Publications by authors named "Xin Jin"

1,295 Publications

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Long non‑coding RNA H19 regulates LASP1 expression in osteosarcoma by competitively binding to miR‑29a‑3p.

Oncol Rep 2021 Sep 30;46(3). Epub 2021 Jul 30.

Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

A prevalent type of bone tumor, osteosarcoma (OS) is prone to pulmonary metastasis, which results in a high relapse risk and poor prognosis for patients. The progression of OS is significantly associated with the expression of long non‑coding (lnc)RNA H19. To the best of our knowledge, however, the exact molecular mechanism of this lncRNA has not been fully investigated. The present study verified the effect of H19 on the proliferation and invasion of osteosarcoma cells via and experiments, including Cell Counting Kit‑8, western blot, reverse transcription‑quantitative PCR, wound healing and Transwell assays. H19 was found to be overexpressed in OS compared with corresponding normal adjacent tissue. In addition, H19 served as a competing endogenous ncRNA targeting microRNA‑29a‑3p and activating LIM and SH3 domain protein 1 and modulating the OS cell phenotype. The results of the present study may improve understanding of OS pathogenesis.
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http://dx.doi.org/10.3892/or.2021.8158DOI Listing
September 2021

USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway.

Int J Biol Sci 2021 11;17(10):2417-2429. Epub 2021 Jun 11.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Bladder cancer is the fourth and tenth most common malignancy in men and women worldwide, respectively. One of the main reasons for the unsatisfactory therapeutic control of bladder cancer is that the molecular biological mechanism of bladder cancer is complex. Gasdermin B (GSDMB) is one member of the gasdermin family and participates in the regulation of cell pyroptosis. The role of GSDMB in bladder cancer has not been studied to date. TCGA database was used to exam the clinical relevance of GSDMB. Functional assays such as MTT assay, Celigo fluorescent cell-counting assay, Annexin V-APC assay and xenografts were used to evaluate the biological role of GSDMB in bladder cancer. Mass spectrometry and immunoprecipitation were used to detect the protein interaction between GSDMB and STAT3, or GSDMB and USP24. Western blot and immunohistochemistry were used to study the relationship between USP24, GSDMB and STAT3. In this study, bioinformatics analysis indicated that the mRNA expression level of GSDMB in bladder cancer tissues was higher than that in adjacent normal tissues. Then, we showed that GSDMB promoted bladder cancer progression. Furthermore, we demonstrated that GSDMB interacted with STAT3 to increase the phosphorylation of STAT3 and modulate the glucose metabolism and promote tumor growth in bladder cancer cells. Besides, we also showed that USP24 stabilized GSDMB to activate STAT3 signaling, which was blocked by the USP24 inhibitor. We suggested that aberrantly up-regulated GSDMB was responsible for enhancing the growth and invasion ability of bladder cancer cells. Then, we showed that GSDMB could bind to STAT3 and activate STAT3 signaling in bladder cancer. Furthermore, we also demonstrated that USP24 interacted with GSDMB and prevented GSDMB from degradation in bladder cancer cells. Therefore, the USP24/GSDMB/STAT3 axis may be a new targetable signaling pathway for bladder cancer treatment.
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http://dx.doi.org/10.7150/ijbs.54442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315027PMC
June 2021

Infer HIV transmission dynamics from gene sequences among young men who have sex with men in China.

Infect Dis Model 2021 10;6:832-838. Epub 2021 Jul 10.

Department of Mathematics, Shanghai University, 99 Shangda Road, Shanghai, 200444, PR China.

To investigate the transmission dynamics and temporal and spatial migration characteristics of HIV spread among men who have sex with men (MSM) in China, a total of 1012 HIV-1 partial pol sequences, including five subtypes, were studied. Bayesian analysis were applied for each subtype to infer its dynamic characters including the effective reproductive number ( ) and migration process. The mean curve of each was almost always greater than 1 (even the 95% highest posterior density (HPD) lower value) along with time, which supports the necessity for a comprehensive study about risk behaviors among young MSM group in China. We also should reappraise the free treatment strategy, especially the therapeutic effect during the free treatment policy.
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http://dx.doi.org/10.1016/j.idm.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286960PMC
July 2021

RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway.

Adv Sci (Weinh) 2021 Jul 28:e2100881. Epub 2021 Jul 28.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Renal cell carcinoma (RCC) is a malignant tumor of the kidneys. Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel-Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD-1/PD-L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib-resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti-tumor efficiency of PD-1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC.
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http://dx.doi.org/10.1002/advs.202100881DOI Listing
July 2021

The trans-omics landscape of COVID-19.

Nat Commun 2021 07 27;12(1):4543. Epub 2021 Jul 27.

BGI-Shenzhen, Shenzhen, China.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.
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http://dx.doi.org/10.1038/s41467-021-24482-1DOI Listing
July 2021

SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis.

Cancer Lett 2021 Jul 24. Epub 2021 Jul 24.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

SGLT2 is overexpressed in various cancers, including pancreatic cancer. However, the mechanisms underlying the tumorigenic effects of SGLT2 in pancreatic cancer remain unclear. In this study, we demonstrated that SGLT2 inhibition significantly suppressed the growth of pancreatic cancer cells in vitro and in vivo. RNA sequencing, real-time PCR, and Western blot analyses revealed that SGLT2 silencing or inhibition suppressed Hippo signaling activation by downregulating YAP1 expression. Liquid chromatography-mass spectrometry and immunoprecipitation analyses showed that SGLT2 interacted with hnRNPK, promoting its nuclear translocation and thereby enhancing hnRNPK-induced YAP1 transcription. Importantly, YAP1 inhibitor enhanced the anti-pancreatic cancer effect of SGLT2 inhibitor in mice bearing pancreatic tumors. These findings suggest that SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway through the hnRNPK-YAP1 axis. Hence, SGLT2 inhibition alone or combined with YAP1 inhibition may represent a promising therapeutic approach for pancreatic cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.07.035DOI Listing
July 2021

Advances in forensic diagnosis of electric shock death in the absence of typical electrical marks.

Int J Legal Med 2021 Jul 27. Epub 2021 Jul 27.

Forensic and Pathology Laboratory, Judicial Expertise Center, Jiaxing University Medical College, Jiaxing, 314001, ZJ, China.

Electrical injury is a relatively uncommon but potentially devastating form of multi-system injury with high morbidity and mortality. In common electric injury cases, it is usually difficult to find characteristic changes of electric injury in major organs by using routine histopathological test methods unless there are landmark traces of electric injury, known as electric marks. How to determine electric shock death, especially in the absence of typical electrical marks on the body surface in some cases (which account for about two-thirds of electric injury cases), remains a challenging problem in forensic practice. Our summary shows that many current related studies have focused their efforts to find characteristic histopathological changes in major organs of the body caused by electric injury. Based on the results obtained through comparison of the literature, we find that it may be more urgent and important to find the optimal autopsy or sampling sites in cases with no typical electric marks, knowing that these sites may often reflect the most significant histopathological changes of electric injury, for instance anatomy and sampling of the anterior wrist and the medial malleolus in cases involving the hand-to-foot electric circuit pathway. In this article, we make a summary of advances in identification methods of electric injury, hoping that it could provide some new insights for further research in this field.
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http://dx.doi.org/10.1007/s00414-021-02658-0DOI Listing
July 2021

TRIM15 promotes the invasion and metastasis of pancreatic cancer cells by mediating APOA1 ubiquitination and degradation.

Biochim Biophys Acta Mol Basis Dis 2021 Jul 24;1867(11):166213. Epub 2021 Jul 24.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Most pancreatic ductal adenocarcinomas (PDACs) are diagnosed at an advanced or metastatic stage. Metastasis is the one of the major obstacles to prolonging the survival time of patients with pancreatic cancer. The tripartite motif (TRIM) family member TRIM15 has been implicated in cancer development. Our bioinformatics analysis indicated that TRIM15 might be involved in the regulation of pancreatic cancer metastasis. However, the role of TRIM15 in PDAC remains unclear. Metabolic reprogramming involving dysregulated lipid synthesis is common in patients with PDAC. Targeting lipid anabolism has been proposed as a strategy to treat PDAC. In this study, we demonstrated that TRIM15 expression was elevated in PDAC tissues, and this elevated expression was associated with a poor prognosis. TRIM15 silencing suppressed the invasion and migration of pancreatic cancer cells. Importantly, the mass spectrometry analysis suggested that Apolipoprotein A1 (APOA1), the main component of high-density lipoprotein (HDL) that is involved in lipid transport and metabolism, might be one of the binding partners of TRIM15. Further experiment indicated that TRIM15 interacted with APOA1 through its PRY/SPRY domain and promoted APOA1 polyubiquitination via its RING domain. APOA1 degradation enhanced lipid anabolism and promoted lipid droplet accumulation in pancreatic cancer cells. Furthermore, we showed that TRIM15 might promote PDAC metastasis by regulating lipid metabolism via the APOA1-LDLR axis. Consequently, targeting the TRIM15-APOA1-LDLR axis may be a strategy to inhibit PDAC metastasis by blocking triglyceride synthesis.
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http://dx.doi.org/10.1016/j.bbadis.2021.166213DOI Listing
July 2021

Machine Learning Prediction Models for Mechanically Ventilated Patients: Analyses of the MIMIC-III Database.

Front Med (Lausanne) 2021 1;8:662340. Epub 2021 Jul 1.

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.

Mechanically ventilated patients in the intensive care unit (ICU) have high mortality rates. There are multiple prediction scores, such as the Simplified Acute Physiology Score II (SAPS II), Oxford Acute Severity of Illness Score (OASIS), and Sequential Organ Failure Assessment (SOFA), widely used in the general ICU population. We aimed to establish prediction scores on mechanically ventilated patients with the combination of these disease severity scores and other features available on the first day of admission. A retrospective administrative database study from the Medical Information Mart for Intensive Care (MIMIC-III) database was conducted. The exposures of interest consisted of the demographics, pre-ICU comorbidity, ICU diagnosis, disease severity scores, vital signs, and laboratory test results on the first day of ICU admission. Hospital mortality was used as the outcome. We used the machine learning methods of -nearest neighbors (KNN), logistic regression, bagging, decision tree, random forest, Extreme Gradient Boosting (XGBoost), and neural network for model establishment. A sample of 70% of the cohort was used for the training set; the remaining 30% was applied for testing. Areas under the receiver operating characteristic curves (AUCs) and calibration plots would be constructed for the evaluation and comparison of the models' performance. The significance of the risk factors was identified through models and the top factors were reported. A total of 28,530 subjects were enrolled through the screening of the MIMIC-III database. After data preprocessing, 25,659 adult patients with 66 predictors were included in the model analyses. With the training set, the models of KNN, logistic regression, decision tree, random forest, neural network, bagging, and XGBoost were established and the testing set obtained AUCs of 0.806, 0.818, 0.743, 0.819, 0.780, 0.803, and 0.821, respectively. The calibration curves of all the models, except for the neural network, performed well. The XGBoost model performed best among the seven models. The top five predictors were age, respiratory dysfunction, SAPS II score, maximum hemoglobin, and minimum lactate. The current study indicates that models with the risk of factors on the first day could be successfully established for predicting mortality in ventilated patients. The XGBoost model performs best among the seven machine learning models.
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http://dx.doi.org/10.3389/fmed.2021.662340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280779PMC
July 2021

NR5A2 Is One of 12 Transcription Factors Predicting Prognosis in HNSCC and Regulates Cancer Cell Proliferation in a p53-Dependent Manner.

Front Oncol 2021 1;11:691318. Epub 2021 Jul 1.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Head and neck squamous cell carcinoma (HNSCC) rank seventh among the most common type of malignant tumor worldwide. Various evidences suggest that transcriptional factors (TFs) play a critical role in modulating cancer progression. However, the prognostic value of TFs in HNSCC remains unclear. Here, we identified a risk model based on a 12-TF signature to predict recurrence-free survival (RFS) in patients with HNSCC. We further analyzed the ability of the 12-TF to predict the disease-free survival time and overall survival time in HNSCC, and found that only NR5A2 down-regulation was strongly associated with shortened overall survival and disease-free survival time in HNSCC. Moreover, we systemically studied the role of NR5A2 in HNSCC and found that NR5A2 regulated HNSCC cell growth in a TP53 status-dependent manner. In p53 proficient cells, NR5A2 knockdown increased the expression of and activated the p53 pathway to enhance cancer cells proliferation. In contrast, NR5A2 silencing suppressed the growth of HNSCC cells with p53 loss/deletion by inhibiting the glycolysis process. Therefore, our results suggested that NR5A2 may serve as a promising therapeutic target in HNSCC harboring loss-of-function mutations.
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http://dx.doi.org/10.3389/fonc.2021.691318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280457PMC
July 2021

Mechanisms for the dissolved biochar promoted iron dissolution and consequential chromium release.

Sci Total Environ 2021 Jul 9;796:148923. Epub 2021 Jul 9.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China. Electronic address:

Biochar is widely applied in soil for agricultural and environmental purposes. Soluble fraction of biochar may be released from bulk biochar as dissolved biochar (DBC) after irrigation or rainfall. DBC had been reported to possess high chemical activity in aqueous system, while less attention was paid to the impact of DBC on the soil environmental processes. In this work, the impact of DBC on ferric (hydro) oxides was systematically examined. Our study showed that DBC prepared from rice straw could significantly promote the dissolution of ferric oxides with unstable and metastable crystalline structures, e.g., ferrihydrite under relatively acidic condition. Organic ligand-promoted dissolution was the main mechanism for iron release from ferrihydrite, and the low-molecular-weight DBC component (less than 1000 Da) was the major contributor for this process. Furthermore, the organic carbon content normalized ligand-promoted dissolution capacity for DBC was much higher than common dissolved organic matters. More importantly, DBC could promote the release of Cr from dichromate-adsorbed ferric mineral. Our results suggest that in soils with relatively low pH and high contents of ferric hydroxides, e.g., red soil in southern China, DBC derived from applied biochar could enhance the mobility and bioavailability of iron and other heavy metals. The dissolved metals would play active roles in soil redox cycle and biotic processes. Therefore, it's necessary to evaluate the long-term impact of biochar application on acidic field soils with high iron content.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148923DOI Listing
July 2021

Enhancement of Scattering and Near Field of TiO-Au Nanohybrids Using a Silver Resonator for Efficient Plasmonic Photocatalysis.

ACS Appl Mater Interfaces 2021 Jul 16;13(29):34714-34723. Epub 2021 Jul 16.

Institute of Quantum and Sustainable Technology (IQST), School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.

Recently, localized surface plasmon resonances (SPRs) of metallic nanoparticles (NPs) have been widely used to construct plasmonic nanohybrids for heterogeneous photocatalysis. For example, the combination of plasmonic Au NPs and TiO provides pure TiO visible-light activity. The SPR effect induces an electric field and consequently enhances light scattering and absorption, favoring the transfer of photon energy to hot carriers for catalytic reactions. Numerous approaches have been dedicated to the improvement of SPR absorption in photocatalysts. Here, we have designed a [email protected] nanohybrid catalyst whereby an Ag NP core, as a plasmonic resonator featuring unique dual functions of strong scattering and near-field enhancement, is encapsulated by SiO and TiO layers in sequence, with Au NPs on the outer surface, [email protected]@TiO-Au, for efficient plasmonic photocatalysis. By varying the size and number of Ag NP cores, the Au SPR can be tailored over the visible and near-infrared spectral region to reabsorb the scattered photons. In the presence of the Ag core, the incident light is efficiently confined in the reaction suspension by undergoing multiple scattering, thus leading to an increase of the optical path to the photocatalysis. Moreover, using numerical analysis and experimental verifications, we demonstrate that the Ag core also induces a strong near-field enhancement at the Au-TiO interface via SPR coupling with Au. Consequently, the activity of the TiO-Au plasmonic photocatalyst is significantly enhanced, resulting in a high H production rate under visible light. Thus, the design of a single structural unit with strong scattering and field enhancement, induced by a plasmonic resonator, is a highly effective strategy to boost photocatalytic activity.
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http://dx.doi.org/10.1021/acsami.1c07410DOI Listing
July 2021

Designing an intelligent monitoring system for corn seeding by machine vision and Genetic Algorithm-optimized Back Propagation algorithm under precision positioning.

PLoS One 2021 15;16(7):e0254544. Epub 2021 Jul 15.

College of Agricultural Equipment Engineering, Henan University of Science and Technology, Luoyang City, China.

Objective: To realize the regulation of the position of corn seed planting in precision farming, an intelligent monitoring system is designed for corn seeding based on machine vision and the Genetic Algorithm-optimized Back Propagation (GABP) algorithm.

Methods: Based on the research on precision positioning seeding technology, comprehensive application of sensors, Proportional Integral Derivative (PID) controllers, and other technologies, combined with modern optimization algorithms, the online dynamic calibration controls of line spacing and plant spacing are implemented. Based on the machine vision and GABP algorithm, a test platform for the seeding effect detection system is designed to provide a reference for further precision seeding operations. GA can obtain better initial network weights and thresholds and find the optimal individual through selection, crossover, and mutation operations; that is, the optimal initial weight of the Back Propagation (BP) neural network. Field experiments verify the seeding performance of the precision corn planter and the accuracy of the seeding monitoring system.

Results: 1. The deviation between the average value of the six precision positioning seeding experiments of corn under the random disturbance signal and the ideal value of the distance is less than or equal to 0.5 cm; the deviation between the average value of the six precision positioning seeding experiments of corn under the sine wave disturbance signal (1 Hz) is less than or equal to 0.4 cm; the qualified rate of grain distance reaches 100%. 2. The precision control index, replay index, and missed index of the designed corn precision seeding intelligent control system have all reached the national standard. During the operation of the seeder, an alarm of the seeder leaking occurred, and the buzzer sounded and the screen displayed 100 times each; therefore, the reliability of the alarm system is 100%.

Conclusion: The intelligent corn seeder designed based on precision positioning seeding technology can reduce the seeding rate of the seeder and ensure the stability of the seed spacing effectively. Based on the machine vision and GABP algorithm, the seeding effect detection system can provide a reference for the further realization of precision seeding operations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282075PMC
July 2021

capCLIP: a new tool to probe translational control in human cells through capture and identification of the eIF4E-mRNA interactome.

Nucleic Acids Res 2021 Jul 13. Epub 2021 Jul 13.

Lifelong Health, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.

Translation of eukaryotic mRNAs begins with binding of their m7G cap to eIF4E, followed by recruitment of other translation initiation factor proteins. We describe capCLIP, a novel method to comprehensively capture and quantify the eIF4E (eukaryotic initiation factor 4E) 'cap-ome' and apply it to examine the biological consequences of eIF4E-cap binding in distinct cellular contexts. First, we use capCLIP to identify the eIF4E cap-omes in human cells with/without the mTORC1 (mechanistic target of rapamycin, complex 1) inhibitor rapamycin, there being an emerging consensus that rapamycin inhibits translation of TOP (terminal oligopyrimidine) mRNAs by displacing eIF4E from their caps. capCLIP reveals that the representation of TOP mRNAs in the cap-ome is indeed systematically reduced by rapamycin, thus validating our new methodology. capCLIP also refines the requirements for a functional TOP sequence. Second, we apply capCLIP to probe the consequences of phosphorylation of eIF4E. We show eIF4E phosphorylation reduces overall eIF4E-mRNA association and, strikingly, causes preferential dissociation of mRNAs with short 5'-UTRs. capCLIP is a valuable new tool to probe the function of eIF4E and of other cap-binding proteins such as eIF4E2/eIF4E3.
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http://dx.doi.org/10.1093/nar/gkab604DOI Listing
July 2021

[Analysis of genetic variant in a fetus featuring pontocerebellar hypoplasia type 6].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jul;38(7):667-670

Department of Gynecology and Obstetrics, Huaian Maternal and Child Health Care Hospital, Huaian, Jiangsu 223002, China.

Objective: To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.

Methods: The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.

Results: Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).

Conclusion: The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200512-00340DOI Listing
July 2021

Knockdown of MicroRNA160a/b by STTM leads to root architecture changes via auxin signaling in Solanum tuberosum.

Plant Physiol Biochem 2021 Jun 29;166:939-949. Epub 2021 Jun 29.

Gansu Provincial Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou, 730070, China; College of Life Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China.

The root phenotype is an important aspect of plant architecture and plays a critical role in plant facilitation of the extraction of water and nutrition from the soil. MicroRNAs (miRNAs) are classes of small RNAs with important roles in regulating endogenous gene expression at the post-transcriptional level that function in a range of plant development processes and in the response to abiotic stresses. However, little is known concerning the molecular mechanism of miRNAs in regulating the generation and development of plant root architecture. Herein, we demonstrated that potato miR160a/b acted as a critical regulator and affected plant root architecture by targeting the mRNA of StARF10 and StARF16 for cleavage. The miR160a/b precursor was cloned from potato. Quantitative PCR assays showed that the expression levels of miR160 and its targets were down- or up-regulated with the development of potato roots, respectively. Moreover, transgenic lines with suppressed stu-miR160 expression were established with the short tandem targets mimic (STTM), and the results showed that the ectopic expression of miR160a/b altered the levels of auxin and the expression of auxin signaling-related genes and caused drastic change in root architecture compared with that in control plants. Suppressing the expression of miR160 led to a severe reduction in root length, an increase in the number of lateral roots, and a decrease in fresh root weight in potato. Collectively, our data established a key role of miR160 in modulating plant root architecture in potato.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.051DOI Listing
June 2021

A Comparison Study of Fenton-like and Fenton Reactions in Dichloromethane Removal.

Environ Technol 2021 Jul 8:1-28. Epub 2021 Jul 8.

Beijing Key Laboratory of Water Resources & Environmental Engineering, China University of Geosciences (Beijing), Beijing, 100083, P.R. China; Fax: 86-10-82321081.

Dichloromethane (DCM) as a low-chlorinated organic compound is hardly to be degraded through reductive dechlorination pathway. In this study, the removal of DCM in Fenton-like system using activated carbon fibers supported zero-valence Fe/Ni nanoparticles (ACF-Fe/Ni) as catalyst was investigated and compared with that of traditional Fenton system (Fe/HO). The influence of vital parameters including initial solution pH, DCM concentration, catalyst and HO dosages, temperature and cosolute on the removal of DCM was systematically studied. The results showed that 94.2% of DCM with an initial concentration of 5 mg/L could be removed in the Fenton-like reaction under the optimum condition: initial pH of 2.0, 0.4 g/L of ACF-Fe/Ni, 10 mM of HO and temperature of 30°C. In comparison, the removal of DCM in the Fenton-like system was faster than that of the Fenton system and the corresponding activation energies were 39.69 and 33.82 kJ/mol, respectively. The coexistence of solute was adverse to the removal of DCM in the both Fenton-like and Fenton systems. Moreover, the active species for DCM removal in the Fenton-like system was confirmed as hydroxyl radical (·OH) via the quenching experiment and EPR measurement. The incomplete mineralization (41.7%) of DCM after reaction indicated that the Fenton-like technology had a potential to realize DCM non-toxic and harmless conversion and organic intermediates formed needed to take longer to be decomposed.
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http://dx.doi.org/10.1080/09593330.2021.1954096DOI Listing
July 2021

circALPL Sponges miR-127 to Promote Gastric Cancer Progression by Enhancing MTDH Expression.

J Cancer 2021 11;12(16):4924-4932. Epub 2021 Jun 11.

Affiliated Hengyang Hospital, Southern Medical University (Hengyang Central Hospital), 12# Yancheng road, Hengyang 421001, Hunan province, China.

CircRNA plays an important role in cancer progression. However, the potential mechanism of circRNA in gastric cancer remains unknown. In this study, we aimed to investigate the specific mechanism of circALPL in gastric cancer. : Using a high-throughput microarray, we found that circALPL was upregulated in gastric cancer cell lines. RT-qPCR was used to measure the circALPL expression level in gastric cell lines and tissue. Transwell, CCK-8, and metastasis assays were performed to learn the function after circALPL was inhibited. : circALPL downregulation suppresses the invasion and proliferation ability of gastric cancer cells. Additionally, the underlying pathway of circALPL was studied using luciferase reporter assays and RNA immunoprecipitation assays. The results showed that circALPL promotes gastric cancer progression by sponging miR-127, thus upregulating MTDH. The circALPL-miR-127-MTDH pathway plays a vital role in gastric cancer proliferation and metastasis. circALPL might be a new therapeutic target in gastric cancer.
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http://dx.doi.org/10.7150/jca.49942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247368PMC
June 2021

Genomic epidemiology of SARS-CoV-2 in the UAE reveals novel virus mutation, patterns of co-infection and tissue specific host immune response.

Sci Rep 2021 07 7;11(1):13971. Epub 2021 Jul 7.

Group42 Healthcare, Abu Dhabi, United Arab Emirates.

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.
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http://dx.doi.org/10.1038/s41598-021-92851-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263779PMC
July 2021

RAB7 activity is required for the regulation of mitophagy in oocyte meiosis and oocyte quality control during ovarian aging.

Autophagy 2021 Jul 7:1-18. Epub 2021 Jul 7.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.

There is increasing evidence that mitophagy, a specialized form of autophagy to degrade and clear long-lived or damaged mitochondria, is impaired in aging and age-related disease. Previous study has demonstrated the obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. However, it remains unknown whether mitophagy functions in oocyte and what's the regulatory mechanism in oocyte aging. In the study, when fully grown oocytes were treated with CCCP, an uncoupling agent to induce mitophagy, we found the activation of the PRKN-mediated mitophagy pathway accompanied the blockage of meiosis at metaphase I stage. Our result then demonstrated its association with the decreased activity of RAB7 and all the observed defects in CCCP treated oocytes could be effectively rescued by microinjection of mRNA encoding active RAB7 or treatment with the RAB7 activator ML098. Further study indicated PRKN protein level as a rate-limiting factor to facilitate degradation of RAB7 and its GEF (guanine nucleotide exchange factor) complex CCZ1-MON1 through the ubiquitin-proteasome system. In GV oocytes collected during ovarian aging, we found the age-related increase of PINK1 and PRKN proteins and a significant decrease of RAB7 which resulted in defects of mitophagosome formation and the accumulation of damaged mitochondria. The age-related retardation of female fertility was improved after in vivo treatment of ML098. Thus, RAB7 activity is required to maintain the balance between mitophagy and chromosome stability and RAB7 activator is a good candidate to ameliorate age-related deterioration of oocyte quality. ATG9: autophagy related 9A; ATP: adenosine triphosphate; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CCZ1: CCZ1 vacuolar protein trafficking and biogenesis associated; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GAPs: GTPase-activating proteins; GEF: guanine nucleotide exchange factor; GV: germinal vesicle; GVBD: germinal vesicle breakdown; LAMP1: lysosomal-associated membrane protein 1; MI: metaphase I stage of meiosis; MII: metaphase II stage of meiosis; Mito: MitoTracker; mtDNA: mitochondrial DNA; MON1: MON1 homolog, secretory trafficking associated; OPTN: optineurin; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RAB7: RAB7, member RAS oncogene family; ROS: reactive oxygen species; TEM: transmission electron microscopy; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin, beta; UB: ubiquitin.
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http://dx.doi.org/10.1080/15548627.2021.1946739DOI Listing
July 2021

Behaviour of ozone in the hybrid ozonation-coagulation (HOC) process for ibuprofen removal: Reaction selectivity and effects on coagulant hydrolysis.

Sci Total Environ 2021 Jun 24;794:148685. Epub 2021 Jun 24.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an, Shaanxi Province 710055, China.

Simultaneous ozonation and coagulation can be realized in one unit in the developed hybrid ozonation-coagulation (HOC) process. To reveal the reaction sequence within the HOC process, the ibuprofen (IBP) removal efficiency of the ozonation only, HOC and HOC-PO (inhibition of the reactions between ozone and metal coagulant) processes at pH 5 and different ozone dosages were investigated. The removal efficiency is almost the same for the three processes at a low ozone dosage (4.8 mg/L), and higher removal performance can be achieved by the HOC process with increasing ozone dosage. It can be implied that ozone preferentially reacts with OH to generate OH which react with IBP in the HOC process, and subsequently reacts with the surface hydroxyl groups of hydrolysed Al species to enhance OH generation. Moreover, based on the kinetics, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR) analyses, the synergistic reactions between ozone and the metal coagulants (SOC) started to take effect from ozone dosage of 9.6 mg/L, which further verified that ozone will be involved in the IBP ozonation prior to the SOC reactions. The subsequent SOC reactions also resulted in the increased generation of polymeric Al species and more abundant intermediates in the HOC process.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148685DOI Listing
June 2021

Prognostic implications of tumour-infiltrating lymphocytes for recurrence in epithelial ovarian cancer.

Clin Exp Immunol 2021 Jun 30. Epub 2021 Jun 30.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The recurrence of patients with epithelial ovarian cancer (EOC) is largely attributed to tumour cells escaping from the surveillance of immune cells. However, to date there is a lack of studies that have systematically evaluated the associations between the infiltration fraction of immune cells and the recurrence risk of EOC. Based on the micro-ribonucleic acid (microRNA) expression profiles of 441 EOC patients, we constructed a microRNA-based panel with recurrence prediction potential using non-negative matrix factorization consensus clustering. Then, we evaluated the association between recurrence risk and infiltration proportions among 10 immune cell types by CIBERSORT and a multivariable Cox regression model. As a result, we identified a 72-microRNA-based panel that could stratify patients into high and low risk of recurrence. The infiltration of plasma cells and M1 macrophages was consistently significantly associated with the risk of recurrence in patients with EOC. Plasma cells were significantly associated with a decreased risk of relapse [hazard ratio (HR) = 0.58, p = 0.006), while M1 macrophages were associated with an increased risk of relapse (HR = 1.59, p = 0.003). Therefore, the 72-microRNA-based panel, M1 macrophages and plasma cells may hold potential to serve as recurrence predictors of EOC patients in clinical practice.
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http://dx.doi.org/10.1111/cei.13639DOI Listing
June 2021

NHF-Induced Morphology Control of CoP Nanostructures to Enhance the Hydrogen Evolution Reaction.

Inorg Chem 2021 Jul 30;60(14):10781-10790. Epub 2021 Jun 30.

School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China.

Developing non-noble metal catalysts with superior catalytic activity and excellent durability is critically essential to promote electrochemical water splitting for hydrogen production. Morphology control as a promising and effective strategy is widely implemented to change the surface atomic coordination and thus enhance the intrinsic catalytic performance of current electrocatalysts. Herein, a series of cobalt phosphide (CoP) electrocatalysts with tunable morphologies of nanosheets, nanowires, nanorods, and nanoblocks have been prepared for the enhanced hydrogen evolution reaction (HER) by only adjusting the amount of ammonium fluoride (NHF) in the hydrothermal process. Benefiting from the large active area, high surface activity, and favorable ion and gas diffusion channels, the clustered CoP nanorods obtained at a concentration of 0.15 M NHF show the best HER performance with only an overpotential of 71 mV at a current density of 10 mA cm and a low Tafel slope of 60.75 mV dec in 1 M KOH. After 3000 CV cycles and 24 h durability tests, there is only a very slight degradation of performance owing to its outstanding stability and robust substrate adhesion.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01484DOI Listing
July 2021

Low-dose decitabine plus venetoclax is safe and effective as post-transplant maintenance therapy for high-risk acute myeloid leukemia and myelodysplastic syndrome.

Cancer Sci 2021 Jun 29. Epub 2021 Jun 29.

Department of Hematology, Tianjin First Central Hospital, Tianjin, China.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients.
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http://dx.doi.org/10.1111/cas.15048DOI Listing
June 2021

DUSP26 induces aortic valve calcification by antagonizing MDM2-mediated ubiquitination of DPP4 in human valvular interstitial cells.

Eur Heart J 2021 Jun 28. Epub 2021 Jun 28.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277# Jiefang Avenue, Wuhan, Hubei 430022, China.

Aims : The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. Here, we evaluated the role and therapeutic value of dual-specificity phosphatase 26 (DUSP26) in CAVD.

Methods And Results : Microarray profiling of human calcific aortic valves and normal controls demonstrated that DUSP26 was significantly up-regulated in calcific aortic valves. ApoE-/- mice fed a normal diet or a high cholesterol diet (HCD) were infected with adeno-associated virus serotype 2 carrying DUSP26 short-hairpin RNA to examine the effects of DUSP26 silencing on aortic valve calcification. DUSP26 silencing ameliorated aortic valve calcification in HCD-treated ApoE-/- mice, as evidenced by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased peak transvalvular jet velocity and mean transvalvular pressure gradient, as well as increased aortic valve area), and decreased levels of osteogenic markers (Runx2, osterix, and osteocalcin) in the aortic valves. These results were confirmed in osteogenic medium-induced human valvular interstitial cells. Immunoprecipitation, liquid chromatography-tandem mass spectrometry, and functional assays revealed that dipeptidyl peptidase-4 (DPP4) interacted with DUSP26 to mediate the procalcific effects of DUSP26. High N6-methyladenosine levels up-regulated DUSP26 in CAVD; in turn, DUSP26 activated DPP4 by antagonizing mouse double minute 2-mediated ubiquitination and degradation of DPP4, thereby promoting CAVD progression.

Conclusion : DUSP26 promotes aortic valve calcification by inhibiting DPP4 degradation. Our findings identify a previously unrecognized mechanism of DPP4 up-regulation in CAVD, suggesting that DUSP26 silencing or inhibition is a viable therapeutic strategy to impede CAVD progression.
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http://dx.doi.org/10.1093/eurheartj/ehab316DOI Listing
June 2021

FATTY ACID SYNTHESIS IS REQUIRED FOR BREAST CANCER BRAIN METASTASIS.

Nat Cancer 2021 Apr 1;2(4):414-428. Epub 2021 Apr 1.

Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain. We determine that this phenotype is an adaptation to decreased lipid availability in brain relative to other tissues, resulting in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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http://dx.doi.org/10.1038/s43018-021-00183-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223728PMC
April 2021

Circular RNA profiling reveals a potential role of hsa_circ_IPCEF1 in papillary thyroid carcinoma.

Mol Med Rep 2021 Aug 24;24(2). Epub 2021 Jun 24.

School of Medicine, Nankai University, Tianjin 300071, P.R. China.

Circular RNAs (circRNAs) are a novel type of non‑coding RNAs that are expressed across species and are implicated in cellular biological processes, displaying dysregulated expression in various tumorigeneses. Therefore, circRNA deregulation could be a crucial event in thyroid carcinoma. The present study identified circRNA signatures in several patients with papillary thyroid carcinoma (PTC) to complement the understanding of PTC pathogenesis. Using microarray technology, the circRNA profiles in three pairs of PTC tumors and matching adjacent normal tissues were screened. Differentially expressed circRNAs were further validated by reverse transcription‑quantitative PCR in whole blood from 57 pairs of subjects. Bioinformatics data analyses including miRNA response element prediction, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, competing endogenous RNA and KEGG Orthology‑Based Annotation System analyses were performed to predict circRNA associations with cancer‑related putative downstream miRNAs and target genes. Receiver operating characteristic curves and the area under the curve (AUC) values were acquired to assess the performance of validated circRNAs in predicting potential associations with PTC. In total, 158 dysregulated circRNAs were identified in PTC tumors relative to adjacent normal tissues. Notably, one downregulated circRNA (hsa_circ_IPCEF1) showed the preferable predictive power (AUC=0.8010, P<0.0001) and interactions with four cancer‑related genes (CASR, CDC25B, NFκB1 and SHOC2). From these analyses, one PTC‑related miRNA (hsa‑miR‑3619‑5p) was identified as a potential target for hsa_circ_IPCEF1 sponging, indicating the hsa_circ_IPCEF1/hsa‑miR‑3619‑5p axis in pathogenesis.
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http://dx.doi.org/10.3892/mmr.2021.12241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240180PMC
August 2021

Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model.

Int J Stem Cells 2021 Jun 30. Epub 2021 Jun 30.

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Sciences, Central South University, Changsha, China.

Background And Objectives: Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored.

Methods And Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×10, 2.5×10 and 1×10 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3CD4CD25FoxP3 cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3CD4CD25 FoxP3 cells was decreased.

Conclusions: UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.
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http://dx.doi.org/10.15283/ijsc20002DOI Listing
June 2021

[Expression of RASGRP2 in Lung Adenocarcinoma and Its Effect 
on Immune Microenvironment].

Zhongguo Fei Ai Za Zhi 2021 Jun;24(6):404-411

Department of Lung Cancer Surgery; Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer still has the highest incidence rate and mortality rate nowadays. In recent years, with the emergence of new drugs and the optimization of treatment mode, especially the clinical application of immunotherapy, the prognosis of lung cancer patients has been improved. However, the benefits of immunotherapy are still limited. Therefore, it is necessary to find new biomarkers to predict the prognosis of lung adenocarcinoma patients and explore its impact on the immune microenvironment.

Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the gene sequencing and clinical data of patients with lung adenocarcinoma. The distribution of RASGRP2 in lung adenocarcinoma was determined by using the human protein mapping database. The Kaplan-Meier plotter database was used to explore the relationship between the expression of RASGRP2 and the prognosis of patients with lung adenocarcinoma. KEGG and GO gene enrichment analysis was performed in patients with high and low expression of RASGRP2. TCGA database was used to analyze the co-expression genes of RASGRP2 and TIMER database was used to calculate the immune related lymphoid infiltration of RASGRP2 and its coexpression genes. The relationship between RASGRP2 expression and immune checkpoint expression was analyzed by using TIMER 2.0 database.

Results: We found that RASGRP2 was low expressed in lung adenocarcinoma, and its expression level was related to the prognosis of patients. The high expression of RASGRP2 was involved in the process of hematopoietic cell formation and cell adhesion, and RASGRP2 played an important role in the process of T cell activation. Through TCGA database analysis, ZAP70, TBC1D10C, RASAL3, FGD2, CD37 and ACAP1 were significantly correlated with RASGRP2. The high expression of these genes leaded to the increase of the proportion of CD8+ T cells, memory CD4+ T cells, and the decrease of the proportion of neutrophils and Treg cells. Finally, we found that the expression of RASGRP2 was significantly correlated with the expression of CD274, CTLA4, LAG3 and TIGIT.

Conclusions: RASGRP2 was abnormally expressed in lung adenocarcinoma and correlated with the infiltration level of immune related cells, which might influence the efficacy of immunotherapy.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.105.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246396PMC
June 2021

A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis.

Nutr Res 2021 May 21;92:1-11. Epub 2021 May 21.

Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared to other lipid emulsions. A systematic review and meta-analysis was conducted to evaluate the effect of SMOFlipid on liver function, triglycerides (TG), inflammatory markers, and clinical outcomes in hospitalized adults after short-term use compared to others. A search of the PubMed, Medline, Embase, China National Knowledge Infrastructure, and Wanfang databases was performed to identify the included randomized controlled trials. Trials with adults who were administrated a short-term course of SMOFlipid were included. A meta-analysis on liver function markers, TG, inflammatory markers, and clinical outcomes was conducted. A total of 18 randomized controlled trials with 1188 patients were included. Compared to other lipid emulsions, SMOFlipid was associated with a significant reduction in ALT, AST, γ-glutamyltransferase, total bilirubin, TG, C-reactive protein and length of hospital stay. No effect on serum interleukin-6 levels or adverse events were observed. For adult patients, our meta-analysis indicated that SMOFlipid may be beneficial to the liver and prone to prevent hyperlipidemia. The SMOFlipid also shortened length of hospital stay.
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http://dx.doi.org/10.1016/j.nutres.2021.05.003DOI Listing
May 2021
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