=63) and a research group (RG; n=69) according to different prenatal examination methods. Patients in CG were given ultrasound, while those in RG underwent 1.5T MRI examination. The image quality of 1.5T MRI in different amniotic fluid, different gestational weeks with normal amniotic fluid and different fetal positions with normal amniotic fluid were compared. The detection rate and diagnostic value of the two methods were also compared, with the histological and pathological results as the gold standard.

Results: The image quality of 1.5T MRI was not affected by different gestational age with normal amniotic fluid, different fetal positions with normal amniotic fluid, or different amniotic fluid, indicating the feasibility of 1.5T MRI in fetal malformation examination. Histopathological diagnosis revealed 39 cases of head and abdominal deformities in CG and 50 cases in RG. Based on the results of ultrasound examination, there were 32 cases of deformities and 31 of non-deformities in CG. In RG, 1.5T MRI revealed 48 malformations and 21 non-malformations. The sensitivity, specificity, accuracy, missed diagnosis and misdiagnosis rates were 82.05%, 75.00%, 79.37%, 17.95% and 25.00% respectively in CG where ultrasonography was performed, and were 96.00%, 94.74%, 95.65%, 4.00% and 5.26% respectively in RG where 1.5T MRI was performed. The data identified significant differences in sensitivity, accuracy and missed diagnosis between RG and CG.

Conclusion: 1.5T MRI is effective in diagnosing fetal head and abdominal malformations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430194PMC
August 2021

Genetic characterization of Carbapenem-Resistant Escherichia coli from China, 2015-2017.

BMC Microbiol 2021 09 17;21(1):248. Epub 2021 Sep 17.

Laboratory Medicine Department, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.

Background: The molecular characteristics of carbapenem-resistant Escherichia coli (CREco) remain unclear.

Methods: We conducted a multi-center bacterial resistance monitoring project from 2015 to 2017.The minimum inhibitory concentrations ofCREco were determined bybroth microdilution method. The genome sequencing of CREcoisolates was performed, and single-nucleotide polymorphism (SNP) was analyzed.

Results: A total of 144CREcoisolatescollected from 10 cities in China were involved in this study. ST167 (n = 43) is the most popular type, followed by ST410(n = 14), ST131(n = 9). There were 102 (70.83%) CREco isolates that produced various NDMs, including NDM-1 (n = 16), NDM-4(n = 1), NDM-5(n = 79), NDM-6(n = 2) and NDM-9(n = 4). In addition, 15 isolates produced KPC-2, three isolates wereIMP-4 positive, and three isolates produced OXA-48. Genetic relatedness and phylogenetic analysis showed that isolates with the same ST had a high degree of homology. Some STs (including ST167, ST410, ST131, ST46, ST405 and ST617) exhibited a trend of outbreak.

Conclusions: The majority of CREco belonged to ST167, followed by ST410 and ST131, and most of them carried various NDM-coding genes. The spread of high-risk clones of CREco has occurred in different regions of China.
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http://dx.doi.org/10.1186/s12866-021-02307-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449468PMC
September 2021

Effect of age stratification on the association between carotid intima-media thickness and cognitive impairment in Chinese hypertensive patients: new insight from the secondary analysis of the China Stroke Primary Prevention Trial (CSPPT).

Hypertens Res 2021 Nov 7;44(11):1505-1514. Epub 2021 Sep 7.

Department of Cardiovascular, Nanchang University Second Affiliated Hospital, Nanchang, China.

The current study aimed to explore the association between carotid intima-media thickness (CIMT) and cognitive function assessed by the Mini-Mental State Examination (MMSE) and to examine possible effect modifiers in hypertensive patients. A total of 14,322 hypertensive participants (mean age 64.2 ± 7.4 years; 40.9% male) from the China Stroke Primary Prevention Trial (CSPPT) were included in the final analysis. CIMT was measured by ultrasound, and data were collected at the last follow-up visit; MMSE was used to evaluate cognitive function. Nonparametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the relationship between the CIMI and cognitive function and effect modification. The mean CIMT was 0.74 ± 0.11 mm, and the mean MMSE score was 23.5 ± 4.8. There was a significant interaction (P interaction < 0.05) in both male and female populations stratified by age (<60 vs. ≥60 years), and higher CIMT was significantly associated with decreased MMSE scores only in participants aged ≥60 years (male: β = -2.29, 95% CI -3.23 to -1.36; female: β = -1.96, 95% CI -2.97 to -0.95). Males with abnormal HDL-C showed a stronger negative association (β = -3.16, 95% CI -4.85 to -1.47) than those with normal HDL-C (normal vs. abnormal, P for interaction = 0.004). We observed that increased CIMT was significantly associated with cognitive impairment in the hypertensive population, especially among individuals with an age greater than 60 years and HDL-C deficiency. Overall, upon diagnosis of hypertension, treatment should start at the earliest opportunity to prevent end-organ damage and cognitive decline.
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http://dx.doi.org/10.1038/s41440-021-00743-wDOI Listing
November 2021

Metabolic syndrome and its components are associated with thyroid volume in adolescents.

BMC Endocr Disord 2021 Aug 28;21(1):176. Epub 2021 Aug 28.

Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine (Jiangsu Province Hospital on Integration of Chinese and Western Medicine), Nanjing, China.

Objective: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria.

Methods: A total of 1097 school students (610 males and 487 females, ages 12-15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume.

Results: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (β = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (β = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria.

Conclusions: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.
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http://dx.doi.org/10.1186/s12902-021-00833-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399830PMC
August 2021

The high platelet counts as predictor for early foetal demise.

Ann Med 2021 12;53(1):1502-1508

Department of Obstetrics and Gynecology, Tongji University School of Medicine, Shanghai Tenth People's Hospital, Shanghai, China.

Early fetal demise (absence of cardiac activity in a visible fetus) is a very common event, but there are no reliable biomarkers to predict it. The purpose of the study was to assess the association of platelet parameters with early fetal demise. In this case-control study, we included women with normal deliveries or those ultrasound diagnosed as early fetal demise. For those who were identified with early fetal demise, the platelet parameters were analyzed before the ultrasound diagnosis, which is based on the absence of either an embryo within a gestational sac or cardiac activity in a visible embryo in the 5-10 weeks of gestation. The association between the risk of early fetal demise with the women's mean platelet volume (MPV) and platelet counts was calculated by logistic regression. Duplicate measurements of platelet aggregation were performed with VerifyNow. In total, 99 women identified with early fetal demise and 170 women who had an uncomplicated pregnancy with normal delivery from January 2017 and August 2020 were included in the study. We found that platelet counts in the early fetal demise group were significantly higher than healthy pregnancies. In addition, platelet reactivity is higher in the normal delivery group than those in early fetal demise group ( < .05). High levels of platelet counts resulted in an adjusted odds ratio (OR) of 2.075 (95% confidence interval [95% CI], 1.215-3.544; = .008) for early fetal demise. Increased platelet counts in the first trimester may be a predictor for the risk of early fetal demise.
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http://dx.doi.org/10.1080/07853890.2021.1968027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405072PMC
December 2021

Impact of initial chemotherapy regimen on outcomes for patients with double-expressor lymphoma: A multi-center analysis.

Hematol Oncol 2021 Oct 4;39(4):473-482. Epub 2021 Aug 4.

Department of Pathology, University of Wisconsin Carbone Cancer Center Madison, Wisconsin, USA.

Diffuse large B-cell lymphoma featuring overexpression of MYC and B-Cell Lymphoma 2 (double expressor lymphoma, DEL) is associated with poor outcomes. Existing evidence suggesting improved outcomes for DEL with the use of more intensive regimens than R-CHOP is restricted to younger patients and based on limited evidence from low patient numbers. We retrospectively evaluated the impact of intensive frontline regimens versus R-CHOP in a multicenter analysis across 7 academic medical centers in the United States. We collected 90 cases of DEL, 46 out of 90 patients (51%) received R-CHOP and 44/90 (49%) received an intensive regimen, which was predominantly DA-EPOCH-R. Treatment cohorts were evenly balanced for demographics and disease characteristics, though the intensive group had a higher lactate dehydrogenase (LDH, 326 vs. 230 U/L p = 0.06) and presence of B-symptoms (50% vs. 22%, p = 0.01) compared to the R-CHOP cohort. There was no difference in PFS (median 53 vs. 38 months, p = 0.49) or overall survival (67 vs. not reached months, p = 0.14) between the R-CHOP and intensive therapy cohorts, respectively. On multivariate analysis, intensive therapy was associated with a hazard ratio of 2.35 (95% CI 0.74-7.41), though this was not statistically significant. Additionally, a subgroup analysis of intermediate high-risk lymphoma defined by IPI ≥3 did not identify a difference in survival outcomes between regimens. We conclude that in our multi-center cohort there is no evidence supporting the use of intensive regimens over R-CHOP, suggesting that R-CHOP remains the standard of care for treating DEL.
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http://dx.doi.org/10.1002/hon.2902DOI Listing
October 2021

Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae based on mass spectrometry.

J Clin Lab Anal 2021 Sep 31;35(9):e23915. Epub 2021 Jul 31.

College of Medical Technology, Xuzhou Medical University, Xuzhou, China.

Background: Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive.

Methods: Mouse models of BSI were first established. MALDI-TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry.

Results: 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A-2 protein (SAA2) as the source of the 5 serum peptides.

Conclusions: We successfully established a serum peptide-based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI-TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug-resistant bacteria where identification is urgent.
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http://dx.doi.org/10.1002/jcla.23915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418493PMC
September 2021

Electrochemical reduction of CO and N to synthesize urea on metal-nitrogen-doped carbon catalysts: a theoretical study.

Dalton Trans 2021 Aug 30;50(32):11158-11166. Epub 2021 Jul 30.

Key Laboratory of Magnetic Molecules & Magnetic Information Materials, Ministry of Education, The School of Chemistry and Material Science, Shanxi Normal University, Linfen 041004, China.

Fossil fuels have been increasingly consumed since the industrial revolution, causing rapid increases in carbon dioxide emissions and disrupting the global carbon cycle. With increasing attention being paid to the harmful effects of carbon dioxide as a "greenhouse gas", its use as a feedstock for basic chemical production is an attractive topic. Nature benefits humans through "crops brought by thunderstorms". Combining these two methods to produce urea containing nitrogen is the focus of this paper. In this paper, a series of catalysts supported on the substituted corrole substrates in the form of a double transition metal are investigated by DFT calculations. The best catalyst was selected and combined with carbon and nitrogen reduction to further explore the catalytic performance of urea synthesis. Based on this study, it was found that the synergistic catalytic strategy of double active sites had broad prospects in urea synthesis, and could also provide new development strategies for the design of other efficient molecular catalysts.
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http://dx.doi.org/10.1039/d1dt01390dDOI Listing
August 2021

"Cytokine-microfactories" recruit DCs and deliver tumor antigens via gap junctions for immunotherapy.

J Control Release 2021 09 27;337:417-430. Epub 2021 Jul 27.

School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou 510006, PR China. Electronic address:

The majority (~80%) of patients with cancer do not derive clinical benefit from current immunotherapy, largely due to attenuation of immune responses imposed by robust immunosuppression at tumor sites. Here, a cell-based tumor antigen delivery strategy was developed to boost tumor-specific immunity. Notably, the platform constructing ferric oxide nanoparticle-trained macrophages loading tumor antigens (M-N) acquired an immunostimulatory program and functioned as the tumoritropic "cytokine-microfactories" to sustainably produce high levels of multiple therapeutic cytokines (GM-CSF, TNFα, and MIP-1α), which are important in activation of immune cells with antitumor potential. Indeed, M-N markedly enhanced recruitment of the professional antigen-presenting cells, dendritic cells (DCs), to the tumor sites of an established B16F10 mouse melanoma model. Subsequently, M-N effectively delivered tumor antigens to DCs by gap junction-mediated cell-to-cell transmission. And this trafficking was critical for DC maturation to augment antitumor T-cell responses. Simultaneously, the "cytokine-microfactories" elicited high production of the tumoricidal effectors, and in turn blunted the pro-angiogenic activity of tumor-associated macrophages, resulting in conversion of the tumor-supporting milieu to a tumoricidal function that favored infiltration of antitumor T-cells. The findings provided a novel "cytokine-microfactories" harnessing effective delivery of tumor antigens and production of therapeutic cytokines to robustly promote antigen presentation and reshape the tumor immune milieu for priming antitumor immunity. This can enhance existing T-cell mediated immunotherapeutic potency and extend the curative potential immunotherapy to a broader range of patients.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.040DOI Listing
September 2021

Combinatorial constraint coding based on the EORS algorithm in DNA storage.

Authors:
Li Xiaoru Guo Ling

PLoS One 2021 29;16(7):e0255376. Epub 2021 Jul 29.

Baidu Co., Ltd., Shanghai, China.

The development of information technology has produced massive amounts of data, which has brought severe challenges to information storage. Traditional electronic storage media cannot keep up with the ever-increasing demand for data storage, but in its place DNA has emerged as a feasible storage medium with high density, large storage capacity and strong durability. In DNA data storage, many different approaches can be used to encode data into codewords. DNA coding is a key step in DNA storage and can directly affect storage performance and data integrity. However, since errors are prone to occur in DNA synthesis and sequencing, and non-specific hybridization is prone to occur in the solution, how to effectively encode DNA has become an urgent problem to be solved. In this article, we propose a DNA storage coding method based on the equilibrium optimization random search (EORS) algorithm, which meets the Hamming distance, GC content and no-runlength constraints and can reduce the error rate in storage. Simulation experiments have shown that the size of the DNA storage code set constructed by the EORS algorithm that meets the combination constraints has increased by an average of 11% compared with previous work. The increase in the code set means that shorter DNA chains can be used to store more data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255376PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320985PMC
November 2021

Effects of pulsed electromagnetic fields on tumor cell viability: a meta-analysis of in vitro randomized controlled experiments.

Electromagn Biol Med 2021 Oct 26;40(4):467-474. Epub 2021 Jul 26.

Department of Radiation Protection Medicine, Shaanxi Key Laboratory of Free Radical Biology and Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Faculty of Preventive Medicine, Air Force Medical University, Xi'an, Shaanxi Province, China.

Malignant tumor treatment remains a big challenge till now, and expanding literature indicated that pulsed electromagnetic fields (PEMF) is promising in tumor treatment with the advantage of safety and being economical, but it is still controversial on whether PEMF could affect the tumor cell viability. Therefore, we conducted the meta-analysis to evaluate effects of PEMF on tumor cell viability. The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published up to February 2021. Studies on the direct effects of PEMF on tumor cell viability, determined using colorimetric analysis, were included. Two authors extracted the data and completed the quality assessment. A meta-analysis was performed to calculate the absorbance values and 95% confidence intervals (CIs) using random-effects models. Seven studies, including 32 randomized controlled experiments, were analyzed. Compared with the control group, tumor cell viability in the PEMF exposure group was obviously lower (SMD, -0.67; 95% CI: -1.12 to -0.22). The subgroup meta-analysis results showed that PEMF significantly reduced epithelial cancer cell viability (SMD, -0.58; 95% CI: -0.92 to -0.23) but had no influence on stromal tumor cell viability (SMD, -0.93; 95% CI: -0.21 to 0.15). Our study demonstrated that PEMF could inhibit tumor cell proliferation to some extent, but the risk of bias and high heterogeneity (I > 75%) weakened the strength of the conclusions drawn from the analysis.
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http://dx.doi.org/10.1080/15368378.2021.1958341DOI Listing
October 2021

Effects of 5.8 GHz microwave on hippocampal synaptic plasticity of rats.

Int J Environ Health Res 2021 Jul 22:1-13. Epub 2021 Jul 22.

Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, Shaanxi, China.

5.8 GHz spectrum is gaining more attention in wireless technology. To explore the potential hazards, we investigated the effect of exposure to 5.8 GHz microwave on learning and memory ability of rats. Morris Water maze (MWM), Novel object recognition (NOR) and Fear conditioning test (FCT) were used to evaluate the ability of spatial and non-spatial memory of rats. The hippocampal morphology, the level of brain injury factors in serum and the mitochondrial membrane potential of hippocampal neurons was examined to evaluate the damage of hippocampal neurons. The density of dendritic spines, the ultrastructure of synapses and the level of PSD95, Synaptophysin, p-CREB and CREB were detected to evaluate the hippocampal synaptic plasticity. Compared with Sham group, there was no significant difference in the performance of ethology (in MWM, NOR, FCT) in Microwave 2 h group or Microwave 4 h group. The hippocampal morphology, the serum level of brain injury factors and the content of mitochondrial JC-1 monomer in Microwave 2 h group or Microwave 4 h group did not change obviously, compared with Sham group. The density of dendritic spines, the ultrastructure of synapse and the level of PSD95, Synaptophysin, p-CREB and CREB in hippocampus in Microwave 2 h group or Microwave 4 h group did not significantly change, compared with Sham group. Under this experimental condition, exposure to 5.8 GHz microwave could not affect the hippocampal synaptic plasticity of rats.
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http://dx.doi.org/10.1080/09603123.2021.1952165DOI Listing
July 2021

Genetic characteristics of OXA-48-producing Enterobacterales from China.

J Glob Antimicrob Resist 2021 09 18;26:285-291. Epub 2021 Jul 18.

Department of Laboratory Medicine, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. Electronic address:

Objectives: In China, OXA-48-producing Enterobacterales have been identified sporadically, causing small-scale regional outbreaks. This study investigated the molecular epidemiology, transmission and evolution of OXA-48-producing Enterobacterales and pOXA48 from mainland China.

Methods: We conducted a multicentre resistance monitoring project from 2013-2018. Genome sequencing of OXA-48-produicng isolates was performed. SNPs were analysed. Eleven isolates were selected for subsequent SMRT sequencing. Genome sequences were annotated, and alignment of the complete sequences of bla-carrying plasmids from a subset of isolates that underwent long-read sequencing was performed.

Results: In total, 41 OXA-48-producing Enterobacterales were included in this study (34 Klebsiella pneumoniae, 3 Escherichia coli, 3 Enterobacter cloacae complex and 1 Klebsiella oxytoca). OXA-48-produicng K. pneumoniae (OXAKp) ST383, ST147 and ST11 caused outbreaks of different scales in our hospital. OXA-48-producing E. coli ST156 and ST648, E. cloacae complex ST414 and ST418, and K. oxytoca ST34 were also identified. bla was embedded in a Tn1999.2 structure located in IncL plasmids with different sizes (63.58-109.14 kb). Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 was identified in our hospital and it is possible that KPC-2-producing K. pneumoniae ST11 obtained the bla-carrying plasmid during its spread. A novel 109-kb bla-carrying IncL plasmid was identified from OXAKp ST11. Possibly, two plasmids in OXAKp ST383 were integrated to form this larger plasmid.

Conclusion: OXA-48-produicng Enterobacterales were sporadic in China. Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has emerged causing an outbreak in China. This high-risk multidrug-resistant clone exhibited high compatibility and strong integration ability with foreign resistance plasmids.
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http://dx.doi.org/10.1016/j.jgar.2021.07.006DOI Listing
September 2021

PINCH-1 promotes Δ-pyrroline-5-carboxylate synthase expression and contributes to proline metabolic reprogramming in lung adenocarcinoma.

Amino Acids 2021 Jul 20. Epub 2021 Jul 20.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

Proline metabolic reprogramming is intimately involved in cancer progression. We recently identified a critical role of PINCH-1, a cell-extracellular matrix (ECM) adhesion protein whose expression is elevated in lung adenocarcinoma, in the promotion of proline biosynthesis, fibrosis and lung adenocarcinoma growth. How PINCH-1 promotes proline biosynthesis, however, was incompletely understood. In this study, we show that PINCH-1 promotes the expression of Δ-pyrroline-5-carboxylate synthase (P5CS), a key enzyme that links glutamate metabolism to proline biosynthesis. Depletion of PINCH-1 from lung adenocarcinoma cells reduced the protein but not mRNA level of P5CS, resulting in down-regulation of the cellular level of P5C and cell proliferation. Treatment of the cells with protease inhibitor leupeptin effectively reversed PINCH-1 deficiency-induced reduction of the P5CS level. At the molecular level, PINCH-1, through its LIM2 domain, physically associated with P5CS in lung adenocarcinoma cells. Re-expression of wild type PINCH-1, but not that of the PINCH-1 LIM2 deletion mutant, in PINCH-1 deficient lung adenocarcinoma cells restored P5CS expression, proline biosynthesis and cell proliferation. Finally, P5CS expression, like that of PINCH-1, is elevated in human and mouse lung adenocarcinoma. Using a mouse model of lung adenocarcinoma in which PINCH-1 is conditionally ablated, we show that knockout of PINCH-1 from lung adenocarcinoma effectively reduced the P5CS level in vivo. Our results reveal an important role of PINCH-1 in the promotion of P5CS expression, which likely contributes to proline metabolic reprogramming and consequently lung adenocarcinoma progression.
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http://dx.doi.org/10.1007/s00726-021-03050-3DOI Listing
July 2021

Metagenomic Sequencing Analysis of the Effects of Colistin Sulfate on the Pig Gut Microbiome.

Front Vet Sci 2021 2;8:663820. Epub 2021 Jul 2.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China.

The gut microbiome plays important roles in maintaining host health, and inappropriate use of antibiotics can cause imbalance, which may contribute to serious disease. However, despite its promise, using metagenomic sequencing to explore the effects of colistin on gut microbiome composition in pig has not been reported. Herein, we evaluated the roles of colistin in gut microbiome modulation in pigs. Metagenomic analysis demonstrated that overall microbial diversity was higher in the colistin group compared with the control group. Antibiotic Resistance Genes Database analysis demonstrated that following colistin treatment, expression levels of , and were significantly upregulated, indicating that colistin may induce transformation of antibiotic resistance genes. Colistin also affected the microbiome distribution patterns at both genus and phylum levels. In addition, at the species level, colistin significantly reduced the abundance of , and and enhanced the abundance of and compared to the control group. Gene Ontology analysis demonstrated that following treatment with colistin, metabolic process, cellular process, and single-organism process were the dominant affected terms. Kyoto Encyclopedia of Genes and Genomes analysis showed that oxidative phosphorylation, protein processing in endoplasmic reticulum, various types of N-glycan biosynthesis, protein processing in endoplasmic reticulum, pathogenic infection, and mitogen-activated protein kinase signaling pathway-yeast were the dominant signaling pathways in the colistin group. Overall, our results suggested that colistin affects microbial diversity and may modulate gut microbiome composition in pig, potentially providing novel strategy or antibiotic rationalization pertinent to human and animal health.
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http://dx.doi.org/10.3389/fvets.2021.663820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282896PMC
July 2021

Coordinated increase of reliable cortical and striatal ensemble activations during recovery after stroke.

Cell Rep 2021 Jul;36(2):109370

Neurology and Rehabilitation Service, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA; Department of Neurology & Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Bioengineering Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

Skilled movements rely on a coordinated cortical and subcortical network, but how this network supports motor recovery after stroke is unknown. Previous studies focused on the perilesional cortex (PLC), but precisely how connected subcortical areas reorganize and coordinate with PLC is unclear. The dorsolateral striatum (DLS) is of interest because it receives monosynaptic inputs from motor cortex and is important for learning and generation of fast reliable actions. Using a rat focal stroke model, we perform chronic electrophysiological recordings in motor PLC and DLS during long-term recovery of a dexterous skill. We find that recovery is associated with the simultaneous emergence of reliable movement-related single-trial ensemble spiking in both structures along with increased cross-area alignment of spiking. Our study highlights the importance of consistent neural activity patterns across brain structures during recovery and suggests that modulation of cross-area coordination can be a therapeutic target for enhancing motor function post-stroke.
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http://dx.doi.org/10.1016/j.celrep.2021.109370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357409PMC
July 2021

Congenital dyserythropoiesis and polymyopathy without cardiac disease in male Labrador retriever littermates.

J Vet Intern Med 2021 Sep 5;35(5):2409-2414. Epub 2021 Jul 5.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Two Labrador retriever littermates were identified based on incidentally noted marked microcytosis and inappropriate metarubricytosis. Muscle atrophy was noted and associated with distinctive pathological findings in biopsy samples from 1 dog studied. The disorder represents a rare clinical entity of suspected congenital dyserythropoiesis and polymyopathy. Clinicopathologic changes were similar to a previously reported syndrome of congenital dyserythropoiesis, congenital polymyopathy, and cardiac disease in 3 related English Springer Spaniel (ESS) dogs, but the dogs reported here did not have apparent cardiac disease.

Interventions: Bone marrow aspiration, electromyography, muscle biopsies, and an echocardiogram were performed on dog 1. Results supported dyserythropoiesis and congenital polymyopathy similar to reports in ESS dogs, but did not identify obvious cardiac disease.

Conclusion: The clinicopathologic changes of dyserythropoiesis and polymyopathy provide an easily recognizable phenotype for what appears to be a low morbidity syndrome. Early recognition may decrease unnecessary testing or euthanasia.
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http://dx.doi.org/10.1111/jvim.16214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478025PMC
September 2021

How signaling pathways link extracellular mechano-environment to proline biosynthesis: A hypothesis: PINCH-1 and kindlin-2 sense mechanical signals from extracellular matrix and link them to proline biosynthesis.

Bioessays 2021 09 3;43(9):e2100116. Epub 2021 Jul 3.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

We propose a signaling pathway in which cell-extracellular matrix (ECM) adhesion components PINCH-1 and kindlin-2 sense mechanical signals from ECM and link them to proline biosynthesis, a vital metabolic pathway for macromolecule synthesis, redox balance, and ECM remodeling. ECM stiffening promotes PINCH-1 expression via integrin signaling, which suppresses dynamin-related protein 1 (DRP1) expression and mitochondrial fission, resulting in increased kindlin-2 translocation into mitochondria and interaction with Δ -pyrroline-5-carboxylate (P5C) reductase 1 (PYCR1). Kindlin-2 interaction with PYCR1 protects the latter from proteolytic degradation, leading to elevated PYCR1 level. Additionally, PINCH-1 promotes P5C synthase (P5CS) expression and P5C synthesis, which, together with increased PYCR1 level, support augmented proline biosynthesis. This signaling pathway is frequently activated in fibrosis and cancer, resulting in increased proline biosynthesis and excessive collagen matrix production, which in turn further promotes ECM stiffening. Targeting this signaling pathway, therefore, may provide an effective strategy for alleviating fibrosis and cancer progression.
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http://dx.doi.org/10.1002/bies.202100116DOI Listing
September 2021

Hepatocyte-derived L-carnitine restricts hepatitis B surface antigen loss through an immunosuppressive effect on germinal center-related immune cells.

J Infect Dis 2021 Jul 2. Epub 2021 Jul 2.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: The outcome of hepatitis B virus (HBV) infection is significantly affected by host immune response; herein, we aim to dissect the effect of L-carnitine (L-Cn) on germinal center (GC)-related immune cells and the influence on the prognosis of HBV infection.

Methods: In vitro and in vivo experiments were performed in patients with chronic HBV infection and a hydrodynamic injection mouse model.

Results: In vitro assays revealed that L-Cn significantly reduced GC-related immune responses and enhanced immunosuppressive profiles. Intriguingly, L-Cn released from lysed hepatocytes was associated with the degree of liver damage. Besides, the administration of L-Cn in an HBV mouse model resulted in delayed clearance of HBsAg in serum and decreased GC formation in the spleen. Notably, patients with HBsAg loss showed decreased plasma L-Cn levels, and longitudinal observations found that low baseline levels of L-Cn were associated with a favorable treatment response in chronic hepatitis B patients.

Conclusions: The suppressive effect of hepatocyte-derived L-Cn on GC-related immune cells may contribute to the inability of HBsAg clearance in chronic HBV infection, indicating that L-Cn might serve as a potential therapeutic target for the treatment of HBV infection.
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http://dx.doi.org/10.1093/infdis/jiab344DOI Listing
July 2021

Prognostic significance of a combined and controlled nutritional status score and EBV-DNA in patients with advanced nasopharyngeal carcinoma: a long-term follow-up study.

Cancer Biol Med 2021 Jun 16. Epub 2021 Jun 16.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Objective: Several studies have reported that the controlling nutritional status (CONUT) score is a prognostic predictor for survival among patients with different types of cancer. We assessed the prognostic value of changes in the CONUT score during treatment and the ΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma (NPC).

Methods: We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011; the patients underwent radical concurrent chemoradiotherapy (CCRT) at Sun Yat-sen University Cancer Center and were grouped based on their ΔCONUT and ΔCONUT-EBV DNA scores. Kaplan-Meier curves were used to compare the patient outcomes according to the cut-off ΔCONUT score and the ΔCONUT-EBV DNA scoring system.

Results: Among all patients, overall survival (OS) was independently predicted by a high ΔCONUT score ( = 0.031) and high EBV DNA ( < 0.001). The ΔCONUT-EBV DNA score [OS area under the curve (AUC) = 0.621; progression free survival (PFS)-AUC = 0.612; distant metastasis-free survival (DMFS)-AUC = 0.622] was more predictive of OS, PFS, and DMFS in patients with advanced NPC than the ΔCONUT score (OS-AUC = 0.547; PFS-AUC = 0.533; DMFS-AUC = 0.522) and pretreatment plasma EBV DNA levels alone (OS-AUC = 0.600; PFS-AUC = 0.591, DMFS-AUC = 0.610). The ΔCONUT-EBV DNA score was significantly correlated with OS, PFS, and DMFS in patients with advanced NPC treated with CCRT.

Conclusions: The ΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0627DOI Listing
June 2021

Biodegradation of the pyridinecarboxamide insecticide flonicamid by Microvirga flocculans and characterization of two novel amidases involved.

Ecotoxicol Environ Saf 2021 Sep 3;220:112384. Epub 2021 Jun 3.

Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Science, Nanjing Normal University, Nanjing 210023, People's Republic of China. Electronic address:

Flonicamid (N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a new type of pyridinecarboxamide insecticide that exhibits particularly good efficacy in pest control. However, the extensive use of FLO in agricultural production poses environmental risks. Hence, its environmental behavior and degradation mechanism have received increasing attention. Microvirga flocculans CGMCC 1.16731 rapidly degrades FLO to produce the intermediate N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) and the end acid metabolite 4-(trifluoromethyl) nicotinol glycine (TFNG). This bioconversion is mediated by the nitrile hydratase/amidase system; however, the amidase that is responsible for the conversion of TFNG-AM to TFNG has not yet been reported. Here, gene cloning, overexpression in Escherichia coli and characterization of pure enzymes showed that two amidases-AmiA and AmiB-hydrolyzed TFNG-AM to TFNG. AmiA and AmiB showed only 20-30% identity to experimentally characterized amidase signature family members, and represent novel amidases. Compared with AmiA, AmiB was more sensitive to silver and copper ions but more resistant to organic solvents. Both enzymes demonstrated good pH tolerance and exhibited broad amide substrate specificity. Homology modeling suggested that residues Asp191 and Ser195 may strongly affect the catalytic activity of AmiA and AmiB, respectively. The present study furthers our understanding of the enzymatic mechanisms of biodegradation of nitrile-containing insecticides and may aid in the development of a bioremediation agent for FLO.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112384DOI Listing
September 2021
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