Publications by authors named "Chen Lu"

2,007 Publications

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Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells.

Bioengineered 2021 Oct 26. Epub 2021 Oct 26.

Department of Emergency, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, China.

Preeclampsia (PE) is a pregnancy disorder characterized by excessive trophoblast cell death. This study aims to explore the exact mechanism of the ubiquitination level of FUN14 domain containing 1 (FUNDC1) in mitophagy and injury in hypoxic trophoblast cells. In this study, HTR-8/SVneo trophoblast cells were cultured under normoxic and hypoxic conditions and PE mouse model was established. We found low ubiquitination level of FUNDC1 in hypoxic trophoblast cells and placenta of pregnant women with PE. Proteasome inhibitor MG-132 and protease activator MF-094 were added into HTR-8/SVneo trophoblast cells. Proteasome inhibitor MG-132 decreased FUNDC1 ubiquitination level while protease activator MF-094 increased FUNDC1 ubiquitination level. Inhibition of FUNDC1 ubiquitination promoted mitophagy and mitochondrial membrane potential (Δψm) in normoxic trophoblast cells, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased levels of glutathione (GSH) and superoxide dismutase (SOD). In addition, FUNDC1 ubiquitination alleviated cell injury in PE mice . In conclusion, increased FUNDC1 ubiquitination level inhibited mitophagy and Δψm changes in hypoxic trophoblast cells, and thus alleviated oxidative injury.
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http://dx.doi.org/10.1080/21655979.2021.1997132DOI Listing
October 2021

Metal-Free Cascade Formation of Intermolecular C-N Bonds Accessing Substituted Isoindolinones under Cathodic Reduction.

J Org Chem 2021 Oct 26. Epub 2021 Oct 26.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529090, P. R. China.

An electrochemical protocol for the construction of substituted isoindolinones via reduction/amidation of 2-carboxybenzaldehydes and amines has been realized. Under metal-free and external-reductant-free electrolytic conditions, the reaction achieves the cascade formation of intermolecular C-N bonds and provides a series of isoindolinones in moderate to good yields. The deuterium-labeling experiment proves that the hydrogen in the methylene of the product is mainly provided by HO in the system.
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http://dx.doi.org/10.1021/acs.joc.1c01845DOI Listing
October 2021

Trends in the Use of Benzodiazepines, Z-Hypnotics, and Serotonergic Drugs Among US Women and Men Before and During the COVID-19 Pandemic.

JAMA Netw Open 2021 Oct 1;4(10):e2131012. Epub 2021 Oct 1.

Department of Internal Medicine-Geriatrics and Palliative Medicine, University of Texas Medical Branch, Galveston.

Importance: The ongoing COVID-19 pandemic and associated mitigation measures have disrupted access to psychiatric medications, particularly for women.

Objective: To assess the sex differences in trends in the prescribing of benzodiazepines, Z-hypnotics and serotonergic (selective serotonin reuptake inhibitors [SSRIs] and serotonin and norepinephrine reuptake inhibitors [SNRIs]), which are commonly prescribed for anxiety, insomnia, and depression.

Design, Setting, And Participants: This cohort study used data from Clinformatics Data Mart, one of the largest commercial health insurance databases in the US. Enrollees 18 years or older were required to have complete enrollment in a given month during our study period, January 1, 2018, to March 31, 2021, to be included for that month.

Main Outcomes And Measures: Prescription of a benzodiazepine, Z-hypnotic, or SSRI or SNRI. For each month, the percentage of patients with benzodiazepine, Z-hypnotic, or SSRI or SNRI prescriptions by sex was calculated.

Results: The records of 17 255 033 adults (mean [SD] age, 51.7 [19.5] years; 51.3% female) were examined in 2018, 17 340 731 adults (mean [SD] age, 52.5 [19.7] years; 51.6% female) in 2019, 16 916 910 adults (mean [SD] age, 53.7 [19.8] years; 51.9% female) in 2020, and 15 135 998 adults (mean [SD] age, 56.2 [19.8] years; 52.5% female) in 2021. Compared with men, women had a higher rate of prescriptions for all 3 drugs classes and had larger changes in prescription rates over time. Benzodiazepine prescribing decreased from January 2018 (women: 5.61%; 95% CI, 5.60%-5.63%; men: 3.03%; 95% CI, 3.02%-3.04%) to March 2021 (women: 4.91%; 95% CI, 4.90%-4.93%; men: 2.66%; 95% CI, 2.65%-2.67%), except for a slight increase in April 2020 among women. Z-hypnotic prescribing increased from January 2020 for women (1.39%; 95% CI, 1.38%-1.40%) and February 2020 for men (0.97%; 95% CI, 0.96%-0.98%) to October 2020 (women: 1.46%; 95% CI, 1.46%-1.47%; men: 1.00%; 95% CI, 0.99%-1.01%). Prescribing of SSRIs and SNRIs increased from January 2018 (women: 12.77%; 95% CI; 12.75%-12.80%; men: 5.56%; 95% CI, 5.44%-5.58%) to April 2020 for men (6.73%; 95% CI, 6.71%-6.75%) and October 2020 for women (15.18%; 95% CI, 15.16%-15.21%).

Conclusions And Relevance: In this cohort study, coinciding with the COVID-19 pandemic onset was an increase in Z-hypnotic as well as SSRI and SNRI prescriptions in both men and women along with an increase in benzodiazepine prescriptions in women, findings that suggest a substantial mental health impact of COVID-19-associated mitigation measures.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.31012DOI Listing
October 2021

Light-driven directional ion transport for enhanced osmotic energy harvesting.

Natl Sci Rev 2021 Aug 8;8(8):nwaa231. Epub 2020 Sep 8.

Key Laboratory of Bio-inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry, Beihang University, Beijing 100191, China.

Light-driven ion (proton) transport is a crucial process both for photosynthesis of green plants and solar energy harvesting of some archaea. Here, we describe use of a TiO/CN semiconductor heterojunction nanotube membrane to realize similar light-driven directional ion transport performance to that of biological systems. This heterojunction system can be fabricated by two simple deposition steps. Under unilateral illumination, the TiO/CN heterojunction nanotube membrane can generate a photocurrent of about 9 μA/cm, corresponding to a pumping stream of ∼5500 ions per second per nanotube. By changing the position of TiO and CN, a reverse equivalent ionic current can also be realized. Directional transport of photogenerated electrons and holes results in a transmembrane potential, which is the basis of the light-driven ion transport phenomenon. As a proof of concept, we also show that this system can be used for enhanced osmotic energy generation. The artificial light-driven ion transport system proposed here offers a further step forward on the roadmap for development of ionic photoelectric conversion and integration into other applications, for example water desalination.
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http://dx.doi.org/10.1093/nsr/nwaa231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363323PMC
August 2021

Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers.

Clin Epigenetics 2021 Oct 24;13(1):197. Epub 2021 Oct 24.

School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.

Background: 5-Hydroxymethylcytosine (5hmC) is a significant DNA epigenetic modification. However, the 5hmC modification alterations in genomic regions encoding long non-coding RNA (lncRNA) and their clinical significance remain poorly characterized.

Results: A three-phase discovery-modeling-validation study was conducted to explore the potential of the plasma-derived 5hmC modification level in genomic regions encoding lncRNAs as a superior alternative biomarker for cancer diagnosis and surveillance. Genome-wide 5hmC profiles in the plasma circulating cell-free DNA of 1632 cancer and 1379 non-cancerous control samples from different cancer types and multiple centers were repurposed and characterized. A large number of altered 5hmC modifications were distributed at genomic regions encoding lncRNAs in cancerous compared with healthy subjects. Furthermore, most 5hmC-modified lncRNA genes were cancer-specific, with only a relatively small number of 5hmC-modified lncRNA genes shared by various cancer types. A 5hmC-LncRNA diagnostic score (5hLD-score) comprising 39 tissue-shared 5hmC-modified lncRNA gene markers was developed using elastic net regularization. The 5hLD-score was able to accurately distinguish tumors from healthy controls with an area under the curve (AUC) of 0.963 [95% confidence interval (CI) 0.940-0.985] and 0.912 (95% CI 0.837-0.987) in the training and internal validation cohorts, respectively. Results from three independent validations confirmed the robustness and stability of the 5hLD-score with an AUC of 0.851 (95% CI 0.786-0.916) in Zhang's non-small cell lung cancer cohort, AUC of 0.887 (95% CI 0.852-0.922) in Tian's esophageal cancer cohort, and AUC of 0.768 (95% CI 0.746-0.790) in Cai's hepatocellular carcinoma cohort. In addition, a significant association was identified between the 5hLD-score and the progression from hepatitis to liver cancer. Finally, lncRNA genes modified by tissue-specific 5hmC alteration were again found to be capable of identifying the origin and location of tumors.

Conclusion: The present study will contribute to the ongoing effort to understand the transcriptional programs of lncRNA genes, as well as facilitate the development of novel invasive genomic tools for early cancer detection and surveillance.
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http://dx.doi.org/10.1186/s13148-021-01183-6DOI Listing
October 2021

Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis.

BMC Neurol 2021 Oct 22;21(1):405. Epub 2021 Oct 22.

Department of Neurology, Peking University Third Hospital, No. 49, North Garden Road, Haidian District, Beijing, 100191, China.

Background: Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed.

Methods: Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared.

Results: 115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival (P < 0.001). The cutoff duration was 20 months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20 months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group (P = 0.047; P = 0.004; P = 0.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64 months and 26 months, respectively; P < 0.001).

Conclusions: A cutoff duration of 20 months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.
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http://dx.doi.org/10.1186/s12883-021-02438-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532334PMC
October 2021

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos.

Stem Cell Reports 2021 Oct 4. Epub 2021 Oct 4.

Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China. Electronic address:

Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor-cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, were able to remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, thymine DNA glycosylase (TDG) was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression promoted DNA demethylation and enhanced the blastocyst-forming rates of SCNT embryos, thus offering valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes.
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http://dx.doi.org/10.1016/j.stemcr.2021.09.012DOI Listing
October 2021

Suppression of neuronal cholesterol biosynthesis impairs brain functions through insulin-like growth factor I-Akt signaling.

Int J Biol Sci 2021 27;17(14):3702-3716. Epub 2021 Aug 27.

School of Basic Medical Sciences, Shenyang Medical College, Shenyang, 110034, China.

Some relationship between abnormal cholesterol content and impairment of insulin/insulin-like growth factor I (IGF-1) signaling has been reported in the pathogenesis of Alzheimer's disease (AD). However, the underlying mechanism of this correlation remains unclear. It is known that 3-β hydroxycholesterol Δ 24 reductase (DHCR24) catalyzes the last step of cholesterol biosynthesis. To explore the function of cholesterol in the pathogenesis of AD, we depleted cellular cholesterol by targeting DHCR24 with siRNA (siDHCR24) or U18666A, an inhibitor of DHCR24, and studied the effect of the loss of cholesterol on the IGF-1-Akt signaling pathway in vitro and in vivo. Treatment with U18666A reduced the cellular cholesterol level and blocked the anti-apoptotic function of IGF-1 by impairing the formation of caveolae and the localization of IGF-1 receptor in caveolae of the PC12 cells. Downregulation of the DHCR24 expression induced by siRNA against DHCR24 also yielded similar results. Furthermore, the phosphorylation levels of IGF-1 receptor, insulin receptor substrate (IRS), Akt, and Bad in response to IGF-1 were all found to decrease in the U18666A-treated cells. Rats treated with U18666A via intracerebral injection also exhibited a significant decrease in the cholesterol level and impaired activities of IGF-1-related signaling proteins in the hippocampus region. A significant accumulation of amyloid β and a decrease in the expression of neuron-specific enolase (NSE) was also observed in rats with U18666A. Finally, the Morris water maze experiment revealed that U18666A-treated rats showed a significant cognitive impairment. Our findings provide new evidence strongly supporting that a reduction in cholesterol level can result in neural apoptosis via the impairment of the IGF-1-Akt survival signaling in the brain.
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http://dx.doi.org/10.7150/ijbs.63512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495388PMC
August 2021

Discovery of a naturally occurring broad-spectrum inhibitor against gut bacterial β-glucuronidases from .

Food Funct 2021 Oct 20. Epub 2021 Oct 20.

College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Gut bacterial β-glucuronidases (GUS) play an important role in deconjugation of various -glucuronides, which are tightly linked with the drug-induced intestinal toxicity. Increasing evidence has indicated that inhibition of bacterial GUS could alleviate GUS-associated intestinal toxicity, but the potent and broad-spectrum inhibitors against multiple bacterial GUS have been rarely reported. This study aimed to find potent and broad-spectrum GUS inhibitors from . It was found that amentoflavone displayed relatively strong inhibition on three GUS including GUS, GUS and GUS. Further investigations demonstrated that amentoflavone could inhibit GUS-mediated PNPG hydrolysis in a dose-dependent manner with IC values of 2.36 μM, 2.88 μM and 3.43 μM for GUS, GUS and GUS, respectively. Inhibition kinetic studies showed that amentoflavone functioned as a non-competitive inhibitor against all tested GUS with values of less than 2 μM. Docking simulations indicated that amentoflavone could tightly bind on allosteric sites of three GUS mainly hydrogen bonding interactions, and the number of hydroxyl groups of amentoflavone played crucial roles in these interactions. Collectively, our findings suggested that amentoflavone was a potent broad-spectrum inhibitor against bacterial GUS, which can be used as a promising lead compound for developing novel agents to alleviate GUS-associated intestinal toxicity.
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http://dx.doi.org/10.1039/d1fo01748aDOI Listing
October 2021

Predictive Modeling of MAFLD Based on Hsp90α and the Therapeutic Application of Teprenone in a Diet-Induced Mouse Model.

Front Endocrinol (Lausanne) 2021 30;12:743202. Epub 2021 Sep 30.

Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Background And Aims: The heat shock protein (Hsp) 90α is induced by stress and regulates inflammation through multiple pathways. Elevated serum Hsp90α had been found in nonalcoholic steatohepatitis (NASH). Geranylgeranylacetone (GGA, also called teprenone) is a terpenoid derivative. It was reported to induce Hsp and alleviate insulin resistance. We aimed to evaluate the Hsp90α as a biomarker in predicting metabolic-associated fatty liver disease (MAFLD) and define the therapeutic effects of geranylgeranylacetone for the disease.

Methods: A clinical study was conducted to analyze the elements associated with Hsp90α, and a predictive model of MAFLD was developed based on Hsp90α. The histopathological correlation between Hsp90α and MAFLD was investigated through a diet-induced mouse model. Furthermore, GGA was applied to the mouse model.

Results: Serum Hsp90α was increased in patients with MAFLD. A positive linear relationship was found between age, glycosylated hemoglobin (HbA1c), MAFLD, and serum Hsp90α. Meanwhile, a negative linear relationship with body mass index (BMI) was found. A model using Hsp90α, BMI, HbA1c, and ALT was established for predicting MAFLD. The area under the receiver operating characteristic (ROC) curves was 0.94 (95% CI 0.909-0.971, = 0.000). The sensitivity was 84.1%, and the specificity was 93.1%. experiments, GGA induced Hsp90α in steatosis cells. In the mice model, Hsp90α decreased in the GGA treatment group. Hepatic steatosis, inflammation, insulin resistance, and glucose intolerance were improved in the GGA-treated group. Serum Hsp90α was positively correlated with steatohepatitis activity according to hepatic histopathology.

Conclusions: Serum Hsp90α was elevated in MAFLD, and a positive correlation between serum Hsp90α and the grade of activity of steatohepatitis was observed. The model using BMI, HbA1c, and alanine aminotransferase (ALT) had a good value to predict MAFLD. The findings also revealed the effectiveness of GGA in the treatment of MAFLD.
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http://dx.doi.org/10.3389/fendo.2021.743202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515197PMC
September 2021

Melatonin mitigates Chloroquine-induced defects in porcine immature Sertoli cells.

Theriogenology 2021 Oct 8;177:1-10. Epub 2021 Oct 8.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, Heilongjiang, China; College of Animal Science, Yangtze University, Jingzhou, 434025, Hubei, China. Electronic address:

Chloroquine (CQ) could function as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway, and is widely used on malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here we showed that CQ could reduce iSC viability in a dose-dependent manner. CQ treatment (20 μM) on iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis, which could be partially rescued by melatonin (MT) (10 nM). Transcriptome profiling identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20 μM CQ vs. DMSO), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, only 467 (224 up- and 243 down-regulated) DEGs (CQ + MT vs. DMSO) could be found after MT (10 nM) addition, enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction pathways. Therefore, the partial rescue effects of MT on CQ treatment were confirmed by multiple assays (cell viability, ROS level, mitochondrial function, apoptosis, and mRNA levels of selected genes). Collectively, CQ treatment could impair porcine iSC viability by deranging the signaling pathways related to apoptosis and autophagy, which could be partially rescued by MT supplementation.
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http://dx.doi.org/10.1016/j.theriogenology.2021.10.005DOI Listing
October 2021

Meisoindigo attenuates dextran sulfate sodium-induced experimental colitis via its inhibition of TAK1 in macrophages.

Int Immunopharmacol 2021 Oct 12;101(Pt B):108239. Epub 2021 Oct 12.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China. Electronic address:

At present, inflammatory bowel disease (IBD) seriously threatens human health, and its treatment is a huge challenge for people. In our studies, we found that meisoindigo, a derivative of indirubin, significantly ameliorated dextran sulfate sodium (DSS)-induced experimental colitis in mice. Meisoindigo treatment markedly elevated the level of glutathione, while suppressed the activities of alkaline phosphatase and myeloperoxidase in colonic tissues. Moreover, the mRNA expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, cyclooxygenase-2 which are important colitis-related molecules and the levels of the inflammatory cytokines interleukin (IL)-18, IL-1β, IL-6, tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were suppressed dose-dependently following treatment with meisoindigo. Immunofluorescence results indicated that meisoindigo inhibited macrophage infiltration and nuclear factor (NF)-κB activation in colons from DSS-treated mice. Therefore, mouse RAW264.7 and human THP-1 cells were treated with lipopolysaccharide (LPS) alone or combined adenosine triphosphate to activate NF-κB pathway in vitro. It was shown that meisoindigo reduced the elevated levels of NO, IL-18, IL-1β and TNF-α after LPS treatment in both cells. In addition, meisoindigo showed inhibitory effects on NF-κB by using a luciferase reporter gene that depends on NF-κB. Through molecular docking, microscale thermophoresis and cellular thermal shift assay. It was further found that meisoindigo targeted transforming growth factor β activated kinase-1 (TAK1), which is an important regulator in the upstream of NF-κB pathway. In conclusion, our findings show that meisoindigo can alleviate IBD effectively at low doses, and negatively regulate proinflammatory responses by inhibiting the activation of TAK1, which provides new ideas for clinical anti-inflammatory therapy.
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http://dx.doi.org/10.1016/j.intimp.2021.108239DOI Listing
October 2021

[Comparison of effectiveness of femoral neck system and cannulate compression screw in treatment of femoral neck fracture in young and middle-aged patients].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Oct;35(10):1286-1292

Department of Orthopedics, Affiliated Hospital of North Sichuan Medical College, Nanchong Sichuan, 637000, P.R.China.

Objective: To compare the effectiveness of femoral neck system (FNS) and cannulate compression screw (CCS) in the treatment of femoral neck fractures in young and middle-aged patients.

Methods: The clinical data of 82 young and middle-aged patients with femoral neck fracture treated between January 2018 and September 2020 were retrospectively analyzed. They were divided into FNS group (24 cases) and CCS group (58 cases) according to different surgical methods. There was no significant difference between the two groups ( >0.05) in general data such as gender, age, height, body mass, cause of injury, complications, fracture location, and fracture classification (Garden classification and Pauwells classification). The operation time, intraoperative blood loss, complications (nonunion, osteonecrosis of the femoral head, shortening of femoral neck, etc.), visual analogue scale (VAS) score at 2 days after operation, clinical healing time of fracture, and Harris score of hip joint after operation were recorded and compared between the two groups.

Results: The operation time and VAS score at 2 days after operation in FNS group were significantly lower than those in CCS group ( <0.05); there was no significant difference in intraoperative blood loss between the two groups ( =0.263, =0.796). The patients in CCS group were followed up 6-18 months, with an average of 13.6 months; and the follow-up time in FNS group was 3-12 months, with an average of 7.3 months. There was no complication of internal fixator loosening in both groups. There were 2 cases of osteonecrosis of the femoral head, 1 case of bone nonunion, and 13 cases of femoral neck shortening in CCS group and only 2 cases of femoral neck shortening in FNS group. The difference in the incidence of complications between the two groups (27.6% 8.3%) was significant ( =36.670, =0.015). In CCS group, 3 cases underwent secondary artificial hip arthroplasty due to bone nonunion and osteonecrosis of the femoral head, and the remaining 55 cases achieved clinical healing; in FNS group, 6 patients excluded in the statistics because the follow-up time was less than 6 months, and the remaining 18 fractures healed clinically; there was significant difference in fracture healing time between the two groups ( =4.481, =0.000). The difference of Harris score of hip joint between 9 months and 6 months after operation in FNS group was significantly higher than that in CCS group ( <0.05), and the Harris score at 9 months after operation was significantly higher than that at 6 months after operation in both groups ( <0.05).

Conclusion: FNS can accelerate the healing of femoral neck fractures in young and middle-aged patients, so that patients can start functional exercise as soon as possible, thereby reducing the incidence of related complications.
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http://dx.doi.org/10.7507/1002-1892.202103099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505931PMC
October 2021

Association Between Time to Endovascular Therapy and Outcomes in Patients With Acute Basilar Artery Occlusion.

Neurology 2021 Oct 14. Epub 2021 Oct 14.

Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China

Objective: To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice.

Methods: Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes included function independence (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable).

Results: Among 639 eligible patients, the median age was 65 years, and median OPT was 328 min (interquartile range, 220-490). Treatment within 4-8 hours and 8-12 hours were associated with lower rates of favorable outcome (adjusted OR, 0.63 [95% CI, 0.40-0.98] and 0.47 [95% CI, 0.23-0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome ( =0.028) and functional independence ( =0.025), with significant benefit loss throughout the first 9 hours but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then levelled off ( =0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant.

Conclusion: Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards.

Classification Of Evidence: This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier endovascular treatment is associated with better outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000012858DOI Listing
October 2021

A Mammography-Based Nomogram for Prediction of Malignancy in Breast Suspicious Calcification.

Acad Radiol 2021 Oct 11. Epub 2021 Oct 11.

School of graduate (L.C., H.D.), Bengbu Medical College, Bengbu Anhui 233030, China; Department of Radiology (X.T., C.M., L.Y., Z.X., Z.G.), the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China; School of Medical Imaging (J.C.), Bengbu Medical College, Bengbu Anhui 233030, China. Electronic address:

Aim: To establish a predictive nomogram for malignancy risk stratification of micro-calcifications (MCCs) detected on mammography.

Materials And Methods: Consecutive mammograms from January 2017 to March 2021 were retrospectively reviewed. Traditional clinical features were recorded and mammographic features were estimated according to the 5th BI-RADS. A nomogram was developed to graphically predict the malignancy risk based on multivariate logistic regression analysis. The discrimination and calibration performance of the prediction model was assessed.

Results: There were 123 cases of suspicious MCCs with final pathological results identified with a malignancy rate of 55.2%. The malignancy rates of subgroups divided according to the morphology and distribution of MCCs, age, menopausal status and the maximum diameter of MCCs were significantly different. Multivariate logistic analysis showed that a menopause status of postmenopausal, maximum diameters of MCCs ≥2 cm, the morphology of MCCs as fine pleomorphic or fine linear or branching, and the distribution of MCCs as linear or segmental were predictive of a higher probability of malignancy. A prediction nomogram was developed based on four risk factors, including menopausal status as well as the maximum diameters, distribution and morphology of the MCCs. The AUC of that nomogram was 0.839 (95%CI:0.771-0.903).

Conclusion: In mammography, the morphology, distribution and maximum diameter of MCCs, and the menopausal status are independent predictors of malignant suspicious MCCs and are readily available in the clinical setting. The nomogram developed in this study for individualized malignancy risk stratification of suspicious MCCs shows a reliable discrimination performance.
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http://dx.doi.org/10.1016/j.acra.2021.09.003DOI Listing
October 2021

Transcriptome analysis of messenger RNA and long noncoding RNA related to different developmental stages of tail adipose tissues of sunite sheep.

Food Sci Nutr 2021 Oct 25;9(10):5722-5734. Epub 2021 Aug 25.

College of Food Science and Engineering Inner Mongolia Agricultural University Hohhot China.

The tail fat of sheep is the most typical deposited fat, and it can be widely used in human daily life, such as diet, cosmetics, and industrial raw materials. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6, 18, and 30 months. A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep. Based on functional analysis, we found that fat-related DEGs were mainly expressed at 6 months of age and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their transregulators. Further, we obtained several fat-related differentially expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Finally, we concluded that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process.
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http://dx.doi.org/10.1002/fsn3.2537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498062PMC
October 2021

A Numerical Simulation Method for the One-Step Compression-Stamping Process of Continuous Fiber Reinforced Thermoplastic Composites.

Polymers (Basel) 2021 Sep 24;13(19). Epub 2021 Sep 24.

State Key Laboratory of Materials Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Continuous fiber reinforced thermoplastic (CFRTP) composites have many advantages, such as high strength, high stiffness, shorter cycle, time and enabling the part consolidation of structural components. However, the mass production of the CFRTP parts is still challenging in industry and simulations can be used to better understand internal molding mechanisms. This paper proposes a three-dimensional simulation method for a one-step compression-stamping process which can conduct thermoplastic compression molding and continuous fiber reinforced thermoplastic composite stamping forming in one single mold, simultaneously. To overcome the strongly coupled non-isothermal moving boundary between the polymer and the composites, arbitrary Lagrangian-Eulerian based Navier-Stokes equations were applied to solve the thermoplastic compression, and a fiber rotation based objective stress rate model was used to solve for the composite stamping. Meanwhile, a strongly coupled fluid structure interaction framework with dual mesh technology is proposed to address the non-isothermal moving boundary issue between the polymer and the composites. This simulation method was compared against the experimental results to verify its accuracy. The polymer flow fronts were measured at different molding stages and the error between simulation and experiment was within 3.5%. The final composites' in-plane deformation error was less than 2.5%. The experiment shows that this work can accurately simulate the actual molding process.
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http://dx.doi.org/10.3390/polym13193237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512096PMC
September 2021

Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of Gene A593C in a Chinese Family.

Front Pediatr 2021 23;9:692727. Epub 2021 Sep 23.

Division of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

Pathogenic variants in the gene encoding podocin in kidney podocytes are associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) by disrupting podocyte function and the integrity of the glomerular filtration barrier. The outcome is generally poor by progressing into end-stage kidney disease (ESKD). With the help of gene diagnostics, we can further understand the role of podocin of podocytes in the development and progression of SRNS. However, the pathological mutation of and clinical relevance remain further elusive. Two siblings, a 15-year-old girl and her 10-year-old younger brother from a consanguineous Chinese family, presented with nephrotic syndrome. Both of them developed progressive proteinuria starting from the 5-year-old of age. The renal pathological lesions for them revealed focal segmental glomerulosclerosis (FSGS). There was no response to the glucocorticoid, calcineurin inhibitors, and rituximab treatment. The female affected patient received the hemodialysis treatment due to ESKD in June 2020; the male patient was still in follow-up presenting with SRNS. The mutational screening of the two patients and their parents using Trio whole-exome sequencing showed the gene missense mutation in exon 5 (A593C), for which the two siblings were homozygous and their parents confirmed heterozygous asymptomatic carriers. No other SRNS-related gene variants with the SRNS were determined. Pathological gene variants screening in children clinically suspected with SRNS might be helpful in the diagnosis as well as appropriate decisions on treatment strategies and prediction of prognosis.
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http://dx.doi.org/10.3389/fped.2021.692727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497038PMC
September 2021

Angiogenesis-Related Molecular Subtypes and a Novel Prognostic Signature in Clear Cell Renal Cell Carcinoma Patients.

Int J Gen Med 2021 2;14:6325-6342. Epub 2021 Oct 2.

Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People's Republic of China.

Background: This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis.

Materials And Methods: The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively.

Results: We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P<0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P<0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies.

Conclusion: We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.
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http://dx.doi.org/10.2147/IJGM.S332732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497487PMC
October 2021

Coordinated regulation of the ribosome and proteasome by PRMT1 in the maintenance of neural stemness in cancer cells and neural stem cells.

J Biol Chem 2021 Oct 4;297(5):101275. Epub 2021 Oct 4.

Research Institute of Nanjing University in Shenzhen, Shenzhen, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine of the Medical School, Nanjing University, Nanjing, China. Electronic address:

Previous studies suggested that cancer cells resemble neural stem/progenitor cells in regulatory network, tumorigenicity, and differentiation potential, and that neural stemness might represent the ground or basal state of differentiation and tumorigenicity. The neural ground state is reflected in the upregulation and enrichment of basic cell machineries and developmental programs, such as cell cycle, ribosomes, proteasomes, and epigenetic factors, in cancers and in embryonic neural or neural stem cells. However, how these machineries are concertedly regulated is unclear. Here, we show that loss of neural stemness in cancer or neural stem cells via muscle-like differentiation or neuronal differentiation, respectively, caused downregulation of ribosome and proteasome components and major epigenetic factors, including PRMT1, EZH2, and LSD1. Furthermore, inhibition of PRMT1, an oncoprotein that is enriched in neural cells during embryogenesis, caused neuronal-like differentiation, downregulation of a similar set of proteins downregulated by differentiation, and alteration of subcellular distribution of ribosome and proteasome components. By contrast, PRMT1 overexpression led to an upregulation of these proteins. PRMT1 interacted with these components and protected them from degradation via recruitment of the deubiquitinase USP7, also known to promote cancer and enriched in embryonic neural cells, thereby maintaining a high level of epigenetic factors that maintain neural stemness, such as EZH2 and LSD1. Taken together, our data indicate that PRMT1 inhibition resulted in repression of cell tumorigenicity. We conclude that PRMT1 coordinates ribosome and proteasome activity to match the needs for high production and homeostasis of proteins that maintain stemness in cancer and neural stem cells.
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http://dx.doi.org/10.1016/j.jbc.2021.101275DOI Listing
October 2021

Targeting epigenetically maladapted vascular niche alleviates liver fibrosis in nonalcoholic steatohepatitis.

Sci Transl Med 2021 Oct 6;13(614):eabd1206. Epub 2021 Oct 6.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

[Figure: see text].
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http://dx.doi.org/10.1126/scitranslmed.abd1206DOI Listing
October 2021

TRPV1 mediates itch-associated scratching and skin barrier dysfunction in DNFB-induced atopic dermatitis mice.

Exp Dermatol 2021 Oct 4. Epub 2021 Oct 4.

School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.

In chronic pruritic diseases such as atopic dermatitis (AD), pruritus and skin lesions are exacerbated by scratching in clinical and experimental settings. TRPV1 is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in itch-associated scratching in AD is poorly understood. In this study, we examined the efficacy of cutting off nails and TRPV1 antagonist, ruthenium red (RR) in a murine model of AD induced by DNFB and further investigated the underlying mechanism. Nail clipping or RR could markedly ameliorate the general AD-like symptoms as manifested by the reduced clinical severity of dermatitis, IgE and Th2-related cytokine levels, and mast cell degranulation. Moreover, scratching behaviour, the levels of pruritogenic mediators, including HIS, TSLP, IL-31 and SP, and skin pH and TEWL were all significantly decreased in nail clipping or RR-treated mice, suggesting a reduction in itch-associated scratching and skin barrier defects. Immunofluorescence staining and Western blot results revealed that antipruritic effect of nail clipping or RR in AD may be explained, at least in part, by the suppression of TRPV1 activation. In summary, these data show that TRPV1 mediates itch-associated scratching and subsequent skin barrier defects, suggesting its potential as a therapeutic target in AD.
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http://dx.doi.org/10.1111/exd.14464DOI Listing
October 2021

LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) silence reduces the proliferation, invasion, migration and angiogenesis in esophageal squamous cell carcinoma via KIF14 (kinesin family member 14).

Bioengineered 2021 Dec;12(1):7656-7665

Department of Surgical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (Ibmc), Chinese Academy of Sciences, Hangzhou, Zhejiang, P.R. China.

Esophageal squamous cell carcinoma (ESCC), a major form of esophageal cancer, is a serious threat to human health. This study was conducted to investigate the pathogenesis of ESCC and find effective therapies to improve it. Protein expression of transfected plasmids was detected by RT-qPCR and western blot. Co-immunoprecipitation assay was performed to verify the binding of LETM1 and KIF14. CCK-8, wound healing and transwell assays were used to assess the proliferation, invasion and migration of ESCC cells. Finally, the angiogenesis was assessed using tubule formation assay. The co-immunoprecipitation results showed that LETM1 could bind to KIF14. The cytological and protein results demonstrated that interference with LETM1 caused downregulation of KIF14 expression, which led to inhibition of proliferation, invasion, migration and angiogenesis in ESCC cells. Taken together, interfering with LETM1 to downregulate KIF14 may become a new target for ESCC treatment.
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http://dx.doi.org/10.1080/21655979.2021.1982275DOI Listing
December 2021

Why Was There More Household Stock Market Participation During the COVID-19 Pandemic?

Financ Res Lett 2021 Sep 25:102481. Epub 2021 Sep 25.

Southwestern University of Finance and Economics, Chengdu, China.

Although the nation was experiencing an economic downturn due to the COVID-19 pandemic outbreak, we nonetheless observed an increase in household equity share value relative to both domestic market capitalization and retail investors' trading volume. In this paper, we aim to interpret the reasons underlying this seemingly unexpected phenomenon. We investigate portfolio choices with stocks, bonds, and life annuities under an inverse S-shaped probability distortion function. The results indicate that people invest more heavily in risky assets and buy more annuities when reducing their savings in risk-free accounts, which is indeed consistent with the reality.
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http://dx.doi.org/10.1016/j.frl.2021.102481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465266PMC
September 2021

Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.

Front Cell Dev Biol 2021 14;9:714383. Epub 2021 Sep 14.

Shenzhen Research Institute of Nanjing University, Shenzhen, China.

Our studies have demonstrated that cell tumorigenicity and pluripotent differentiation potential stem from neural stemness or a neural ground state, which is defined by a regulatory network of higher levels of machineries for basic cell physiological functions, including cell cycle, ribosome biogenesis, protein translation, spliceosome, epigenetic modification factors, reprogramming factors, etc., in addition to the neural stemness specific factors. These machineries and neural stemness factors mostly play cancer-promoting roles. It can be deduced that differentiation requires the repression of neural ground state and causes the reduction or loss of neural ground state and thus tumorigenicity in tumorigenic cells. Formerly, we showed that neuronal differentiation led to reduced tumorigenicity in tumorigenic cells. In the present study, we show that non-neural pro-differentiation factors, such as GATA3, HNF4A, HHEX, and FOXA3 that specify mesodermal or/and endodermal tissues during vertebrate embryogenesis, suppress tumorigenicity via repression of neural stemness and promotion of non-neural property in tumorigenic cells. Mechanistically, these transcription factors repress the transcription of neural enriched genes and meanwhile activate genes that specify non-neural properties via direct binding to the promoters of these genes. We also show that combined expression of HHEX and FOXA3 suppresses tumorigenesis effectively in the AOM/DSS model of colitis-associated cancer. We suggest that targeting the property of neural stemness could be an effective strategy for cancer therapy.
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http://dx.doi.org/10.3389/fcell.2021.714383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476888PMC
September 2021

An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer.

Front Oncol 2021 14;11:736725. Epub 2021 Sep 14.

Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Background: C5AR2 (GPR77, C5L2) is the second receptor for C5a that is a potent protein generated by complement activation. C5AR2 can mediate its own signaling events and exert significant immunomodulatory effects through those events. However, research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer.

Methods: The expression of C5AR2 and its correlations with prognosis, immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) in more than thirty types of cancers were described through GTEx, TCGA, PrognoScan, TIMER2.0, CCLE, HPA, and TISIDB database. C5AR2 showed strong relationships to those immune marker sets in breast cancer. Otherwise, CCK8 assay and Transwell assay were conducted to illustrate the role of C5AR2 in migration, invasion, and proliferation of breast cancer cells.

Results: Generally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD. Moreover, C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer. Gene set enrichment analysis confirmed that C5AR2 participates in regulating multiple signaling pathways involved in tumorigenesis as well as tumor immunity. C5AR2 overexpression facilitated the functions such as migration, invasion, and proliferation in breast cancer cells, which is consistent with bioinformatics analysis.

Conclusions: C5AR2 is involved in immune infiltration and malignant characteristics of breast cancer, which may be a prospective biomarker for breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.736725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476960PMC
September 2021

Tetrandrine promotes angiogenesis via transcriptional regulation of VEGF-A.

Vascul Pharmacol 2021 Sep 27:106920. Epub 2021 Sep 27.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Angiogenesis is crucial for tissue damage repair in ischemic cardiovascular diseases. Vascular endothelial growth factor A (VEGF-A) acts as a vital mediator in angiogenesis. In this study, tetrandrine (Tet) was found from 23 herbal chemicals to increase VEGF-A mRNA expression in H9c2 cells and the effect was confirmed in freshly isolated neonatal rat cardiomyocytes. The effect of Tet on VEGF-A expression and the possible mechanism were investigated. Tet treatment increased de novo VEGF-A mRNA synthesis and did not affect VEGF-A mRNA stability. The circulating chromosome conformation capture (4C) experiments indicated that Tet enhanced VEGF-A transcription by targeting a regulatory element beyond the 2.6 kb region of the translation start site. Tet augmented the angiogenic activities of endothelial cells. It also enhanced blood flow restoration and capillary vessel density following ischemic limb injury associated with an escalation of VEGF-A expression. Moreover, in myocardial infarction (MI) model Tet treatment elevated neovascularization, reduced infarction size, and improved heart function via upregulating VEGF-A levels. Our results suggested that Tet increased VEGF-A transcription through a novel mechanism that likely involves a distant regulatory element and may be useful for therapeutic angiogenesis for ischemic diseases.
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http://dx.doi.org/10.1016/j.vph.2021.106920DOI Listing
September 2021

Up-Regulation of SLC26A6 in Hepatocellular Carcinoma and Its Diagnostic and Prognostic Significance.

Crit Rev Eukaryot Gene Expr 2021 ;31(5):79-94

Department of Rheumatoid Osteoarthropathy, Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan 610041, China.

Hepatocellular carcinoma (HCC), is one of the most common malignancies worldwide, which is globally the third most common cause of cancer-related mortality. This study aims to identify new potential early-stage diagnostic and prognostic biomarker for HCC. The candidate gene SLC26A6 expression was analyzed based on the Oncomine and Tumor Immune Estimation Resource (TIMER) databases and verified forwards with Gene Expression Omnibus (GEO) datasets. The protein expression was retrieved from Human Protein Atlas (HPA) database. We also validated the diagnostic and prognostic value in HCC, and the relationship between SLC26A6 and clinicopathologic parameters were also accessed. The Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) network were constructed to analyze the SLC26A6-related pathway. These results reveal that SLC26A6 expression was elevated in HCC, and the diagnostic sensitivity of SLC26A6 was higher than α-fetoprotein (AFP). SLC26A6 expression was independent prognostic factor for HCC. SLC26A6 up-regulation was mainly associated with excision repair, DNA replication, etc. SLC26A6-related mR-NAs was enriched in PI3K-AKT signaling pathway, axon guidance, pathways in cancer, and so on. PPI network indicated that SLC26A6 was interacted with solute carrier members, ABC transporters and other ion transport molecule. We further analyzed three positively correlated microRNAs and 10 negatively correlated microRNAs, all of these were reported participating or inhibiting in cancer progression. This is the first study demonstrated that SLC26A6 is up-regulated in HCC and correlated with poor prognosis, which might be served as a diagnostic marker or prognostic biomarker for HCC.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021039703DOI Listing
January 2021

Joint t-SNE for Comparable Projections of Multiple High-Dimensional Datasets.

IEEE Trans Vis Comput Graph 2021 Sep 29;PP. Epub 2021 Sep 29.

We present Joint t-Stochastic Neighbor Embedding (Joint t-SNE), a technique to generate comparable projections of multiple high-dimensional datasets. Although t-SNE has been widely employed to visualize high-dimensional datasets from various domains, it is limited to projecting a single dataset. When a series of high-dimensional datasets, such as datasets changing over time, is projected independently using t-SNE, misaligned layouts are obtained. Even items with identical features across datasets are projected to different locations, making the technique unsuitable for comparison tasks. To tackle this problem, we introduce edge similarity, which captures the similarities between two adjacent time frames based on the Graphlet Frequency Distribution (GFD). We then integrate a novel loss term into the t-SNE loss function, which we call vector constraints, to preserve the vectors between projected points across the projections, allowing these points to serve as visual landmarks for direct comparisons between projections. Using synthetic datasets whose ground-truth structures are known, we show that Joint t-SNE outperforms existing techniques, including Dynamic t-SNE, in terms of local coherence error, Kullback-Leibler divergence, and neighborhood preservation. We also showcase a real-world use case to visualize and compare the activation of different layers of a neural network.
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http://dx.doi.org/10.1109/TVCG.2021.3114765DOI Listing
September 2021

Aberrant activation of m6A demethylase FTO renders HIF2α clear cell renal cell carcinoma sensitive to BRD9 inhibitors.

Sci Transl Med 2021 Sep 29;13(613):eabf6045. Epub 2021 Sep 29.

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.

[Figure: see text].
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http://dx.doi.org/10.1126/scitranslmed.abf6045DOI Listing
September 2021
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