Publications by authors named "Qing Wang"

3,569 Publications

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Neuroadaptive Output Formation Tracking for Heterogeneous Nonlinear Multiagent Systems With Multiple Nonidentical Leaders.

IEEE Trans Neural Netw Learn Syst 2022 Aug 11;PP. Epub 2022 Aug 11.

This article investigates the practical time-varying output formation tracking (TVOFT) problem for heterogeneous nonlinear multiagent systems (MASs) having multiple leaders, where agents herein could have heterogeneous dynamics and interact with each other under event-triggered communications. It is required that the outputs of followers not only track the predefined convex combination of multiple leaders but also achieve the desired time-varying formation simultaneously. The existing works on formation tracking problems for MASs with multiple leaders depend on the assumption that each follower is a well-informed or uninformed follower, where the well-informed follower is required to have all the leaders as its neighbor. To remove the limitation, a fully distributed observer-based formation tracking control protocol is developed and employed. First, an adaptive state observer with an edge-based event-triggered mechanism for estimating the states of multiple leaders is proposed based on the neighboring interactions, which eliminates the unexpected Zeno behavior. Second, a novel observer is constructed for each follower by exploiting the output information of the follower, in which the adaptive neural network (NN)-based approximation is exploited to compensate for the unknown nonlinearity. A practical TVOFT control protocol is then generated by the proposed observers, where the parameters are determined by an algorithm including five steps. With the help of Lyapunov stability theory and output regulation method, a practical TVOFT criterion for the considered closed-loop system is derived. Finally, the effectiveness of the proposed control scheme is illustrated by a numerical example.
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http://dx.doi.org/10.1109/TNNLS.2022.3196118DOI Listing
August 2022

Diagnosis of pelvic endometriosis: a preliminary study on the added value of R2*MFGRE sequence in magnetic resonance imaging.

Acta Radiol 2022 Aug 8:2841851221117260. Epub 2022 Aug 8.

Department of Radiology, 91623Qilu Hospital of Shandong University, Jinan, PR China.

Background: Identifying and locating endometriotic lesions is crucial for preoperative planning, so new magnetic resonance imaging (MRI) techniques are urgently needed to improve the diagnostic sensitivity for pelvic endometriosis.

Purpose: To evaluate the feasibility of R2* multiple fast gradient recalled echo (MFGRE) imaging in the diagnosis of pelvic endometriosis.

Material And Methods: A total of 46 patients with suspected endometriosis underwent routine pelvic MRI and R2*MFGRE imaging. Clinical diagnosis was pathologically confirmed one month after MRI examination. Three radiologists who were blinded to the pathological results evaluated the number of ovarian endometriomas (OMAs) and deep infiltrating endometriosis (DIE) lesions using routine MRI and its combination with R2*MFGRE. The diagnostic sensitivity for OMA or DIE using the two examination methods was determined. Two-correlation sample rank-sum tests were used to compare both methods. Additionally, for all lesions, the R2* values were measured and statistically analyzed.

Results: Among 46 patients, 47 OMAs and 30 DIE lesions were found surgically and pathologically confirmed. The diagnostic sensitivity of the routine MRI was 87.2% for OMA and 46.7% for DIE. The diagnostic sensitivity of the routine imaging combined with R2*MFGRE was 100% for OMA and 90% for DIE. The two-correlation sample rank-sum test showed a significant difference between both methods <0.01, z = -4.26). The median R2* value was 25.20 (IQR=14) for the OMA group, and 45.21 (IQR=40) for the DIE group. The difference between both groups was statistically significant (<0.01, z = -4.89).

Conclusion: R2*MFGRE imaging, as a supplement to the routine MRI, could improve the diagnostic sensitivity for pelvic endometriosis, especially for DIE.
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http://dx.doi.org/10.1177/02841851221117260DOI Listing
August 2022

Chilling injury of tomato fruit was alleviated under low-temperature storage by silencing Sly-miR171e with short tandem target mimic technology.

Front Nutr 2022 25;9:906227. Epub 2022 Jul 25.

School of Food Science and Engineering, Hainan University, Haikou, China.

In this study, the role of Sly-miR171e on post-harvest cold tolerance of tomato fruit was researched. The results showed that overexpression of Sly-miR171e (miR171e-OE) promoted postharvest chilling injury (CI) of tomato fruit at the mature red (MR) and mature green (MG) stage. Contrasted with the wild type (WT) and miR171e-OE fruit, the knockdown of Sly-miR171e (miR171e-STTM) showed a lower CI index, lower hydrogen peroxide (HO) content, and higher fruit firmness after harvest. In the fruit of miR171e-STTM, the expression level of , and , and the GA3 content were ascended, while the expression levels of and were descended. The research demonstrated that CI in tomato fruit was alleviated at low temperature storage by silencing Sly-miR171e with short tandem target mimic (STTM) technology. Furthermore, it also provided helpful information for genetic modification of miR171e and control of CI in the postharvest fruit.
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http://dx.doi.org/10.3389/fnut.2022.906227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355414PMC
July 2022

Comparison Analysis Based on Complete Chloroplast Genomes and Insights into Plastid Phylogenomic of Four Species.

Biomed Res Int 2022 27;2022:2194021. Epub 2022 Jul 27.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.

species, commonly known as rainbow flowers because of their attractive flowers, are extensively grown in landscape gardens. A few species, including , the synonym of and , are known for their medicinal properties. However, research on the genomes and evolutionary relationships of species is scarce. In the current study, the complete chloroplast (CP) genomes of , , , and were sequenced and compared for their identification and relationship. The CP genomes of the four species were circular quadripartite with similar lengths, GC contents, and codon usages. A total of 113 specific genes were annotated, including the pseudogene in all species and in alone. All the species had mononucleotide (A/T) simple sequence repeats (SSRs) and long forward and palindromic repeats in their genomes. A comparison of the CP genomes based on mVISTA and nucleotide diversity (Pi) identified three highly variable regions (, , and ). Phylogenetic analysis based on the complete CP genomes concluded that is a sister of , and the subgenus with several clustered into one branch is a sister of These findings confirm the feasibility of superbarcodes (complete CP genomes) for species authentication and could serve as a resource for further research on phylogeny.
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http://dx.doi.org/10.1155/2022/2194021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348943PMC
August 2022

Improved Survival With Surgical Treatment of Primary Lung Lesions in Non-Small Cell Lung Cancer With Brain Metastases: A Propensity-Matched Analysis of Surveillance, Epidemiology, and End Results Database.

Front Oncol 2022 22;12:888999. Epub 2022 Jul 22.

Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.

Objectives: Non-small cell lung cancer (NSCLC) with Brain metastases (BM) is an advanced disease with poor prognosis and low survival rate. Our study evaluated the survival benefit of primary lung resection with mediastinal lymph node dissection in NSCLC patients with BM using Surveillance, Epidemiology, and End-result (SEER) databases.

Methods: All cases analyzed were from Surveillance, Epidemiology, and End Results database. The data of the patients with BM of NSCLC from 2010 to 2016 was retrospectively analyzed. Patients (N=203) patients who underwent radical surgical treatment for primary lung lesions and patients (N=15500) who did not undergo surgery were compared. We successfully analyzed patients using propensity score matching (PSM). Kaplan-Meier and Cox- regression analyses were applied to assess prognosis.

Results: The median survival in the surgery group was longer than in the control group (27 months vs 5 months; P < 0.001) in the overall sample, 21 months longer compared to the control group (27 months vs 6 months; P<0.001) in a PSM cohort. Cox regression analysis showed that underwent surgery patients in the propensity-matched sample had a significantly lower risk of mortality (HR:0.243, 95%CI: 0.162-0.365, P < 0.001) compared with untreated patients. Multivariate analysis identified the following as independent risk factors for NSCLC with BM: no primary resection surgery, age >65 years, worse differentiation, squamous cell carcinoma, lymphatic metastasis, no systemic therapy. Subgroup analysis revealed that radical resection of the primary lung provided a survival benefit regardless of marital status, tumor size, tumor grade, tumor T stage, and mediastinal lymph node metastasis after PSM.

Conclusion: Radical resection of primary lung can improve the survival of NSCLC patients with BM. Male, age>65years, poorly differentiated tumor, tumor size>5cm, and mediastinal lymph node metastasis were factors for poor survival.
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http://dx.doi.org/10.3389/fonc.2022.888999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354689PMC
July 2022

Deciphering the focuses and trends in skin regeneration research through bibliometric analyses.

Front Med (Lausanne) 2022 22;9:947649. Epub 2022 Jul 22.

Department of Oral and Maxillofacial Surgery, Xi'an Daxing Hospital, Xi'an, China.

Increasing attention to skin regeneration has rapidly broadened research on the topic. However, no bibliometric analysis of the field's research trends has yet been conducted. In response to this research gap, this study analyzed the publication patterns and progress of skin regeneration research worldwide using a bibliometric analysis of 1,471 papers comprising 1,227 (83.4%) original articles and 244 (16.6%) reviews sourced from a Web of Science search. Publication distribution was analyzed by country/region, institution, journal, and author. The frequency of keywords was assessed to prepare a bibliometric map of the development trends in skin regeneration research. China and the United States were the most productive countries in the field: China had the greatest number of publications at 433 (29.4%) and the United States had the highest H-index ranking (59 with 15,373 citations or 31.9%). Author keywords were classified into four clusters: stem cell, biomaterial, tissue engineering, and wound dressing. "Stem cells," "chitosan," "tissue engineering," and "wound dressings" were the most frequent keywords in each cluster; therefore, they reflected the field's current focus areas. "Immunomodulation," "aloe vera," "extracellular vesicles," "injectable hydrogel," and "three-dimensional (3D) bioprinting" were relatively new keywords, indicating that biomaterials for skin regeneration and 3D bioprinting are promising research hotspots in the field. Moreover, clinical studies on new dressings and techniques to accelerate skin regeneration deserve more attention. By uncovering current and future research hotspots, this analysis offers insights that may be useful for both new and experienced scholars striving to expand research and innovation in the field of skin regeneration.
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http://dx.doi.org/10.3389/fmed.2022.947649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355679PMC
July 2022

LncRNA MIR9-3HG enhances LIMK1 mRNA and protein levels to contribute to the carcinogenesis of lung squamous cell carcinoma via sponging miR-138-5p and recruiting TAF15.

Pathol Res Pract 2022 May 13;237:153941. Epub 2022 May 13.

Department of Thoracic Surgery,Shandong Second Provincial General Hospital, No.4 West Road of Duanxing, Huaiyin District, Jinan, Shandong 250299, China. Electronic address:

The aberrantly expressed long non-coding RNAs (lncRNAs) are closely correlated with the malignant progression of cancer cells. In our study, we identified lncRNA MIR9-3 host gene (MIR9-3HG) as the research target and explored its roles in lung squamous cell carcinoma (LUSC). RT-qPCR was conducted to reveal that MIR9-3HG was observably overexpressed in LUSC cells. Functional assays encompassing colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, transwell and flow cytometry assays and western blot detecting related proteins demonstrated that MIR9-3HG depletion hampered cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) while accelerating cell apoptosis in LUSC. Subcellular fractionation assay were performed to demonstrate that MIR9-3HG was prominently distributed in the cytoplasm of LUSC cells. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), immunofluorescence (IF), fluorescent in situ hybridization (FISH) and RNA pull down assays were implemented to confirm that MIR9-3HG modulates LIM domain kinase 1 (LIMK1) mRNA and protein levels by sequestering microRNA-138-5p (miR-138-5p) and recruiting TATA-box binding protein associated factor 15 (TAF15) protein. Taken together, our research determined that MIR9-3HG up-regulated LIMK1 mRNA and protein levels to promote LUSC carcinogenesis, which offers a novel insight into mechanisms of LUSC.
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http://dx.doi.org/10.1016/j.prp.2022.153941DOI Listing
May 2022

Melatonin maintained higher contents of unsaturated fatty acid and cell membrane structure integrity in banana peel and alleviated postharvest chilling injury.

Food Chem 2022 Aug 1;397:133836. Epub 2022 Aug 1.

School of Food Science and Engineering, Hainan University, Haikou 570228, China. Electronic address:

Exogenous melatonin confers the chilling tolerance of banana fruit by promoting reactive oxygen species (ROS) scavenging system and inducing the unsaturated fatty acid synthesis. The results showed that melatonin treatment increased the contents of phospholipids, promoted the ROS scavenging enzyme, and restrained the activities of lipoxygenase (LOX), and thus reduced the lipid peroxidation of banana peel. In addition, melatonin treatment increased the flavonoids and proline contents, which was conducive to antioxidant capacity. Interestingly, the enhanced antioxidant capacity is conducive to the stability of unsaturated fatty acids and reduce the enzymatic browning reaction. Moreover, melatonin treatment induced the expression of omega-3/6 fatty acid desaturase and triggered the fatty acid metabolism activity, by which maintained higher contents of unsaturated fatty acid in banana peel. Moreover, melatonin treatment stimulated the accumulation of fatty acids in banana peel, and was involved in alleviating fruit chilling injury.
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http://dx.doi.org/10.1016/j.foodchem.2022.133836DOI Listing
August 2022

Transcription factors Vrf1 and Hox7 coordinately regulate appressorium maturation in the rice blast fungus Magnaporthe oryzae.

Microbiol Res 2022 Jul 30;263:127141. Epub 2022 Jul 30.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, College of Life Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China. Electronic address:

Magnaporthe oryzae infects rice, wheat and other grass crops through appressoria. The formation of the appressorium is regulated by the external environment, signal transduction pathways, and transcription factors. Transcription factors Vrf1 and Hox7 are involved in the regulation of appressorium formation. In this study, we demonstrate that Vrf1 and Hox7 play vital roles in coordinately regulating appressorium maturation. In strain 70-15, deletion of VRF1 resulted in the inability to continue melanization and maturation of the incipient appressorium, and deletion of HOX7 also resulted in defects in appressorium melanization and maturation. The defects in appressorium formation in Δhox7Δvrf1 were similar to those in Δhox7 and Δvrf1. The gene expression profiles of the incipient appressoria at 5 h post-inoculation (hpi) showed that the expression levels of 704 genes (25.94 % of all differentially expressed genes in the three mutants) were significantly downregulated (606 genes) or upregulated (98 genes). In the appressoria of Δhox7, Δvrf1, and Δhox7Δvrf1 at 5 hpi, the expression level of genes related to cell wall remodeling was changed. Genes for melanin synthesis, chitin and glucan degradation, and extracellular cell wall degrading enzyme were significantly downregulated, while genes for chitin and glucan synthesis were upregulated. After 8 hpi, the incipient appressoria of Δhox7, Δvrf1, and Δhox7Δvrf1 regerminated and formed swollen hyphal-like structures with multiple nuclei. The ratio of the nuclear number of the hyphal-like structures of Δhox7, Δhox7Δvrf1, and Δvrf1 was close to 6:4:2 at 24 hpi. Therefore, although Vrf1 and Hox7 are somewhat functionally different, they synergistically regulate appressorium maturation in M. oryzae.
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http://dx.doi.org/10.1016/j.micres.2022.127141DOI Listing
July 2022

Protein kinase A participates in hyphal and appressorial development by targeting Efg1-mediated transcription of a Rab GTPase in Setosphaeria turcica.

Mol Plant Pathol 2022 Aug 5. Epub 2022 Aug 5.

State Key Laboratory of North China Crop Improvement and Regulation, Baoding, China.

The cyclic adenosine monophosphate (cAMP) signalling pathway plays an important role in the regulation of the development and pathogenicity of filamentous fungi. cAMP-dependent protein kinase A (PKA) is the conserved element downstream of cAMP, and its diverse mechanisms in multiple filamentous fungi are not well known yet. In the present study, gene knockout mutants of two catalytic subunits of PKA (PKA-C) in Setosphaeria turcica were created to illustrate the regulatory mechanisms of PKA-Cs on the development and pathogenicity of S. turcica. As a result, StPkaC2 was proved to be the main contributor of PKA activity in S. turcica. In addition, it was found that both StPkaC1 and StPkaC2 were necessary for conidiation and invasive growth, while only StPkaC2 played a negative role in the regulation of filamentous growth. We reveal that only StPkaC2 could interact with the transcription factor StEfg1, and it inhibited the transcription of StRAB1, a Rab GTPase homologue coding gene in S. turcica, whereas StPkaC1 could specifically interact with a transcriptional regulator StFlo8, which could rescue the transcriptional inhibition of StEfg1 on StRAB1. We also demonstrated that StRAB1 could positively influence the biosynthesis of chitin in hyphae, thus changing the filamentous growth. Our findings clarify that StPkaC2 participates in chitin biosynthesis to modulate mycelium development by targeting the Efg1-mediated transcription of StRAB1, while StFlo8, interacting with StPkaC1, acts as a negative regulator during this process.
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http://dx.doi.org/10.1111/mpp.13253DOI Listing
August 2022

Accurate detection of atrial fibrillation events with R-R intervals from ECG signals.

PLoS One 2022 4;17(8):e0271596. Epub 2022 Aug 4.

Cardiovascular Medicine, Weinan Central Hospital, Weinan, China.

Atrial fibrillation (AF) is a typical category of arrhythmia. Clinical diagnosis of AF is based on the detection of abnormal R-R intervals (RRIs) with an electrocardiogram (ECG). Previous studies considered this detection problem as a classification problem and focused on extracting a number of features. In this study we demonstrate that instead of using any specific numerical characteristic as the input feature, the probability density of RRIs from ECG conserves comprehensive statistical information; hence, is a natural and efficient input feature for AF detection. Incorporated with a support vector machine as the classifier, results on the MIT-BIH database indicates that the proposed method is a simple and accurate approach for AF detection in terms of accuracy, sensitivity, and specificity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271596PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352004PMC
August 2022

Protects Against Pancreatic and Intestinal Injury After Severe Acute Pancreatitis Downregulation of MMP9.

Front Pharmacol 2022 18;13:919010. Epub 2022 Jul 18.

Department of Gastroenterology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.

Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAP modulating MMP9. In this study, the fecal samples of patients with SAP ( = 72) and healthy controls ( = 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cells and generated a MMP9 knockout (MMP9-/-) mouse model of SAP . We found that the abundance of (C. ) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells ( < 0.05). However, C. or butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells ( < 0.05). Importantly, C. or butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C. or butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9-/- mice compared with the SAP group. Collectively, C. could protect against pancreatic and intestinal injury after SAP downregulation of MMP9 and .
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http://dx.doi.org/10.3389/fphar.2022.919010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342915PMC
July 2022

Distribution of pediatric keratoconus by different age and gender groups.

Front Pediatr 2022 18;10:937246. Epub 2022 Jul 18.

Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, People's Hospital of Zhengzhou University, Henan University People's Hospital, Zhengzhou, China.

Purpose: To evaluate the distribution of pediatric keratoconus patients and the disease severity based on different age and gender groups in China.

Materials And Methods: A total of 446 keratoconus eyes in 266 pediatric patients from January 2019 to January 2022 were included in the cross-sectional study. The clinical findings and severity of keratoconus were recorded and Kruskal-Wallis test, chi-squared test, and Cochran-Mantel-Haenszel (CMH) test were used to compare the parameters between different gender and age groups.

Results: The male/female ratio was 353/93 (3.8:1), and the median age was 16 years (range: 6-17 years). Male patients were statistically younger than female patients ( = 0.041). The male/female ratio decreased with age ( for trend = 0.011). The distribution of the topographic keratoconus classification (TKC) stage was significantly different between gender and age groups (all < 0.05). Male patients had a higher ratio of advanced keratoconus eyes (TKC ≥ 3) than female patients ( < 0.001), and CMH analysis indicated that being a male was a risk factor for advanced keratoconus after controlling for age (odds ratio: 2.581, < 0.001).

Conclusion: Male keratoconus patients were younger, with a higher ratio of advanced keratoconus than female patients in the Chinese pediatric patients evaluated. Multicenter studies with larger sample sizes are necessary in the future.
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http://dx.doi.org/10.3389/fped.2022.937246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339668PMC
July 2022

Efficacy of repetitive transcranial magnetic stimulation in Parkinson's disease: A systematic review and meta-analysis of randomised controlled trials.

EClinicalMedicine 2022 Oct 29;52:101589. Epub 2022 Jul 29.

Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, PR China.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive form of brain stimulation that positively regulates the motor and non-motor symptoms of Parkinson's disease (PD). Although, most reviews and meta-analysis have shown that rTMS intervention is effective in treating motor symptoms and depression, very few have used randomised controlled trials (RCTs) to analyse the efficacy of this intervention in PD. We aimed to review RCTs of rTMS in patients with PD to assess the efficacy of rTMS on motor and non-motor function in patients with PD.

Methods: In this systematic review and meta-analysis, we searched PubMed, MEDLINE and Web of Science databases for RCTs on rTMS in PD published between January 1, 1988 to January 1, 2022. Eligible studies included sham-controlled RCTs that used rTMS stimulation for motor or non-motor symptoms in PD. RCTs not focusing on the efficacy of rTMS in PD were excluded. Summary data were extracting from those RCTs by two investigators independently. We then calculated standardised mean difference with random-effect models. The main outcome included motor and non-motor examination of scales that were used in PD motor or non-motor assessment. This study was registered with PROSPERO, CRD42022329633.

Findings: Fourteen studies with 469 patients met the criteria for our meta-analysis. Twelve eligible studies with 381 patients were pooled to analyse the efficacy of rTMS on motor function improvement. The effect size on motor scale scores was 0.51 ( < 0.0001) and were not distinctly heterogeneous (I = 29%). Five eligible studies with 202 patients were collected to evaluate antidepressant-like effects. The effect size on depression scale scores was 0.42 ( = 0.004), and were not distinctly heterogeneous (I = 25%), indicating a significant anti-depressive effect (P = 0.004). The results suggest that high-frequency of rTMS on primary motor cortex (M1) is effective in improving motor symptoms; while the dorsolateral prefrontal cortex (DLPFC) may be a potentially effective area in alleviating depressive symptom.

Interpretation: The findings suggest that rTMS could be used as a possible adjuvant therapy for PD mainly to improve motor symptoms, but could have potential efficacy on depressive symptoms of PD. However, further investigation is needed.

Funding: The National Natural Science Foundation of China (NO: 81873777, 82071414), Initiated Foundation of Zhujiang Hospital (NO: 02020318005), Scientific Research Foundation of Guangzhou (NO: 202206010005), and Science and Technology Program of Guangdong of China (NO: 2020A0505100037).
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http://dx.doi.org/10.1016/j.eclinm.2022.101589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340539PMC
October 2022

The variation of antenatal corticosteroids administration for the singleton preterm birth in China, 2017 to 2018.

BMC Pediatr 2022 08 3;22(1):469. Epub 2022 Aug 3.

Department of Neonatology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, #2699, Gaoke western Road, Pudong District, Shanghai, 201204, China.

Background: The administration of antenatal corticosteroids (ACS) to women who are at risk of preterm birth has been proven to reduce not only the mortality, but also the major morbidities of the preterm infants. The rate of ACS and the risk factors associated with ACS use in Chinese population is unclear. This study aimed to investigate the rate of ACS use and the associated perinatal factors in the tertiary maternal centers of China.

Methods: Data for this retrospective observational study came from a clinical database of preterm infants established by REIN-EPIQ trial. All infants born at < 34 weeks of gestation and admitted to 18 tertiary maternal centers in China from 2017 to 2018 were enrolled. Any dose of dexamethasone was given prior to preterm delivery was recorded and the associated perinatal factors were analyzed.

Results: The rate of ACS exposure in this population was 71.2% (range 20.2 - 92%) and the ACS use in these 18 maternal centers varied from 20.2 to 92.0% in this period. ACS exposure was higher among women with preeclampsia, caesarean section delivery, antibiotic treatment and who delivered infants with lower gestational age and small for gestational age. ACS use was highest in the 28-31 weeks gestational age group, and lowest in the under 26 weeks of gestational age group (x = 65.478, P < 0.001). ACS exposure was associated with lower odds of bronchopulmonary dysplasia or death (OR, 0.778; 95% CI 0.661 to 0.916) and invasive respiration requirement (OR, 0.668; 95% CI 0.585 to 0.762) in this population.

Conclusion: The ACS exposure was variable among maternity hospitals and quality improvement of ACS administration is warranted.
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http://dx.doi.org/10.1186/s12887-022-03529-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347139PMC
August 2022

Observational and model studies on transport and inventory of microplastics from a leak accident on the beaches of Yantai.

Mar Pollut Bull 2022 Jul 31;182:113976. Epub 2022 Jul 31.

Research and Development Center for Efficient Utilization of Coastal Bioresources, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, PR China.

We investigated an unexpected microplastic (MP) leakage event that occurred along the coastline of Yantai in January 2021. Sediment samples were collected from three zones on 9 beaches. MPs were identified with an average abundance of 247.6 ± 125.6 items/m on 7 beaches. The total amount of MPs from the leak accident was estimated to be 1.50 × 10 items (514.67 kg). The MPs were identified as polyethylene (PE), polypropylene (PP), and PP/PE blends using μ-FT-IR analysis. By utilizing a numerical model, the transmission process and potential source of MPs were demonstrated. The modeling results showed that the MPs might originate from the central and western part of the Bohai Sea and be driven to the beaches of Yantai by northwest wind and wind-induced surface current. However, due to the absence of direct evidence, the simulation results might only indicate the range of the leaking source, which was the movement trajectory of MPs.
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http://dx.doi.org/10.1016/j.marpolbul.2022.113976DOI Listing
July 2022

Correlation Between Sacral Slope and Pedicle Morphology of the Fourth Lumbar Vertebra in Degenerative Lumbar Spondylolisthesis.

Global Spine J 2022 Aug 3:21925682221117151. Epub 2022 Aug 3.

Department of Orthopaedics, 556508The Affiliated Hospital of Southwest Medical University, Lu Zhou, China.

Study Design: Retrospective Radiographic Review.

Objectives: The purpose of this study was to investigate the correlation between the sacral slope (SS) and pedicle morphological parameters of the fourth lumbar vertebra in degenerative lumbar spondylolisthesis (DLS).

Methods: Our study included 134 patients with L4-5 DLS. We used preoperative multi-slice spiral computed tomography to measure a range of pedicle morphological parameters, and the SS and percentage of slip distance (SDP) of the L4 vertebra were measured on preoperative standing neutral lumbar radiography. Patients were divided into three groups based on their degree of SS: the low sacral slope (LSS) group with SS values of <35°, the mean sacral slope (MSS) group with SS of 35°-45°, and the high sacral slope (HSS) group with SS > 45°.

Results: As the SS increased across groups, the pedicles of L4 became longer and thinner and the pedicle camber angle was smaller. The SDP, pedicle length parameters were positively correlated with the SS, while pedicle width, height, and camber angle were negatively correlated with the SS in the three groups.

Conclusions: SS had an impact on the degree of spondylolisthesis and on pedicle morphological parameters in patients with DLS, with greater slope resulting in greater impact. The progression of DLS occurred due to the increasing forward shear force of the vertebra being greater than the reverse resistance. The pedicle at the slip level adaptively remodeled, becoming slenderer and tilting inward due to the long-term traction of the two opposing forces.
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http://dx.doi.org/10.1177/21925682221117151DOI Listing
August 2022

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin.

PLoS Pathog 2022 Aug 3;18(8):e1010765. Epub 2022 Aug 3.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen resulting in manifestations as pneumonia and septic shock. The upper respiratory tract is typically thought to be the main colonization and entry site of SS2 in pigs, but the mechanism through which it penetrates the respiratory barrier is still unclear. In this study, a mutant with low invasive potential to swine tracheal epithelial cells (STECs) was screened from the TnYLB-1 transposon insertion mutant library of SS2, and the interrupted gene was identified as autolysin (atl). Compared to wild-type (WT) SS2, Δatl mutant exhibited lower ability to penetrate the tracheal epithelial barrier in a mouse model. Purified Atl also enhanced SS2 translocation across STEC monolayers in Transwell inserts. Furthermore, Atl redistributed the tight junctions (TJs) in STECs through myosin light chain kinase (MLCK) signaling, which led to increased barrier permeability. Using mass spectrometry, co-immunoprecipitation (co-IP), pull-down, bacterial two-hybrid and saturation binding experiments, we showed that Atl binds directly to vimentin. CRISPR/Cas9-targeted deletion of vimentin in STECs (VIM KO STECs) abrogated the capacity of SS2 to translocate across the monolayers, SS2-induced phosphorylation of myosin II regulatory light chain (MLC) and MLCK transcription, indicating that vimentin is indispensable for MLCK activation. Consistently, vimentin null mice were protected from SS2 infection and exhibited reduced tracheal and lung injury. Thus, MLCK-mediated epithelial barrier opening caused by the Atl-vimentin interaction is found to be likely the key mechanism by which SS2 penetrates the tracheal epithelium.
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http://dx.doi.org/10.1371/journal.ppat.1010765DOI Listing
August 2022

Study of the effect of minerals on the pyrolysis of oil shale in Fushun, China.

RSC Adv 2022 Jul 13;12(31):20239-20250. Epub 2022 Jul 13.

Engineering Research Centre of Oil Shale Comprehensive Utilization, Ministry of Education, Northeast Electric Power University Jilin City Jilin 132012 China

Herein, the effect of Fushun oil shale minerals on its kerogen has been investigated. The samples were obtained under non-isothermal conditions at different final temperatures. Scanning electron microscope (SEM) analysis revealed that the silicates were layered and the carbonates were tightly bound to each other. The combination of silicates and carbonates led to close combination of minerals and organic matter and the organic matter was contained in the minerals. The Brunner-Emmet-Teller (BET) experiments conclude that during the non-isothermal pyrolysis process, the specific surface area increased, and then, decreased, which proves the adsorption effect of silicates on oil shale pyrolysis products and the adsorption effect of carbonates was weak. The activation energy of four samples was calculated Flynn-Wall-Ozawa (FWO) and Friedman kinetic analysis under different heating rates in a non-isothermal process, wherein the average activation energy of the sample containing silicate was 177.60 kJ mol at minimum while that of carbonate was 250.45 kJ mol at maximum, which proves that the catalytic promotion effect of silicate was greater than the inhibition effect of carbonate. The pyrolysis products obtained by Flash pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) under isothermal pyrolysis conditions were primarily composed of aliphatic hydrocarbon structures, which had different degrees of impact on the production of heteroatoms. This work provides a reliable theoretical basis for future studies on the influence of minerals on pyrolysis of organic matter in oil shale.
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http://dx.doi.org/10.1039/d2ra02822kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277521PMC
July 2022

A pyridyl functionalized rhodamine chemodosimeter for selective fluorescent detection of mercury ions and cell imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jul 28;282:121688. Epub 2022 Jul 28.

School of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002, China. Electronic address:

Rhodamines gain sustained attention owing to their great potential for probe design applications. Herein, the facile preparation of a new pyridyl functionalized rhodamine dye PR is reported, which has stable fluorescence signal in water with maximum emission peak at 594 nm and Stokes shift of 81 nm. Based on dye PR, a new fluorescent probe PRHg has been developed by modifying the spirolactone of PR with hydrazine hydrate so as to produce spirolactam recognizing group for sensing of Hg. PRHg exhibits high selectivity and sensitivity towards Hg in water/ethanol (v/v = 4/1, pH = 7.0) by a specific Hg-binding promoted spirolactam ring opening and hydrolyzing process. And, the detection limit for Hg is evaluated to be 8.5 nM. Besides, the probe can respond to Hg within 40 min and over a wide pH range from 4.0 to 10.0. Moreover, PRHg (40 µM) performs low cytotoxicity to HeLa cells (over 91.0 % cell survival rate), which allows the probe to be employed for tracing intracellular Hg by fluorescence imaging.
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http://dx.doi.org/10.1016/j.saa.2022.121688DOI Listing
July 2022

Association of Adverse Childhood Experiences With Frailty Index Level and Trajectory in China.

Authors:
Qing Wang

JAMA Netw Open 2022 Aug 1;5(8):e2225315. Epub 2022 Aug 1.

Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

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http://dx.doi.org/10.1001/jamanetworkopen.2022.25315DOI Listing
August 2022

The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone-induced testicular injury in adolescent mice.

Environ Toxicol 2022 Aug 1. Epub 2022 Aug 1.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, China.

Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low-, medium-, and high-dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three-dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10  M), medium dose (1 × 10  M), and high dose (3 × 10  M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR-212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose-response relationship. Besides, we have identified that low doses of PCM could activate the Ire1-Xbp1 pathway, whereas the medium and high doses activated the Perk-Elf2α-Atf4, Ire1-Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.
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http://dx.doi.org/10.1002/tox.23622DOI Listing
August 2022

Depressive Symptoms and Cognitive Decline Among Chinese Rural Elderly Individuals: A Longitudinal Study With 2-Year Follow-Up.

Front Public Health 2022 13;10:939150. Epub 2022 Jul 13.

Department of Health Service Management, School of Health Service Management, Anhui Medical University, Hefei, China.

Background: Depressive symptoms and mild cognitive impairment (MCI) are highly prevalent in rural China. The study aimed to investigate the longitudinal associations between changes in depressive symptoms and cognitive decline and MCI incidence among Chinese rural elderly individuals.

Methods: A 2-year follow-up study was conducted among 1,477 participants from the Anhui Healthy Longevity Survey (AHLS). Depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9), and cognitive status was evaluated by the Mini Mental State Examination (MMSE). Multivariable linear regression and logistic regression were employed.

Results: Every 1-unit PHQ-9 score increase was significantly associated with more cognitive decline (β = 0.157, 95% CI: 0.092, 0.221, < 0.001) and a higher risk of MCI incidence (OR = 1.063, 95% CI: 1.025, 1.103, = 0.001). The participants who experienced worsening of depression symptoms had a larger decline in the 2-year MMSE score (β = 0.650, 95% CI: 0.039, 1.261, = 0.037) and elevated risks of incident MCI (OR = 1.573, 95% CI: 1.113, 2.223, = 0.010).

Limitations: Screening tools rather than standard diagnostic procedures were used in the study. Moreover, the long-term associations still need further exploration since the follow-up time was short.

Conclusions: Increased depressive symptoms were associated with more cognitive decline and higher risks of incident MCI among Chinese rural residents.
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http://dx.doi.org/10.3389/fpubh.2022.939150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326072PMC
August 2022

Optimization of Fracturing Fluid and Retarded Acid for Stimulating Tight Naturally Fractured Bedrock Reservoirs.

ACS Omega 2022 Jul 14;7(29):25122-25131. Epub 2022 Jul 14.

State Key Laboratory of Oil and Gas Resources and Prospecting, China University of Petroleum at Beijing, Beijing 102249, China.

In tight naturally fractured bedrock reservoirs, hydrocarbons are typically stored in fractures, where hydraulic fracturing is needed to connect these fractures to the wellbore. The cross-linked gel is used as the fracturing fluid to reduce the fluid leak-off through natural fractures; however, it can cause formation damage due to its high content of residues after breaking. A synthetic polymer is introduced and evaluated that can maintain a high viscosity to minimize the leak-off , while having a low residue content after breaking. To further enhance the conductivity of the created fracture network, acid is applied to etch and roughen the created fracture faces. Because the target reservoir has a complex mineral composition, a three-step coreflood sequence using reservoir rock samples with controlled fracture widths is established to quantify the enhancement of different retarded acids and to reveal the mechanism behind it. The results indicate the synergy effect of reducing the acid concentration and surfactant adsorption on rock surfaces can lead to an obvious enhancement of the fracture permeability after acidizing, while the mud acid or hydrofluoric acid is not suitable for the target reservoir where concentrations of silicates and clays are relatively high.
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http://dx.doi.org/10.1021/acsomega.2c01612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330227PMC
July 2022

Benzene Exposure Leads to Lipodystrophy and Alters Endocrine Activity and .

Front Endocrinol (Lausanne) 2022 13;13:937281. Epub 2022 Jul 13.

Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using and experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 μM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level ( = 0.330, 0.344, both < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.
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http://dx.doi.org/10.3389/fendo.2022.937281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326257PMC
July 2022

Acid-promoted intra- and intermolecular [2+2] cycloaddition of indoles to aryl alkynes to access cyclobutene-fused indolines.

Chem Commun (Camb) 2022 Jul 29. Epub 2022 Jul 29.

Xiangya School of Pharmaceutical Science, Central South University, Changsha, Hunan, 410013, P. R. China.

Herein, we have reported the first example of both intra- and intermolecular [2+2] cycloaddition of the electron-rich indoles and unactivated aryl alkynes promoted by the combination of Fe(NO) and HNO, which highlights efficient and selective access to several different types of functionalized cyclobutene-fused indolines from readily available starting materials with cheap catalysts and simple operations.
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http://dx.doi.org/10.1039/d2cc02840aDOI Listing
July 2022

The causal association between empty nest and depressive symptoms with cognitive impairments in China.

J Affect Disord 2022 Jul 25;315:7-12. Epub 2022 Jul 25.

National Institute of Health Data Science of China, Shandong University, Jinan, Shandong, China; Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. Electronic address:

Background: In the context of rapid aging, "empty nest syndrome" is becoming a major public health concern. The causal effects of empty nest on depressive symptoms have been studied in developed countries, but the mediating mechanism of depressive symptoms in the association between empty nest and cognitive impairments has not been studied. This study estimated the causal association of empty nest with depressive symptoms and cognitive impairments in China, and then estimated how depression mediates the association between empty nest and cognitive impairments.

Methods: Using data of 23,614 urban older adults (65+) obtained from the Shandong Province Aging and Mental Health Survey in 2020, a weighted linear regression model combined with instrumental variable was applied to explore the causal effects of empty nest, and a four-step mediation model was run to test the mediator of depressive symptoms. The Ascertain Dementia 8-item Questionnaire and Patient Health Questionnaire-9 were used to measure cognitive impairments and depressive symptoms.

Results: Empty nest was associated with 0.13 (95%CI: 0.04-0.23) and 0.23 (95%CI: 0.14-0.33) increases in the Ascertain Dementia 8-item Questionnaire and the Patient Health Questionnaire-9 scores, respectively. The association between empty nest and the Ascertain Dementia 8-item Questionnaire scores was mediated by the Patient Health Questionnaire-9 scores.

Conclusions: Empty nest affected depression in adulthood with cognitive impairments. A focus on integrative intervention for empty nesters is recommended, taking depression and cognition into account.

Limitations: It is a cross-sectional study and the data is not nationally representative.
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http://dx.doi.org/10.1016/j.jad.2022.07.050DOI Listing
July 2022

Self-determination in Physical Exercise Predicts Creative Personality of College Students: The Moderating Role of Positive Affect.

Front Sports Act Living 2022 11;4:926243. Epub 2022 Jul 11.

Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China.

Although previous studies indicated that intrinsic motivation and positive affect were important for creativity and proved the benefits of physical exercise for creativity, little is known about underlying this relationship between self-determination in physical exercise and creative personality among college students. Based on prior studies and theoretical models, the current study investigated the relationship between self-determination in physical exercise and creativity and the moderating role of positive affect in the relationship between self-determination in physical exercise and creative personality. This model was analyzed with 1,201 Chinese college students (Mean age = 20.10 years, SD = 0.93). Participants filled out the physical exercise self-determination scale, the Williams creativity assessment packet, and the satisfaction with life scale. The results indicated that self-determination in physical exercise was significantly positively correlated with the creative personality of college students, including risk-taking, curiosity, challenge, and imagination. Moreover, self-determination in physical exercise could significantly positively predict the creative personality of college students. Moderation analysis further showed that the relationship between self-determination in physical exercise and creative personality was robust for college students with low levels of positive affect. These findings suggest the importance of cultivating students' creative ability through improving exercise autonomy, especially for those college students with a low level of positive affect.
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http://dx.doi.org/10.3389/fspor.2022.926243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309356PMC
July 2022

Circulating MicroRNAs as Potential Diagnostic Biomarkers for Diabetic Retinopathy: A Meta-Analysis.

Front Endocrinol (Lausanne) 2022 8;13:929924. Epub 2022 Jul 8.

Department of Endocrinology and Metabolism, China-Japan Union Hospital of Jilin University, Changchun, China.

Objective: Diabetic retinopathy (DR) is a common diabetic microvascular complication and a major cause of acquired vision loss. Finding effective biomarkers for the early identification and diagnosis of DR is crucial. This study aimed to comprehensively evaluate the accuracy of microRNAs (miRNAs) in the diagnosis of DR a meta-analysis of previously published diagnostic studies. This study has been registered on the PROSPERO website, with the number CRD42022323238.

Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, China Wanfang database, and China Knowledge Network database to identify relevant articles published from the time of database creation to April 10, 2022. Stata 14.0 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the summary receiver operating characteristic (ROC) curve to assess the accuracy of miRNAs in the diagnosis of DR. Heterogeneity between studies was assessed using Cochran-Q test and I statistic for quantitative analysis. The random-effect model was selected due to significant heterogeneity. Subgroup analysis and regression analysis were also performed to determine the potential sources of heterogeneity.

Results: We included 25 articles detailing 52 studies with 1987 patients with DR and 1771 non-DR controls. The findings demonstrated overall sensitivity (0.82, 95% CI: 0.78 ~ 0.85), specificity (0.84, 95% CI: 0.81 ~ 0.86), PLR (5.0, 95% CI: 4.2 ~ 5.9), NLR (0.22, 95% CI: 0.18 ~ 0.26), and the area under the summary ROC curve (0.90, 95% CI: 0.87 ~ 0.92). Furthermore, we performed subgroup analysis and found that panels of multiple miRNAs could enhance the pooled sensitivity (sensitivity, specificity, and AUC values were 0.89, 0.87, and 0.94, respectively).

Conclusion: The meta-analysis showed that miRNAs can be used as potential diagnostic markers for DR, with high accuracy of diagnoses observed with the detection of miRNAs in plasma and serum.
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http://dx.doi.org/10.3389/fendo.2022.929924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309261PMC
July 2022

TRAF4 maintains deubiquitination of Caveolin-1 to drive glioblastoma stemness and Temozolomide resistance.

Cancer Res 2022 Jul 27. Epub 2022 Jul 27.

China Pharmaceutical University, Nanjing, China.

Glioblastoma (GBM) is the most common type of primary adult brain tumor. Glioma stem cell (GSC) residence and Temozolomide (TMZ) resistance in GBM both contribute to poor patient outcome. TRAF4 is a scaffold protein with E3 ubiquitin ligase activity that has recently been discovered to promote invasion and metastasis in several malignancies, but the effects and functions of TRAF4 in GBM remain to be determined. Here, we report that TRAF4 is preferentially overexpressed in GSCs and is required for stem-like properties as well as TMZ sensitivity in GBM cells. TRAF4 specifically interacted with the N-terminal tail of Caveolin-1 (CAV1), an important contributor to the tumorigenicity of GBM cells. TRAF4 regulated CAV1 stability by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination independently of its E3 ubiquitin ligase catalytic activity. TRAF4-mediated stabilization of CAV1 activated protumorigenic AKT/ERK1/2 signaling, and disruption of this axis resulted in defects in stemness maintenance. In addition, expression of TRAF4 and CAV1 was positively correlated and predicted poor prognosis in human GBM samples. Screening of common nervous system drugs identified Risperidone interaction with TRAF4, and Risperidone treatment resulted in the dissociation of TRAF4 and CAV1. Importantly, pharmacological inhibition of TRAF4 with Risperidone potently inhibited self-renewal, abrogated tumorigenicity, and reversed TMZ resistance in GBM. Overall, TRAF4-mediated stabilization of CAV1 promotes stemness and TMZ resistance in GBM, providing a therapeutic strategy that could improve patient outcomes.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-3882DOI Listing
July 2022
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