Publications by authors named "Xiang Wang"

2,137 Publications

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Development and evaluation studies of Corylin loaded nanostructured lipid carriers gel for topical treatment of UV-induced skin aging.

Exp Gerontol 2021 Jul 27:111499. Epub 2021 Jul 27.

State Key Laboratory of Component Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

We prepared nanostructured lipid carriers (NLC) to promote skin permeation of Corylin so that it can increase its effect on photoaging. Corylin-NLCs were prepared and characterized based on morphology, particle size, zeta potentials, FTIR and DSC. In vitro, we assess the cytotoxicity and lactate dehydrogenase (LDH) of HaCaT cells irradiated by UVB. Expression of antioxidant enzymes was evaluated by commercial kits. The effects of Corylin-NLC on apoptosis were confirmed by flow cytometry and western blotting. In vivo, we use UV irradiated mouse as the oxidative stress model to assess the therapeutic effect of Corylin loaded NLC gel. We identified the Corylin-NLCs can significantly suppress the LDH release, decrease MDA content, increase in CAT, SOD, GSH-Px activity, increase the expression of Bcl-2/Bax protein and reduce the expression of cleaved caspase-3/caspase-3 protein on UVB induced HaCaT cells. The histopathological lesions were significantly improved and observably decreased MDA level, increase in antioxidant enzymes activity in serum of mice by pretreatment of Corylin-NLCs gel. Overall, this study proposes a promising strategy for improving the therapeutic efficacy of photoaging.
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http://dx.doi.org/10.1016/j.exger.2021.111499DOI Listing
July 2021

Psychometric properties of the Chinese version of the Courtauld Emotional Control Scale in women newly diagnosed with breast cancer.

Qual Life Res 2021 Jul 30. Epub 2021 Jul 30.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Renmin Middle Road 139#, Furong District, Changsha, 410011, Hunan, China.

Purpose: Emotional control, the attempt to suppress the expression of negative effects, is an essential factor in the prevalence of psychological distress in women with breast cancer. The Courtauld Emotional Control Scale (CECS) is a commonly used self-report tool for assessing emotional suppression in both clinical and general groups. This study aimed to validate the Chinese version of the Courtauld Emotional Control Scale (CECS) in women newly diagnosed with breast cancer.

Methods: The study involved 680 women newly diagnosed with breast cancer aged 25 to 76 (mean age = 48.19, standard deviation (SD) = 8.57) from Changsha (China). Data analysis included Cronbach's alpha coefficients, the intraclass correlation coefficient (ICC), Pearson's correlations, Independent-Samples T test, confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) were conducted to determine the optimal model. For the best fitting model stability was assessed with tests for invariance across age, educational level, and employment status.

Results: Internal consistency (α = 0.987) and test-retest reliability (ICC = 0.715) of the CECS were presented. Results confirm the structure of the Chinese version of the CECS with 21 items divided into three dimensions, anger suppression (CECS_AG), depression suppression (CECS_MD), and anxiety suppression (CECS_AX). Convergent and known-groups validity were acceptable. Additionally, this model remained invariant across age, educational levels, and employment status.

Conclusions: The Chinese version of the CECS has good psychometric properties in terms of reliability and validity, remaining invariant across age, educational levels, and employment status in women newly diagnosed with breast cancer.
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http://dx.doi.org/10.1007/s11136-021-02953-8DOI Listing
July 2021

Wheat SHORT ROOT LENGTH 1 gene TaSRL1 regulates root length in an auxin-dependent pathway.

J Exp Bot 2021 Jul 30. Epub 2021 Jul 30.

National Key Facility for Crop Gene Resources and Genetic Improvement/Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Root is the unique organ of water and nutrients uptake and sensing environmental stimulus in the soil. The optimization of root system architecture contributes to the stress tolerance and yield improvement. ERF (ETHYLENE RESPONSIVE FACTOR) is one of plant specific transcription factor families associated with various developmental processes and stress tolerance. We cloned a novel ERF transcription factor gene TaSRL1 (SHORT ROOT LENGTH 1) from wheat (Triticum aestivum) which is mainly expressed in root. Ectopic expression of TaSRL1 in rice exhibited short root length and plant height. TaSRL1 regulated expression of genes related to auxin synthesis, transport and signaling. Further studies revealed that TaSRL1 induced expression of the auxin transport gene TaPIN2 by directly binding to its promoter, while the interaction of TaSRL1 and TaTIFY9 repressed TaPIN2 expression. Sequence polymorphisms and association analysis showed that TaSRL1-4A was associated with root depth and angle, plant height and 1000-grain weight of wheat. The haplotype Hap-4A-2 with shallow roots, short plant height and high 1000-grain weight has been positively selected in the Chinese wheat breeding process. Therefore, we demonstrated that TaSRL1 functions as a direct regulator of TaPIN2 in the auxin-dependent pathway, and integrates auxin and JA signaling by interacting with TaTIFY9 to repress root growth. Furthermore, the molecular marker of TaSRL1-4A is valuable for the improvement of root system, plant architecture and yield in wheat breeding process.
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http://dx.doi.org/10.1093/jxb/erab357DOI Listing
July 2021

Non-Contrast CT-Based Radiomics Score for Predicting Hematoma Enlargement in Spontaneous Intracerebral Hemorrhage.

Clin Neuroradiol 2021 Jul 29. Epub 2021 Jul 29.

Department of Radiology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiangan District, 430014, Wuhan City, Hubei Province, China.

Purpose: To develop a non-contrast computed tomography-(CT)-based radiomics score for predicting the risk of hematoma early enlargement in spontaneous intracerebral hemorrhage.

Methods: A total of 258 patients from a single-center database with acute spontaneous intracerebral parenchymal hemorrhage were collected. Radiomics software was explored to segment hematomas on baseline non-contrast CT images, and the texture features were extracted. Minimal Redundancy and Maximal Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO), were used to select optimized subset of features and radiomics score was calculated. The radiomics model (radiomics score-based), radiomics nomogram (radiomics score combined with clinical factors-based) and clinical model (clinical factors-based) were built in a training cohort and validated in a test cohort. The discrimination, calibration, and clinical usefulness of the models were evaluated. Finally, a subgroup analysis was performed to assess the predictive value of radiomics score in specific hemorrhage location.

Results: Radiomics score was composed of 12 radiomics features. The radiomics model and radiomics nomogram both showed good performance in predicting hematoma enlargement (area under the curve, AUC 0.83 [0.71-0.95], AUC 0.82 [0.72, 0.93]), and were both better than clinical model (AUC 0.66 [0.54-0.79]). The radiomics model and radiomics nomogram showed satisfactory calibration and clinical usefulness for detecting hematoma enlargement. For subgroup analysis, radiomics score also showed good predictive value for hematoma enlargement in different locations (AUC were 0.828, 0.940, 0.836 and 0.904, respectively, for supratentorial, subtentorial, deep and lobes).

Conclusion: A radiomics score based on non-contrast CT may be considered as a potential biomarker for prediction of hematoma enlargement in patients with spontaneous intracerebral hemorrhage (SICH), and it presented a high incremental value to clinical factors for hematoma enlargement prediction.
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http://dx.doi.org/10.1007/s00062-021-01062-wDOI Listing
July 2021

Factor structure and sex invariance of the temporal experience of pleasure scale (TEPS) in Chinese university students and clinical population.

BMC Psychiatry 2021 Jul 28;21(1):378. Epub 2021 Jul 28.

Medical Psychological Center, the Second Xiangya Hospital,Central South University, Changsha, 410011, China.

Background: A motivation dimension of the core psychiatric symptom anhedonia additional has been suggested. The Temporal Experience of Pleasure Scale (TEPS) has been reported to assess anticipatory and consummatory pleasure separately in multiple factor-structure models. This study explored the factor structure of a Chinese version of the 18-item TEPS and further explored the measurement invariance of the TEPS across sex and clinical status (non-clinical, psychiatric).

Methods: Best-fit factor structure of the TEPS was examined in a non-clinical cohort of 7410 undergraduates, randomized into sample 1 (N = 3755) for exploratory factor analysis (EFA) and sample 2 (N = 3663) for confirmatory factor analysis (CFA). Additionally, serial CFA was conducted to evaluate measurement invariance across sex and between clinical (N = 313) and non-clinical (N = 341) samples.

Results: EFA supported a new four-factor structure with a motivation component, based on the original two-factor model (consummatory pleasure with/without motivation drive, anticipatory pleasure with/without motivation drive). CFA confirmed the four-factor model as the best-fit structure and revealed a second-order hierarchy in non-clinical and clinical samples. Full scalar invariance was observed across clinical and non-clinical samples and across sex in the clinical sample; only partial scalar invariance was observed across sex in the non-clinical sample.

Conclusions: A four-factor structured TEPS can assess motivation-driving dimensions of anticipatory and consummatory pleasure, consistent with the recently advanced multidimensional structure of anhedonia. CFA and measurement invariance results support application of the TEPS for assessing motivation aspects of anhedonia.
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http://dx.doi.org/10.1186/s12888-021-03379-9DOI Listing
July 2021

LINC00337 induces tumor development and chemoresistance to paclitaxel of breast cancer by recruiting M2 tumor-associated macrophages.

Mol Immunol 2021 Jul 24;138:1-9. Epub 2021 Jul 24.

National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Breast Cancer Department, China. Electronic address:

Background: M2 tumor-associated macrophages are closely related to the progression and prognosis of breast cancer (BCa), and could be regulated by long intergenic non-coding RNAs (lincRNAs). Moreover, the differential expression of lincRNAs affects tumor resistance. This study focused on the potential involvement and mechanism of LINC00337 in BCa.

Methods: The expression of LINC00337 in BCa was detected by bioinformatics analysis and RT-qPCR. Cell viability and proliferation were analyzed by cell counting kit-8 (CCK-8) and clone formation assay. BCa cells were treated with different concentrations of paclitaxel (PAX) to determine the chemotherapy resistance of LINC00337. Tumor formation assay, Western blot, ELISA and immunohistochemistry were performed to determine the relationship between LINC00337 and PAX in vivo. Macrophages were induced to M2-like polarization, and then functional experiments (CCK-8, wound healing) and molecular experiments (ELISA, RT-qPCR, Western blot) were used to verify the role of LINC00337.

Results: LINC00337 was up-regulated in BCa. High-expressed LINC00337 accelerated viability and proliferation of BCa cells, improved the resistance of BCa cells to PAX, and accelerated tumor growth. Overexpressed LINC00337 up-regulated the expressions of M2 macrophage markers and M-CSF, and reduced the level of GM-CSF. PAX significantly reduced the viability of BCa cells and down-regulated LINC00337. Furthermore, the successfully induced M2 type macrophages to promote BCa cell activity, migration and EMT protein expression, and LINC00337 enhanced the effect of M2 type macrophages. ShLINC00337 had the opposite effect to overexpressed LINC00337.

Conclusion: LINC00337 accelerated the malignant phenotype of BCa cells and promoted chemoresistance to paclitaxel through M2-like macrophages.
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http://dx.doi.org/10.1016/j.molimm.2021.07.009DOI Listing
July 2021

Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors.

Cancer Chemother Pharmacol 2021 Jul 26. Epub 2021 Jul 26.

Institute of Clinical Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.

Purpose: CHMFL-KIT-110, a selective c-KIT kinase inhibitor for gastrointestinal stromal tumors (GISTs), possesses a poorly water-soluble, limiting the further development of the drug. This study was to investigate the antitumor efficacy of CHMFL-KIT-110 and CHMFL-KIT-110 solid dispersion (laboratory code: HYGT-110 SD) in GIST tumor xenograft models and to explore the PK/PD relationship of HYGT-110 SD.

Methods: Plasma concentrations of HYGT-110 and HYGT-110 SD were determined by LC-MS/MS in KM mice. Antitumor activity was evaluated by measuring tumor volume and weight in c-KIT-dependent GIST xenograft models. PK/PD relationship was assessed by LC-MS/MS and Western Blot in the GIST-T1 xenografted mice.

Results: HYGT-110 exhibited a low oral bioavailability (10.91%) in KM mice. Compared with HYGT-110 treatment, the C and AUC of HYGT-110 SD in mice plasma were substantially increased by 18.81 and 6.76-fold, respectively. HYGT-110 SD (10, 30, and 100 mg/kg/day) also could dose-dependently decrease the tumor volume and weight in the GIST-882 cell-inoculated xenograft mouse models and show 86.35% tumor growth inhibition (TGI) at 28 days at a 25 mg/kg bid dosage in the GIST-T1 cell-inoculated xenograft mouse model. The free concentration of HYGT-110 in plasma was closely correlated with the inhibition of c-KIT phosphorylation levels in tumor tissues.

Conclusions: In comparison with the HPMC formulation, both improved PK and PD characteristics of the solid dispersion formulation of CHMFL-KIT-110 were observed in in vivo animal experiments.
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http://dx.doi.org/10.1007/s00280-021-04332-zDOI Listing
July 2021

Generation of three iPSC lines from different types of pediatric acute leukemia patients.

Stem Cell Res 2021 Jul 13;55:102460. Epub 2021 Jul 13.

Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China. Electronic address:

Leukemia is the most common malignant tumor in childhood. The pathogenesis of leukemia is still unclear. Therefore, it is imperative to establish effective disease models. In our study, we reprogrammed different types of pediatric acute leukemia cells into iPSCs using CytoTune®Sendai virus. All generated iPSCs maintained pluripotency and spontaneous in vivo differentiation capacity.
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http://dx.doi.org/10.1016/j.scr.2021.102460DOI Listing
July 2021

Genome-wide characterization and expression profiling of B3 superfamily during ethylene-induced flowering in pineapple (Ananas comosus L.).

BMC Genomics 2021 Jul 21;22(1):561. Epub 2021 Jul 21.

Key Laboratory of Tropical Fruit Tree Biology of Hainan Province, Institute of Tropical Fruit Trees, Hainan Academy of Agricultural Sciences, Haikou, 571100, China.

Background: The B3 superfamily (B3s) represents a class of large plant-specific transcription factors, which play diverse roles in plant growth and development process including flowering induction. However, identification and functional surveys of B3 superfamily have not been reported in ethylene-induced pineapple flowering (Ananas comosus).

Results: 57 B3 genes containing B3 domain were identified and phylogenetically classified into five subfamilies. Chromosomal localization analysis revealed that 54 of 57 AcB3s were located on 21 Linkage Groups (LG). Collinearity analysis demonstrated that the segmental duplication was the main event in the evolution of B3 gene superfamily, and most of them were under purifying selection. The analysis of cis-element composition suggested that most of these genes may have function in response to abscisic acid, ethylene, MeJA, light, and abiotic stress. qRT-PCR analysis of 40 AcB3s containing ethylene responsive elements exhibited that the expression levels of 35 genes were up-regulated within 1 d after ethephon treatment and some were highly expressed in flower bud differentiation period in stem apex, such as Aco012003, Aco019552 and Aco014401.

Conclusion: This study provides a basic information of AcB3s and clues for involvement of some AcB3s in ethylene-induced flowering in pineapple.
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http://dx.doi.org/10.1186/s12864-021-07854-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296579PMC
July 2021

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model.

J Immunol Res 2021 5;2021:9998517. Epub 2021 Jul 5.

Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which usually results in extended recovery periods and multiple complications. Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has been demonstrated to have anti-inflammatory, antibacterial, and antioxidant activities. The aim of this study was to investigate whether the administration of alpinetin could attenuate PICS in a septic mouse model. Mice were randomly divided into four groups: the (1) sham-operated group, (2) sham+alpinetin (1 mg/kg intravenously infused for once per day after sham operation), (3) cecal ligation and puncture (CLP), and (4) CLP+alpinetin (50 mg/kg intravenously infused for once per day after CLP). Eight days after sham operation or CLP surgery, mice were euthanized for subsequent examination. Alpinetin significantly improved the survival of septic mice. Also, it attenuated the CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome. The level of plasma proinflammatory cytokines and apoptosis of T lymphocytes were obviously decreased by alpinetin as well. Moreover, oxidative stress in the organs was compelling lower in the alpinetin-treated CLP mice. In this clinically relevant model of sepsis, alpinetin ameliorates CLP-induced organ dysfunction and improves the likelihood of survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis. These findings suggested that alpinetin could be a potential novel therapeutic approach to prevent sepsis-induced PICS.
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http://dx.doi.org/10.1155/2021/9998517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275435PMC
July 2021

Identification of prognostic long non-coding RNA signature with potential drugs in hepatocellular carcinoma.

Aging (Albany NY) 2021 Jul 20;13(undefined). Epub 2021 Jul 20.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Hepatocellular carcinoma (HCC) is the primary malignancy in the liver with high rate of death and recurrence. Novel prognostic model would be crucial for early diagnosis and improved clinical decision. The study aims to provide an effective lncRNA-based signature to predict survival time and tumor recurrence for HCC. Based on public database, lncRNA-based classifiers for overall survival and tumor recurrence were built with regression analysis and cross validation strategy. According to the risk-score of the classifiers, the whole cohorts were divided into groups with high and low risk. Afterwards, the efficiency of the lncRNA-based classifiers was evaluated and compared with other clinical factors. Finally, candidate small molecules for high risk groups were further screened using drug response databases to explore potential drugs for HCC treatment.
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http://dx.doi.org/10.18632/aging.203322DOI Listing
July 2021

Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma.

PeerJ 2021 7;9:e11687. Epub 2021 Jul 7.

Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of ferroptosis-related genes on prognosis has been poorly studied. The purpose of this study was to explore the prognostic value of ferroptosis-related genes.

Methods: Lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to establish a predictive signature for risk stratification. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the signature. We further explored the potential correlation between the risk score model and tumor immune status.

Results: A 15-gene ferroptosis signature was constructed to classify patients into different risk groups. The overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The signature could predict OS independent of other risk factors. Single-sample gene set enrichment analysis (ssGSEA) identified the difference in immune status between the two groups. Patients in the high-risk group had stronger immune suppression, especially in the antigen presentation process.

Conclusions: The 15-gene ferroptosis signature identified in this study could be a potential biomarker for prognosis prediction in lung adenocarcinoma. Targeting ferroptosis might be a promising therapeutic alternative for lung adenocarcinoma.
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http://dx.doi.org/10.7717/peerj.11687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272465PMC
July 2021

Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation.

EMBO J 2021 Jul 16:e107480. Epub 2021 Jul 16.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Institute of Nutrition and Health Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

The mTORC1 pathway plays key roles in regulating various biological processes, including sensing amino acid deprivation and driving expression of ribosomal protein (RP)-coding genes. In this study, we observed that depletion of glutamate dehydrogenase 1 (GDH1), an enzyme that converts glutamate to α-ketoglutarate (αKG), confers resistance to amino acid deprivation on kidney renal clear cell carcinoma (KIRC) cells. Mechanistically, under conditions of adequate nutrition, GDH1 maintains RP gene expression in a manner dependent on its enzymatic activity. Following amino acid deprivation or mTORC1 inhibition, GDH1 translocates from mitochondria to the cytoplasm, where it becomes ubiquitinated and degraded via the E3 ligase RNF213. GDH1 degradation reduces intracellular αKG levels by more than half and decreases the activity of αKG-dependent lysine demethylases (KDMs). Reduced KDM activity in turn leads to increased histone H3 lysine 9 and 27 methylation, further suppressing RP gene expression and preserving nutrition to support cell survival. In summary, our study exemplifies an economical and efficient strategy of solid tumor cells for coping with amino acid deficiency, which might in the future be targeted to block renal carcinoma progression.
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http://dx.doi.org/10.15252/embj.2020107480DOI Listing
July 2021

Optimization of light scattering enhancement by gold nanoparticles in fused silica optical fiber.

Opt Express 2021 Jun;29(13):19450-19464

A conventional distributed fiber optic sensing system offers close to linear sensitivity along the fiber length. However gold nanoparticles (NP) have been shown to be able to enhance the contrast ratio to improve the quality of signal detection. The challenge in improving the contrast of reflected signals is to optimise the nanoparticle doping concentration over the densed sensing length to make best use of the distributed fiber sensing hardware. In this paper, light enhancement by spherical gold NPs in the optical fibers was analyzed by considering the size-induced NP refractive index changes. This was achieved by building a new model to relate backscattered light from a gold NP suspension between the optical fiber end tips and backscattered light from gold NPs in the core of the optical fiber. The paper provides a model to determine the optimized sizes and concentrations of NPs for sensing at different desired penetration depths in the optical fiber.
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http://dx.doi.org/10.1364/OE.427967DOI Listing
June 2021

A biocompatible theranostic agent based on stable bismuth nanoparticles for X-ray computed tomography/magnetic resonance imaging-guided enhanced chemo/photothermal/chemodynamic therapy for tumours.

J Colloid Interface Sci 2021 Jul 1;604:80-90. Epub 2021 Jul 1.

College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China. Electronic address:

Cancer is a leading cause of death worldwide and seriously threatens the health of humans. The current clinical treatments for cancer are not efficient and always lead to significant side effects. Herein, a biocompatible and powerful theranostic agent ([email protected]@MnO/DOX) is fabricated using a facile stepwise reaction method. The Bi nanoparticles (NPs) are coated by mesoporous silica to protect the Bi NPs from oxidation, which guarantees the stable photothermal effect of the Bi NPs. When the [email protected]@MnO/DOX nanocomposites (NCs) accumulate in the tumour site, hyperthermia is generated by Bi NPs under near-infrared (NIR) light irradiation for photothermal therapy (PTT), and the generated heat triggers the release of DOX for chemotherapy in the tumour. In addition, the MnO of the NCs responsively catalyses endogenous HO to generate O, raising the oxygen level to enhance the effect of chemotherapy in the tumour microenvironment (TME), and consumes glutathione (GSH) to produce Mn for magnetic resonance (MR) imaging. Under acidic TME conditions, HO and Mn also produce toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT). Furthermore, the Bi NPs can also be used as excellent contrast agents for X-ray computed tomography (CT) imaging of tumours with a high CT value (6.865 HU mM). The [email protected]@MnO/DOX NCs exhibit a powerful theranostic performance for CT/MR imaging-guided enhanced PTT/CDT/chemotherapy, which opens a new prospect to rationally design theranostic agents for tumour imaging.
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http://dx.doi.org/10.1016/j.jcis.2021.06.174DOI Listing
July 2021

Genome-wide identification and expression analysis of the growth regulating factor (GRF) family in Jatropha curcas.

PLoS One 2021 15;16(7):e0254711. Epub 2021 Jul 15.

College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, China.

GRF genes have been confirmed to have important regulatory functions in plant growth, development and response to abiotic stress. Although the genome of Jatropha curcas is sequenced, knowledge about the identification of the species' GRF genes and their expression patterns is still lacking. In this study, we characterized the 10 JcGRF genes. A detailed investigation into the physic nut GRF gene family is performed, including analysis of the exon-intron structure, conserved domains, conserved motifs, phylogeny, chromosomal locations, potential small RNA targets and expression profiles under both normal growth and abiotic stress conditions. Phylogenetic analysis indicated that the 10 JcGRF genes were classified into five groups corresponding to group I, II, III, IV and V. The analysis of conserved domains showed that the motifs of JcGRF genes were highly conserved in Jatropha curcas. Expression analysis based on RNA-seq and qRT-PCR showed that almost all JcGRF genes had the highest expression in seeds, but very low expression was detected in the non-seed tissues tested, and four JcGRF genes responded to at least one abiotic stress at at least one treatment point. Our research will provide an important scientific basis for further research on the potential functions of JcGRF genes in Jatropha curcas growth and development, and response to abiotic stress, and will eventually provide candidate genes for the breeding of Jatropha curcas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254711PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282010PMC
July 2021

Tumor Microenvironment Modulation Platform Based on Composite Biodegradable Bismuth-Manganese Radiosensitizer for Inhibiting Radioresistant Hypoxic Tumors.

Small 2021 Jul 15:e2101015. Epub 2021 Jul 15.

Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, 200093, China.

Solid tumors possess a unique internal environment with high-level thiols (mainly glutathione), over-expressed H O , and low oxygen partial pressure, which severely restrict the radiotherapy (RT) efficacy. To overcome the imperfections of RT alone, there is vital to design a multifunctional radiosensitizer that simultaneously achieves multimodal therapy and tumor microenvironment (TME) regulation. Bismuth (Bi)-based nanospheres are wrapped in the MnO layer to form core-shell-structured radiosensitizer ([email protected]) that can effectively load docetaxel (DTX). The solubility of [email protected] is further improved via folic acid-modified amphiphilic polyethylene glycol (PFA). [email protected] can specifically respond to the TME to realize multimodal therapy. Primarily, the outer MnO layer responds with H O and glutathione to release oxygen and generate •OH, thereby alleviating hypoxia and achieving chemodynamic therapy (CDT). Afterward, the strong coordination between Bi and deprotonated thiol groups in glutathione allows the mesoporous Bi-containing core bonding with glutathione to form a water-soluble complex. These actions conduce [email protected] degradation, further releasing DTX to implement chemotherapy (CHT). In addition, the degradation in vivo and tumor enrichment of [email protected] are explored via T -weighted magnetic resonance and computed tomography imaging. The biodegradable composite [email protected] can simultaneously modulate the TME and achieve multimodal treatment (RT/CDT/CHT) for hypoxic tumors.
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http://dx.doi.org/10.1002/smll.202101015DOI Listing
July 2021

A chalcogenide-cluster-based semiconducting nanotube array with oriented photoconductive behavior.

Nat Commun 2021 Jul 13;12(1):4275. Epub 2021 Jul 13.

College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou, China.

The interesting physical and chemical properties of carbon nanotubes (CNTs) have prompted the search for diverse inorganic nanotubes with different compositions to expand the number of available nanotechnology applications. Among these materials, crystalline inorganic nanotubes with well-defined structures and uniform sizes are suitable for understanding structure-activity relationships. However, their preparation comes with large synthetic challenges owing to their inherent complexity. Herein, we report the example of a crystalline nanotube array based on a supertetrahedral chalcogenide cluster, K[K(CuGeSe)(HO)] (1). To the best of our knowledge, this nanotube array possesses the largest diameter of crystalline inorganic nanotubes reported to date and exhibits an excellent structure-dependent electric conductivity and an oriented photoconductive behavior. This work represents a significant breakthrough both in terms of the structure of cluster-based metal chalcogenides and in the conductivity of crystalline nanotube arrays (i.e., an enhancement of ~4 orders of magnitude).
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http://dx.doi.org/10.1038/s41467-021-24510-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277832PMC
July 2021

Antifungal agent Terbinafine restrains tumor growth in preclinical models of hepatocellular carcinoma via AMPK-mTOR axis.

Oncogene 2021 Jul 10. Epub 2021 Jul 10.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.

The prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory due to limited effective treatment options. In this work, we investigated the therapeutic efficacy of Terbinafine for HCC and the underlying mechanism. The influence of Terbinafine on cell growth, 3D spheroid formation, clonogenic survival, and protein synthesis was investigated in human HCC cell lines. Co-immunoprecipitation, immunofluorescence, and other techniques were employed to explore how Terbinafine exerts its anticancer effect. Subcutaneous tumorigenicity assay, orthotopic and patient-derived xenograft (PDX) HCC models were used to evaluate the anticancer effect of Terbinafine monotherapy and the combinatorial treatment with Terbinafine and sorafenib against HCC. The anticancer activity of Terbinafine was Squalene epoxidase (SQLE)-independent. Instead, Terbinafine robustly suppressed the proliferation of HCC cells by inhibiting mTORC1 signaling via activation of AMPK. Terbinafine alone or in combination with sorafenib delayed tumor progression and markedly prolonged the survival of tumor-bearing mice. The synergy between Terbinafine and sorafenib was due to concomitant inhibition of mTORC1 and induction of severe persistent DNA double-strand breaks (DSBs), which led to the delayed proliferation and accelerated cell death. Terbinafine showed promising anticancer efficacy in preclinical models of HCC and may serve as a potential therapeutic strategy for HCC.
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http://dx.doi.org/10.1038/s41388-021-01934-yDOI Listing
July 2021

Recent Progress in External-Stimulus-Responsive 2D Covalent Organic Frameworks.

Adv Mater 2021 Jul 8:e2101175. Epub 2021 Jul 8.

Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China.

Recently, smart 2D covalent organic frameworks (COFs), combining the advantages of both inherent structure features and functional building blocks, have been demonstrated to show reversible changes in conformation, color, and luminescence in response to external stimuli. This review provides a summary on the recent progress of 2D COFs that are responsive to external stimuli such as metal ions, gas molecules, pH values, temperature, electricity, light, etc. Moreover, the responsive mechanisms and design strategies, along with the applications of these stimulus-responsive 2D COFs in chemical sensors and photoelectronic devices are also discussed. It is believed that this review would provide some guidelines for designing novel single-/multistimulus-responsive 2D COFs with controllable responsive behaviors for advanced photoelectronic applications.
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http://dx.doi.org/10.1002/adma.202101175DOI Listing
July 2021

Dual-energy computed tomography for the diagnosis of acute gouty arthritis.

Curr Med Imaging 2021 Jul 7. Epub 2021 Jul 7.

Department of Radiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Avenue, Jiangan, Wuhan, Hubei 430014, China.

Aims: To investigate the diagnostic value of dual-energy computed tomography (DECT) in acute gouty arthritis (AGA) or patients presenting with suspected gouty arthritis.

Methods: This retrospective study was performed in a single centre from May 2017 to August 2018. Two hundred and twenty-six patients with an initial diagnosis of AGA in the preceding 15 days were included. All patients were referred for a DECT scan of the affected joints. The diagnosis criteria of gout with the American College of Rheumatology Classification Standard were regarded as the reference standard.

Results: Two hundred patients were included in the present study at last. The sensitivity, specificity, positive predictive value, and negative predictive value of DECT in the diagnosis of all AGA were 83.83%, 60.61%, 91.5% and 42.55% respectively. When AGA was subdivided according to the joint site, the sensitivity, specificity, positive predictive value, and negative predictive value were 80.68%, 61.11%, 91.03%, and 39.29% in feet, 93.55%, 40%, 93.55%, and 40% in knees and 87.5%, 71.43%, 91.3%, and 62.5% in ankles, respectively.

Conclusions: DECT had a high sensitivity for the diagnosis of AGA. However, the specificity was limited, particularly for the diagnosis of acute gouty knee arthritis. Prospective multicenter studies of large samples will enhance the application of DECT among the AGA patients in the future.
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http://dx.doi.org/10.2174/1573405617666210707164124DOI Listing
July 2021

A Specific Assessment of the Normal Anatomy of the Aortic Root in Relation to Age and Gender.

Int J Gen Med 2021 25;14:2827-2837. Epub 2021 Jun 25.

Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.

Background: A limitation associated with coronary computed tomography angiography (CCTA) is the lack of a normal reference value for aortic root dimensions and the uncertainty of the influence of age and gender on these dimensions. The purpose of the present study was to identify the normal values and variations of aortic root dimensions in healthy individuals and investigate how gender and age affect aortic root size.

Methods: A total of 1286 healthy yellow population (52.7 ± 11.0 years, 634 male) who underwent CCTA were retrospectively included in the present study. Male and female patients were divided into seven groups according to age (< 30 years old, 30-39, 40-49, 50-59, 60-69, 70-79, ≥ 80 years old). In these age groups, we measured and compared the parameters of the aortic root.

Results: After body surface area (BSA) correction, the aortic root parameters of females were found to be greater than those of males in the 40-49 age group (P<0.05). There were no significant differences in aortic root parameters between genders in other age groups, except for the diameter of the ascending aorta, which was greater in females (P<0.05). In males, age was positively correlated with aortic root parameters (P<0.05), except for the annulus short diameter and LVOT short diameter. In females, age was positively correlated with aortic root parameters (P<0.05), except for the left coronary ostia height and the LVOT short diameter.

Conclusion: Aortic root dimensions are affected by age and gender. After BSA correction, females show larger aortic root dimensions than males, and aortic root diameters increase with age.
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http://dx.doi.org/10.2147/IJGM.S312439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242149PMC
June 2021

A Novel Nomogram Based on Machine Learning-Pathomics Signature and Neutrophil to Lymphocyte Ratio for Survival Prediction of Bladder Cancer Patients.

Front Oncol 2021 17;11:703033. Epub 2021 Jun 17.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Traditional histopathology performed by pathologists through naked eyes is insufficient for accurate survival prediction of bladder cancer (BCa). In addition, how neutrophil to lymphocyte ratio (NLR) could be used for prognosis prediction of BCa patients has not been fully understood. In this study, we collected 508 whole slide images (WSIs) of hematoxylin-eosin strained BCa slices and NLR value from the Shanghai General Hospital and The Cancer Genome Atlas (TCGA), which were further processed for nuclear segmentation. Cross-verified prediction models for predicting clinical prognosis were constructed based on machine learning methods. Six WSIs features were selected for the construction of pathomics-based prognosis model, which could automatically distinguish BCa patients with worse survival outcomes, with hazard ratio value of 2.19 in TCGA cohort (95% confidence interval: 1.63-2.94, p <0.0001) and 3.20 in General cohort (95% confidence interval: 1.75-5.87, p = 0.0014). Patients in TCGA cohort with high NLR exhibited significantly worse clinical survival outcome when compared with patients with low NLR (HR = 2.06, 95% CI: 1.29-3.27, p <0.0001). External validation in General cohort also revealed significantly poor prognosis in BCa patients with high NLR (HR = 3.69, 95% CI: 1.83-7.44 p <0.0001). Univariate and multivariate cox regression analysis proved that both the MLPS and the NLR could act as independent prognostic factor for overall survival of BCa patients. Finally, a novel nomogram based on MLPS and NLR was constructed to improve their clinical practicability, which had excellent agreement with actual observation in 1-, 3- and 5-year overall survival prediction. Decision curve analyses both in the TCGA cohort and General cohort revealed that the novel nomogram acted better than both the tumor grade system in prognosis prediction. Our novel nomogram based on MLPS and NLR could act as an excellent survival predictor and provide a scalable and cost-effective method for clinicians to facilitate individualized therapy. Nevertheless, prospective studies are still needed for further verifications.
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http://dx.doi.org/10.3389/fonc.2021.703033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247435PMC
June 2021

A Five-Gene Prognostic Nomogram Predicting Disease-Free Survival of Differentiated Thyroid Cancer.

Dis Markers 2021 15;2021:5510780. Epub 2021 Jun 15.

Transfusion Section, Chongqing University Three Gorges Hospital, Chongqing, China.

Background: Differentiated thyroid cancer (DTC) is the most common type of thyroid tumor with a high recurrence rate. Here, we developed a nomogram to effectively predict postoperative disease-free survival (DFS) in DTC patients.

Methods: The mRNA expressions and clinical data of DTC patients were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Seventy percent of patients were randomly selected as the training dataset, and thirty percent of patients were classified into the testing dataset. Multivariate Cox regression analysis was adopted to establish a nomogram to predict 1-year, 3-year, and 5-year DFS rate of DTC patients.

Results: A five-gene signature comprised of TENM1, FN1, APOD, F12, and BTNL8 genes was established to predict the DFS rate of DTC patients. Results from the concordance index (C-index), area under curve (AUC), and calibration curve showed that both the training dataset and the testing dataset exhibited good prediction ability, and they were superior to other traditional models. The risk score and distant metastasis (M) of the five-gene signature were independent risk factors that affected DTC recurrence. A nomogram that could predict 1-year, 3-year, and 5-year DFS rate of DTC patients was established with a C-index of 0.801 (95% CI: 0.736, 0.866).

Conclusion: Our study developed a prediction model based on the gene expression and clinical characteristics to predict the DFS rate of DTC patients, which may be applied to more accurately assess patient prognosis and individualized treatment.
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http://dx.doi.org/10.1155/2021/5510780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221860PMC
June 2021

Developing fluoromodule-based probes for in vivo monitoring the bacterial infections and antibiotic responses.

Talanta 2021 Oct 15;233:122610. Epub 2021 Jun 15.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address:

Recently, antibiotic resistant has become a serious public health concern, which warrants new generations of antibiotics to be developed. Pharmacodynamic evaluation is crucial in drug discovery processes. Despite numerous advanced imaging systems are available nowadays, technologies for the sensitive in vivo diagnosis of bacterial infections and direct visualization of drug efficacy are yet to be developed. In this study, we have developed novel near-infrared (NIR) fluorogenic probes. These probes are dark in solution but highly fluorescent when bound to the cognate reporter, fluorogen-activating protein (FAP). We established the in vivo bacterial infection model using FAP_dH6.2 recombinantly expressed E. coli and applied this NIR fluoromodule-based system for diagnosing bacterial infections and monitoring disease progressions and its responses to a type of antibiotics through classic mechanism of membrane lysis. This NIR fluoromodule-based system will discover new information on bacterial infections and identify newer antibacterial entities.
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http://dx.doi.org/10.1016/j.talanta.2021.122610DOI Listing
October 2021

Strain variability in growth and thermal inactivation characteristics of Listeria monocytogenes strains after acid adaptation.

J Food Prot 2021 Jul 1. Epub 2021 Jul 1.

University of Shanghai for Science and Technology Jungong Road CHINA Shanghai 200093.

Given the importance of strain variability to predictive microbiology and risk assessment, the present study aimed to quantify the magnitude of strain variability in growth and thermal inactivation kinetics behaviors after acid adaptation. Thirty-three Listeria monocytogenes strains were exposed to acid-adapted tryptic soy broth with yeast extract and nonacid-adapted TSB-YE (pH 7.0) for 20 hours. Then, the growth parameters of these adapted and non-adapted strains that grew in non-buffered TSB-YE at 25℃ were estimated. The tested strains were inactivated at 60°C in non-buffered broth to obtain the heat resistance parameters. The results revealed that strain variability was present in the growth and thermal inactivation characteristics. The maximum specific growth rate ( μ max ) ranged within 0.21-0.44 and 0.20-0.45 h -1 after acid and non-acid adaptation, respectively. The lag times ( λ ) were 0.69-2.56 and 0.24-3.36 hours for acid-adapted and non-acid adapted cells, respectively. The apparent D -values at 60°C ( D 60 -values) of the pathogen ranged within 0.56-3.93 and 0.52-3.63 minutes for the presence and absence of acid adaptation condition, respectively. Acid adaptation increased the magnitude of strain variability in the thermal inactivation characteristics of the organism ( P <0.05), with the coefficient of variation (CV) increasing to 0.17, while acid adaptation did not significantly influence the variabilities in the growth parameters of the tested strains ( P ≥0.05). Furthermore, the subsequent growth behaviors of all strains did not exhibit significant changes ( P >0.05) after exposure to acidic broth. However, the thermal resistance of most of the tested strains (25/33) increased ( P <0.05) after growing in acid-adapted broth. The relevant data generated in the present study can be used to describe the strain variability in predictive microbiology, and deeply understand the behavior responses of different strains to acid adaptation.
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http://dx.doi.org/10.4315/JFP-20-387DOI Listing
July 2021

Microrisk Lab: An Online Freeware for Predictive Microbiology.

Foodborne Pathog Dis 2021 Jun 30. Epub 2021 Jun 30.

University of Shanghai for Science and Technology, Shanghai, China.

Microrisk Lab is an R-based online modeling freeware designed to realize parameter estimation and model simulation in predictive microbiology. A total of 36 peer-reviewed models were integrated for parameter estimation (including primary models of bacterial growth/inactivation under static and nonisothermal conditions, secondary models of specific growth rate, and competition models of two-flora growth) and model simulation (including integrated models of deterministic or stochastic bacterial growth/inactivation under static and nonisothermal conditions) in Microrisk Lab. Each modeling section was designed to provide numerical and graphical results with comprehensive statistical indicators depending on the appropriate data set and/or parameter setting. In this study, six case studies were reproduced in Microrisk Lab and compared in parallel with DMFit, GInaFiT, IPMP 2013/GraphPad Prism, Bioinactivation FE, and @Risk, respectively. The estimated and simulated results demonstrated that the performance of Microrisk Lab was statistically equivalent to that of other existing modeling systems. Microrisk Lab allows for a friendly user experience when modeling microbial behaviors owing to its interactive interfaces, high integration, and interconnectivity. Users can freely access this application at https://microrisklab.shinyapps.io/english/ or https://microrisklab.shinyapps.io/chinese/.
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http://dx.doi.org/10.1089/fpd.2020.2919DOI Listing
June 2021

Loganin exerts a protective effect on ischemia-reperfusion-induced acute kidney injury by regulating JAK2/STAT3 and Nrf2/HO-1 signaling pathways.

Drug Dev Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Nephrology, People's Hospital of Jianshi County, Enshi Autonomous, Hubei, China.

To investigate the role of loganin in hypoxia/reperfusion (H/R)-induced renal tubular epithelial cells and ischemia/reperfusion-induced acute kidney injury (AKI). Cells were received H/R treatment and cultured with different concentrations of loganin. The cell activity and apoptosis were detected. The expressions of apoptosis-related proteins, inflammatory factors, oxidative stress related molecules, and related molecules of JAK2/STAT3 and Nrf2/HO-1 signaling pathways were measured. AKI model of mice was established by I/R procedure, and the kidney was collected for hematoxylin and eosin (HE) staining. H/R treatment inhibited cell activity and apoptosis, but loganin attenuated the effect of H/R. Moreover, loganin inhibited H/R-induced inflammatory response and oxidative stress in tubular epithelial cells. Loganin down-regulated the expression of apoptosis-related proteins, suppressed JAK2/STAT3 pathway, and activated Nrf2/HO-1 pathway. In animal experiment, loganin reduced tubular injury in AKI mice.Loganin had anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects on H/R-induced tubular epithelial cells, and could improve AKI in mice induced by I/R. This effect might be achieved by inhibiting JAK2/STAT3 and activating the Nrf2/HO-1 signaling pathway.
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http://dx.doi.org/10.1002/ddr.21853DOI Listing
June 2021

TMEM229A suppresses non‑small cell lung cancer progression via inactivating the ERK pathway.

Oncol Rep 2021 Aug 29;46(2). Epub 2021 Jun 29.

Department of Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang 313000, P.R. China.

Transmembrane protein 229A (TMEM229A) is a member of the TMEM family that plays an important role in tooth differentiation and development. However, the expression level and biological role of TMEM229A in cancer remains unknown. The present study aimed to investigate the expression level of TMEM229A in non‑small cell lung cancer (NSCLC), as well as its effect and mechanism on NSCLC progression. Clinical specimens from patients with NSCLC were enrolled from the First People's Hospital of Huzhou (Huzhou, China). TMEM229A expression was detected using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunohistochemical analysis. The relationship between TMEM229A expression and the survival rate of patients with NSCLC was analyzed using Kaplan‑Meier Plotter datasets. The effects of TMEM229A on cell proliferation, migration and invasion were detected using Cell Counting Kit‑8, colony formation, soft agar, real‑time cellular analysis and Transwell assays. The expression levels of epithelial‑mesenchymal transition (EMT)‑related proteins, as well as ERK and AKT phosphorylation were determined via RT‑qPCR and western blot analysis. The results demonstrated that TMEM229A expression was significantly downregulated in human NSCLC tissues and in several cell lines compared with adjacent normal lung tissues and BEAS‑2B cells, respectively. Survival analysis of lung adenocarcinoma and squamous cell lung carcinoma cases identified that low TMEM229A expression was associated with a poor prognosis. The assays indicated that overexpressing TMEM229A significantly inhibited cell proliferation, migration and invasion, while TMEM229A knockdown had the opposite effect. Mechanistically, TMEM229A overexpression effectively increased E‑cadherin expression and reduced N‑cadherin, snail family transcriptional repressor 1 and MMP2 expression, indicating that EMT was suppressed. In addition, overexpression of TMEM229A reduced the expression levels of phosphorylated (p)‑ERK and p‑AKT, and this effect was partially suppressed by the incorporation of specific ERK inhibitor PD98059. Collectively, the results of the present study demonstrated that the effects of TMEM229A on inhibiting cell proliferation, migration and invasion were partially mediated by inactivating the ERK signaling pathway, thereby providing a potential therapeutic target for the treatment of NSCLC.
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http://dx.doi.org/10.3892/or.2021.8127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261197PMC
August 2021

N6-Methyladenosine RNA Methylation Regulator-Related Alternative Splicing (AS) Gene Signature Predicts Non-Small Cell Lung Cancer Prognosis.

Front Mol Biosci 2021 11;8:657087. Epub 2021 Jun 11.

Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

Aberrant N6-methyladenosine (m6A) RNA methylation regulatory genes and related gene alternative splicing (AS) could be used to predict the prognosis of non-small cell lung carcinoma. This study focused on 13 m6A regulatory genes (METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, and ALKBH5) and expression profiles in TCGA-LUAD ( = 504) and TCGA-LUSC ( = 479) datasets from the Cancer Genome Atlas database. The data were downloaded and bioinformatically and statistically analyzed, including the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. There were 43,948 mRNA splicing events in lung adenocarcinoma (LUAD) and 46,020 in lung squamous cell carcinoma (LUSC), and the data suggested that m6A regulators could regulate mRNA splicing. Differential HNRNPC and RBM15 expression was associated with overall survival (OS) of LUAD and HNRNPC and METTL3 expression with the OS of LUSC patients. Furthermore, the non-small cell lung cancer prognosis-related AS events signature was constructed and divided patients into high- low-risk groups using seven and 14 AS genes in LUAD and LUSC, respectively. The LUAD risk signature was associated with gender and T, N, and TNM stages, but the LUSC risk signature was not associated with any clinical features. In addition, the risk signature and TNM stage were independent prognostic predictors in LUAD and the risk signature and T stage were independent prognostic predictors in LUSC after the multivariate Cox regression and receiver operating characteristic analyses. In conclusion, this study revealed the AS prognostic signature in the prediction of LUAD and LUSC prognosis.
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http://dx.doi.org/10.3389/fmolb.2021.657087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226009PMC
June 2021
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