Publications by authors named "Yuanyuan Zhao"

430 Publications

Activatable Biomineralized Nanoplatform Remodels the Intracellular Environment of Multidrug-Resistant Tumors for Enhanced Ferroptosis/Apoptosis Therapy.

Small 2021 Sep 23:e2102269. Epub 2021 Sep 23.

School of Life Sciences, Chongqing University, Huxi, G75 Lanhai, Chongqing, 400052, China.

Ferroptosis is a new form of regulated cell death with significant therapeutic prospect, but its application against drug-resistant tumor cells is challenging due to their ability to effuse antitumor agents via p-glycoprotein (P-gp) and anti-lipid peroxidation alkaline intracellular environment. Herein, an amorphous calcium phosphate (ACP)-based nanoplatform is reported for the targeted combinational ferroptosis/apoptosis therapy of drug resistant tumor cells by blocking the MCT4-mediated efflux of lactic acid (LA). The nanoplatform is fabricated through the biomineralization of doxorubicin-Fe (DOX-Fe ) complex and MCT4-inhibiting siRNAs (siMCT4) and can release them to the tumor cytoplasm after the hydrolysis of ACP and dissociation of DOX-Fe in the acidic lysosomes. siMCT4 can inhibit MCT4 expression and force the glycolysis-generated lactic acid (LA) to remain in cytoplasm for rapid acidification. The nanoplatform-induced remodeling of the tumor intracellular environment can not only interrupt the ATP supply required for P-gp-dependent DOX effusion to enhance H O production, but also increase the overall catalytic efficiency of Fe for the initiation and propagation of lipid peroxidation. These features could act in concert to enhance the efficacy of the combinational ferroptosis/chemotherapy and prolong the survival of tumor-bearing mice. This study may provide new avenues for the treatment of multidrug-resistant tumors.
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http://dx.doi.org/10.1002/smll.202102269DOI Listing
September 2021

Association of triglyceride-glucose index and high-sensitivity C-reactive protein with asymptomatic intracranial arterial stenosis: A cross-sectional study.

Nutr Metab Cardiovasc Dis 2021 Jul 29. Epub 2021 Jul 29.

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. Electronic address:

Background And Aims: Triglyceride-glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) have been shown to play important roles in the pathophysiological mechanisms of atherogenesis. However, the cumulative value of TyG and hsCRP in identifying asymptomatic intracranial arterial stenosis (aICAS), as well as its severity and numerical burden, is uncertain. This study seeks to fill this knowledge gap.

Methods And Results: This study included 1938 participants aged ≥40 years who were free of stroke or transient ischemic attack. All participants were classified into four groups based on the participants' TyG and hsCRP levels, including low-TyG and low-hsCRP, low-TyG and high-hsCRP, high-TyG and low-hsCRP, and high-TyG and high-hsCRP groups. The presence of aICAS was screened via transcranial Doppler ultrasound and confirmed by magnetic resonance angiography. The TyG was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We used multinomial logistic regression analysis to investigate the cumulative value of TyG and hsCRP on identifying the severity of aICAS or its numerical burden. After adjustment for conventional confounders, isolated high-hsCRP, isolated high-TyG, and high-TyG combined with high-hsCRP were independently associated with moderate-to-severe aICAS. Compared with the low-TyG and low-hsCRP group, participants with high-TyG and high-hsCRP had a 2.6 times higher odds ratio (OR) of having a single moderate-to-severe aICAS and a 3.3 times higher OR of having multiple moderate-to-severe aICASs.

Conclusion: The cumulative value of TyG and hsCRP may better identify moderate-to-severe aICAS as well as its numerical burden.
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http://dx.doi.org/10.1016/j.numecd.2021.07.009DOI Listing
July 2021

Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

Bioengineered 2021 12;12(1):5516-5528

Department Of Tumor Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.
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http://dx.doi.org/10.1080/21655979.2021.1965694DOI Listing
December 2021

Effects of Fermented Residue on Nutrient Digestibility and Reproductive Performance of Sows.

Front Nutr 2021 30;8:715713. Epub 2021 Aug 30.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

This study was conducted to investigate the effect of fermented residue (FRPR) on reproductive performance, apparent total tract digestibility (ATTD) of nutrients, and fecal short-chain fatty acid (SCFA) contents of sows. A total of 36 landrace × large white multiparous sows were randomly arranged into three treatments, representing supplementation with 0, 2, and 4% FRPR to a corn-soybean meal and wheat bran-based diet during the whole gestation period. The results showed that dietary FRPR had no effects on litter size and the number of total alive piglets ( > 0.05), and that the number of weaned piglets and weaning weight of litter were increased in sows with 4% FRPR treatment compared with control treatment ( < 0.05). Dietary 4% FRPR significantly decreased constipation rate, improved the ATTD of dry matter and organics, and fecal contents of acetate, propionate, and total SCFAs ( < 0.05). In the offspring piglets, serum concentrations of total protein, alkaline phosphatase, IgG, IL-10, and TGF-β were increased, but blood urea nitrogen content was decreased with 4% FRPR treatment ( < 0.05). There were no significant differences in all determined indexes except for fecal acetic acid and total SCFAs between control and 2% FRPR treatment ( > 0.05). These findings indicated that FRPR used in the diets of sows showed positive effects on fecal characteristics, utilization of nutrients, and reproductive performance. Maternal supplementation with 4% FRPR is recommended for improving immune responses, weaning litter size, and litter weight of offspring piglets, which provide useful information for the application of residues of .
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http://dx.doi.org/10.3389/fnut.2021.715713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435608PMC
August 2021

Multi-region exome sequencing reveals the intratumoral heterogeneity of surgically resected small cell lung cancer.

Nat Commun 2021 Sep 14;12(1):5431. Epub 2021 Sep 14.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.
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http://dx.doi.org/10.1038/s41467-021-25787-xDOI Listing
September 2021

Seasonal changes in cambium activity from active to dormant stage affect the formation of secondary xylem in Pinus tabulaeformis Carr.

Tree Physiol 2021 Sep 9. Epub 2021 Sep 9.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China.

Understanding the changing patterns of vascular cambium during seasonal cycles is crucial to reveal the mechanisms that control cambium activity and wood formation, but this area has been underexplored, especially in conifers. Here, we quantified the changing cellular morphology patterns of cambial zones during the active, transition and dormant stages. With the help of toluidine blue and periodic acid Schiff staining to visualize cell walls and identify their constituents, we observed decreasing cambial cell layers, thickening of newly formed xylem cell walls and increased polysaccharide granules in phloem from June to the following March over the course of our collecting period. Pectin immunofluorescence showed that dormant stage cambium can produce highly abundant de-esterified homogalacturonan and (1-4)-β-D-galactan epitopes, while active cambium can strong accumulate high methylesterified homogalacturonan. Calcofluor white staining and confocal Raman spectroscopy analysis revealed regular changes in the chemical composition of cell walls, such as relative lower cellulose deposition in transition stage in vascular cambium, and higher lignin accumulation was found in dormant stage in secondary xylem. Moreover, RT-qPCR analysis suggested that various IAA (Aux/IAA protein), CesA, CslA and HDZ genes, as well as NAC, PME3 and PME4, may be involved in cambium activities and secondary xylem formation. Taken together, these findings provide new information about cambium activity and cell differentiation in the formation, structure, and chemistry in conifers during the active-dormant transition.
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http://dx.doi.org/10.1093/treephys/tpab115DOI Listing
September 2021

A Comparison of Two Monoterpenoid Synthases Reveals Molecular Mechanisms Associated With the Difference of Bioactive Monoterpenoids Between and .

Front Plant Sci 2021 12;12:695551. Epub 2021 Aug 12.

Key Laboratory of Chinese Medicinal Resource from Lingnan (Ministry of Education), Guangzhou University of Chinese Medicine, Guangzhou, China.

The fruits of and are both used medicinally as the famous traditional Chinese medicine, however, the medicinal quality of is better than that of . Volatile terpenoids in the seeds, especially bornyl acetate and borneol, are the medicinal components of The volatile terpenoids and transcriptome of developing seeds of and were compared in this study. The result revealed that the bornyl acetate and borneol contents were higher in than in . Additionally, six terpenoid synthase genes () were screened from the transcriptome of , and and were found to share 98 and 83% identity with and (bornyl diphosphate synthase) from , respectively. BPPS is the key enzyme for the biosynthesis of borneol and bornyl acetate. Biochemical assays improved that AlTPS2 had an identical function to AvTPS2 as linalool synthase; however, AlTPS3 produced camphene as the major product and bornyl diphosphate (BPP) as the secondary product, whereas AvBPPS produced BPP as its major product. There was only one different amino acid between AlTPS3 (A496) and AvBPPS (G495) in their conserved motifs, and the site-directed mutation of A496G in DTE motif of AlTPS3 changed the major product from camphene to BPP. Molecular docking suggests that A496G mutation narrows the camphene-binding pocket and decreases the BPP-binding energy, thus increases the product BPP selectivity of enzyme. In addition, the expression level of was significantly higher than that of in seeds, which was consistent with the related-metabolites contents. This study provides insight into the TPS-related molecular bases for the biosynthesis and accumulation differences of the bioactive terpenoids between and . , the key gene involved in the biosynthesis of the active compound, was identified as a target gene that could be applied for the quality-related identification and breeding of .
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http://dx.doi.org/10.3389/fpls.2021.695551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406774PMC
August 2021

Development and Validation of a Nomogram of In-hospital Major Adverse Cardiovascular and Cerebrovascular Events in Patients With Acute Coronary Syndrome.

Front Cardiovasc Med 2021 9;8:699023. Epub 2021 Aug 9.

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

This study aims to develop and validate a nomogram for the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) in acute coronary syndrome (ACS) patients. A total of 1,360 ACS patients admitted between November 2014 and October 2019 from Zhongda Hospital and Yancheng Third People's Hospital were included. Patients admitted in Zhongda Hospital before 2018 were split into the training cohort ( = 793). Those admitted after 2018 in Zhongda Hospital and patients from Yancheng Third People's Hospital were split into the validation cohort ( = 567). Twenty eight clinical features routinely assessed including baseline characteristics, past medical history and auxiliary examinations were used to inform the models to predict in-hospital MACCE (all-cause mortality, reinfarction, stroke, and heart failure) in ACS patients. The best-performing model was tested in the validation cohort. The accuracy and clinical applicability were tested by the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses (DCA). The in-hospital MACCE occurred in 93 (6.83%) patients. The final prediction model consists of four variables: age, Killip grading, fasting blood-glucose (FBG) and whether percutaneous coronary intervention (PCI) was performed at early stage. A nomogram was used to present the final result. Individualized nomogram exhibited comparable discrimination to the Global Registry of Acute Coronary Events (GRACE) score [AUC: 0.807 (95% CI 0.736-0.878) vs. 0.761 (95% CI 0.69-0.878)], = 0.10) and a better discrimination than the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) score [AUC: 0.807 (95% CI 0.736-0.878) vs. 0.723(95% CI 0.648-0.798), = 0.01] in predicting the risk of in-hospital MACCE in ACS patients. A good prediction performance was maintained in the validation cohort (AUC =0.813, 95% CI 0.738-0.889). The prediction model also exhibited decent calibration ( = 0.972) and clinical usefulness. The nomogram may be a simple and effective tool in predicting the occurrence of in-hospital MACCE in ACS patients. Further longitudinal studies are warranted to validate its value in guiding clinical decision-making and optimizing the treatment of high-risk patients.
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http://dx.doi.org/10.3389/fcvm.2021.699023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380764PMC
August 2021

The expectations and acceptability of a smart nursing home model among Chinese elderly people: A mixed methods study protocol.

PLoS One 2021 23;16(8):e0255865. Epub 2021 Aug 23.

Faculty of Medicine and Health Sciences, Department of Family Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Nursing homes integrated with smart information such as the Internet of Things, cloud computing, artificial intelligence, and digital health could improve not only the quality of care but also benefit the residents and health professionals by providing effective care and efficient medical services. However, a clear concept of a smart nursing home, the expectations and acceptability from the perspectives of the elderly people and their family members are still unclear. In addition, instruments to measure the expectations and acceptability of a smart nursing home are also lacking. The study aims to explore and determine the levels of these expectations, acceptability and the associated sociodemographic factors. This exploratory sequential mixed methods study comprises a qualitative study which will be conducted through a semi-structured interview to explore the expectations and acceptability of a smart nursing home among Chinese elderly people and their family members (Phase I). Next, a questionnaire will be developed and validated based on the results of a qualitative study in Phase I and a preceding scoping review on smart nursing homes by the same authors (Phase II). Lastly, a nationwide survey will be carried out to examine the levels of expectations and acceptability, and the associated sociodemographic factors with the different categories of expectations and acceptability (Phase III). With a better understanding of the Chinese elderly people's expectations and acceptability of smart technologies in nursing homes, a feasible smart nursing home model that incorporates appropriate technologies, integrates needed medical services and business concepts could be formulated and tested as a solution for the rapidly ageing societies in many developed and developing countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255865PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382194PMC
August 2021

Single-Nucleotide Polymorphisms in the 3' Untranslated Region of Associated With Cardiovascular Diseases in a Chinese Han Population: A Case-Control Study.

Front Cardiovasc Med 2021 2;8:625072. Epub 2021 Aug 2.

Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Corin is a transmembrane serine protease that activates pro-forms of atrial and brain natriuretic peptides. Numerous studies have indicated that corin played an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of and CVDs. The aims of this study were to investigate the associations of three SNPs (rs3749585, rs4695253, and rs12641823) in the 3'UTR of with CVDs and to find the seed regions of microRNAs (miRNAs) that bind to SNPs of . A case-control study ( = 3,537) was performed in a Han population of northeastern China. CVDs included essential hypertension (EH), atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Genotyping was performed using high-resolution melt analysis. In the EH-control study, rs3749585 was significantly associated with the risk of EH after adjusting for sex and age in allelic ( = 0.049; : 1.113) and dominant ( = 0.015, : 1.233) models. Rs4695253 was significantly associated with the risk of EH in the recessive model after adjusting for sex and age ( = 0.005, : 2.084). Rs3749585 was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM, and CAD (dominant: = 0.009, : 0.762; additive: = 0.048, : 0.873). In the HF-control study and CAD-control study, none of the three SNPs was associated with HF and CAD after adjusting for covariates in any models ( > 0.05). The levels of high-density lipoprotein (HDL) in rs4695253 were lower than the levels of HDL in rs4695253 (42.47 ± 10.30 vs. 48.0 ± 10.24 mg/dl, = 0.008). The levels of total cholesterol (TC) in rs4695253 were lower than the levels of TC in rs4695253 (164.01 ± 49.15 vs. 180.81 ± 43.92 mg/dl, = 0.036). Luciferase assay revealed that the relative luciferase activity of rs3749585-transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585 ( < 0.001). A significant decrease in the relative luciferase activity of rs3749585 reporter was observed as compared with rs3749585 reporter in the presence of miR-1323 or miR-548o-3p ( = 0.017 and 0.012, respectively). We found significant associations between rs3749585 and rs4695253 and EH, between rs4695253 and the levels of TC and HDL, and between rs3749585 and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.
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http://dx.doi.org/10.3389/fcvm.2021.625072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365884PMC
August 2021

Short-term exposure to ambient air pollution and type 2 diabetes mortality: A population-based time series study.

Environ Pollut 2021 Jul 31;289:117886. Epub 2021 Jul 31.

Department of Global Health, School of Health Sciences, Wuhan University, Wuhan, China. Electronic address:

Acute health effects of air pollution on diabetes risk have not been fully studied in developing countries and the results remain inconsistent. This study aimed to investigate the association between short-term exposure to ambient air pollution and Type 2 diabetes mellitus (T2DM) mortality in China. Data on T2DM mortality from 2013 to 2019 were obtained from the Cause of Death Reporting System (CDRS) of Wuhan Center for Disease Control and Prevention. Air pollution data for the same period were collected from 10 national air quality monitoring stations of Wuhan Ecology and Environment Institute, including daily average PM, PM, SO, and NO. Meteorological data including daily average temperature and relative humidity were collected from Wuhan Meteorological Bureau. Generalized additive models (GAM) based on quasi-Poisson distribution were applied to evaluate the association between short-term exposure to air pollution and daily T2DM deaths. A total of 9837 T2DM deaths were recorded during the study period in Wuhan. We found that short-term exposure to PM, PM, SO, and NO were positively associated with T2DM mortality, and gaseous pollutants appeared to have greater effects than particulate matter (PM). For the largest effect, per 10 μg/m increment in PM (lag 02), PM (lag 02), SO (lag 03), and NO (lag 02) were significantly associated with 1.099% (95% CI: 0.451, 1.747), 1.016% (95% CI: 0.517, 1.514), 3.835% (95% CI: 1.480, 6.189), and 1.587% (95% CI: 0.646, 2.528) increase of daily T2DM deaths, respectively. Stratified analysis showed that females or elderly population aged 65 and above were more susceptible to air pollution exposure. In conclusion, short-term exposure to air pollution was significantly associated with a higher risk of T2DM mortality. Further research is required to verify our findings and elucidate the underlying mechanisms.
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http://dx.doi.org/10.1016/j.envpol.2021.117886DOI Listing
July 2021

Identification of a Three-RNA Binding Proteins (RBPs) Signature Predicting Prognosis for Breast Cancer.

Front Oncol 2021 12;11:663556. Epub 2021 Jul 12.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: To date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.

Methods: Based on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan-Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments , and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.

Results: Here, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells . Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer targeting MRPL12, MRPL13 and POP1 simultaneously.

Conclusion: This study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.663556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311660PMC
July 2021

Application of intra-abdominal pressure monitoring in early enteral nutrition after abdominal surgery.

Am J Transl Res 2021 15;13(6):7140-7147. Epub 2021 Jun 15.

Department of Orthopaedics, The Second People's Hospital of Hengshui Hengshui, Hebei, China.

Objective: To explore the effect of intra-abdominal pressure monitoring in early enteral nutrition therapy after abdominal surgery.

Methods: 164 patients who underwent elective abdominal surgery in our hospital from January 2019 to January 2020 were selected and divided into an observation group and a control group according to the random number table method, with 82 cases in each group. On the basis of conventional enteral nutrition nursing, the control group received conventional gastric residual monitoring, and the observation group received intra-abdominal pressure monitoring. The clinical treatment effect, intra-abdominal pressure, incidence of intra-abdominal hypertension, APACHE-II score, and enteral nutrition tolerance were compared. Correlation of early enteral nutrition intolerance and intra-abdominal pressure was analyzed in the ROC curve.

Results: The time of abdominal pain relief, adjusted enteral nutrition, and hospitalization were significantly shorter in the observation group (P < 0.05). The intra-abdominal pressure, intra-abdominal hypertension rate, and APACHE-II scores were comparable before treatment (P > 0.05) and all were significantly reduced after treatment in the two groups (P < 0.05). After treatment, the above items were significantly lower in the observation group (P < 0.05). The enteral nutrition's tolerance level of the observation group was significantly higher than that of the control group (P < 0.05). The Pearson correlation analysis revealed that the early enteral nutrition tolerance of patients after abdominal surgery was correlated with the level of intra-abdominal pressure (P < 0.05). The ROC reveled that the baseline level of intra-abdominal pressure and the average level of intra-abdominal pressure 3 days before enteral nutrition were of diagnostic values in predicting the intolerance during enteral nutrition.

Conclusion: Intraperitoneal pressure monitoring can significantly improve patients' symptoms, and it should be accurately measured for doctors to make timely diagnoses and provide proper treatments.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290724PMC
June 2021

The applied research on the intra-abdominal pressure monitoring in early enteral nutrition in patients with severe pneumonia.

Am J Transl Res 2021 15;13(6):6987-6993. Epub 2021 Jun 15.

Department of Orthopaedics, The Second People's Hospital of Hengshui Hengshui, Hebei, China.

Objective: To explore the applied value of intra-abdominal pressure (IAP) monitoring in early enteral nutrition (EEN) in patients with severe pneumonia.

Methods: 96 patients with severe pneumonia who underwent EEN treatment in our hospital from June 2017 to June 2019 were selected. According to the random number table method, they were divided into a control group (48 patients) and an observation group (48 patients). The control group was treated using the conventional EN method, and the observation group was treated using the intra-abdominal pressure monitoring besides the conventional EN method. The incidence of EN intolerance, the acute physiology and chronic health evaluation (APECHEll) scores, the positive end expiratory pressure (PEEP) value, mechanical ventilation time, EN implementation days, length of stay in ICU, the incidence of ventilator-associated pneumonia, mortality, and the incidence of multiple organ dysfunction syndrome were compared between the two groups.

Results: Compared with the control group, the incidence of EEN intolerance in the observation group was significantly reduced. The results of univariate analysis showed that, in the EN intolerance group, the IAP, the PEEP value and APACHEII scores after 3 days of EEN implementation were higher than the EEN tolerance group, indicating a influencing factor of EEN intolerance (P<0.05). The results of multivariate analysis showed that IAP value was a risk factor for EEN intolerance (P<0.05). The ROC curve analysis result for IAP to predict EEN tolerance showed that the area under the curve for IAP value to predict EN tolerance was 0.856, the optimal cut-off value was 10.73 mmHg, the sensitivity was 95.10%, and the specificity was 89.60%.

Conclusion: The intra-abdominal pressure monitoring during the EEN in patients with severe pneumonia is a preferred method to guide the patients' EEN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290670PMC
June 2021

Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth.

Stem Cells Int 2021 29;2021:9989790. Epub 2021 Jun 29.

School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.
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http://dx.doi.org/10.1155/2021/9989790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263240PMC
June 2021

Genome-Wide Identification and Analysis of the Polycomb Group Family in .

Int J Mol Sci 2021 Jul 14;22(14). Epub 2021 Jul 14.

State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.

Polycomb group (PcG) proteins, which are important epigenetic regulators, play essential roles in the regulatory networks involved in plant growth, development, and environmental stress responses. Currently, as far as we know, no comprehensive and systematic study has been carried out on the PcG family in . In the present study, we identified 64 PcG genes with distinct gene structures from the genome. All of the PcG genes were distributed unevenly over eight chromosomes, of which 26 genes underwent gene duplication. The prediction of protein interaction network indicated that 34 PcG proteins exhibited protein-protein interactions, and MtMSI1;4 and MtVRN2 had the largest number of protein-protein interactions. Based on phylogenetic analysis, we divided 375 PcG proteins from 27 species into three groups and nine subgroups. Group I and Group III were composed of five components from the PRC1 complex, and Group II was composed of four components from the PRC2 complex. Additionally, we found that seven PcG proteins in were closely related to the corresponding proteins of . Syntenic analysis revealed that PcG proteins had evolved more conservatively in dicots than in monocots. had the most collinearity relationships with (36 genes), while collinearity with three monocots was rare (eight genes). The analysis of various types of expression data suggested that PcG genes were involved in the regulation and response process of in multiple developmental stages, in different tissues, and for various environmental stimuli. Meanwhile, many differentially expressed genes (DEGs) were identified in the RNA-seq data, which had potential research value in further studies on gene function verification. These findings provide novel and detailed information on the PcG family, and in the future it would be helpful to carry out related research on the PcG family in other legumes.
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http://dx.doi.org/10.3390/ijms22147537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303337PMC
July 2021

Pectin and homogalacturonan with small molecular mass modulate microbial community and generate high SCFAs via in vitro gut fermentation.

Carbohydr Polym 2021 Oct 10;269:118326. Epub 2021 Jun 10.

Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS)/Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Beijing 100193, China; Hebei Normal University of Science & Technology, Qin Huangdao 066000, Heibei, China. Electronic address:

The intestinal fermentability of pectic polysaccharides is largely determined by its molecular size. In this study, fermentation properties of enzymatic-modified apple pectin (AP) and homogalacturonans (HG) with high, medium and low molecular weight (Mw) were evaluated by in vitro fermentation model, and their structural changes were also investigated. Results showed that Mw, monosaccharide contents and molecular linearity of the AP hydrolysates were reduced after microbial degradation. On the other hand, culture media supplemented with low-Mw AP (60,300 g/mol) and low-Mw HG (861 g/mol) exhibited lower pH (5.1 and 5.7, respectively) and produced higher total short-chain fatty acid contents (SCFA, 230.40 mmol/L and 187.19 mmol/L, respectively). However, reduced trends in abundance of the pectinolytic microorganisms Faecalibacterium and Eubacterium were showed as Mw of the HG decreased, whereas growth of the SCFA-producer genera Bifidobaacterium, Megasphaera and Allisonella were improved. This work confirmed that low-Mw pectin and homogalacturonan generated more beneficial metabolites, developing structure-microbiota-gut health relationship.
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http://dx.doi.org/10.1016/j.carbpol.2021.118326DOI Listing
October 2021

Magnetic field sensor based on helical long-period fiber grating with a three-core optical fiber.

Opt Express 2021 Jun;29(13):20649-20656

A high sensitivity optical fiber magnetic field sensor is proposed and implemented by using a helical long-period fiber grating (HLPFG) based on a three-core fiber (TCF) bonded to a U-shaped aluminum (Al) wire. An electrical current flowing through the Al wire in a perpendicular magnetic field can generate Ampere force, which changes the distance between the two arms of the U-shaped Al wire. Thus, when the intensity and direction of the magnetic field change, the bending curvature of TCF-HLPFG bonded to the U-shaped Al wire varies with the change of Ampere force, which is represented as the shift of resonant wavelength in the spectrum. The as-fabricated sensor can respond to the magnetic field direction and the intensity with a range from -15 mT to 15 mT, and the measured sensitivity is 456.5 pm/mT with Al wire electrical current 1A. The proposed sensor has the advantages of low cost, nondestructive measurement method and ease manufacture, and is expected to be applied to weak magnetic field measurements.
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http://dx.doi.org/10.1364/OE.429957DOI Listing
June 2021

Enhanced hole extraction by electron-rich alloys in all-inorganic CsPbBr perovskite solar cells.

Chem Commun (Camb) 2021 Jul;57(61):7577-7580

College of Information Science and Technology, Jinan University, Guangzhou, 510632, P. R. China.

We present the fabrication of electron-rich Pt3M alloy-tailored carbon electrodes to maximize hole extraction. Through optimizing the doses and alloy species systematically, the best all-inorganic CsPbBr3 perovskite solar cell achieved a power conversion efficiency of 9.08% and showed excellent long-term stability at 80% RH over 20 days.
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http://dx.doi.org/10.1039/d1cc02773eDOI Listing
July 2021

Acute graft-versus-host disease after liver transplantation in a close contact with COVID-19: A case report.

Transpl Immunol 2021 10 1;68:101435. Epub 2021 Jul 1.

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1905 Jiefang Avenue, Wuhan City, Hubei Province, Wuhan 430030, China. Electronic address:

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.
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http://dx.doi.org/10.1016/j.trim.2021.101435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245304PMC
October 2021

Clinical Significance of Kinetics of Low-Density Lipoprotein Cholesterol and Its Prognostic Value in Limited Stage Small Cell Lung Cancer Patients.

Cancer Control 2021 Jan-Dec;28:10732748211028257

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

Objectives: To investigate the clinical significance of dynamic alteration of serum lipids in limited stage small cell lung cancer (LS-SCLC) patients and the risk that different lipid profiles poses to patients' health.

Methods: We retrospectively analyzed the variation trends and prognostic values of serum lipids in 310 LS-SCLC patients who had received standard chemotherapy between 2002 and 2017. In addition to serum lipid level, which were measured at the time of pretreatment, after-chemotherapy and during disease progression and later analyzed, the dynamic lipid alteration trend and its correlation to progression-free survival (PFS) and overall survival (OS) were also statistically analyzed using Log-rank test and COX regression analyses.

Results: A significant decrease in HDL-C level was observed after standard chemotherapy (Post-CT baseline = -0.08 ± 0.34, < 0.001), and this trend of reduction was further enhanced by thoracic radiotherapy ( = 0.046). Increase in LDL-C level was also observed to be associated with higher likelihood of disease progression ( = 0.003). Moreover, the extent of the increase in LDL-C was also associated with the number of progression sites, as patients with higher increase in LDL-C in exhibiting a progression at more than 2 sites outside thorax ( = 0.037). The patients' median PFS and OS were 14.04 months (95%CI: 25.12-33.81) and 22.40 months (95%CI: 33.19-42.13), respectively. For both PFS and OS, LDL-C elevation remained an independent prognostic factor in the multivariate model ( = 0.007 and = 0.022, respectively).

Conclusion: Overall, for LS-SCLC patients, standard chemotherapy decreases the level of HDL-C, the level of increase in LDL-C could predict disease progression and even the number of progression sites, and LDL-C elevation could be an independent prognostic factor for poor OS and PFS.
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http://dx.doi.org/10.1177/10732748211028257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246505PMC
June 2021

A Retrospective Study Comparison Between Stenting and Standardized Medical Treatment for Intracranial Vertebrobasilar Stenosis in a Real-World Chinese Cohort.

Front Neurol 2021 31;12:629644. Epub 2021 May 31.

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

To date, there has been no consensus regarding the benefits of percutaneous transluminal angioplasty and stenting (PTAS) vs. those of standardized medical treatment (SMT) for patients with symptomatic intracranial vertebrobasilar stenosis (IVBS). The purpose of this retrospective study was to compare the effects of PTAS or SMT on symptomatic IVBS in a real-world Chinese population. We included 238 patients with ischemic stroke caused by IVBS stenosis who were admitted to Shandong Provincial Hospital Affiliated to Shandong University between September 2012 and May 2018; 62 of these patients were treated with SMT and 176 underwent PTAS. Ischemic stroke in the territory of the responsible artery, hemorrhage, and death within 1 year were recorded as primary endpoints. Secondary endpoints included assessment of stroke severity and the incidence of re-stenosis. The primary endpoint rates were compared between the PTAS and SMT groups at 7 days, 1, 6 months, and 1 year. In the PTAS group, the success rate of stent placement was 98.9%. During the entire trial, except for 7 days, the SMT group had a higher frequency of primary endpoint events than did the PTAS group. The primary endpoint was 17.7% (11/62) vs. 8.6% (15/174) at 1 month ( = 0.049), 29% (18/62) vs. 14.4% (25/174) at 6 months ( = 0.01), and 32.2% (20/62) vs. 17.2% (30/174) at 1 year ( = 0.013). The restenosis rate of the target lesion was 13.8%; 60% were symptomatic restenosis and 40% were asymptomatic restenosis. The rate of severe stroke at 1 year after PTAS was 0%, while that in the SMT group was 9.7%. In a real-world Chinese cohort, PTAS for patients might be superior to SMT, and provide better long-term neurological function recovery and lower disability rate.
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http://dx.doi.org/10.3389/fneur.2021.629644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200490PMC
May 2021

Enhancement of Solubility, Purification, and Inclusion Body Refolding of Active Human Mitochondrial Aldehyde Dehydrogenase 2.

ACS Omega 2021 May 28;6(18):12004-12013. Epub 2021 Apr 28.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is predominantly linked with acetaldehyde detoxification in the second stage of alcohol metabolism. To intensively study ALDH2 function, a higher purity and uniform composition of the protein is required. An efficient system for ALDH2 expression was developed by using His and a small ubiquitin-related modifier fusion tag. Most of the recombinant ALDH2s were expressed in the form of inclusion bodies. The ALDH2-enriched inclusion bodies were denatured with 6 M guanidine hydrochloride, and then ALDH2 was ultrafitrated. Finally, ALDH2 was successfully purified through affinity and gel filtration chromatography. The purified ALDH2 was finally preserved by the vacuum freeze-drying method, and its purity was determined to be higher than 95%, with a final media yield of 33.89 mg/L. The specific activity of ALDH2 was 6.1 × 10 U/mg. This work was the first to report pET-SUMO-ALDH2 recombinant plasmid expression in , and the inclusion bodies were isolated and refolded. Finally, the purified ALDH2 had relatively higher purity, yield, and biological activity.
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http://dx.doi.org/10.1021/acsomega.1c00577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154035PMC
May 2021

Association Between Metabolic Syndrome and Asymptomatic Cerebral Arterial Stenosis: A Cross-Sectional Study in Shandong, China.

Front Neurol 2021 12;12:644963. Epub 2021 May 12.

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Metabolic syndrome (MetS) can worsen cerebral arterial atherosclerosis stenosis in patients with stroke; however, its effect on patients without stroke remains ambiguous. This study explored the association of MetS and its individual components with asymptomatic intracranial arterial stenosis (aICAS) and asymptomatic extracranial arterial stenosis (aECAS) among older Chinese adults. A total of 1988 participants from the Kongcun Town study aged ≥40 years and without a history of stroke were enrolled. The baseline data were obtained via face-to-face interviews. MetS was defined according to International Diabetes Federation criteria. Detection of aICAS was conducted using transcranial Doppler ultrasound, followed by diagnosis via magnetic resonance angiography. The evaluation of aECAS was performed using bilateral carotid ultrasonography. The aICAS and aECAS groups were 1:1 matched separately to the non-stenosis group by age and sex. The association between MetS and aICAS or aECAS was analyzed using multivariate logistic regression. Among the 1988 participants, 909 were diagnosed with MetS. The prevalence of MetS was higher in the aICAS group than in the non-stenosis group ( <0.001), but did not differ significantly between the aECAS and non-stenosis groups. The prevalence of aICAS increased with the number of MetS components from 3.4% in the ≤ 1 component group to 12.7% in the ≥4 components group ( for trend <0.001). After adjusting for confounding factors, MetS components associated with aICAS included central obesity, elevated triglyceride levels, and elevated blood pressure. None of the MetS components was associated with aECAS. MetS was positively associated with aICAS, but not with aECAS. Further, different components play different roles in the pathological process leading to aICAS.
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http://dx.doi.org/10.3389/fneur.2021.644963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149894PMC
May 2021

Identification of Gingivitis-Related Genes Across Human Tissues Based on the Summary Mendelian Randomization.

Front Cell Dev Biol 2020 6;8:624766. Epub 2021 May 6.

School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Periodontal diseases are among the most frequent inflammatory diseases affecting children and adolescents, which affect the supporting structures of the teeth and lead to tooth loss and contribute to systemic inflammation. Gingivitis is the most common periodontal infection. Gingivitis, which is mainly caused by a substance produced by microbial plaque, systemic disorders, and genetic abnormalities in the host. Identifying gingivitis-related genes across human tissues is not only significant for understanding disease mechanisms but also disease development and clinical diagnosis. The Genome-wide association study (GWAS) a commonly used method to mine disease-related genetic variants. However, due to some factors such as linkage disequilibrium, it is difficult for GWAS to identify genes directly related to the disease. Hence, we constructed a data integration method that uses the Summary Mendelian randomization (SMR) to combine the GWAS with expression quantitative trait locus (eQTL) data to identify gingivitis-related genes. Five eQTL studies from different human tissues and one GWAS studies were referenced in this paper. This study identified several candidates SNPs and genes relate to gingivitis in tissue-specific or cross-tissue. Further, we also analyzed and explained the functions of these genes. The R program for the SMR method has been uploaded to GitHub(https://github.com/hxdde/SMR).
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http://dx.doi.org/10.3389/fcell.2020.624766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134671PMC
May 2021

Galectin-3 Derived from HucMSC Exosomes Promoted Myocardial Fibroblast-to-Myofibroblast Differentiation Associated with -catenin Upregulation.

Int J Stem Cells 2021 Aug;14(3):320-330

School of Medicine, Jiangsu University, Zhenjiang, China.

Background And Objectives: Galectin-3 promotes fibroblast-to-myofibroblast differentiation and facilitates injury repair. Previous studies have shown that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) promote the differentiation of myocardial fibroblasts into myofibroblasts under inflammatory environment. Whether hucMSC-ex derived Galectin-3 (hucMSC-ex-Galectin-3) plays an important role in fibroblast-to-myofibroblast differentiation is the focus of this study.

Methods And Results: Galectin-3 was knocked-down by siRNA in hucMSCs, and then exosomes were extracted. Fibroblasts were treated with LPS, LPS+hucMSC-ex, LPS+negative control-siRNA-ex (NC-ex), or LPS+ Galectin-3-siRNA-ex (si-ex) . The coronary artery of the left anterior descending (LAD) branch was permanently ligated, followed by intramyocardial injection with phosphate buffered saline(PBS), hucMSC-ex, hucMSC-NC-ex, or hucMSC-si-ex . Western blot, RT-PCR, and immunohistochemistry were used to detect the expression of markers related to fibroblast-to-myofibroblast differentiation and inflammatory factors. Migration and contraction functions of fibroblasts were evaluated using Transwell migration and collagen contraction assays, respectively. -catenin expression was detected by western blot and immunofluorescence. The results showed that hucMSC-ex increased the protein expression of myofibroblast markers, anti-inflammatory factors, and -catenin. HucMSC-ex also reduced the migration and promoted the contractility of fibroblasts. However, hucMSC-si-ex did not show these activities.

Conclusions: HucMSC-ex-Galectin-3 promoted the differentiation of cardiac fibroblasts into myofibroblasts in an inflammatory environment, which was associated with increased -catenin levels.
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http://dx.doi.org/10.15283/ijsc20186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429944PMC
August 2021

NSDHL promotes triple-negative breast cancer metastasis through the TGFβ signaling pathway and cholesterol biosynthesis.

Breast Cancer Res Treat 2021 Jun 16;187(2):349-362. Epub 2021 Apr 16.

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Build 7, Room 303, Shanghai, 200032, China.

Purpose: Metastasis is the main cause of breast cancer mortality. Recent studies have proved that lipid metabolic reprogramming plays critical roles in breast cancer carcinogenesis and metastasis. We aim to identify critical lipid metabolism genes in breast cancer metastasis.

Methods: We designed and cloned a CRISPR pooled library containing lipid metabolic gene guide RNAs and performed a genetic screen in vivo. Transwell assay and animal experiments were used to evaluate cell metastatic ability in vitro or in vivo, respectively. We performed immunohistochemistry with breast cancer tissue microarray to study the clinical significance of NSDHL.

Findings: We identified a cholesterol metabolic enzyme, NSDHL, as a potential metastatic driver in triple-negative breast cancer. NSDHL was highly expressed in breast cancer tissues and predicted a poor prognosis. NSDHL knockdown significantly suppressed cell proliferation and migration. Mechanistically, NSDHL activated the TGFβ signaling pathway by inhibiting the endosomal degradation of TGFβR2. In addition, blocking the upstream metabolism of NSDHL with ketoconazole rescued cancer metastasis and TGFβR2 degradation. However, the inactivation of NSDHL (Y151X) did not rescue the migration ability and the TGFβR2 protein expression.

Conclusion: Taken together, our findings established that NSDHL serves as a metastatic driver, and its function depends on its enzyme activity in cholesterol biosynthesis and is mediated by the NSDHL-TGFβR2 signal pathway. Our study indicated that NSDHL and steroid biosynthesis may serve as new drug targets for patients with advanced breast cancer.
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http://dx.doi.org/10.1007/s10549-021-06213-8DOI Listing
June 2021

Combined Transcriptome Analysis Reveals the Ovule Abortion Regulatory Mechanisms in the Female Sterile Line of Carr.

Int J Mol Sci 2021 Mar 19;22(6). Epub 2021 Mar 19.

College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.

Ovule abortion is a common phenomenon in plants that has an impact on seed production. Previous studies of ovule and female gametophyte (FG) development have mainly focused on angiosperms, especially in . However, because it is difficult to acquire information about ovule development in gymnosperms, this remains unclear. Here, we investigated the transcriptomic data of natural ovule abortion mutants (female sterile line, STE) and the wild type (female fertile line, FER) of Carr. to evaluate the mechanism of ovule abortion during the process of free nuclear mitosis (FNM). Using single-molecule real-time (SMRT) sequencing and next-generation sequencing (NGS), 18 cDNA libraries via Illumina and two normalized libraries via PacBio, with a total of almost 400,000 reads, were obtained. Our analysis showed that the numbers of isoforms and alternative splicing (AS) patterns were significantly variable between FER and STE. The functional annotation results demonstrate that genes involved in the auxin response, energy metabolism, signal transduction, cell division, and stress response were differentially expressed in different lines. In particular, , , , and had significantly lower expression in STE, showing that auxin might be insufficient in STE, thus hindering nuclear division and influencing metabolism. Apoptosis in STE might also have affected the expression levels of these genes. To confirm the transcriptomic analysis results, nine pairs were confirmed by quantitative real-time PCR. Taken together, these results provide new insights into ovule abortion in gymnosperms and further reveal the regulatory mechanisms of ovule development.
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http://dx.doi.org/10.3390/ijms22063138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003466PMC
March 2021

Correlation of Blastocyst Quality and Pregnancy Outcome during Freeze - Thaw Cycle.

J Coll Physicians Surg Pak 2021 Mar;31(3):278-281

Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, Baoding, China.

Objective: To explore the relationship between the blastocyst quality and biochemical pregnancy or early embryonic cessation of development during the freeze-thaw cycle of in vitro fertilisation embryo transfer (IVF-ET).

Study Design: Descriptive study.

Place And Duration Of Study: Reproductive Centre of Baoding Maternal and Child Health Hospital, from January 2014 to August 2019.

Methodology: Eight hundred and twenty-nine embryos, treated by frozen-thawed blastocyst transfer, were analysed, retrospectively. These included 232 embryos in inner cell mass (ICM) Grade C, 272 embryos with trophoderm (TE) Grade C, and 325 embryos with Grades excluding C; ICM Grade and TE Grade were A or B. The pregnancy rate, rate of early embryonic cessation of development, and biochemical pregnancy rate were compared among the three groups after transfer.

Results: Compared with embryos with Grades excluding C in the score (with 55.7% in clinical pregnancy rate, 6.5% in biochemical pregnancy rate, and 5.2% in early embryonic development arrest rate), the embryos with ICM Grade C has lower clinical pregnancy rate (43.5%), higher biochemical pregnancy rate (15.1%), and rate of early embryonic cessation of development (19.8%), while the embryos with TE Grade C has lower pregnancy rate (41.2%) and higher biochemical pregnancy rate (14.3%). The differences were statistically significant (all p <0.05). There was no significant difference about the above indicators between the ICM Grade C and TE Grade C groups (p >0.05).

Conclusion: Embryos with Grades excluding C in the score had better developmental potential and better prognosis. The rate of early embryonic development arrest in the ICM Grade C group was higher than that in the TE Grade C group. Key Words: Embryo quality and score, Blastocyst, Biochemical pregnancy, Early embryonic cessation of development.
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http://dx.doi.org/10.29271/jcpsp.2021.03.278DOI Listing
March 2021
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