Publications by authors named "Qian Zhang"

4,974 Publications

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MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling.

Korean J Physiol Pharmacol 2022 Jul;26(4):239-253

Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213003, China.

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.
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http://dx.doi.org/10.4196/kjpp.2022.26.4.239DOI Listing
July 2022

Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives.

RSC Adv 2022 Jun 14;12(27):17629-17636. Epub 2022 Jun 14.

Department of Applied Chemistry, College of Science, China Agricultural University Beijing 100193 People's Republic of China

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through -benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by H, C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC < 0.5 μM.
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http://dx.doi.org/10.1039/d2ra02898kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194939PMC
June 2022

Endoplasmic reticulum stress modulates the fate of lung resident mesenchymal stem cell to myofibroblast via C/EBP homologous protein during pulmonary fibrosis.

Stem Cell Res Ther 2022 Jun 28;13(1):279. Epub 2022 Jun 28.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuai Fu Yuan Street, Dong Cheng District, Beijing, 100730, People's Republic of China.

Background: As a fatal interstitial lung disease, idiopathic pulmonary fibrosis (IPF) was characterized by the insidious proliferation of extracellular matrix (ECM)-producing mesenchymal cells. Recent studies have demonstrated that lung resident mesenchymal/stromal cells (LR-MSC) are the source of myofibroblasts. Endoplasmic reticulum (ER) stress is prominent in IPF lung. This study sought to investigate the effects of ER stress on the behavior of LR-MSC during pulmonary fibrosis.

Methods: ER stress and myofibroblast differentiation of LR-MSC in patients with IPF were evaluated. Primary mouse LR-MSC was harvested and used in vitro for testing the effects of ER stress and C/EBP homologous protein (CHOP) on LR-MSC. Adoptive transplantation of LR-MSC to bleomycin-induced pulmonary fibrosis was done to test the in vivo behavior of LR-MSC and its influence on pulmonary fibrosis.

Results: We found that myofibroblast differentiation of LR-MSC is associated with ER stress in IPF and bleomycin-induced mouse fibrotic lung. Tunicamycin-induced ER stress impairs the paracrine, migration, and reparative function of mouse LR-MSC to injured type 2 alveolar epithelial cells MLE-12. Overexpression of the ER stress responder C/EBP homologous protein (CHOP) facilitates the TGFβ1-induced myofibroblast transformation of LR-MSC via boosting the TGFβ/SMAD signaling pathway. CHOP knockdown facilitates engraftment and inhibits the myofibroblast transformation of LR-MSC during bleomycin-induced pulmonary fibrosis, thus promoting the efficacy of adopted LR-MSC in alleviating pulmonary fibrosis.

Conclusion: Our work revealed a novel role that ER stress involved in pulmonary fibrosis by influencing the fate of LR-MSC and transformed to "crime factor" myofibroblast, during which CHOP acts as the key modulator. These results indicate that pharmacies targeting CHOP or therapies based on CHOP knockdown LR-MSC may be promising ways to treat pulmonary fibrosis.
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http://dx.doi.org/10.1186/s13287-022-02966-1DOI Listing
June 2022

[Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats].

Zhen Ci Yan Jiu 2022 Jun;47(6):525-30

Affiliated Hospital of Guizhou Medical University, Guiyang 550004.

Objective: To observe the effect of moxibustion combined with acupoint catgut embedding on the content of interleukin 6 (IL-6), and the expressions of janus activated kinase (JAK), signal transducer and activator of transcription 3 (STAT3) in colonic mucosa of rats with ulcerative colitis (UC), so as to explore its mechanism underlying improvement of UC.

Methods: Thirty SD rats were randomly divided into normal, model, acupoint catgut embedding (ACE), moxibustion and acupoint catgut embedding combined with moxibustion (combination) groups (=6 rats in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral "Tianshu" (ST25), "Dachangshu" (BL25) and "Shangjuxu" (ST37) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed by H.E. staining, the level of IL-6 in colonic mucosa was assayed by ELISA, and the expressions of JAK and STAT3 in colonic mucosa were detected by immunohistochemistry and Western blot.

Results: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and combination groups. After modeling, the content of colonic IL-6, and the expression levels of JAK and STAT3 were obviously increased (<0.01) in the model group relevant to the normal group. Following the intervention, the increase of IL-6 contents, and JAK and STAT3 expressions were reversed (<0.05, <0.01) in moxibustion, ACE and combination groups. The therapeutic effects of moxibustion combined with ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of JAK and STAT3 expression (<0.01).

Conclusion: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effect in suppressing the activation of IL-6/JAK/STAT3 signaling pathway.
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http://dx.doi.org/10.13702/j.1000-0607.20211375DOI Listing
June 2022

Factors influencing parents' willingness to vaccinate their preschool children against COVID-19: Results from the mixed-method study in China.

Hum Vaccin Immunother 2022 Jun 28:2090776. Epub 2022 Jun 28.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

During the COVID-19 pandemic, little is known about parental hesitancy to receive the COVID-19 vaccine for preschool children who are the potential vaccinated population in the future. The purpose of this mixed-method study was to explore the factors influencing Chinese parents' decision to vaccinate their children aged 3-6 years old against COVID-19. In July 2021, we conducted semi-structured interviews (n = 19) and a cross-sectional survey (n = 2605) with parents of kindergarten children in an urban-rural combination pilot area in China. According to the qualitative study, most parents were hesitant to vaccinate their children with the COVID-19 vaccine. In the quantitative study, we found that three-fifths of 2605 participants were unwilling to vaccinate their children against COVID-19. Furthermore, the main predictors of parents' intention to vaccinate their children were fathers, lower level of education, and positive attitudes toward vaccination. Based on our findings, targeted health education techniques may be able to boost childhood COVID-19 immunization rates.
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http://dx.doi.org/10.1080/21645515.2022.2090776DOI Listing
June 2022

Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.

Folia Histochem Cytobiol 2022 Jun 28. Epub 2022 Jun 28.

Affifiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, NO 648 DongFeng East Road, 071000 Baoding, China.

Introduction: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC.

Material And Methods: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a-5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh7 HCC cells' proliferation, invasion and migration were determined.

Results: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh7 HCC cells.

Conclusions: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.
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http://dx.doi.org/10.5603/FHC.a2022.0019DOI Listing
June 2022

Stress hyperglycemia is predictive of clinical outcomes in patients with spontaneous intracerebral hemorrhage.

BMC Neurol 2022 Jun 27;22(1):236. Epub 2022 Jun 27.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.

Background: Stress hyperglycemia is a common condition in patients suffering from critical illness such as spontaneous intracerebral hemorrhage (ICH). Our study aimed to use glucose-to-glycated hemoglobin (HbA1c) ratio to investigate the impact of stress hyperglycemia on clinical outcomes in patients with ICH.

Methods: A sample of eligible 586 patients with spontaneous intracerebral hemorrhage from a multicenter, hospital-based cohort between 2014 and 2016 were recruited in our study. Stress hyperglycemia was evaluated by the index of the glucose-to-HbA1c ratio that was calculated by fasting blood glucose (mmol/L) divided by HbA1c (%). Patients were divided into two groups based on the median of the glucose-to-HbA1c ratio. The main outcomes were poor functional outcomes (modified Rankin Scale score of 3-6) at discharge and 90 days. Multivariable logistic regression and stratified analyses were performed to explore the association of stress hyperglycemia with poor prognosis of ICH.

Results: On multivariable analysis, higher glucose-to-HbA1c ratio (≥1.02) was independently correlated with poor functional outcomes at discharge (adjusted OR = 3.52, 95%CI: 1.98-6.23) and 90 days (adjusted OR = 2.27, 95%CI: 1.38-3.73) after adjusting for potential confounding factors. The correlation between glucose-to-HbA1c ratio and worse functional outcomes still retained in patients with or without diabetes mellitus.

Conclusions: Stress hyperglycemia, calculated by glucose-to-HbA1c ratio, was independently correlated with worse functional outcomes at discharge and 90 days in patients with ICH. Moreover, glucose-to-HbA1c ratio, might not only be used as a simple and readily available index to predict clinical outcomes of ICH but also provide meaningful insight into future analysis to investigate the optimal range of glucose levels among ICH patients and develop tailored glucose-lowering strategies.
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http://dx.doi.org/10.1186/s12883-022-02760-9DOI Listing
June 2022

A case of 5-Aminolevulinic acid photodynamic therapy(ALA-PDT)combined with surgery for the treatment of acne conglobata.

Photodiagnosis Photodyn Ther 2022 Jun 24:102986. Epub 2022 Jun 24.

Department of Dermatologic Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China.

We report the case of a 20-year-old man with acne conglobata (AC) who was treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) sequentially to deroofing, and finally used fractional carbon dioxide laser for aesthetic requirements, achieving satisfying results. AC is a severe form of acne vulgaris that can lead to significant scarring and has serious negative effects on a patient's psychological well-being and quality of life. Some cases are likely resistant to currently available treatments. This report describes a promising, and effective method for the treatment of AC.
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http://dx.doi.org/10.1016/j.pdpdt.2022.102986DOI Listing
June 2022

TRPM7 promotes lipopolysaccharide-induced inflammatory dysfunction in renal tubular epithelial cells.

Immun Inflamm Dis 2022 Jul;10(7):e641

Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China.

Background: Sepsis-associated acute kidney injury (S-AKI) has been reported to affect 30%-50% of all sepsis patients; this condition is associated with a notable fatality rate. Following lipopolysaccharide (LPS) stimulation, the expression of transient receptor potential cation channel subfamily M member 7 (TRPM7), a nonselective cation channel expressed by the renal tubular epithelial cells (RTECs) was found to be upregulated. We aimed to determine how TRPM7 functions in S-AKI.

Methods: To establish an in vitro model of S-AKI, RTECs were treated with LPS. The effect of TRPM7 knockdown on cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress was studied. The binding site between Kruppel-like factor 2 (KLF2) and TRPM7 was predicted using JASPAR. The influence of KLF2 on the regulatory roles of TRPM7 in cells, as well as the effect of their knockdown on the MAPK signaling pathway, was investigated.

Results: TRPM7 was upregulated in LPS-treated cells, and knocking improved cell viability, reduced LDH levels, and minimized apoptosis, inflammation, and oxidative stress. KLF2 was shown to be associated with TRPM7 and its level decreased in LPS-treated cells. KLF2 knockdown increased TRPM7 expression and reversed the effects of TRPM7 knockdown in LPS-treated cells, including suppression of p38 MAPK, ERK1/2, and JNK activation.

Conclusion: Taken together, our results show that TRPM7 is negatively regulated by KLF2 and promotes LPS-induced inflammatory dysfunction by activating the MAPK pathway in RTECs. The theoretical foundation for the prevention and management of S-AKI is laid out in this article.
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http://dx.doi.org/10.1002/iid3.641DOI Listing
July 2022

MicroRNA-877-5p Inhibits Cell Progression by Targeting FOXM1 in Lung Cancer.

Can Respir J 2022 15;2022:4256172. Epub 2022 Jun 15.

Department of Respiratory and Critical Care Medicine, The Jiangyin Clinical College of Xuzhou Medical University, Jiangyin 214400, Jiangsu, China.

Background: Many researches revealed that microRNAs (miRNAs) function as potential oncogene or tumor suppressor gene. As an antioncogene, miR-877-5p was reduced in many tumors.

Objective: This research aimed to explore the biological role and mechanisms of miR-877-5p, which may help patients with non-small-cell lung cancer (NSCLC) find effective therapeutic targets.

Methods: The downstream targets of miR-877-5p were predicted by Bioinformatics software. RT-qPCR and western blot were employed to analyze the gene levels. The impacts of miR-877-5p and FOXM1 were assessed by cell function experiments.

Results: The miR-877-5p was reduced in NSCLC. In addition to this, it also inhibited cell progression of NSCLC cells . Moreover, the upregulation of FOXM1 expression restored the inhibitory effect of enhancement of miR-877-5p.

Conclusions: Taken together, miR-877-5p inhibited cell progression by directly targeting FOXM1, which may provide potential biomarkers for targeted therapy of NSCLC.
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http://dx.doi.org/10.1155/2022/4256172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217556PMC
June 2022

Chemical regulation of the cGAS-STING pathway.

Curr Opin Chem Biol 2022 Jun 23;69:102170. Epub 2022 Jun 23.

MOE Laboratory of Biosystems Homeostasis and Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Nucleic acids represent a major class of pathogen and damage signatures, recognized by a variety of host sensors to initiate signaling cascades and immune responses, such as mechanisms of RLR-MAVS, cGAS-STING, TLR-TRIF, and AIM2 inflammasome. Yet, an outstanding challenge is understanding how nucleic acid sensing initiates immune responses and its tethering in various infectious, cancerous, autoimmune, and inflammatory diseases. However, the discovery and application of a plethora of small molecule compounds have substantially facilitated this process. This review provides an overview and recent development of the innate DNA-sensing pathway of cGAS-STING and highlights the multiple agonists and inhibitors in fine-tuning the pathway that can be exploited to improve disease treatment, focusing primarily on crucial pathway components and regulators.
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http://dx.doi.org/10.1016/j.cbpa.2022.102170DOI Listing
June 2022

Anti-melanogenesis effect from Wampee fruit pectin via α-MSH/TRY pathway in A375 cells.

BMC Complement Med Ther 2022 Jun 25;22(1):174. Epub 2022 Jun 25.

Marine Biomedical Research Institution, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.

Background: Polysaccharides from wampee have been reported to process various biological activities, while the relationship between structure and bioactivities has been barely addressed. Pectin, an abundant water-soluble polysaccharide in wampee, showed significant antioxidant activity, which was associated with the anti-melanogenic activity. Therefore, this study investigated the physicochemical characteristics and the anti-melanogenesis effect of pectin extracted from wampee fruit in A375 cells.

Methods: The physicochemical characterization of pectin from wampee fruit was investigated by gel chromatography (GCP), FT-IR spectroscopy, and NMR spectroscopy methods. The anti-melanogenesis effects and mechanism were evaluated by mushroom tyrosine enzyme and human melanin cell model in vitro.

Results: The results showed that a molecular weight of 5.271 × 10 Da wampee fruit pectin (WFP) were mainly composed of mannose (Man), ribose (Rib), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galacturonic acid (Gal A), galactose (Gal), and arabinose (Ara), which linked with →4)-β-D-Galp-(1 → units. The current study revealed that WFP could significantly suppress mushroom TRY activity in vitro. Furtherly, WFP significantly reduced intracellular and extracellular melanin formation in A375 melanoma cells depending on the presence of alpha-melanocyte stimulating hormone (α-MSH). TRY activity was only inhibited in α-MSH treated A375 cells. Western blot analysis demonstrated that WFP reverse α-MSH induced melanogenesis in A375 melanoma cells, including in down-regulated TRY, TYRP-1, TYRP-2, MITF and CREB expressions.

Conclusion: These results indicated that WFP could inhibit α-MSH induced melanogenesis in A375 melanoma cells via α-MSH/TRY pathway. In conclusion, these data provided a new perspective to annotate WFP anti-melanogenesis activity mechanism.
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http://dx.doi.org/10.1186/s12906-022-03646-6DOI Listing
June 2022

Bioaugmentation with Acinetobacter sp. TAC-1 to enhance nitrogen removal in swine wastewater by moving bed biofilm reactor inoculated with bacteria.

Bioresour Technol 2022 Jun 22;359:127506. Epub 2022 Jun 22.

School of Chemistry and Chemical Engineering, Chongqing University of Technology, Chongqing 40054, China. Electronic address:

To enhance the performance of moving bed biofilm reactor (MBBR) inoculated with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, bioaugmentation with Acinetobacter sp. TAC-1 was firstly employed and then the treatment performance for real swine wastewater was presented in this study. Results indicated that NH-N and TN removal rates of bioaugmented reactor were significantly improved from 16.53 mg/L/h and 16.15 mg/L/h to 24.58 mg/L/h and 24.45 mg/L/h, respectively. The efficient removal performance (NH-N 95.01%, TN 86.40%) for real swine wastewater was achieved within 24 h. Microbial analysis indicated that the composition of functional bacteria varied with the introduction of Acinetobacter sp. TAC-1, especially the abundance of Acinetobacter, Paracoccus and Rhodococcus related to the nitrogen removal. Furthermore, bioaugmentation with Acinetobacter sp. TAC-1 increased abundance of enzymes and functional genes (nirS, nirK and norZ) corresponding to denitrification that may be responsible for the enhanced nitrogen removal performance.
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http://dx.doi.org/10.1016/j.biortech.2022.127506DOI Listing
June 2022

New Sights Into Long Non-Coding RNA LINC01133 in Cancer.

Front Oncol 2022 7;12:908162. Epub 2022 Jun 7.

Key Laboratory of Preservation of Human Genetic Resources and DiseaseControl, Ministry of Education, Harbin Medical University, Harbin, China.

LINC01133 is a long intergenic non-coding RNA that regulates malignancy in several cancers, including those of the digestive, female reproductive, respiratory, and urinary system. LINC01133 is an extensively studied lncRNA that is highly conserved, and its relatively stable expression is essential for its robust biological function. Its expression is highly tissue-specific with a distinct subcellular localization. It functions as an oncogene or a tumor suppressor gene in different cancers multiple mechanisms, such as those that involve competing with endogenous RNA and binding to RNA-binding proteins or DNA. Moreover, the secretion and transportation of LINC01133 by extracellular vesicles in the tumor micro-environment is regulated by other cells in the tumor micro-environment. To date, two mechanisms, an increase in copy number and regulation of transcription elements, have been found to regulate LINC01133 expression. Clinically, LINC01133 is an ideal marker for cancer prognosis and a potential therapeutic target in cancer treatment regimes. In this review, we aimed to summarize the aforementioned information as well as posit future directions for LINC01133 research.
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http://dx.doi.org/10.3389/fonc.2022.908162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209730PMC
June 2022

Antibacterial and Anti-Inflammatory Properties of a Novel Antimicrobial Peptide Derived from LL-37.

Antibiotics (Basel) 2022 Jun 1;11(6). Epub 2022 Jun 1.

School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China.

Peri-implantitis is a pathological condition involving tissues around dental implants that are characterized by inflammation of the peri-implant mucosa and progressive loss of supporting bone. We found that the antimicrobial peptide KR-12-3 (KRIVKWIKKFLR) derived from LL-37 had antibacterial properties against . The purpose of this study was to evaluate its antibacterial and anti-inflammatory activities and its underlying mechanisms. We evaluated the antibacterial activities of antimicrobial peptides in planktonic and biofilm states by measuring their minimum inhibitory concentration, minimum bactericidal concentration, and biofilm susceptibility. The effects of antimicrobial peptides on the production of IL-6 and IL-8 in LPS-stimulated RAW264.7 cells were detected by enzyme-linked immunosorbent assay and other experiments, and their toxicity to MC3T3-E1 cells was also studied. While maintaining low cytotoxicity, KR-12-3 exhibited growth inhibitory effects on in planktonic and biofilm states. Lower concentrations of KR-12-3 treatment reduced the production of inflammatory cytokines in LPS-stimulated RAW264.8 cells. The mechanisms underlying the inhibition of biofilm formation and anti-inflammatory effects have been associated with the low expression of related genes. KR-12-3 may be used to develop an antibacterial, anti-infective, and anti-inflammatory drugs for peri-implantitis.
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http://dx.doi.org/10.3390/antibiotics11060754DOI Listing
June 2022

DNA origami-based single-molecule CRISPR machines for spatially resolved searching.

Angew Chem Int Ed Engl 2022 Jun 23. Epub 2022 Jun 23.

Shanghai Jiao Tong University, School of Chemistry and Chemical Engineering, CHINA.

Repurposing the RNA-guided endonuclease Cas9 to develop artificial CRISPR molecular machines represents a new direction toward synthetic molecular information processing. The operation of CRISPR-Cas9-based machines, nevertheless, relies on the molecular recognition of freely diffused sgRNA/Cas9, making it practically challenging to perform spatially regulated localized searching or navigation. Here, we develop a DNA origami-based single-molecule CRISPR machine that can perform spatially resolved DNA cleavage via either free or localized searching modes. When triggered at a specific site on the DNA origami with nanoscale accuracy, the free searching mode leads to searching activity that gradually decays with the distance, whereas the localized mode generates spatially-confined searching activity. Our work expands the function of CRISPR molecular machines and lays foundations to develop integrated molecular circuits and high-throughput nucleic acid detection.
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http://dx.doi.org/10.1002/anie.202205460DOI Listing
June 2022

A Novel Light Field Image Compression Method Using EPI Restoration Neural Network.

Biomed Res Int 2022 13;2022:8324438. Epub 2022 Jun 13.

School of Mechanical, Electrical & Information Engineering, Putian University, Putian, Fujian 351100, China.

Different from traditional images, light field images record not only spatial information but also angle information. Due to the large volume of light field data brings great difficulties to storage and compression, light field compression technology has attracted much attention. The epipolar plane image (EPI) contains a lot of low rank information, which is suitable for recovering the complete EPI from a part of EPI. In this paper, a light field image coding framework based on EPI restoration neural network has been proposed. Compared with previous algorithms, the proposed algorithm further takes advantage of the inherent similarity in light field images, and the proposed framework has higher performance and robustness. Experimental results show that the proposed method has superior performance compared to the state-of-the-art both in quantitatively and qualitatively.
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http://dx.doi.org/10.1155/2022/8324438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209000PMC
June 2022

HOXA cluster antisense RNA 2 elevates KIAA1522 expression through microRNA-520d-3p and insulin like growth factor 2 mRNA binding protein 3 to promote the growth of vascular smooth muscle cells in thoracic aortic aneurysm.

ESC Heart Fail 2022 Jun 21. Epub 2022 Jun 21.

Department of Cardiovascular Surgery, Shengli Oilfield Central Hospital, Dongying, China.

Aims: Recently, long non-coding RNAs (lncRNAs) have been revealed to mediate smooth muscle dysfunction in thoracic aortic aneurysm (TAA). LncRNA HOXA-AS2 has been proposed to engage in the regulation of diverse diseases. However, its function in TAA remains unknown. This study aimed to reveal the role and mechanism of HOXA-AS2 in VSMCs which were implicated in TAA formation.

Methods And Results: RT-qPCR or western blot was performed to detect RNA or protein expression levels. The role of HOXA-AS2 in VSMCs was explored by functional assays. The relationship among HOXA-AS2/miR-520d-3p/KIAA1522/IGF2BP3 was analysed via mechanism assays. HOXA-AS2 was detected to have significantly high expression in TAA tissues and function as an oncogene to promote proliferation of VSMCs, while inhibiting cell apoptosis (Figure 1, **P < 0.01). HOXA-AS2 was unveiled to bind with miR-520d-3p (Figure 2, *P < 0.05, **P < 0.01) and further up-regulate KIAA1522 to facilitate the growth of VSMCs (Figure 3-4, *P < 0.05, **P < 0.01). HOXA-AS2 was also found to recruit IGF2BP3 to stabilize KIAA1522 mRNA (Figure 5, **P < 0.01). All data were displayed as mean ± standard deviation.

Conclusions: HOXA-AS2 up-regulates KIAA1522 through targeting miR-520d-3p/IGF2BP3 to drive VSMC growth in TAA.
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http://dx.doi.org/10.1002/ehf2.13968DOI Listing
June 2022

Relationship of pathogenic mutations and responses to zoledronic acid in a cohort of osteogenesis imperfecta children.

J Clin Endocrinol Metab 2022 Jun 21. Epub 2022 Jun 21.

Department of Endocrinology, Key Laboratory of Endocrinology of National Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

Context: Osteogenesis imperfecta (OI) is a rare, heterogeneous genetic disorder characterized by bone fragility and recurrent fractures. Bisphosphonates (BPs) are the most commonly used medications for OI, but their efficacy has great variability.

Objective: We investigate the relationship of pathogenic gene mutations and responses to zoledronic acid (ZOL) in a large cohort of OI children.

Methods: Children with OI were included who received ZOL treatment and followed up for at least one year. Bone mineral density (BMD), serum levels of β-isomerized carboxy-telopeptide of type I collagen (β-CTX, bone resorption marker) were measured at baseline and during follow-up. Causative mutations of OI were identified using next-generation sequencing and Sanger sequencing.

Results: 201 OI children were included who initiated ZOL treatment at a median age of 5 years, with mutations identified in 11 genes. After 3 years of treatment, the increase of femoral neck BMD Z-score in OI patients with autosomal dominant inheritance (AD) was greater than that in patients with autosomal recessive or X-linked inheritance (non-AD) (4.5±2.9 vs. 2.0±1.0, P<0.001). Collagen structural defects were negatively correlated with the increase of femoral neck BMD Z-score. Patients with collagen structural defects had higher incidence of new fracture (35.1% vs. 18.4%, Relative risk 0.52, P=0.044) and less decline in β-CTX level than those with collagen quantitative reduction. Increase in lumbar spine BMD as well as change in height Z-score was not associated with the genotype of OI children.

Conclusion: OI patients with non-AD inheritance or with pathogenic mutations leading to collagen structural defects may have relatively poor responses to ZOL treatment, which is possibly associated with their more severe phenotypes. New therapeutic agents are worth developing in these patients.
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http://dx.doi.org/10.1210/clinem/dgac366DOI Listing
June 2022

Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with heart failure.

Health Qual Life Outcomes 2022 Jun 20;20(1):98. Epub 2022 Jun 20.

School of Management, Beijing University of Chinese Medicine, Beijing, 102488, China.

Purpose: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment.

Methods: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values.

Results: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value.

Conclusion: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.
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http://dx.doi.org/10.1186/s12955-022-02004-xDOI Listing
June 2022

SEC61G participates in endoplasmic reticulum stress by interacting with CREB3 to promote the malignant progression of lung adenocarcinoma.

Oncol Lett 2022 Jul 30;24(1):233. Epub 2022 May 30.

Shanghai East Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

As the most common type of lung cancer, lung adenocarcinoma (LUAD) poses a great threat to human health worldwide and severely compromises the quality of life of the patients. The present study aimed to explore the potential pathogenesis of LUAD. Reverse transcription-quantitative PCR and western blotting were applied to measure the expression levels of SEC61 translocon subunit γ (SEC61G) and cyclic AMP-responsive element-binding protein 3 (CREB3). Western blotting was also used to determine the expression of endoplasmic reticulum (ER) stress-, apoptosis- and migration-related proteins. Cell Counting Kit-8, colony formation, TUNEL, wound healing and Transwell assays were used, respectively, to determine the viability, proliferation, apoptosis, migration and invasion of LUAD A549 cells. The association between SEC61G and CREB3 was verified by co-immunoprecipitation assay. The results revealed that SEC61G was upregulated in A549 cells and its downregulation could activate ER stress. It was also found that silencing SEC61G inhibited the malignant development of LUAD through ER stress. In addition, SEC61G was verified to participate in ER stress in LUAD via CREB3 and silencing SEC61G exerted inhibitory effects on the malignant progression of LUAD by regulating CREB3. In summary, SEC61G participated in ER stress and its knockdown exerted inhibitory effects on A549 cells via regulating CREB3, which suggests that SEC61G may be a potential therapy for patients with LUAD.
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http://dx.doi.org/10.3892/ol.2022.13316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178705PMC
July 2022

Cytosolic Nuclear Sensor Dhx9 Controls Medullary Thymic Epithelial Cell Differentiation by p53-Mediated Pathways.

Front Immunol 2022 3;13:896472. Epub 2022 Jun 3.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

Thymic epithelial cells (TECs) critically participate in T cell maturation and selection for the establishment of immunity to foreign antigens and immune tolerance to self-antigens of T cells. It is well known that many intracellular and extracellular molecules elegantly have mastered the development of medullary TECs (mTECs) and cortical TECs (cTECs). However, the role played by NTP-dependent helicase proteins in TEC development is currently unclear. Herein, we created mice with a TEC-specific DExD/H-box helicase 9 () deletion ( cKO) to study the involvement of Dhx9 in TEC differentiation and function. We found that a Dhx9 deficiency in TECs caused a significant decreased cell number of TECs, including mTECs and thymic tuft cells, accompanied by accelerated mTEC maturation but no detectable effect on cTECs. Dhx9-deleted mTECs transcriptionally expressed poor tissue-restricted antigen profiles compared with WT mTECs. Importantly, cKO mice displayed an impaired thymopoiesis, poor thymic T cell output, and they suffered from spontaneous autoimmune disorders. RNA-seq analysis showed that the Dhx9 deficiency caused an upregulated DNA damage response pathway and Gadd45, Cdkn1a, Cdc25, Wee1, and Myt1 expression to induce cell cycle arrest in mTECs. In contrast, the p53-dependent upregulated RANK-NF-κB pathway axis accelerated the maturation of mTECs. Our results collectively indicated that Dhx9, a cytosolic nuclear sensor recognizing viral DNA or RNA, played an important role in mTEC development and function in mice.
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http://dx.doi.org/10.3389/fimmu.2022.896472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203851PMC
June 2022

-Methyladenosine-Related Long Non-Coding RNAs Are Identified as a Potential Prognostic Biomarker for Lung Squamous Cell Carcinoma and Validated by Real-Time PCR.

Front Genet 2022 3;13:839957. Epub 2022 Jun 3.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Currently, the precise mechanism by which -methyladenosine (mA) modification of long non-coding RNAs (lncRNAs) promotes the occurrence and development of lung squamous cell carcinoma (LUSC) and influences tumor microenvironment (TME) remains unclear. Therefore, we studied the prognostic value of mA-related lncRNAs and their relationship with TME in LUSC samples from The Cancer Genome Atlas (TCGA) database. Pearson's correlation and univariate Cox regression analysis identified 6 mA-related lncRNAs with prognostic values for LUSC patients. LUSC patients were divided into two subgroups (clusters 1 and 2) using principal component analysis. The expression of PD-L1 was lower in tumor tissues and cluster 2 of LUSC patients. Cluster 2 of LUSC patients had a high immune score, stromal score, and unique immune cell infiltration. The focal adhesion kinase (FAK) pathway and cytokine receptor pathways are enriched in cluster 1. The mA-related lncRNA prognostic markers (mA-LPMs) were established using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The risk score was calculated by 4 mA-LPMs and associated with OS, TME, clinicopathological characteristics of LUSC patients. After adjusting for age, gender, and stage, the risk score was also an independent prognostic factor for LUSC patients. Real-time PCR results showed that the expression of 4 mA-LPMs was consistent with our prediction results. Our study found that 4 mA-LPMs (AC138035.1, AC243919.2, HORMAD2-AS1, and AL122125.1) are closely associated with LUSC prognosis, in future, they may as novel diagnostic biomarkers for LUSC and provide new immunotherapy targets for LUSC patients.
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http://dx.doi.org/10.3389/fgene.2022.839957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204524PMC
June 2022

Mechanism and efficiency research of P- and N-codoped graphene for enhanced paracetamol electrocatalytic degradation.

Environ Sci Pollut Res Int 2022 Jun 17. Epub 2022 Jun 17.

College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China.

Electrocatalytic oxidation is an effective technology for treatment of refractory organic pollutants, and its performance strongly depends on anode materials. Among all anode materials, graphene (GN) owns the advantages of high stability and lack of secondary pollution. The catalytic performance of GN can be further improved through heteroatom doping. Here, P/N-codoped graphene (PN-GN) materials were optimized and used as an anode material for 4-acetamidophenol (APAP) electrocatalytic degradation. Result indicated that PN-GN had lower internal resistance, larger specific surface area, and higher electrochemical activity than single-doped graphene materials. The catalytic activity of GN was greatly improved by P/N codoping. When PN-GN (P8.4%-N7.6%-500 °C) was used as catalyst (current of 20 mA, initial pH of 7, reaction time of 60 min), the degradation efficiency of APAP reached 98.2% ± 1.8%, which was 17.9% ± 3.6% higher than P-codoped graphene (P-GN), 14.7% ± 4.6% higher than N-codoped graphene (N-GN), and 54.0% ± 5.2% higher than GN. After 180 min of reaction, the degradation efficiency of total organic carbon (TOC) was 78.5%. The reaction conditions were optimized and the degradation pathway of APAP was estimated to elucidate the catalytic mechanism. The main active substances generated in the system were identified as active chlorine and O.
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http://dx.doi.org/10.1007/s11356-022-21241-7DOI Listing
June 2022

Chemical characterization of PM in heavy polluted industrial zones in the Guanzhong Plain, northwest China: Determination of fingerprint source profiles.

Sci Total Environ 2022 Sep 15;840:156729. Epub 2022 Jun 15.

SKLLQG, Key Lab of Aerosol Chemistry & Physics, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an 710061, China.

Industrial emission has been proved to be an important source of atmospheric PM, which causes serious air pollution and health impacts. The air quality of the industrial zones, which are the intermediate stationary areas between the direct emissions and diffusion to the atmosphere, is always overlooked. In this study, the PM filter samples were collected in the six representative types of industrial zones in four cities of the Guanzhong Plain in 2020. The chemical characteristics of fine particulate matter (PM) in the zones were investigated. The mass concentrations of 13 elements and 39 polycyclic aromatic hydrocarbons (PAHs) in PM were quantified. Cement and concrete (CC) and brick production (BP) exhibited a similar chemical composition profile characterized by high proportions of calcium (Ca), aluminum (Al), benzo[k]fluoranthene (BkF), 1-nitronaphthalene (1N-NAP), and 3-nitrofluoranthene (3N-FLA). Glassware and ceramics (GC) showed a distinguishable profile with a relatively low ratio of copper/cadmium (Cu/Cd) and lead (Pb)/Cd. The profile for metal forging (MF) was abundant in vanadium (V), Pb, indeno[1,2,3-cd]pyrene (IcdP) and also recognized by particular diagnostic ratios of nitrated-PAHs (n-PAHs). The highest proportions of several metals such as chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), zinc (Zn), Cd, and fluoranthene (FLA) were found in the thermoelectric industry (TI) due to a large amount of coal consumption in the manufacture processing. Chemical production (CP) was the only industrial type using natural gas as the main fuel in this study, which shows the distinguishing feature of relatively high proportions of low molecular weight parent-PAHs (p-PAHs) and 2-ring oxygenated-PAHs (o-PAHs). This study not only attains the detailed chemical fingerprints, but also the potential tracers and ratios, which are of great significance for refining source apportionment and relieving PM pollution contributed by the industrial sources.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156729DOI Listing
September 2022

A Study on the Use of Phase Transition Lysozyme-Loaded Minocycline Hydrochloride in the Local Treatment of Chronic Periodontitis.

ACS Appl Bio Mater 2022 Jun 17. Epub 2022 Jun 17.

School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China.

Periodontitis is the most important oral disease causing human tooth loss. Although supragingival and subgingival scaling is the main strategy of periodontitis clinical treatments, drug treatment has an indispensable auxiliary role to some degree. Periodontitis medical treatment is divided into systemically administered treatments and local periodontally administered treatments. Compared with systemic administration, local administration can increase local drug concentrations, reduce dosages, and prolong action times while also improving patient compliance and avoiding possible adverse effects due to systemic administration responses. However, some studies show that minocycline ointment, a clinical local drug commonly used in periodontal pockets, has an unstable release rate; 80% of the drug is usually released within 2-3 days after pocket placement. This release is not conducive to controlling periodontal infection and may hinder the periodontal tissue repair and regeneration. Therefore, choosing a suitable carrier for minocycline hydrochloride is necessary to control its local release in periodontal tissue. Phase transition lysozyme (PTL) has been widely used in many studies and the development of macromolecular carrier material, and we selected PTL as the carrier for minocycline hydrochloride drugs because of its good biocompatibility, good drug-carrying capacity, and stable release. Due to its release characteristics and simple preparation, PTL is a promising carrier material.
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http://dx.doi.org/10.1021/acsabm.2c00079DOI Listing
June 2022

CRISPR/Cas9‑induced saturated mutagenesis identifies haplotype as a marker of PARP inhibitor sensitivity in breast cancer.

Mol Med Rep 2022 Aug 17;26(2). Epub 2022 Jun 17.

Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei 071000, P.R. China.

Breast cancer treatment with poly(ADP‑ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, , a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9‑based saturated mutation approach for the WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib‑resistant cells. Two haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.
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http://dx.doi.org/10.3892/mmr.2022.12774DOI Listing
August 2022

Denitrification performance and characteristics of untreated corncob for enhanced nitrogen removal of municipal sewage with low C/N ratio.

Environ Res 2022 Jun 13;213:113673. Epub 2022 Jun 13.

College of Environment and Ecology, Chongqing University, Chongqing, 400045, China; Key Laboratory of Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing, 400045, China. Electronic address:

Unpretreated corncob was applied in denitrification bio-filter (DNBF) and anoxic tank of AAO system, respectively, to treat sewage with low C/N ratio, and both two approaches achieved good denitrification performance. Although shorter HRT could effectively decrease effluent chroma and COD of corncob-DNBF, nitrogen removal efficiency declined unexpectedly. Higher internal reflux ratio was beneficial for corncob-AAO without damage to anoxic environment for denitrification, while there was no risk of effluent chroma and excessive COD. Different supplement modes could realize same denitrification effect with distinct advantages, which were higher specific denitrification rate and biomass amount, respectively. The latter mode, applying corncob at secondary treatment, was preferable for its operational stability and convenience. Stoichiometry analysis indicated the unit COD demand of AAO decreased from 5.70 to 5.04 g COD/g N after adding corncob, and the oxygen demand (or energy consumption of aeration) decreased as well. The dominant substrates decomposer in corncob-AAO altered to Kouleothrix (affiliated to phylum Chloroflexi), and the main denitrifying bacteria were unclassified_f__Methylophilaceae and Azospira. Accordingly, functional enzymes for degrading glucan, xylan and lignin and processing denitrification showed satisfying abundance in the integrated system, especially in the newly formed biofilm.
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http://dx.doi.org/10.1016/j.envres.2022.113673DOI Listing
June 2022
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