Publications by authors named "Yanqing Li"

211 Publications

Th2 Modulation of Transient Receptor Potential Channels: An Unmet Therapeutic Intervention for Atopic Dermatitis.

Front Immunol 2021 30;12:696784. Epub 2021 Jun 30.

School of Life Sciences, Henan University, Kaifeng, China.

Atopic dermatitis (AD) is a multifaceted, chronic relapsing inflammatory skin disease that affects people of all ages. It is characterized by chronic eczema, constant pruritus, and severe discomfort. AD often progresses from mild annoyance to intractable pruritic inflammatory lesions associated with exacerbated skin sensitivity. The T helper-2 (Th2) response is mainly linked to the acute and subacute phase, whereas Th1 response has been associated in addition with the chronic phase. IL-17, IL-22, TSLP, and IL-31 also play a role in AD. Transient receptor potential (TRP) cation channels play a significant role in neuroinflammation, itch and pain, indicating neuroimmune circuits in AD. However, the Th2-driven cutaneous sensitization of TRP channels is underappreciated. Emerging findings suggest that critical Th2-related cytokines cause potentiation of TRP channels, thereby exaggerating inflammation and itch sensation. Evidence involves the following: (i) IL-13 enhances TRPV1 and TRPA1 transcription levels; (ii) IL-31 sensitizes TRPV1 transcriptional and channel modulation, and indirectly modulates TRPV3 in keratinocytes; (iii) The Th2-cytokine TSLP increases TRPA1 synthesis in sensory neurons. These changes could be further enhanced by other Th2 cytokines, including IL-4, IL-25, and IL-33, which are inducers for IL-13, IL-31, or TSLP in skin. Taken together, this review highlights that Th2 cytokines potentiate TRP channels through diverse mechanisms under different inflammatory and pruritic conditions, and link this effect to distinct signaling cascades in AD. This review strengthens the notion that interrupting Th2-driven modulation of TRP channels will inhibit transition from acute to chronic AD, thereby aiding the development of effective therapeutics and treatment optimization.
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http://dx.doi.org/10.3389/fimmu.2021.696784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278285PMC
June 2021

relieve the visceral hypersensitivity in mice induced by infection with chronic stress.

PeerJ 2021 21;9:e11585. Epub 2021 Jun 21.

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Background: Visceral hypersensitivity is a common symptom in patients with post-infectious irritable bowel syndrome (PI-IBS), and change of the microbiota is a vital etiological factor of it. () is one of the probiotics which is reported as the active components in the treatment of IBS, especially IBS with diarrhea. () is an enteropathogenic bacteria which can produce self-limiting colitis in mice, which have been used to produce a PI-IBS-like mice model. Whether could influence the visceral hypersensitivity and gut microbiota of PI-IBS is still unknown. Our study aimed to examine whether the intervention of or antibiotics could affect the etiology of visceral hypersensitivity.

Methods: C57BL/6 male mice were gavaged with the to induce a infective colitis. The and antibiotic compound were used to intervene the infected mice 3 days later. A 9-day chronic water avoidance stress (WAS) process was implemented to help induce the visceral hypersensitivity. The abdominal withdrawal reflex (AWR) score was assayed to indicate the visceral hypersensitivity of different groups. On the 7th, 14th, and 30th days after infection, mice feces were collected and high-throughput sequencing was carried out to analyze their gut microbiota.

Results: Combined, the infection plus chronic stress (WAS) could induce the visceral hypersensitivity in mice. Treatment of the after infection could relieve visceral hypersensitivity of mice, while no difference was observed in the antibiotic treatment group. The gut microbiota diversity of infected mice was similar to the uninfected mice, while there were different microbial communities structure between them. The Shannon and Chao indexes significantly decreased in the antibiotic treatment group compared to other groups at 7th, 14th, and 30th days post-infection, while treatment of could maintain the indexes within normal range. At day 14 after infection, the structure of microbiota headed towards normality after the treatment. After the WAS, the Shannon and Chao indexes of the control group decreased and the structure of microbiota changed. The treatment could prevent these changes of the gut microbiota induced by WAS.

Conclusion: could relieve the visceral hypersensitivity in mice induced by infection plus chronic stress. It could also remodel the microbiota change caused by the infection and chronic stress. It may be a more effective treatment strategy for PI-IBS than antibiotics.
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http://dx.doi.org/10.7717/peerj.11585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223894PMC
June 2021

A Bacteriophage DNA Mimic Protein Employs a Non-specific Strategy to Inhibit the Bacterial RNA Polymerase.

Front Microbiol 2021 2;12:692512. Epub 2021 Jun 2.

BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

DNA mimicry by proteins is a strategy that employed by some proteins to occupy the binding sites of the DNA-binding proteins and deny further access to these sites by DNA. Such proteins have been found in bacteriophage, eukaryotic virus, prokaryotic, and eukaryotic cells to imitate non-coding functions of DNA. Here, we report another phage protein Gp44 from bacteriophage SPO1 of , employing mimicry as part of unusual strategy to inhibit host RNA polymerase. Consisting of three simple domains, Gp44 contains a DNA binding motif, a flexible DNA mimic domain and a random-coiled domain. Gp44 is able to anchor to host genome and interact bacterial RNA polymerase the β and β' subunit, resulting in bacterial growth inhibition. Our findings represent a non-specific strategy that SPO1 phage uses to target different bacterial transcription machinery regardless of the structural variations of RNA polymerases. This feature may have potential applications like generation of genetic engineered phages with Gp44 gene incorporated used in phage therapy to target a range of bacterial hosts.
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http://dx.doi.org/10.3389/fmicb.2021.692512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208478PMC
June 2021

Nanocellulose aerogel for highly efficient adsorption of uranium (VI) from aqueous solution.

Carbohydr Polym 2021 Sep 21;267:118233. Epub 2021 May 21.

Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Cellulose nanofibers (CNFs) aerogel was prepared via simple covalent crosslinking and freeze-drying method. The porous cellulose aerogel possessed high specific surface area and high metal-chelating capacity, which showed fast adsorption kinetics and high adsorption capacity (440.60 mg g) in static uranium adsorption process. In the dynamic filtration system, the maximum adsorption capacity reached 194 mg g with the initial concentration of 10 mg L. In addition, the CNFs aerogel possessed excellent selectivity and good regeneration ability for uranium adsorption. The integrated analyses of attenuated total reflection Fourier transform infrared (ATR-FTIR), X-Ray photoelectron spectroscopy (XPS) and extended X-ray absorption fine structure (EXAFS) suggested that the predominant UO species formed inner-sphere surface complexes with two active carboxyl groups in the coordination model. This strategy may provide a sustainable route for development of efficient biomass-based adsorbents for selective uranium removal from aqueous solution.
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http://dx.doi.org/10.1016/j.carbpol.2021.118233DOI Listing
September 2021

Influence of Sedation on the Detection Rate of Early Cancer and Precancerous Lesions During Diagnostic Upper Gastrointestinal Endoscopies: A Multicenter Retrospective Study.

Am J Gastroenterol 2021 06;116(6):1230-1237

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Introduction: The influence of sedation on the endoscopic detection rate of upper gastrointestinal (UGI) early cancer (EC) and precancerous lesions, including high-grade intraepithelial neoplasia (HGIN) and low-grade intraepithelial neoplasia, has not been assessed. The aim of this research is to assess whether the use of sedation can help improve the detection rate of UGI EC and precancerous lesions. The second objective is to evaluate its potential influencing factors.

Methods: The study includes 432,202 patients from a multicenter database from January 2012 to July 2019. Information on endoscopic findings and histology biopsies was obtained from endoscopy quality-control system. Associations of sedation with the detection rate of EC and precancerous lesions were assessed.

Results: The sedation group has a higher detection rate of UGI EC and HGIN compared with the no-sedation group, whereas the detection rate of low-grade intraepithelial neoplasia was similar between the 2 groups. There were more cases examined by using staining, image enhancement, or magnifying techniques in the sedation group (P < 0.001). And, the mean observation time was also longer in the sedation group (P < 0.001). The type 0-IIb esophageal HGIN and EC cases were significantly increased in the sedation group. No significant difference was detected on lesion subtypes for gastric HGIN and EC according to the Paris classification. More gastric HGIN and EC were detected at gastric body in the sedation group (P = 0.001).

Discussion: Sedation may improve the endoscopic detection rate of EC and HGIN in the UGI tract probably through enhancing the use of accessary endoscopic techniques, prolonging observation time, and taking more biopsies in different locations (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B926).
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http://dx.doi.org/10.14309/ajg.0000000000001201DOI Listing
June 2021

High-Light-Tolerance PbI Boosting the Stability and Efficiency of Perovskite Solar Cells.

ACS Appl Mater Interfaces 2021 Jun 19;13(21):24692-24701. Epub 2021 May 19.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

Excess lead iodide (PbI) plays a crucial role in passivating the defects of perovskite films and boosting the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, the photolysis of PbI is easily triggered by light illumination, which accelerates the decomposition of perovskite materials and weakens the long-term stability of PSCs. Herein, the high light tolerance of lead iodide (PbI) is reported by introducing an electron-donor molecule, namely, 2-thiophenecarboxamide (2-TCAm), to strengthen the [PbX] frame. Characterization reveals that the retarded decomposition of PbI is attributed to the interactions between Pb and the organic functional groups in 2-TCAm as well as the optimized distribution of PbI. The crystallization and morphology of 2-TCAm-doped perovskite films are improved simultaneously. The 2-TCAm-based PSCs achieve a 16.8% increase in PCE and nearly 12 times increase in the lifetime as compared to the reference device. The demonstrated method provides insight into the stability of PbI and its influence on PSCs.
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http://dx.doi.org/10.1021/acsami.1c02929DOI Listing
June 2021

Donor-Acceptor Couples of Metal and Metal Oxides with Enriched Ni Active Sites for Oxygen Evolution.

ACS Appl Mater Interfaces 2021 Apr 6;13(15):17501-17510. Epub 2021 Apr 6.

CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Exploiting precious-metal-free and high-activity oxygen evolution reaction (OER) electrocatalysts has been in great demands toward many energy storage and conversion processes, for example, carbon dioxide reduction, metal-air batteries, and water splitting. In this study, the simple solid-state method is employed for coupling Ni (electron donors) with lower-Fermi-level MoO or WO (electron acceptors) into donor-acceptor ensembles with well-designed interfaces as robust electrocatalysts for OER. The resulting Ni/MoO and Ni/WO electrocatalysts exhibit smaller overpotentials of 287 and 333 mV at 10 mA cm as well as smaller Tafel slopes of 51 and 65 mV/dec, respectively, with respect to the single Ni, MoO, WO, and even the benchmark RuO in 1 M KOH. Specially, on account of a higher Fermi level of Ni in comparison with MoO and WO, their strong electronic interaction results in directional interfacial electron transfer and increases the hole density over Ni, dramatically enriching the population of high-valence Ni active sites and decreasing the Fermi level of Ni. The existence of Ni can strengthen the chemisorption of OH, and the downshift of the Ni Fermi level can significantly expedite migration of electrons toward the surface of catalysts during OER, thus synergistically boosting the OER catalytic performance. Furthermore, the inner Ni/MoO and Ni/WO heterostructures and the electrochemically induced surface layers of oxides/hydroxides collectively boost the OER kinetics. This study highlights the importance of designing highly efficient OER electrocatalysts with high-valence active species (Ni) and better matched energy levels induced by the work function difference through interfacial engineering.
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http://dx.doi.org/10.1021/acsami.1c00890DOI Listing
April 2021

PGC1α Promotes Cisplatin Resistance in Ovarian Cancer by Regulating the HSP70/HK2/VDAC1 Signaling Pathway.

Int J Mol Sci 2021 Mar 3;22(5). Epub 2021 Mar 3.

Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Mitochondrial apoptosis is one of the main mechanisms for cancer cells to overcome chemoresistance. Hexokinase 2 (HK2) can resist cancer cell apoptosis by expressing on mitochondria and binding to voltage-dependent anion channel 1 (VDAC1). We previously reported that peroxisome proliferator-activated receptor coactivator 1 α (PGC1α) is highly expressed in ovarian cancer cisplatin-resistant cells. However, the underlying mechanism remains unclear. Therefore, we evaluated the interaction between PGC1α and HK2 in ovarian cancer cisplatin-resistant cells. We found that the knockdown of PGC1α promotes the apoptosis of ovarian cancer cisplatin-resistant cells and increases their sensitivity to cisplatin. In addition, we found that the knockdown of PGC1α affects the mitochondrial membrane potential and the binding of HK2 and VDAC1. As the heat shock protein 70 (HSP70) family can help protein transport, we detected it and found that PGC1α can promote HSP70 gene transcription. Furthermore, HSP70 can promote an increase of HK2 expression on mitochondria and an increase of binding to VDAC1. Based on these results, PGC1α may reduce apoptosis through the HSP70/HK2/VDAC1 signaling pathway, thus promoting cisplatin resistance of ovarian cancer. These findings provide strong theoretical support for PGC1α as a potential therapeutic target of cisplatin resistance in ovarian cancer.
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http://dx.doi.org/10.3390/ijms22052537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961780PMC
March 2021

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats.

Front Pharmacol 2021 9;12:616803. Epub 2021 Mar 9.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both and , which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.
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http://dx.doi.org/10.3389/fphar.2021.616803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985071PMC
March 2021

Expression Is a Predictor for Poor Survival of Prostate Cancer Patients.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033820971610

Department of Urology, 117971The First Hospital of Jilin University, Changchun, China.

Objective: Dysregulation of long noncoding RNA is associated with a variety of cancers and LncRNA has anticancer or carcinogenic activities. PVT1, as a long noncoding RNA, plays an important role in the development of cancer.

Methods: We use R to download and analyze the data in TCGA database. ROC curve is generated to evaluate the significance of PVT1 expression for the diagnosis of prostate cancer. Chi-square test is used to test correlation between PVT1 expression and clinical pathological features. Survival curve and univariate and multivariate cox regression analysis is performed to compare differences in the effect on the survival rate between PVT1 high expression and low expression.

Results: The expression of PTV1 in tumor tissues was significantly higher than that in normal tissues(P<2.2e-16). The difference of PTV1 expression was observed according to vital status (P = 0.0051) and Gleason score (P = 0.0012). The expression of PTV1 is significantly associated with T classification (P < 0.0001), N classification (P = 0.0499), PSA (P = 0.0001), Gleason Score (P < 0.0001), targeted molecular therapy (P = 0.0264) and vital status(P = 0.0036). The area under the ROC curve (AUC) was 0.860, which revealed PTV1 expression has excellent diagnostic value in prostate cancer. Patients with high PVT1 expression had a worse prognosis.

Conclusions: PVT1 expression may be a biomarker for the diagnosis and prognosis of prostate cancer.
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http://dx.doi.org/10.1177/1533033820971610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093616PMC
March 2021

L-lactate promotes intestinal epithelial cell migration to inhibit colitis.

FASEB J 2021 04;35(4):e21554

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Lactate, one of the most common primary metabolites of bacteria and human cells, has been shown to play essential roles in the regulation of inflammatory diseases, including inflammatory bowel diseases. However, whether and how host-derived lactate affects intestinal epithelial homeostasis is still not completely understood. Here, we investigated how L-lactate, mainly produced by host cells, regulates intestinal epithelial cell (IEC) migration to promote intestinal wound healing. Using video microscopy and tracking individual cells, we found that L-lactate enhanced IEC migration in direction persistence and speed. Mechanistically, L-lactate promoted IEC mitochondrial ATP production. The mitochondrial ATP synthase inhibitor, oligomycin, significantly decreased IEC persistence and speed, which inhibited cell migration induced by L-lactate. Furthermore, administering mice with L-lactate suppressed colitis induced by dextran sulfate sodium. In conclusion, our study demonstrates that host-derived L-lactate promotes IEC mitochondrial ATP production to drive cell migration, promoting intestinal wound healing to alleviate intestinal inflammation.
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http://dx.doi.org/10.1096/fj.202100095RDOI Listing
April 2021

Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area.

J Gastroenterol Hepatol 2021 Mar 10. Epub 2021 Mar 10.

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Background And Aim: The increase in antibiotic resistance makes the eradication of Helicobacter pylori more difficult. Considering the limitations of the application of susceptibility-guided therapy, it is important to find an effective empirical regimen. The aim of the study is to compare the efficacy, safety, and cost-effectiveness of clarithromycin-based bismuth-containing quadruple therapy (C-BQT) and furazolidone-based bismuth-containing quadruple therapy (F-BQT) in naïve H. pylori positive patients.

Methods: This was an open-label, randomized controlled, crossover trial. The trial comprised two phases. In C-F group, patients received C-BQT in the first phase; those who were still positive for H. pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment. In F-C group, patients were treated with F-BQT firstly and rescued with C-BQT.

Results: As first-line treatments, the eradication rates of C-BQT and F-BQT were 89.7% (157/175) and 92.0% (161/175) (P = 0.458) in intention-to-treat analysis and 93.4% (156/167) and 95.8% (161/168) (P = 0.327) in per-protocol analysis, respectively. The cumulative eradication rates of the C-F group and the F-C group were both 94.3% in intention-to-treat analysis (P = 1.000). Cost-effectiveness indexes of F-BQT and C-BQT were 0.54 and 1.24 in first-line treatments. Frequencies of adverse events in F-BQT and C-BQT had no differences (36.0% in C-BQT vs 32.6% in F-BQT, P = 0.499).

Conclusions: Furazolidone-based bismuth-containing quadruple therapy should be preferred for its excellent cost-effectiveness and acceptable safety.
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http://dx.doi.org/10.1111/jgh.15468DOI Listing
March 2021

Outcome prediction of microdissection testicular sperm extraction based on extracellular vesicles piRNAs.

J Assist Reprod Genet 2021 Jun 9;38(6):1429-1439. Epub 2021 Mar 9.

Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26 Erheng Road, Yuancun, Tianhe District, Guangzhou, People's Republic of China, 510655.

Purpose: Microdissection testicular sperm extraction (micro-TESE) could retrieve sperm from the testicles to help the non-obstructive azoospermia (NOA) patients to get their biological children, but also would cause damage to the testicles. Therefore, it is necessary to preoperatively predict the micro-TESE outcome in NOA patients. For this purpose, we aim to develop a model based on extracellular vesicles' (EVs) piRNAs (EV-piRNAs) in seminal plasma.

Methods: To identify EV-piRNAs that were associated with spermatogenic ability, small RNA-seq was performed between the NOA group (n = 8) and normal group (n = 8). Validation of EV-piRNA expression in seminal plasma EVs and testicles tissues was used to select EV-piRNAs for the model. Candidate EV-piRNAs were further selected by LASSO regression analysis. Binary logistic regression analysis was used for the models' calculation formula. ROC analysis and Hosmer-Lemeshow test was used to assess the models' performance in the training (n = 20) and validation (n = 25) cohorts.

Results: We identified 8 EV-piRNAs which were associated with spermatogenic ability. Two EV-piRNAs (pir-60351 and pir-61927) were selected by LASSO regression analysis. Finally, we developed a favorable model based on the expression of pir-61927 with good discrimination wherein the AUC was 0.82 (95% CI: 0.63~1.00, p = 0.016) in the training cohort and 0.83 (95% CI: 0.66~1.00, p = 0.005) in the validation cohort, as well as good calibration.

Conclusions: A favorable model based on the expression of pir-61927 in seminal plasma EVs was established to predict the micro-TESE outcome in NOA patients.
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http://dx.doi.org/10.1007/s10815-021-02101-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266920PMC
June 2021

Impact of postmortem degradation of cytoskeletal proteins on intracellular gap, drip channel and water-holding capacity.

Meat Sci 2021 Jun 23;176:108472. Epub 2021 Feb 23.

College of Food Science and Technology, Yunnan Agricultural University, Kunming 652021, PR China.

The present study aimed to investigate the impact of the degradation of cytoskeletal proteins (desmin, integrin, vinculin, and talin) on the formation of intracellular gap and drip channel and water-holding capacity in pork. The intensity of intact cytoskeletal proteins and the width of intracellular gap and drip channel were measured in high drip loss and low drip loss groups. The data indicate that the width of intracellular gap and drip channel explained 17% and 62% variation in drip loss, respectively, while the intensity of intact desmin, integrin, and vinculin explained 47%, 34%, and 47% variation in drip loss, respectively. The postmortem formation of intracellular gap is mainly affected by the changes in integrin and vinculin, while the formation of the drip channel is influenced by the changes in desmin. These findings suggest that postmortem formation of wide intracellular gap and drip channels is linked to increased drip loss.
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http://dx.doi.org/10.1016/j.meatsci.2021.108472DOI Listing
June 2021

A 2-pyridone modified zinc phthalocyanine with three-in-one multiple functions for photodynamic therapy.

Chem Commun (Camb) 2021 Mar 25;57(25):3127-3130. Epub 2021 Feb 25.

College of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Nanjing, Jiangsu 210023, China.

A 2-pyridone modified zinc phthalocyanine (denoted ZnPc-PYR) achieves a one stone for three birds outcome in the photodynamic therapy (PDT) treatment of cancer. ZnPc-PYR can be excited by both 665 and 808 nm light to treat superficial and deep tumors, store and slowly release singlet oxygen (O) to improve its utilization and downregulate the HIF-1 (hypoxia-inducible factor 1) expression level to enhance the tumor cell's sensitivity to PDT treatment under hypoxic conditions.
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http://dx.doi.org/10.1039/d1cc00645bDOI Listing
March 2021

Apelin ameliorated acute heart failure via inhibiting endoplasmic reticulum stress in rabbits.

Amino Acids 2021 Mar 20;53(3):417-427. Epub 2021 Feb 20.

Department of Physiology, Hebei Medical University, Zhongshan East Road No. 361, Shijiazhuang, 050017, China.

This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.
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http://dx.doi.org/10.1007/s00726-021-02955-3DOI Listing
March 2021

Shuxuetong injection simultaneously ameliorates dexamethasone-driven vascular calcification and osteoporosis.

Exp Ther Med 2021 Mar 8;21(3):197. Epub 2021 Jan 8.

Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.

Osteoporosis (OP) and vascular calcification (VC) share a number of common risk factors, pathophysiological mechanisms and etiology, which are known as bone-vascular axis. The present study aimed to investigate the effects of Shuxuetong (SXT) injection on VC and osteoporosis. A rat model of VC and osteoporosis was induced by dexamethasone (DEX; 1 mg/kg/day for 4 weeks, intramuscularly). Simultaneously, 0.6 ml/kg/day SXT was intraperitoneally injected. Compared with control rats, DEX induced significantly more VC and OP, as determined by increased calcium deposition and alkaline phosphatase activity in the aorta, disturbed structure, decreased levels of cortical bone thickness and trabecular bone area, and increased apoptosis in the bone. SXT injection ameliorated DEX-induced VC and osteoporosis; furthermore, the osteoblastic differentiation of vascular smooth muscle cells and the activation of endoplasmic reticulum stress in the DEX group was also prevented by SXT injection. Compared with control rats, protein expression levels of sclerostin, a crucial crosslink of the bone-vascular axis, were significantly increased in the aorta and bone of rats with DEX, which was also attenuated by SXT injection. Thus, the present study suggested that SXT injection could ameliorate both VC and OP, and may be mediated by the regulation of sclerostin. The present study may provide the basis a novel strategy for the prevention and treatment of VC and OP, which emerge as side-effects of glucocorticoids.
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http://dx.doi.org/10.3892/etm.2021.9630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812579PMC
March 2021

Resonance assignments of the cytoplasmic domain of ECF sigma factor W pathway protein YsdB from Bacillus subtilis.

Biomol NMR Assign 2021 04 4;15(1):103-106. Epub 2021 Jan 4.

BioBank, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, 710061, China.

Bacterial sigma (σ) factor, along with RNA polymerase core enzyme, initiates gene transcription from specific promoter regions and therefore regulates clusters of genes in response to a particular situation. The extracytoplasmic function (ECF) σ factors are a class of alternative σ factors that are often associated with environmental signal transduction across the bacterial membrane, in which external signal triggers the release of active σ from the membrane-anchored anti-σ factor. Gram-positive model organism Bacillus subtilis (B. subtilis) has seven ECF σ factors: σ, σ, σ, σ, σ, σ and σ. Although all these ECF σ factors were found to be involved in B. subtilis antibiotic resistance, σ is among the most studied and considered to play a pivotal role in responding to antimicrobial stresses. σ is under tight control and remains deactivated until exposure to external stimuli, after which proteases PrsW and RasP cleave the specific anti-sigma factor-RsiW to release and activate σ. Membrane anchored protein YsdB is a negative regulator of this activation, possibly via its direct interaction with PrsW and/or RsiW. Importantly, YsdB is well conserved among Bacilli, including pathogenic bacteria like Bacillus cereus. In this study, we describe the chemical shift assignments of the cytoplasmic domain of YsdB (29-130) of B. subtilis in solution as a basis for further interaction studies and structure determination. The near-complete assignment and the solution structure that will follow could provide a further understanding in σ regulation.
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http://dx.doi.org/10.1007/s12104-020-09990-3DOI Listing
April 2021

Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis.

Biosci Rep 2021 May;41(5)

School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]= 2.70, 95% confidence interval [CI]= 1.97-3.71, P<0.001), DFS (HR = 1.93, 95% CI = 1.49-2.50, P<0.001), and LRFS (HR = 1.86, 95% CI = 1.11-3.12, P=0.019). However, there was no significant association between Ki-67 and DMFS (HR = 1.37, 95% CI = 0.78-2.38, P=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.
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http://dx.doi.org/10.1042/BSR20203334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112845PMC
May 2021

Surface-induced phase engineering and defect passivation of perovskite nanograins for efficient red light-emitting diodes.

Nanoscale 2021 Jan 21;13(1):340-348. Epub 2020 Dec 21.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

Organic-inorganic hybrid lead halide perovskites are potential candidates for next-generation light-emitting diodes (LEDs) in terms of tunable emission wavelengths, high electroluminescence efficiency, and excellent color purity. However, the device performance is still limited by severe non-radiative recombination losses and operational instability due to a high degree of defect states on the perovskite surface. Here, an effective surface engineering method is developed via the assistance of guanidinium iodide (GAI), which allows the formation of surface-2D heterophased perovskite nanograins and surface defect passivation due to the bonding with undercoordinated halide ions. Efficient and stable red-emission LEDs are realized with the improved optoelectronic properties of GAI-modified perovskite nanograins by suppressing the trap-mediated non-radiative recombination loss. The champion device with a high color purity at 692 nm achieves an external quantum efficiency of 17.1%, which is 2.3 times that of the control device. Furthermore, the operational stability is highly improved, showing a half-lifetime of 563 min at an initial luminance of 1000 cd m. The proposed GAI-assisted surface engineering is a promising approach for defect passivation and phase engineering in perovskite films to achieve high-performance perovskite LEDs.
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http://dx.doi.org/10.1039/d0nr07677eDOI Listing
January 2021

RssB-mediated σ Activation is Regulated by a Two-Tier Mechanism via Phosphorylation and Adaptor Protein - IraD.

J Mol Biol 2021 02 18;433(3):166757. Epub 2020 Dec 18.

BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China; Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ London, United Kingdom; Instrument Analysis Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China. Electronic address:

Regulation of bacterial stress responding σ is a sophisticated process and mediated by multiple interacting partners. Controlled proteolysis of σ is regulated by RssB which maintains minimal level of σ during exponential growth but then elevates σ level while facing stresses. Bacteria developed different strategies to regulate activity of RssB, including phosphorylation of itself and production of anti-adaptors. However, the function of phosphorylation is controversial and the mechanism of anti-adaptors preventing RssB-σ interaction remains elusive. Here, we demonstrated the impact of phosphorylation on the activity of RssB and built the RssB-σ complex model. Importantly, we showed that the phosphorylation site - D58 is at the interface of RssB-σ complex. Hence, mutation or phosphorylation of D58 would weaken the interaction of RssB with σ. We found that the anti-adaptor protein IraD has higher affinity than σ to RssB and its binding interface on RssB overlaps with that for σ. And IraD-RssB complex is preferred over RssB-σ in solution, regardless of the phosphorylation state of RssB. Our study suggests that RssB possesses a two-tier mechanism for regulating σ. First, phosphorylation of RssB provides a moderate and reversible tempering of its activity, followed by a specific and robust inhibition via the anti-adaptor interaction.
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http://dx.doi.org/10.1016/j.jmb.2020.166757DOI Listing
February 2021

Inhibition of endoplasmic reticulum stress mediates the ameliorative effect of apelin on vascular calcification.

J Mol Cell Cardiol 2021 03 3;152:17-28. Epub 2020 Dec 3.

Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Laboratory Animal Science, Shijiazhuang 050017, China. Electronic address:

Aims: Apelin is the endogenous ligand of G protein-coupled receptor APJ and play an important role in the regulation of cardiovascular homeostasis. We aimed to investigate whether apelin ameliorates vascular calcification (VC) by inhibition of endoplasmic reticulum stress (ERS).

Methods And Results: VC model in rats was induced by nicotine plus vitamin D, while calcification of vascular smooth muscle cell (VSMC) was induced by beta-glycerophosphate. Alizarin Red S staining showed dramatic calcium deposition in the aorta of rats with VC, while calcium contents and ALP activity also increased in calcified aorta. Protein levels of apelin and APJ were decreased in the calcified aorta. In rats with VC, apelin treatment significantly ameliorated aortic calcification, compliance and stimulation of ERS. The ameliorative effect of apelin on VC and ERS was also observed in calcified VSMCs. ERS stimulator (tunicamycin or DTT) blocked the beneficial effect of apelin. Apelin treatment activated the PI3K/Akt signaling, blockage of which by wortmannin or inhibitor IV prevented the ameliorative effect of apelin, while ERS inhibitor 4-PBA rescued the blockade effect of wortmannin. Akt-induced GSK inhibition prevented the phosphorylation of PERK and IRE1, and the activation of these two major ERS branches. F13A blocked the ameliorative effect of apelin on VC and ERS, which was reversed by treatment with 4-PBA or Akt activator SC79 CONCLUSIONS: Apelin ameliorated VC by binding to APJ and then prevented ERS activation by stimulating Akt signaling. These results might provide new target for therapy and prevention of VC.
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http://dx.doi.org/10.1016/j.yjmcc.2020.11.017DOI Listing
March 2021

Trajectory and weathering of oil spill in Daya bay, the South China sea.

Environ Pollut 2020 Dec 8;267:115562. Epub 2020 Sep 8.

State Key Laboratory of Hydraulic Engineering Simulation and Safety, Tianjin University, Tianjin, 300072, China. Electronic address:

With the development of marine resources and marine transportation, oil spill accidents occur frequently which threaten the marine ecological environment and human life. In this paper, an oil spill model was established. The two-dimensional shallow water equation was discretized by the finite element weighted lumped mass method, and the time is discretized by the forward Euler scheme, then the planar two-dimensional hydrodynamic model was established. The model was verified by measure tidal level data. The oil particle drift model and oil spill weathering model were established in this paper, and it can be used to simulate the oil spill accidents on the sea area by inputting the terrain data, environmental conditions and oil spill information into the hydrodynamic model and oil spill model. The model is applied to Daya Bay, South China Sea, the oil spill behavior and destination under different residual currents were simulated and calculated, the pollution area of oil spill under clockwise residual flow is larger than that under anti-clockwise residual flow. The oil spill model is mainly used to simulate oil spill accidents on the sea surface such as ship oil spill accidents, and the simulation results can provide theoretical basis for taking effective emergency measures and risk assessment after oil spill.
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http://dx.doi.org/10.1016/j.envpol.2020.115562DOI Listing
December 2020

Prognostic Significance and Related Mechanisms of Hexokinase 1 in Ovarian Cancer.

Onco Targets Ther 2020 11;13:11583-11594. Epub 2020 Nov 11.

Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People's Republic of China.

Purpose: Ovarian cancer (OC) has the highest mortality among gynecological malignancies. Therefore, it is urgent to explore prognostic biomarkers to improve the survival of OC patients. One of the most prominent metabolic characteristics of cancer is effective glycolysis. Hexokinase 1 (HK1), as the first rate-limiting enzyme in glycolysis, is closely related to cancer progression. However, the role of HK1 in OC remains unclear.

Materials And Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression of in OC patients. The chi-squared test was performed to examine the correlations between and patients' clinical characteristics. Survival analyses were undertaken to determine the relationship between HK1 and patient survival, while the univariate/multivariate Cox model was used to evaluate the role of HK1 in patient prognosis. Gene Set Enrichment Analysis (GSEA) was performed to ascertain the related signaling pathways of HK1. RT-qPCR was implemented to validate the mRNA expression of in OC cells. MTT was used to detect cell viability after adding 2DG and knocking down in OC cells. HK1 protein expression was examined by Western blotting. Glucose uptake, lactate production, and ATP assays were undertaken following knockdown of in OC cells. Colony formation assays were performed to determine OC cell proliferation after knockdown. Transwell and wound healing assays were carried out to detect the invasion and migration of OC cells after knockdown.

Results: We found that expression was increased in OC tissues and cells, and HK1 was related to the clinical characteristics of OC patients. Survival analysis revealed that OC patients in the overexpression group had poor survival. Moreover, univariant/multivariate analyses showed that may be an independent biomarker for the poor prognosis of OC patients. OC cell viability and proliferation decreased after knockdown of . Consistently, glucose uptake, lactic acid production, ATP production, invasion, and migration were also decreased. Finally, GSEA enrichment analysis and Western blotting showed that HK1 was involved in MAPK/ERK signaling.

Conclusion: may be a biomarker for the poor prognosis of OC patients and a potential therapeutic target.
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http://dx.doi.org/10.2147/OTT.S270688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667154PMC
November 2020

Evaluation of soil erosion and sediment deposition rates by the Cs fingerprinting technique at different hillslope positions on a catchment.

Environ Monit Assess 2020 Oct 21;192(11):717. Epub 2020 Oct 21.

Department of Physical Geography, University of Trier, 54296, Trier, Germany.

Assessment of the variation of soil erosion and sediment mobilization at different hillslope positions using the Cs tracing technique has been carried out for the Dapotou closed watershed, a representative depression in the karst gabin basin in Southwest China. The results showed that the annual soil erosion rates in the shoulders, backslopes, and footslopes were 0.87, 0.35 and 0.49 cm year, respectively, while the soil sediment deposition rate in the depression bottom was 2.68 cm year. The average annual soil erosion modulus of the complete hillslope was 632 t kmyear, which confirmed the seriousness of erosion according to the gradation of the karst soil erosion standards. For the whole catchment, the sediment delivery ratio was estimated as 0.82. To identify which factor could play the most important role in influencing the estimates using Cs, a linear correlation and principal component analysis were conducted. The results showed that Cs concentrations at different soil depths of the different hillslope positions were significantly correlated with soil organic matter and total nitrogen (P < 0.05). As this watershed is a typical karst geomorphological type, these findings are expected to provide data support for larger watershed soil erosion management and ecological restoration in fragile karst ecosystems.
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http://dx.doi.org/10.1007/s10661-020-08680-wDOI Listing
October 2020

Chemotherapy combined with apatinib for the treatment of desmoplastic small round cell tumors: A case report.

J Cancer Res Ther 2020 Sep;16(5):1177-1181

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Desmoplastic small round cell tumor (DSRCT) is a type of soft-tissue sarcoma with poor prognosis. Current treatments include multidisciplinary treatment options such as surgery, chemotherapy, and radiotherapy. Apatinib is an oral, small-molecule, anti-tumor, angiogenesis-targeted drug, which acts mainly on the intracellular binding site of vascular endothelial growth factor receptor-2. In this study, we administered apatinib in combination with chemotherapy to achieve good disease control. This is a 31-year-old male who presented with upper abdominal pain, nausea, and anorexia for over a month. Imaging revealed multiple solid masses and ascites in the liver and abdominal cavity. He was diagnosed as having cholangiocarcinoma with metastasis to the liver, both lungs, bone, and multiple lymph nodes in the neck, abdominal and pelvic cavity, retroperitoneum, and palpitate angle, based on a percutaneous biopsy of the liver and an abdominal mass, and other examinations. Computed tomography revealed disease progression after two cycles of gemcitabine combined with nedaplatin chemotherapy. Next-generation sequencing detection based on the Illumina high-throughput sequencing platform suggested EWSR1 exon7- Wilms tumor 1 exon8 fusion. The pathology was verified and diagnosed as DSRCT. The chemotherapy regimen was changed to cyclophosphamide, epirubicin, vincristine, and oral apatinib for two cycles. The lesions were mostly reduced, and partial response was evaluated. This case is the first report of the efficacy of apatinib combined with systemic chemotherapy in the treatment of DSRCT, which can become an alternative treatment for this disease.
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http://dx.doi.org/10.4103/jcrt.JCRT_589_20DOI Listing
September 2020

STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells.

FASEB J 2020 11 24;34(11):15417-15430. Epub 2020 Sep 24.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

Stimulator of interferon genes (STING) has been shown to play a critical role in orchestrating immune responses to various pathogens through sensing cyclic dinucleotides. However, how STING regulates intestinal homeostasis is still not completely understood. In this study, we found that STING mice were more susceptible to enteric infection with Citrobacter rodentium compared to wild-type (WT) mice evidenced by more severe intestinal inflammation and impaired bacterial clearance. STING mice demonstrated lower expression of REG3γ but not β-defensins and Cramp in IECs. Consistently, STING IECs showed reduced capacity to inhibit bacterial growth. STING agonists, both 10-carboxymethyl-9-acridanone (CMA) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), promoted REG3γ expression IECs. Furthermore, STING agonists promoted WT but not REG3γ-deficient IEC bacterial killing. Mechanistically, STING agonists activated STAT3 and promoted glycolysis in IECs. Inhibition of STAT3 pathway and glycolysis suppressed STING-induced REG3γ production in IECs, and abrogated STING-mediated IEC killing of C. rodentium. Additionally, treatment with the STING ligand, 2,3-cGAMP, inhibited C. rodentium-induced colitis in vivo. Overall, STING promotes IEC REG3γ expression to inhibit enteric infection and intestinal inflammation, thus, maintaining the intestinal homeostasis.
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http://dx.doi.org/10.1096/fj.202001524RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606834PMC
November 2020

Long non-coding RNA BACE1-AS is an independent unfavorable prognostic factor in liver cancer.

Oncol Lett 2020 Nov 8;20(5):202. Epub 2020 Sep 8.

Stem Cell and Cancer Center, First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.

Liver cancer is one of the leading causes of cancer-associated deaths with incidence rates continuously on the rise. Biomarkers are urgently required for early diagnosis and better prognostic classification, which is essential for risk stratification and optimizing treatment strategies in clinical settings. By analyzing the data extracted from The Cancer Genome Atlas database using R, the long noncoding RNA (lncRNA) β-site APP-cleaving enzyme 1 antisense ( was discovered to have both high diagnostic and prognostic values in liver cancer, which could serve as a promising biomarker in clinical settings. Precisely, lncRNA is significantly overexpressed in liver cancer and its levels vary within different subgroups, suggesting its tumorigenic role. Furthermore, higher predicts poorer overall survival and relapse-free survival outcomes. Overall, the present study demonstrated that may be involved in liver cancer progression and could serve as a promising biomarker for diagnosis and prognostic evaluation.
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http://dx.doi.org/10.3892/ol.2020.12065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491030PMC
November 2020

Repeated radon exposure induced lung injury and epithelial-mesenchymal transition through the PI3K/AKT/mTOR pathway in human bronchial epithelial cells and mice.

Toxicol Lett 2020 Nov 16;334:4-13. Epub 2020 Sep 16.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China. Electronic address:

Radon exposure is the most frequent cause of lung cancer in non-smokers. The high linear energy transfer alpha-particles from radon decay cause the accumulation of multiple genetic changes and lead to cancer development. Epithelial-mesenchymal transition (EMT) plays an important role in oncogenesis. However, the mechanisms underlying chronic radon exposure-induced EMT attributed to carcinogenesis are not understood. This study aimed to explore the EMT and potential molecular mechanisms induced by repeated radon exposure. The EMT model of 16HBE and BEAS-2B cells was established with radon exposure (20000 Bq/m, 20 min each time every 3 days). We found repeated radon exposure facilitated epithelial cell migration, proliferation, reduced cell adhesion and ability to undergo EMT through a decrease in epithelial markers and an increase in mesenchymal markers. Radon regulated the expression of matrix metalloproteinase 2 (MMP2) and tissue inhibitors of metalloproteinase 2 (TIMP2) to disrupt the balance of MMP2/TIMP2. In vivo, BALB/c mice were exposed to 10 Bq/m radon gas for cumulative doses of 60 and 120 Working Level Months (WLM). Radon inhalation caused lung damage and fibrosis in mice, which was aggravated with the increase of exposure dose. EMT-like transformation also occurred in lung tissues of radon-exposure mice. Moreover, radon radiation increased p-PI3K, p-AKT and p-mTOR in cells and mice. Radon reduced the GSK-3β level and elevated the active β-catenin in 16HBE cells. The m-TOR and AKT inhibitors attenuated radon exposure-induced EMT by regulation related biomarkers. These data demonstrated that radon exposure induced EMT through the PI3K/AKT/mTOR pathway in epithelial cells and lung tissue.
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http://dx.doi.org/10.1016/j.toxlet.2020.09.008DOI Listing
November 2020

A panel of extracellular vesicle long noncoding RNAs in seminal plasma for predicting testicular spermatozoa in nonobstructive azoospermia patients.

Hum Reprod 2020 11;35(11):2413-2427

Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655 Guangzhou, China.

Study Question: Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients?

Summary Answer: Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA.

What Is Known Already: The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE.

Study Design, Size, Duration: RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples.

Participants/materials, Setting, Methods: RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets.

Main Results And The Role Of Chance: A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended.

Limitations, Reasons For Caution: In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated.

Wider Implications Of The Findings: When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate.

Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa184DOI Listing
November 2020