Publications by authors named "Feng Jin"

709 Publications

Soliton-Mediated Magnetic Reversal in an All-Oxide-Based Synthetic Antiferromagnetic Superlattice.

ACS Appl Mater Interfaces 2021 Apr 20. Epub 2021 Apr 20.

Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China.

All-oxide-based synthetic antiferromagnets (SAFs) are attracting intense research interest due to their superior tunability and great potentials for antiferromagnetic spintronic devices. In this work, using the LaCaMnO/CaRuTiO (LCMO/CRTO) superlattice as a model SAF, we investigated the layer-resolved magnetic reversal mechanism by polarized neutron reflectivity. We found that the reversal of LCMO layer moments is mediated by nucleation, expansion, and shrinkage of a magnetic soliton. This unique magnetic reversal process creates a reversed magnetic configuration of the SAF after a simple field cycling. Therefore, it can enable vertical data transfer from the bottom to the top of the superlattice. The physical origin of this intriguing magnetic reversal process could be attributed to the cooperation of the surface spin-flop effect and enhanced uniaxial magnetic anisotropy of the bottom LCMO layer. This work may pave a way to utilize all-oxide-based SAFs for three-dimensional spintronic devices with vertical data transfer and high-density data storage.
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http://dx.doi.org/10.1021/acsami.1c02506DOI Listing
April 2021

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis.

Int J Biol Sci 2021 27;17(5):1315-1327. Epub 2021 Mar 27.

Department of Cell Biology, Key Laboratory of Cell Biology of National Health Commission of the PRC, Key Laboratory of Medical Cell Biology of Ministry of Education of the PRC, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning, China.

Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. PAK5 inhibits the release of AIF from mitochondria in breast cancer cells by decreasing the mitochondria membrane permeability and increasing the membrane potential. Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation. Functionally, we demonstrate that PAK5-mediated AIF phosphorylation promotes the proliferation of breast cancer cells and accelerates the growth of breast cancer . Significantly, PAK5 and AIF expression in breast cancer are positively correlated with poor patient prognosis. PAK5 expression is negatively correlated with AIF nuclear translocation. These results suggest that PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for the treatment of breast cancer.
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http://dx.doi.org/10.7150/ijbs.58102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040471PMC
March 2021

Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study.

Front Oncol 2021 16;11:606477. Epub 2021 Mar 16.

Department of Pharmacy, Peking University First Hospital, Beijing, China.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 . 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03437837.
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http://dx.doi.org/10.3389/fonc.2021.606477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009183PMC
March 2021

High-dose radiation associated with improved survival in IDH-wildtype low-grade glioma.

Chin Neurosurg J 2021 Apr 1;7(1):22. Epub 2021 Apr 1.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Background: As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG.

Methods: In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy.

Results: In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival.

Conclusions: In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.
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http://dx.doi.org/10.1186/s41016-021-00239-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015052PMC
April 2021

A series of carboxymethyl cellulose-based antimicrobial peptide mimics were synthesized for antimicrobial applications.

Carbohydr Polym 2021 Jun 16;261:117822. Epub 2021 Feb 16.

Guangdong Institute of Microbiology, Guangdong Academy of Sciences, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangzhou 510070, PR China. Electronic address:

Inspired by antimicrobial peptides (AMP) which could alleviate drug resistance pressure, antimicrobial peptide mimics (AMPMs) were designed timely. Here, carboxymethyl cellulose (CMC) -based AMPMs were constructed by introducing different diamines on CMC effectively. Firstly, CMC was degraded to be oligomers with different molecular weights, followed by amination reactions with different diamines respectively. After protonation, a series of AMPMs with different structures were synthesized successfully. Their antibacterial effect has been evaluated by dynamic growth curves and microdilution method. The images snapped by the confocal laser scanning microscope and transmission electron microscope have fully proved its great lethality. And the antibacterial mechanism measured by flow cytometry analysis and zeta potential detection demonstrated that the destruction of membrane potential leads to bacteria death. The excellent blood compatibility and negligible drug resistance has also been confirmed. In addition, the synthesis method is simple and environmental-friendly.
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http://dx.doi.org/10.1016/j.carbpol.2021.117822DOI Listing
June 2021

Corilagin induces apoptosis and autophagy in NRF2‑addicted U251 glioma cell line.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA.

Corilagin, extracted from the Euphorbiaceae and plants, inhibits the growth of a number of types of tumors. Compared with temozolomide, the traditional chemotherapy drug, corilagin has demonstrated stronger antitumor activity. However, the pharmaceutical mechanism of corilagin in glioma remains unclear. Nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2) is positively associated with several types of tumor including glioma. In the present study, NRF2 expression was higher in glioma tissues compared with non‑glioma specimens. Therefore, it was hypothesized that corilagin targets NRF2 regulation of U251 cell apoptosis. The present study used Hoechst 33258 staining to demonstrate that corilagin induced glioma cell apoptosis and observed that the expression of the apoptosis‑related gene Bcl‑2 was reduced. In addition, corilagin induced autophagy and promoted the conversion of light chain 3 (LC3) protein from LC3Ⅰ to LC3II. NRF2 expression was downregulated by corilagin stimulation. Furthermore, the gene expression pattern following knockdown of NRF2 in U251 cells using siRNA was consistent with corilagin stimulation. Therefore, it was preliminarily concluded that corilagin induces apoptosis and autophagy by reducing NRF2 expression.
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http://dx.doi.org/10.3892/mmr.2021.11959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974271PMC
May 2021

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

Cancer Med 2021 Apr 18;10(8):2752-2762. Epub 2021 Mar 18.

Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction.

Methods: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models.

Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (p  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p  = 0.0497). However, these interactions became insignificant after Bonferroni correction.

Conclusion: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.
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http://dx.doi.org/10.1002/cam4.3847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026916PMC
April 2021

Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse.

Vaccine 2021 04 5;39(16):2280-2287. Epub 2021 Mar 5.

Guangdong South China Vaccine, Guangzhou, China; Sino-French Hoffmann Institute of Immunology, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangzhou, China. Electronic address:

The emergence of the global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic underscores the importance of the rapid development of a non-invasive vaccine that can be easily administered. A vaccine administered by nasal delivery is endowed with such characteristics against respiratory viruses. In this study, we generated a recombinant SARS-CoV-2 receptor-binding domain (RBD)-based subunit vaccine. Mice were immunized via intranasal inoculation, microneedle-intradermal injection, or intramuscular injection, after which the RBD-specific immune responses were compared. Results showed that when administrated intranasally, the vaccine elicited a robust systemic humoral immunity with high titers of IgG antibodies and neutralizing antibodies as well as a significant mucosal immunity. Besides, antigen-specific T cell responses were also analyzed. These results indicated that the non-invasive intranasal administration should be explored for the future SARS-CoV-2 vaccine design.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934688PMC
April 2021

Genome-wide 5-hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer.

Genomics Proteomics Bioinformatics 2021 Mar 11. Epub 2021 Mar 11.

Department of Surgical Oncology and Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110000, China. Electronic address:

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epigenetic mark in cancer; its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive primary tumors (MT) exhibit higher 5hmC levels than those in the non-metastatic primary tumors (PT). In contrast, the TETs protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes (MLN) compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
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http://dx.doi.org/10.1016/j.gpb.2019.05.005DOI Listing
March 2021

ERRATUM: Comparison between Craniospinal Irradiation and Limited-Field Radiation in Patients with Non-metastatic Bifocal Germinoma.

Cancer Res Treat 2021 Apr 9;53(2):607-0. Epub 2021 Mar 9.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.4143/crt.2020.437.EDOI Listing
April 2021

Universal Method to Fabricate Transition Metal Single-Atom-Anchored Carbon with Excellent Oxygen Reduction Reaction Activity.

ACS Appl Mater Interfaces 2021 Mar 11;13(11):13534-13540. Epub 2021 Mar 11.

Laboratory of Water Pollution Remediation, School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.

Single-atom catalysts (SACs) have attracted great attention due to their high atom-utilization and catalytic efficiency. However, a universal synthetic route is still lacking, which restricts the SAC-related investigation and application. Here, we report a simple and cost-effective method to fabricate transition metal SACs through ion exchange and annealing procedures. Benefiting from the "egg-box" structure property of alginate, the metal ion can be effectively anchored into the organic center. Using CuCl as a representative transition metal ion, the Cu SAC structure was synthesized and identified by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy and X-ray absorption fine structure spectroscopy. Through optimizing CuCl concentration, the obtained Cu SAC exhibited a good oxygen reduction reaction activity, whose onset potential, half wave potential, and limiting current density are all comparable to those of 20 wt % Pt/C. Cu-N was identified as the responsible catalytic site. More importantly, other transition metal SACs can be easily synthesized altering metallic solution, which proves the universality of our proposed method. This work may be valuable for the cost-effective and universal SAC synthetic method development.
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http://dx.doi.org/10.1021/acsami.0c21641DOI Listing
March 2021

Metabolite Differences of Polyphenols in Different Litchi Cultivars ( Sonn.) Based on Extensive Targeted Metabonomics.

Molecules 2021 Feb 23;26(4). Epub 2021 Feb 23.

Key Laboratory of South Subtropical Fruit Biology and Genetic Resource Utilization, Key Laboratory of Tropical and Subtropical Fruit Tree Researches, Institute of Fruit Tree Research, Guangdong Academy of Agricultural Sciences, Ministry of Agriculture, Guangzhou 510640, China.

Litchi is an important fruit cultivated in tropical and subtropical areas with high nutritious and delicious flavor and the pulp is the main part of the fruit consumed. Previous studies found that litchi had high total phenol content and antioxidant activity, but most of them focused on the identification of single or a few phenolic components with a low throughput test, and the metabolic differences of cultivars are still unknown to a some extent. In this study we used widely targeted metabolome based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) to analyze the polyphenol metabolites of five different genotypes of mature litchi fruit. A total of 126 polyphenol metabolites in eight categories were identified to reveal the composition and differences of polyphenol; 15 common differential metabolites and 20 specific differential metabolites to each cultivar were found for the first time. The results infer that flavonoids, flavonols, hydroxycinnamoyls and catechins are the main polyphenol metabolites of litchi pulp. Cluster analysis showed that there were three groups of polyphenols from high to low; early maturing Feizhixiao is a kind of high polyphenol content cultivars, especially in catechins, anthocyanins, flavonols, quinic acids and hydroxycinnamoyls. The polyphenols in the flesh of mature litchi are rich, and there are significant differences among cultivars; there was a level of correlation between the contents of phenolics and the maturity of litchi cultivars; the content of phenolics in early maturing litchi cultivars appeared higher than those of mid- to late-maturing cultivars. This experiment will provide significant reference information for cultivation, breeding, processing and consumption.
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http://dx.doi.org/10.3390/molecules26041181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926386PMC
February 2021

Gastrointestinal Symptoms During Depressive Episodes in 3256 Patients with Major Depressive Disorders: Findings from the NSSD.

J Affect Disord 2021 May 17;286:27-32. Epub 2021 Feb 17.

Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. Electronic address:

Background: Little is known how often depressive episodes are accompanied by gastrointestinal symptoms in major depressive disorders (MDD). The authors sought to determine the frequency and clinical correlates of gastrointestinal symptoms during episodes of depressive disorder.

Methods: 3,256 MDD patients from the National Survey on Symptomatology of Depression (NSSD), which was designed to investigate the magnitude of symptoms of current major depressive episodes in China, were enrolled and assessed for gastrointestinal symptoms in this study. Illness characteristics were compared in patients with a different frequency of gastrointestinal symptoms. Pearson correlation analysis and multiple linear regression analysis were employed to investigate the associations between gastrointestinal symptoms and psychological characteristics in the patients.

Results: More than 70% of the subjects with depressive episodes had concomitant gastrointestinal symptoms. A higher frequency of gastrointestinal symptoms was associated with an increased risk of suicide ideation, suicide attempts, anxious mood, depressed mood, insomnia, feeling a failure, poor concentration, body pain, hopelessness, anger, and irritability. Pearson correlation analysis indicated moderate but significant associations between gastrointestinal symptoms and psychological characteristics (p<0.001). Multiple linear regression analysis showed that suicide ideation (β=0.161, p<0.001), anxiety mood (β=0.166, p = 0.006), insomnia (β =0.262, p<0.001), anger (β=0.144, p<0.001), feeling a failure (β =0.365, p<0.001), and body pain (β=0.581 p<0.001) were independently associated with gastrointestinal symptoms in MDD patients.

Conclusion: Gastrointestinal symptoms were one of the most prevalent clinical presentations of MDD. The associations between gastrointestinal symptoms and psychological characteristics may prove useful in expanding our understanding of how gastrointestinal symptoms contributes to MDD.
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http://dx.doi.org/10.1016/j.jad.2021.02.039DOI Listing
May 2021

Comparative Analysis of Paper-Based and Web-Based Versions of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) Questionnaire in Breast Cancer Patients: Randomized Crossover Study.

JMIR Med Inform 2021 Mar 2;9(3):e18269. Epub 2021 Mar 2.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Breast cancer remains the most common neoplasm diagnosed among women in China and globally. Health-related questionnaire assessments in research and clinical oncology settings have gained prominence. The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) is a rapid and powerful tool to help evaluate disease- or treatment-related symptoms, both physical and emotional, in patients with breast cancer for clinical and research purposes. Prevalence of individual smartphones provides a potential web-based approach to administrating the questionnaire; however, the reliability of the NFBSI-16 in electronic format has not been assessed.

Objective: This study aimed to assess the reliability of a web-based NFBSI-16 questionnaire in breast cancer patients undergoing systematic treatment with a prospective open-label randomized crossover study design.

Methods: We recruited random patients with breast cancer under systematic treatment from the central hospital registry to complete both paper- and web-based versions of the questionnaires. Both versions of the questionnaires were self-assessed. Patients were randomly assigned to group A (paper-based first and web-based second) or group B (web-based first and paper-based second). A total of 354 patients were included in the analysis (group A: n=177, group B: n=177). Descriptive sociodemographic characteristics, reliability and agreement rates for single items, subscales, and total score were analyzed using the Wilcoxon test. The Lin concordance correlation coefficient (CCC) and Spearman and Kendall τ rank correlations were used to assess test-retest reliability.

Results: Test-retest reliability measured with CCCs was 0.94 for the total NFBSI-16 score. Significant correlations (Spearman ρ) were documented for all 4 subscales-Disease-Related Symptoms Subscale-Physical (ρ=0.93), Disease-Related Symptoms Subscale-Emotional (ρ=0.85), Treatment Side Effects Subscale (ρ=0.95), and Function and Well-Being Subscale (ρ=0.91)-and total NFBSI-16 score (ρ=0.94). Mean differences of the test and retest were all close to zero (≤0.06). The parallel test-retest reliability of subscales with the Wilcoxon test comparing individual items found GP3 (item 5) to be significantly different (P=.02). A majority of the participants in this study (255/354, 72.0%) preferred the web-based over the paper-based version.

Conclusions: The web-based version of the NFBSI-16 questionnaire is an excellent tool for monitoring individual breast cancer patients under treatment, with the majority of participants preferring it over the paper-based version.
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http://dx.doi.org/10.2196/18269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967224PMC
March 2021

MiR-467b alleviates lipopolysaccharide-induced inflammation through targeting STAT1 in chondrogenic ATDC5 cells.

Int J Immunogenet 2021 Mar 1. Epub 2021 Mar 1.

Department of Orthopedics, Community Health Service Center of Shouxiang, Hangzhou, Zhejiang Province, China.

Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide. Chondrocytes are activated in OA patients, accompanied by excessive chondrogenic proliferation and production of inflammatory cytokines. MiR-467b is implicated in the regulation of artherosclerosis and pro-inflammatory cytokine secretion. However, the precise role of miR-467b in OA remains unclear. In the present study, we induced inflammation in chondrogenic ATDC5 cells using lipopolysaccharide (LPS). LPS treatment significantly elevated the production of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α (TNF-α) in ATDC5 cells, accompanied by decreased miR-467 level. Then, we over-expressed miR-467b using its specific mimics in ATDC5 cells, and LPS-induced inflammation was significantly inhibited as evidenced by decreased IL-6, IL-1β and TNF-α levels. MiR-467b agomir also alleviated inflammation in rat knee osteoarthritis (KOA) model. In addition, we validated that signal transducer and activator of transcription 1 (STAT1) was a downstream target of miR-467b. LPS treatment significantly increased the STAT1 expression while miR-467b mimic transfection partially reversed this effect. Moreover, STAT1 knockout reversed the increased contents of IL-6, IL-1β and TNF-α. Furthermore, miR-467b over-expression significantly decreased the production of IL-6, IL-1β and TNF-α induced by LPS treatment, which was partially reversed by further STAT1 over-expression. In summary, our findings demonstrated that miR-467b alleviated LPS-induced inflammation through targeting STAT1, and this miR-467b/STAT1 regulation axis may provide a new therapeutic target for OA clinical management.
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http://dx.doi.org/10.1111/iji.12534DOI Listing
March 2021

Corilagin induces human glioblastoma U251 cell apoptosis by impeding activity of (immuno)proteasome.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA.

Glioma is a type of common primary intracranial tumor, which is difficult to treat. It has been confirmed by research that corilagin (the primary active constituent of the matsumura leafflower herb) has significant antitumor effect. In particular, our previous research demonstrated that corilagin effectively promotes apoptosis of glioma U251 cells and has a synergistic effect when used with temozolomide. However, the mechanism by which corilagin causes apoptosis in U251 cells has yet to be investigated. Proteasomes are catalytic centers of the ubiquitin‑proteasome system, which is the major protein degradation pathway in eukaryotic cells; they are primarily responsible for the degradation of signal molecules, tumor suppressors, cyclins and apoptosis inhibitors and serve an important role in tumor cell proliferation and apoptosis. The present study investigated the pro‑apoptotic effect of corilagin on glioma U251 cells and confirmed that decreased proteasome activity and expression levels serve an important role in corilagin‑induced U251 cell apoptosis.
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http://dx.doi.org/10.3892/or.2021.7985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905533PMC
April 2021

Detoxification of ionic liquids using glutathione, cysteine, and NADH: Toxicity evaluation by Tetrahymena pyriformis.

Environ Pollut 2021 May 12;276:116725. Epub 2021 Feb 12.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China. Electronic address:

Ionic liquids (ILs), also known as green solvents, are widely acknowledged in several fields, such as chemical separation, synthesis, and electrochemistry, owing to their excellent physiochemical properties. However, their poor biodegradability may lead to environmental and health risks, posing a severe threat to humans, thus requiring further research. In this study, the biotoxicities of the imidazolium-based ILs were evaluated in Tetrahymena pyriformis. Moreover, IL detoxification was investigated by addition of glutathione (GSH), cysteine, and nicotinamide adenine dinucleotide (NADH). Reactive oxygen species (ROS) initiated by different IL types caused damage to Tetrahymena, while glutathione, cysteine, and NADH eliminated ROS, achieving the detoxification purposes. Detoxification results showed that NADH exhibited the best detoxification ability, followed by glutathione and cysteine. Finally, RT-PCR results suggested that metallothionein might have participated in IL detoxification.
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http://dx.doi.org/10.1016/j.envpol.2021.116725DOI Listing
May 2021

Self-Assembled Chiral Phosphorescent Microflowers from Au Nanoclusters with Dual-Mode pH Sensing and Information Encryption.

ACS Nano 2021 Mar 25;15(3):4947-4955. Epub 2021 Feb 25.

College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, China.

The self-assembly of chiral metal nanoclusters into supramolecular chiral aggregates is of interest for developing advanced materials. Herein, we manipulated the self-assembly of Au nanoclusters modified by l-/d-cysteine (l-/d-AuNCs) into ordered microstructures featuring enhanced phosphorescence and optical activities. The formation of these aggregates was driven by synergistic effect of coordination and electrostatic interactions assisted by Cd/H. Detailed structural characterization and theoretical studies confirmed that the compact aggregation structures are essential for the emission enhancement and the chirality amplification of l-/d-AuNCs. Interestingly, upon the formation of microflowers, the emission lifetime was prolonged to 3.34 ms with a switch from fluorescence to phosphorescence induced by aurophilic Au(I)···Au(I) interactions and intensive ligand-to-metal charge transfer (LMCT). Moreover, both the CD and photoluminescence (PL) signals of the microflowers exhibited pH-responsiveness. This dual-mode sensitive platform could be developed as a pH sensor with improved accuracy. Additionally, the pH-responsive photoluminescence ON/OFF switch of the microflowers could be employed for reliable information encryption and decryption. This study provides useful ideas for regulating the self-assembly of nanoclusters to generate desired photophysical properties with potential applications.
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http://dx.doi.org/10.1021/acsnano.0c09766DOI Listing
March 2021

Mindray BC-6900 Scattergram Analysis Combined with Peripheral Blood Smear in the Diagnosis of T. Marneffei Infection in an HIV-Positive Patient: a Case Report.

Clin Lab 2021 Feb;67(2)

Background: Rapid and accurate diagnosis of HIV-positive patients with Talaromyces marneffei (T. marneffei) infections remains challenging. A 60-year-old woman came to our inpatient department presenting with hematuria, abdominal pain, and diarrhea for one week. The patient had a past medical history of Acquired Immune Deficiency Syndrome (AIDS). The patient's stool was watery and the color of soy sauce. The patient was without fever, cough, and skin lesions.

Methods: The blood routine was performed with a Mindray BC-6900 hematology analyzer.

Results: Blood routine showed leukocytosis with neutrophilia and basophils and the WBC/DIFF scattergram showed a cluster of neutrophils connected with a monocyte and lymphocyte cluster and an additional cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. Surprisingly, the peripheral blood film evaluation revealed small round-to-ovoid yeast cells within the cytoplasm of neutrophils. A T. marneffei infection was suspected and anti-fungal therapy was initiated. The patient's diarrhea improved after treatment with amphotericin B for two days. A second blood routine showed a normal number of leukocytes and basophils and a diminished cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. After one week, blood cultures had grown T. marneffei.

Conclusions: The WBC/DIFF scattergram obtained from a Mindray BC-6900 analyzer provided significant hints to enhance diagnosis of T. marneffei when combined with results of a peripheral blood smear.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200601DOI Listing
February 2021

Relapse pattern and quality of life in patients with localized basal ganglia germinoma receiving focal radiotherapy, whole-brain radiotherapy, or craniospinal irradiation.

Radiother Oncol 2021 Feb 19;158:90-96. Epub 2021 Feb 19.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, China; Beijing Neurosurgery Institute, Capital Medical University, China.

Background And Purpose: The optimal target volume in localized basal ganglia (BG) germinoma is still undetermined. Thus, based on the relapse pattern and health-related quality of life (HRQOL), we evaluated three target volumes.

Material And Methods: The clinical data of 161 patients with localized BG germinoma were included in this retrospective study. Relapse status and relapse sites after treatment were explored. HRQOL was evaluated using the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (≤15 years) and Short Form-36 (SF-36) (>15 years) questionnaires based on the patients' age at last follow-up.

Results: After a median follow-up duration of 83 months (range, 20-214 months), 19 patients experienced relapse, including 15, 4, and 0 patients in the focal radiotherapy (FR) (n = 35), whole-brain radiotherapy (WBRT) plus boost (n = 109), and craniospinal irradiation (CSI) plus boost (n = 17) groups, respectively. The 5-year disease-free survival rates were 74.3%, 97.2%, and 100%, respectively (p < 0.001). Among the 15 patients who relapsed after FR, 14 had positive radiological findings, including seven (50.0%) with lesions in the periventricular area and seven (50.0%) with frontal lobe lesions. Relapse in both these areas were significantly reduced by WBRT or CSI. HRQOL data were available for 69 patients, who generally scored low. Among 38 patients evaluated by SF-36, those receiving CSI had significantly lower mental component scores than those receiving WBRT (p = 0.027) or FR (p = 0.011).

Conclusions: Considering both disease control and HRQOL, WBRT is the optimal target volume in our series. The relapse pattern identified in patients receiving FR is informative for further treatment volume optimization.
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http://dx.doi.org/10.1016/j.radonc.2021.02.009DOI Listing
February 2021

Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression.

Cell Commun Signal 2021 Feb 15;19(1):18. Epub 2021 Feb 15.

Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Background: Our previous studies have shown that the E3 ubiquitin ligase of HMG-CoA reductase degradation 1 (HRD1) functions as a tumor suppressor, as overexpression of HRD1 suppressed breast cancer proliferation and invasion. However, its role in breast cancer cell glucose metabolism was unclear. Here, our aim was to uncover the role and molecular mechanisms of HRD1 in regulating aerobic glycolysis in breast cancer.

Methods: The effect of HRD1 on robic glycolysis in breast cancer cells were assessed. Then the proliferation, colony formation ability, invasion and migration of breast cancer cells were evaluated. The relationship between HRD1 and PFKP was validated by Mass spectrometry analysis, immunofluorescence and co-immunoprecipitation. The level of PFKP ubiquitination was measured using ubiquitylation assay. Furthermore, the tumor growth and metastasis in mice xenografts were observed.

Results: We found that upregulation of HRD1 clearly decreased aerobic glycolysis, and subsequently inhibited breast cancer proliferation and invasion. Mass spectrometry analysis results revealed a large HRD1 interactome, which included PFKP (platelet isoform of phosphofructokinase), a critical enzyme involved in the Warburg Effect in breast cancer. Mechanistically, HRD1 interacted and colocalized with PFKP in the cytoplasm, targeted PFKP for ubiquitination and degradation, and ultimately reduced PFKP expression and activity in breast cancer cells. HRD1 inhibited breast cancer growth and metastasis in vivo through a PFKP-dependent way CONCLUSIONS: Our findings reveal a new regulatory role of HRD1 in Warburg effect and provide a key contributor in breast cancer metabolism. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00679-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883444PMC
February 2021

RNA mA Methylation Regulators Subclassify Luminal Subtype in Breast Cancer.

Front Oncol 2020 29;10:611191. Epub 2021 Jan 29.

Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.

RNA N-methyladenosine (mA) methylation is the most prevalent epitranscriptomic modification in mammals, with a complex and fine-tuning regulatory system. Recent studies have illuminated the potential of mA regulators in clinical applications including diagnosis, therapeutics, and prognosis. Based on six datasets of breast cancer in The Cancer Genome Atlas (TCGA) database and two additional proteomic datasets, we provide a comprehensive view of all the known mA regulators in their gene expression, copy number variations (CNVs), DNA methylation status, and protein levels in breast tumors and their association with prognosis. Among four breast cancer subtypes, basal-like subtype exhibits distinct expression and genomic alteration in mA regulators from other subtypes. Accordingly, four representative regulators (IGF2BP2, IGF2BP3, YTHDC2, and RBM15) are identified as basal-like subtype-featured genes. Notably, luminal A/B samples are subclassified into two clusters based on the methylation status of those four genes. In line with its similarity to basal-like subtype, cluster1 shows upregulation in immune-related genes and cell adhesion molecules, as well as an increased number of tumor-infiltrating lymphocytes. Besides, cluster1 has worse disease-free and progression-free survival, especially among patients diagnosed with stage II and luminal B subtype. Together, this study highlights the potential functions of mA regulators in the occurrence and malignancy progression of breast cancer. Given the heterogeneity within luminal subtype and high risk of recurrence and metastasis in a portion of patients, the prognostic stratification of luminal A/B subtypes utilizing basal-featured mA regulators may help to improve the accuracy of diagnosis and therapeutics of breast cancer.
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http://dx.doi.org/10.3389/fonc.2020.611191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878528PMC
January 2021

Computed tomographic angiography may be used for assessing the dilatation of the anterior choroidal and posterior communicating arteries in patients with moyamoya syndrome.

Eur Radiol 2021 Feb 9. Epub 2021 Feb 9.

Department of Radiology, the Affiliated Hospital of Jining Medical University, Jining, China.

Objective: To evaluate the feasibility of CT angiography (CTA) for assessing anterior choroidal artery (AChA) and posterior communicating artery (PComA) dilatation in patients with moyamoya syndrome (MMS).

Methods: Eighty-eight MMS patients who underwent digital subtraction angiography (DSA) and CTA within 1 month were enrolled. The AChA was graded using both DSA and CTA. Given the features of dual blood supply, DSA was firstly used for grading of the PComA. Then, the calibers of PComA, P1 or P2 segment of the posterior cerebral artery (PCA), were recorded from CTA. Taking DSA as a reference standard, the optimal cutoff values of the PComA/P1 or PComA/P2 were calculated to determine the dilatation of PComA. Both the AChA and PComA were classified as extreme dilatation (ED, grade 2) or non-extreme dilatation (NED, grade 0 or 1).

Results: The AChA was evaluated in 149 affected hemispheres of 88 patients while the PComA was evaluated in 70 affected hemispheres of 49 patients. The sensitivity and specificity of CTA in diagnosing AChA-ED were 92% and 93.5% respectively. Both the PComA/P1 (p < 0.001) and PComA/P2 (p = 0.4) ratios were increased in the PComA-ED group with the former yielding a better detecting performance than the latter (AUC = 0.92 vs 0.85, p = 0.046). When using 0.71 as a cutoff value, the sensitivity and specificity of the PComA/P1 ratio for diagnosis of PComA-ED cases were 91.3% and 83.3% respectively.

Conclusions: CTA could be used for the AChA classification in MMS patients, while a PComA/P1 ratio greater than 0.71 indicates the existence of PComA-ED.

Key Points: • CTA showed a high sensitivity, specificity, and accuracy in diagnosing AChA-ED in patients with MMS. • PComA/P1 ratio greater than 0.71 on CTA signified an extremely dilated PComA. • CTA could be used to assess the dilatation of AChA and PComA in MMS patients, especially for routine postoperative follow-up.
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http://dx.doi.org/10.1007/s00330-021-07722-2DOI Listing
February 2021

Heterozygosity for a Pathogenic Variant in That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium.

J Am Soc Nephrol 2021 Mar 4;32(3):756-765. Epub 2021 Feb 4.

Program in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Background: Potassium levels regulate multiple physiologic processes. The heritability of serum potassium level is moderate, with published estimates varying from 17% to 60%, suggesting genetic influences. However, the genetic determinants of potassium levels are not generally known.

Methods: A whole-exome sequencing association study of serum potassium levels in 5812 subjects of the Old Order Amish was performed. A dietary salt intervention in 533 Amish subjects estimated interaction between p.R642G and sodium intake.

Results: A cluster of variants, spanning approximately 537 kb on chromosome 16q13, was significantly associated with serum potassium levels. Among the associated variants, a known pathogenic variant of autosomal recessive Gitelman syndrome (p.R642G ) was most likely causal; there were no homozygotes in our sample. Heterozygosity for p.R642G was also associated with lower chloride levels, but not with sodium levels. Notably, p.R642G showed a novel association with lower serum BUN levels. Heterozygotes for p.R642G had a two-fold higher rate of self-reported bone fractures and had higher resting heart rates on a low-salt diet compared with noncarriers.

Conclusions: This study provides evidence that heterozygosity for a pathogenic variant in causing Gitelman syndrome, a canonically recessive disorder, contributes to serum potassium concentration. The findings provide insights into biology and the effects of heterozygosity on electrolyte homeostasis and related subclinical phenotypes that may have implications for personalized medicine and nutrition.
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http://dx.doi.org/10.1681/ASN.2020071030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920171PMC
March 2021

Gut microbiota in antiviral strategy from bats to humans: a missing link in COVID-19.

Sci China Life Sci 2021 Jan 27. Epub 2021 Jan 27.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.

Bats are a potential natural reservoir for SARS-CoV-2 virus and other viruses detrimental to humans. Accumulated evidence has shown that, in their adaptation to a flight-based lifestyle, remodeling of the gut microbiota in bats may have contributed to immune tolerance to viruses. This evidence from bats provides profound insights into the potential influence of gut microbiota in COVID-19 disease in humans. Here, we highlight recent advances in our understanding of the mechanisms by which the gut microbiota helps bats tolerate deadly viruses, and summarize the current clinical evidence on the influence of gut microbiota on the susceptibility to SARS-CoV-2 infection and risk of COVID-19 leading to a fatal outcome. In addition, we discuss the implications of gut microbiota-targeted approaches for preventing infection and reducing disease severity in COVID-19 patients.
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http://dx.doi.org/10.1007/s11427-020-1847-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847806PMC
January 2021

Effects of magnolol on egg production, egg quality, antioxidant capacity, and intestinal health of laying hens in the late phase of the laying cycle.

Poult Sci 2021 Feb 2;100(2):835-843. Epub 2020 Nov 2.

Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Wuhan 430064, China. Electronic address:

Magnolol is a multifunctional plant polyphenol. To evaluate the effects of magnolol on laying hens in the late laying period, 360 (50-week-old) laying hens were randomly assigned to 4 dietary treatments: a non-supplemented control diet (C), and control diets supplemented with 100, 200, and 300 mg/kg of magnolol (M100, M200, and M300), respectively. Each treatment had 6 replicates with 15 hens per replicate. Results showed that dietary supplementation of 200 and 300 mg/kg of magnolol increased the laying rate and the M200 group had a lower feed conversion ratio (P < 0.05). Magnolol supplementation (200 and 300 mg/kg) could linearly increase albumen height and Haugh unit of fresh eggs in the late phase of the laying cycle (P < 0.01). And magnolol linearly alleviated the decline of the albumen height and Haugh unit of eggs stored for 14 d (P < 0.01). The total superoxide dismutase activity in the ovaries of M100 group was greater than that in the other treatments (P < 0.05). As dietary magnolol levels increased, villus height of jejunum and ileum linearly increased (P < 0.01). M200 and M300 groups had higher expression level of occludin in the ileum compared with group C (P < 0.01). The level of nitric oxide production and inducible nitric oxide synthase expression in the ileum of M200 group were lower than that in the C group (P < 0.05). In conclusion, dietary supplementation of 200 and 300 mg/kg magnolol can improve hen performance, albumen quality of fresh and storage eggs, and hepatic lipid metabolism in the late laying cycle. Also, magnolol has a good effect on increasing villi and improving the intestinal mucosal mechanical barrier function.
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http://dx.doi.org/10.1016/j.psj.2020.10.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858092PMC
February 2021

Behavior Disorder and Social Function Impairment in Children with Basal Ganglia Germ Cell Tumors.

Neuropsychiatr Dis Treat 2021 14;17:91-98. Epub 2021 Jan 14.

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People's Republic of China.

Purpose: Basal ganglia intracranial germ cell tumors (iGCTs) can specifically destroy the basal ganglia network, leading to several cognitive, learning, behavioral, and social impairments. This study aimed to investigate the behavior and social disorders of patients with basal ganglia iGCTs.

Patients And Methods: We recruited 30 newly diagnosed iGCTs patients (and their parents) for the current study. The Child Behavior Checklist/6-18 was used to evaluate emotional and behavioral problems. The Conner's Parent Rating Scales was used to assess symptoms of hyperactivity/impulsivity and conduct problems. The health-related quality of life (HRQoL) was assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale. Performance status was assessed using the Lansky play-performance scale and Karnofsky performance scale. The effects of basal ganglia lesions on these scores were examined.

Results: Patients with basal ganglia iGCTs (n = 10) had more behavioral problems (attention problems, aggressive behavior, learning problems, hyperactivity index), social function impairment, anxiety/depression, and poorer HRQoL compared to patients with non-basal ganglia iGCTs (n = 20). There was no significant difference in the Lansky play-performance/Karnofsky performance scale scores.

Conclusion: This study demonstrates the effects of basal ganglia lesions on behavioral and emotional outcomes, social functions, and HRQoL of patients with iGCTs. The results may help to understand the function of basal ganglia and provide evidence for the benefit of early psychological intervention to improve the treatment for this rare disease.
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http://dx.doi.org/10.2147/NDT.S287438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813642PMC
January 2021

HES1 promotes breast cancer stem cells by elevating Slug in triple-negative breast cancer.

Int J Biol Sci 2021 1;17(1):247-258. Epub 2021 Jan 1.

Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, and Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122 Shenyang, Liaoning, China.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC is enriched with breast cancer stem cells (BCSCs), which are responsible for cancer initiation, cancer progression and worse prognosis. Our previous study found that HES1 was overexpressed and promoted invasion in TNBC. However, the role of HES1 in modulating BCSC stemness of TNBC remains unclear. Here, we found that HES1 upregulates Slug both in transcriptional level and in protein level. HES1 also has a positive correlation with Slug expression in 150 TNBC patient samples. TNBC patients with high HES1 and Slug levels show worse prognosis in both progression-free survival and overall survival analyses. Survival analyses indicate that the effects of HES1 on survival prognosis may depend on Slug. Furthermore, we reveal that HES1 is a novel transcriptional activator for Slug through acting directly on its promoter. Meanwhile, HES1 knockdown reduces BCSC self-renewal, BCSC population, and cancer cell proliferation in TNBC, whereas overexpression of Slug restores the oncogenic function of HES1, both and , suggesting that HES1 performs its oncogenic role through upregulating Slug. Taken together, HES1 promotes BCSC stemness properties via targeting Slug, highlighting that HES1 might be a novel candidate for BCSC stemness regulation in TNBC and providing new clues for identifying promising prognostic biomarkers and therapeutic targets of TNBC.
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http://dx.doi.org/10.7150/ijbs.53477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757037PMC
January 2021

Brain Metastases of Non-Small Cell Lung Cancer: Magnetic Resonance Spectroscopy for Clinical Outcome Assessment in Patients with Stereotactic Radiotherapy.

Onco Targets Ther 2020 22;13:13087-13096. Epub 2020 Dec 22.

Department of Radiotherapy & Oncology, Qingdao Center Hospital, Qingdao, People's Republic of China.

Background: Brain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM.

Patients And Methods: MRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis.

Results: The average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (<0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (=0.009) and PFS (=0.006) after stereotactic radiotherapy.

Conclusion: The positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy.
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http://dx.doi.org/10.2147/OTT.S286893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764647PMC
December 2020

Transcriptome Analysis of Walnut ( L.) Embryos Reveals Key Developmental Stages and Genes Involved in Lipid Biosynthesis and Polyunsaturated Fatty Acid Metabolism.

J Agric Food Chem 2021 Jan 29;69(1):377-396. Epub 2020 Dec 29.

State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Tree Breeding and Cultivation of the State Forestry and Grassland Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China.

Walnut ( L.) is a widely cultivated woody oilseed tree species, and its embryo is rich in polyunsaturated fatty acids. Thus far, the pathways and essential genes involved in oil biosynthesis in developing walnut embryos remain largely unclear. Our analyses revealed that a mature walnut embryo accumulated 69% oil, in which 71% were polyunsaturated fatty acids with 64% linoleic acid and 7% linolenic acid. RNA sequencing generated 39 384 unigenes in 24 cDNA libraries prepared from walnut embryos collected at 49, 63, 77, 91, 105, 119, 133, and 147 days after pollination (DAP). The principal components analysis (PCA) of samples and cluster analysis of differentially expressed genes (DEGs) showed that the total samples were divided into three main groups: 49 DAP, 63-119 DAP, and 133-147 DAP. We identified 108 unigenes associated with lipid biosynthesis, including 60 unigenes for fatty acid biosynthesis, 33 for triacylglycerol biosynthesis, 7 for oil bodies, and 8 for transcription factors. The expression levels of the genes encoding WRI1, ACCase, ACP, KASII, SAD, FAD2, FAD3, and PDAT were upregulated at 63-119 DAP relative to the levels at 49 DAP. Additionally, the lipid biosynthesis in walnut embryos began to increase while oil contents increased from 15 to 69%. We identified eight , three , one , one , one , and three genes. In addition, , , and were highly abundantly expressed in the walnut embryo, and their FPKM values achieved were 834, 2205, and 9038, respectively. High expression levels of and may be the reason why walnuts are rich in polyunsaturated fatty acids. Subcellular localization confirmed that the JrFAD3 protein played a role in the endoplasmic reticulum rather than the plastid, suggesting that linolenic acid was mainly synthesized in the endoplasmic reticulum. Weighted gene coexpression network analysis (WGCNA) showed that , , , and were coexpressed with . Our study provides large-scale and comprehensive transcriptome data of walnut embryo development. These data lay the foundation for the metabolic engineering of walnuts to increase oil contents and modify fatty acid compositions.
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http://dx.doi.org/10.1021/acs.jafc.0c05598DOI Listing
January 2021