Publications by authors named "Yang Gu"

222 Publications

The role of non‑coding RNAs in the regulation, diagnosis, prognosis and treatment of osteosarcoma (Review).

Int J Oncol 2021 Sep 23;59(3). Epub 2021 Jul 23.

Guangdong Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510000, P.R. China.

Osteosarcoma (OS) is the most common primary bone tumor worldwide. OS exhibits a range of aggressive behaviors, including early metastasis potential, rapid progression, poor clinical prognosis and insensitivity to chemoradiotherapy. Non‑coding RNAs are transcripts that do not encode proteins. A significant number of studies published on OS have been focused on the aberrant expression of non‑coding RNAs and their involvement in tumor initiation and progression. It has been confirmed that non‑coding RNAs exert their regulatory functions at both the transcriptional and post‑transcriptional level, which leads to tumor initiation or progression in OS. According to present knowledge, this review provides a state‑of‑the‑art overview of the functions and mechanisms of microRNAs, long non‑coding RNAs and circular RNAs in terms of their involvement with OS. The review also covers their potential clinical application in the diagnosis, prognosis and treatment of OS. It is hoped that the information presented in this review on the involvement of non‑coding RNAs in OS will lead to a more comprehensive understanding of OS and provide a useful perspective on the potential diagnostic and therapeutic applications of non‑coding RNAs for patients with OS.
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http://dx.doi.org/10.3892/ijo.2021.5249DOI Listing
September 2021

Functional dissection and modulation of the BirA protein for improved autotrophic growth of gas-fermenting Clostridium ljungdahlii.

Microb Biotechnol 2021 Jul 21. Epub 2021 Jul 21.

Key Laboratory of Synthetic Biology, The State Key Laboratory of Plant Carbon-Nitrogen Assimilation, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.

Gas-fermenting Clostridium species can convert one-carbon gases (CO /CO) into a variety of chemicals and fuels, showing excellent application prospects in green biological manufacturing. The discovery of crucial genes and proteins with novel functions is important for understanding and further optimization of these autotrophic bacteria. Here, we report that the Clostridium ljungdahlii BirA protein (ClBirA) plays a pleiotropic regulator role, which, together with its biotin protein ligase (BPL) activity, enables an effective control of autotrophic growth of C. ljungdahlii. The structural modulation of ClBirA, combined with the in vivo and in vitro analyses, further reveals the action mechanism of ClBirA's dual roles as well as their interaction in C. ljungdahlii. Importantly, an atypical, flexible architecture of the binding site was found to be employed by ClBirA in the regulation of a lot of essential pathway genes, thereby expanding BirA's target genes to a broader range in clostridia. Based on these findings, molecular modification of ClBirA was performed, and an improved cellular performance of C. ljungdahlii was achieved in gas fermentation. This work reveals a previously unknown potent role of BirA in gas-fermenting clostridia, providing new perspective for understanding and engineering these autotrophic bacteria.
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http://dx.doi.org/10.1111/1751-7915.13884DOI Listing
July 2021

Magnetic resonance imaging radiomics predicts preoperative axillary lymph node metastasis to support surgical decisions and is associated with tumor microenvironment in invasive breast cancer: A machine learning, multicenter study.

EBioMedicine 2021 Jul 4;69:103460. Epub 2021 Jul 4.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Breast Tumor Centre, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: in current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer has a low efficiency and is based on an invasive procedure that causes operative-associated complications in many patients. Therefore, we aimed to use machine learning techniques to develop an efficient preoperative magnetic resonance imaging (MRI) radiomics evaluation approach of ALN status and explore the association between radiomics and the tumor microenvironment in patients with early-stage invasive breast cancer.

Methods: in this retrospective multicenter study, three independent cohorts of patients with breast cancer (n = 1,088) were used to develop and validate signatures predictive of ALN status. After applying the machine learning random forest algorithm to select the key preoperative MRI radiomic features, we used ALN and tumor radiomic features to develop the ALN-tumor radiomic signature for ALN status prediction by the support vector machine algorithm in 803 patients with breast cancer from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (training cohort). By combining ALN and tumor radiomic features with corresponding clinicopathologic information, the multiomic signature was constructed in the training cohort. Next, the external validation cohort (n = 179) of patients from Shunde Hospital of Southern Medical University and Tungwah Hospital of Sun Yat-Sen University, and the prospective-retrospective validation cohort (n = 106) of patients treated with neoadjuvant chemotherapy in prospective phase 3 trials [NCT01503905], were included to evaluate the predictive value of the two signatures, and their predictive performance was assessed by the area under operating characteristic curve (AUC). This study was registered with ClinicalTrials.gov, number NCT04003558.

Findings: the ALN-tumor radiomic signature for ALN status prediction comprising ALN and tumor radiomic features showed a high prediction quality with AUC of 0·88 in the training cohort, 0·87 in the external validation cohort, and 0·87 in the prospective-retrospective validation cohort. The multiomic signature incorporating tumor and lymph node MRI radiomics, clinical and pathologic characteristics, and molecular subtypes achieved better performance for ALN status prediction with AUCs of 0·90, 0·91, and 0·93 in the training cohort, the external validation cohort, and the prospective-retrospective validation cohort, respectively. Among patients who underwent neoadjuvant chemotherapy in the prospective-retrospective validation cohort, there were significant differences in the key radiomic features before and after neoadjuvant chemotherapy, especially in the gray-level dependence matrix features. Furthermore, there was an association between MRI radiomics and tumor microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites. Interpretation this study presented a multiomic signature that could be preoperatively and conveniently used for identifying patients with ALN metastasis in early-stage invasive breast cancer. The multiomic signature exhibited powerful predictive ability and showed the prospect of extended application to tailor surgical management. Besides, significant changes in key radiomic features after neoadjuvant chemotherapy may be explained by changes in the tumor microenvironment, and the association between MRI radiomic features and tumor microenvironment features may reveal the potential biological underpinning of MRI radiomics.

Funding: No funding.
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http://dx.doi.org/10.1016/j.ebiom.2021.103460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261009PMC
July 2021

Icariin Inhibits Intestinal Inflammation of DSS-Induced Colitis Mice Through Modulating Intestinal Flora Abundance and Modulating p-p65/p65 Molecule.

Turk J Gastroenterol 2021 04;32(4):382-392

School of Medicine - Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Background: Ulcerative colitis, as a kind of inflammatory bowel disease (IBD) is characterized by abdominal pain. This study aimed to investigate the effect of icariin (ICA) on the intestinal microflora of colitis mice.

Methods: Fifteen female C57BL/6 mice were randomly divided into the Control group, dextran sodium sulfate (DSS)-induced colitis (DSS) group, and ICA treatment (DSS+ICA) group. The severity of inflammation in DSS-induced colitis mice was evaluated using disease activity scoring (considering weight-loss percentage, stool-shape change, and stool-bleeding scoring). Pathological changes of mice intestinal tract were evaluated using hematoxylin-eosin (HE) staining. Serum levels of TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay. Expressions of p65 and p-p65 (p-p65/p65 ratio) were analyzed using Western blot assay. 16S rDNA sequencing was used to analyze the abundance and composition of intestinal microflora.

Results: Compared with DSS group, ICA significantly improved disease activity (P < .05) and reduced inflammatory damage of colon tissues (P < .05) in DSS-induced colitis mice. Compared with the DSS group, mice in the ICA group demonstrated significant weight and colon length (P < .05). ICA significantly inhibited expressions of IL-6 and TNF-α compared to the DSS group (P < .05). p-p65/ p65 ratio in the DSS + ICA group was remarkably enhanced compared to the DSS group (P < .05). ICA significantly reduced the proportion and activity of Bacteroides, Helicobacteraceae, Turicibacter, and significantly increased that of beneficial microflora (Lactobacillus, Lachnospiraceae, Akkermansia), so as improved damages of colon tissues.

Conclusion: ICA can improve intestinal flora abundance and composition of DSS-induced colitis mice, and inhibit tissue damage and inflammatory response through modulating the p-p65/p65 expression.
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http://dx.doi.org/10.5152/tjg.2021.20282DOI Listing
April 2021

Study results suggest less invasive HeartMate 3 implantation is a safe and effective approach for obese patients.

J Heart Lung Transplant 2021 Jun 11. Epub 2021 Jun 11.

Division of Cardiac Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, New York. Electronic address:

Background: Historically, obesity was considered a relative contraindication to left ventricular assist device (LVAD) implantation with less invasive surgery (LIS). The present study aimed to compare the outcomes of obese patients who underwent LVAD implantation through LIS with those who received full sternotomy (FS) implantation.

Methods: We retrospectively reviewed all patients implanted with HeartMate 3 LVAD in our institution between September 2015 and June 2020. Obese patients (BMI ≥ 30 kg/m) were included and dichotomized based on surgical approach into the FS or LIS cohort.

Results: Of 231 implanted patients, 107 (46%) were obese and included in the study. FS was performed in 26 (24%) patients and LIS approach in 81 (76%) patients. Preoperative patient characteristics were similar between the cohorts. Postoperatively, patients in LIS cohort had less bleeding (p = 0.029), fewer transfusions (p = 0.042), shorter duration of inotropic support (p = 0.049), and decreased incidence of severe RV failure (11.1% vs 30.8%, p = 0.028). Survival to discharge for the obese population was 87.5% overall and did not differ based on an approach (91.4% LIS vs 76.9% FS, p = 0.079). More LIS patients were discharged home (60.0% vs 82.4%, p = 0.041) rather than to rehabilitation center.

Conclusion: Our results showed that the LIS approach in obese patients is associated with fewer postoperative complications and a trend towards better short-term survival. These results suggest that less invasive LVAD implantation is a safe and effective approach for obese patients. Future prospective randomized trials are required to substantiate these results.
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http://dx.doi.org/10.1016/j.healun.2021.06.001DOI Listing
June 2021

Recent advances in biotechnological production of polyunsaturated fatty acids by .

Crit Rev Food Sci Nutr 2021 Jun 14:1-15. Epub 2021 Jun 14.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People's Republic of China.

Owing to the important physiological functions, polyunsaturated fatty acids (PUFAs) play a vital role in protecting human health, such as preventing cancer, cardiovascular disease, and diabetes. Specifically, has been identified as the most popular non-conventional oleaginous yeast, which can accumulate the abundant intracellular lipids, indicating that has great potential as an industrial host for production of PUFAs. Notably, some novel engineering strategies have been applied to endow and improve the abilities of to synthesize PUFAs, including construction and optimization of PUFAs biosynthetic pathways, improvement of preucrsors acetyl-coA and NADPH supply, inhibition of competing pathways, knockout of β-oxidation pathways, regulation of oxidative stress defense pathways, and regulation of genes involved in upstream lipid metabolism. Besides, some bypass approaches, such as strain mating, evolutionary engineering, and computational model based on omics, also have been proposed to improve the performance of engineering strains. Generally, in this review, we summarized the recent advances in engineering strategies and bypass approaches for improving PUFAs production by . In addition, we further summarized the latest efforts of CRISPR/Cas genome editing technology in , which is aimed to provide its potential applications in PUFAs production.
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http://dx.doi.org/10.1080/10408398.2021.1937041DOI Listing
June 2021

Calcaneal fractures: 3D-printing model to assist spatial weaving of percutaneous screws versus conventional open fixation-a retrospective cohort study.

Int Orthop 2021 Jun 11. Epub 2021 Jun 11.

Department of Foot and Ankle Surgery, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

Purpose: This study compared the clinical effectiveness and wound complications of a three-dimensional model-assisted spatial weaving screw fixation (3D-SWSF) versus open reduction and internal fixation (ORIF) via an L-shaped extensile lateral approach for calcaneal fractures.

Methods: This single-centre retrospective cohort study was conducted with two cohort groups in which patients with Sanders II and III calcaneal fractures underwent 3D-SWSF or conventional ORIF. The clinical outcome measures included operation duration, time to operation, wound complications, blood loss volume, hospital stays, American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score, and visual analog scale (VAS) score. The pre-operative, post-operative, and one-year follow-up Gissane's angle (GA), Böhler's angle (BA), height, and width and length of the calcaneal fractures were also compared between the two groups.

Results: From Oct 2015 to Oct 2019, 31 patients received 3D-SWSF and 41 received conventional ORIF. A total of 11 (26.8%) patients in ORIF group had wound complications, compared with only two (6.5%) in 3D-SWSF group (p = 0.032). Operative time, blood loss, and hospital stay in 3D-SWSF group were lesser than those in ORIF group. The patients treated with 3D-SWSF had better AOFAS and VAS scores than those treated with ORIF at the last follow-up. The post-operative and one-year follow-up radiographic indexes as well as the GA, BA, length, width, and height of the calcaneal fractures were relatively comparable between the two groups.

Conclusion: Our study revealed that 3D-SWSF could effectively decrease the risk of wound complications, shorten operation time, reduce length of hospitalization, and improve post-operative rehabilitation.
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http://dx.doi.org/10.1007/s00264-021-05094-2DOI Listing
June 2021

YY1-mediated reticulocalbin-2 upregulation promotes the hepatocellular carcinoma progression via activating MYC signaling.

Am J Cancer Res 2021 15;11(5):2238-2251. Epub 2021 May 15.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, People's Republic of China.

Hepatocellular carcinoma (HCC) is a common digestive tumor with high fatality worldwide. Previous studies have shown that Reticulocalbin-2 (RCN2) was a crucial factor for HCC proliferation, but invasion and migration mechanism of RCN2 contributing to HCC is poorly investigated. In this study, we estimated the RCN2 expression in both patient tissues and cell lines by polymerase chain reaction (PCR) and western blotting (WB), as well as the clinical information of HCC patients from public databases. Biological function induced by RCN2 in and was also researched through multiple functional experiments. Upstream and downstream signal of RCN2 was identified by bioinformatics. We found that up-regulated RCN2 was related to poorer prognosis in HCC patients and attached significance to HCC proliferation, invasion and migration. Luciferase reporter assay and chromatin immunoprecipitation validated that YY1 as the upstream transcription factor of RCN2, facilitating the expression of RCN2. Gene set enrichment analysis indicated that HCC progression induced by RCN2 might be related to MYC signaling. Furthermore, we demonstrated RCN2 reduced proteasomal degradation of MYC and lead to HCC progression. The effects of overexpressed RCN2 in HCC were attenuated by MYC silencing. In conclusion, our study highlighted the vital role of RCN2 in tumor progression and the potential benefit for the treatment of HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167676PMC
May 2021

Influence of Preaging Temperature on the Indentation Strength of 3Y-TZP Aged in Ambient Atmosphere.

Materials (Basel) 2021 May 23;14(11). Epub 2021 May 23.

VASIC Research Center, Department of Dentistry, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea.

Yttria-stabilized zirconia (3Y-TZP) containing 0.25% AlO, which is resistant to low temperature degradation (LTD), was aged for 10 h at 130-220 °C in air. The aged specimens were subsequently indented at loads ranging from 9.8 to 490 N using a Vickers indenter. The influence of preaging temperature on the biaxial strength of the specimens was investigated to elucidate the relationship between the extent of LTD and the strength of zirconia restorations that underwent LTD. The indented strength of the specimens increased as the preaging temperature was increased higher than 160 °C, which was accompanied by extensive t-ZrO (t) to m-ZrO (m) and c-ZrO (c) to r-ZrO (r) phase transformations. The influence of preaging temperature on the indented strength was rationalized by the residual stresses raised by the t→m transformation and the reversal of tensile residual stress on the aged specimen surface due to the indentation. The results suggested that the longevity of restorations would not be deteriorated if the aged restorations retain compressive residual stress on the surface, which corresponds to the extent of t→m phase transformation less than 52% in ambient environment.
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http://dx.doi.org/10.3390/ma14112767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197138PMC
May 2021

A posterolateral sheared fracture of the tibial plateau: a case presentation.

BMC Musculoskelet Disord 2021 May 27;22(1):488. Epub 2021 May 27.

Department of Orthopedics Surgery, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Siming District, Fujian, Xiamen, China.

Background: Among tibial plateau fractures, one specialized type is the posterolateral column fracture. There are few published studies on posterolateral tibial plateau fractures with a sheared fragment that was wedged into the intercondylar fossa without the anterior cruciate ligament (ACL) rupture. According to our research, this case presentation is the first to describe in detail the treatment and long-term follow-up for this uncommon subtype of posterolateral tibial plateau fracture.

Case Presentation: A 46-year-old female injured her right knee when she was riding a motorbike and was diagnosed with a posterolateral sheared tibial plateau fracture with a wedge-shaped fragment inserted into the femoral intercondylar fossa. The fracture was repaired with open reduction internal fixation surgery. The patient's recovery was followed for four years. The degree of healing as indicated by clinical and radiological examinations was substantial. The patient exhibited an excellent range of motion for the repaired knee (0-145°) and little discomfort. The Lysholm score was 96, the hospital for special surgery score was 98, the Rasmussen clinical assessment was 28, and the Rasmussen radiological assessment was 18.

Conclusion: This study revealed that a posterolateral sheared tibial plateau, as seen in this case, can be reset and fixed sufficiently to achieve excellent long-term postoperative recovery.
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http://dx.doi.org/10.1186/s12891-021-04373-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161927PMC
May 2021

CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages.

Front Immunol 2021 7;12:635267. Epub 2021 May 7.

Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.

CTRP1 (C1q/TNF-α [tumour necrosis factor-α]-related protein 1), an adiponectin paralog, is associated with diabetes and adverse events in cardiovascular disease. However, its effect on cardiac function post myocardial infarction (MI) is unclear. Our study aimed to explore the role of CTRP1 in cardiac function post MI. CTRP1 global knockout mice were subjected to left anterior descending ligation to establish the MI model. C57BL6J mice were also administered recombinant CTRP1 protein (200 μg/kg) 7 days post MI. As a result, mice with CTRP1 deficiency exhibited an increased survival rate, a reduced infarct area, improved cardiac function and decreased inflammation and oxidative stress levels at 4 weeks post MI compared with those of mice receiving the CRTP1 injection, whose conditions deteriorated. However, cardiomyocytes with either CTRP1 silencing or CTRP1 treatment showed few differences in inflammation and oxidative stress levels compared with those of the control under hypoxic conditions. The activation of macrophages isolated from CTRP1-deficient mice was decreased in response to interferon-γ, while CTRP1 enhanced the activation of macrophages in response to interferon-γ. Macrophage scavengers and clodronate liposomes antagonized the effects of CTRP1 injection in mice. We also found that CTRP1 regulated macrophage activation adiponectin receptor 1, which binds to TLR4 on the macrophage membrane. TLR4 knockout also antagonized the effects of the CTRP1 protein on mice with MI. Taken together, these data indicate that CTRP1 supresses cardiac function post MI TLR4 on macrophages. Targeting CTRP1 may become a promising therapeutic approach to cardiac dysfunction post MI.
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http://dx.doi.org/10.3389/fimmu.2021.635267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137831PMC
May 2021

Conferring thermotolerant phenotype to wild-type Yarrowia lipolytica improves cell growth and erythritol production.

Biotechnol Bioeng 2021 Aug 11;118(8):3117-3127. Epub 2021 Jun 11.

School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

In microbial engineering, heat stress is an important environmental factor modulating cell growth, metabolic flux distribution and the synthesis of target products. Yarrowia lipolytica, as a GARS (generally recognized as safe) nonconventional yeast, has been widely used in the food industry, especially as the host of erythritol production. Biomanufacturing economics is limited by the high operational cost of cooling energy in large-scale fermentation. It is of great significance to select thermotolerant Y. lipolytica to reduce the cooling cost and elucidate the heat-resistant mechanism at molecular level. For this purpose, we performed adaptive evolution and obtained a thermotolerant strain named Y. lipolytica BBE-18. Transcriptome analysis allows us to identify four genes in thiamine metabolism pathway that are responsible for the complicated thermotolerant phenotype. The heat-resistant phenotype was validated with the model strain Y. lipolytica Po1f by overexpression of single and combined genes. Then, conferring the thermotolerant phenotype to the wild-type Y. lipolytica BBE-17 enable the strain to produce three-times more erythritol of the control strain with 3°C higher than optimal cultivation temperature. To our knowledge, this is the first report on engineering heat-resistant phenotype to improve the erythritol production in Y. lipolytica. However, due to the increase of culture temperature, a large amount of adenosine triphosphate is consumed to ensure the life activities of Y. lipolytica which limits the potential of cell synthetic products to a certain extent. Even so, this study provides a reference for Y. lipolytica to produce other products under high temperature.
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http://dx.doi.org/10.1002/bit.27835DOI Listing
August 2021

Long noncoding RNA TP53TG1 suppresses the growth and metastasis of hepatocellular carcinoma by regulating the PRDX4/β-catenin pathway.

Cancer Lett 2021 Aug 3;513:75-89. Epub 2021 May 3.

Department of Hepatobiliary Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, PR China. Electronic address:

Emerging evidence has shown that aberrant expression of lncRNA-TP53TG1 plays important roles in various malignancies. However, the biological functions of lncRNA-TP53TG1 in hepatocarcinogenesis, as well as the underlying mechanisms, remain largely unknown. Here, we assessed whether lncRNA-TP53TG1 plays a key role in the progression of hepatocellular carcinoma (HCC). The expression of lncRNA-TP53TG1 was significantly decreased in HCC tissues and cells. Decreased expression of lncRNA-TP53TG1 was associated with aggressive clinical phenotypes and a poor prognosis. Ectopic expression of lncRNA-TP53TG1 inhibited hepatoma cell proliferation and migration in vitro and in vivo, whereas lncRNA-TP53TG1 knockdown exerted the opposite effects. Furthermore, lncRNA-TP53TG1 played an important role in slowing the epithelial-mesenchymal transition (EMT) process in HCC. Mechanistically, lncRNA-TP53TG1 physically interacted with PRDX4 and promoted its ubiquitin-mediated degradation, resulting in the inactivation of the WNT/β-catenin signaling pathway in hepatoma cells. Our findings demonstrate a novel mechanism by which lncRNA-TP53TG1 exerts its tumor-suppressive effects through the WNT/β-catenin signaling pathway in a PRDX4-mediated manner in HCC. Based on these results, lncRNA-TP53TG1 potentially represents a prognostic indicator and therapeutic target for patients with HCC.
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http://dx.doi.org/10.1016/j.canlet.2021.04.022DOI Listing
August 2021

A novel five-gene signature predicts overall survival of patients with hepatocellular carcinoma.

Cancer Med 2021 Jun 2;10(11):3808-3821. Epub 2021 May 2.

Department of Blood Transfusion, The First People's Hospital of Jingmen, Jingmen, China.

Hepatocellular carcinoma (HCC) is one of the most common public health challenges, worldwide. Because of molecular complexity and tumor heterogeneity, there are no effective predictive models for prognosis of HCC. This underlines the unmet need for accurate prognostic models for HCC. Analysis of GSE14520 data from gene omnibus (GEO) database identified multiple differentially expressed mRNAs (DEMs) between HCC and normal tissues. After randomly stratifying the patients into the training and testing groups, we performed univariate, lasso, and multivariable Cox regression analyses to delineate the prognostic gene signature in training set. We then used Kaplan-Meier plot, time-dependent receiver operating characteristic (ROC), multivariable Cox regression analysis of clinical information, nomogram, and decision curve analysis (DCA) to evaluate the predictive and overall survival value of a novel five-gene signature (CNIH4, SOX4, SPP1, SORBS2, and CCL19) within and across sets, separately and combined. We also validated the prognostic value of the five-gene signature using The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE54236 and International Cancer Genome Consortium (ICGC) sets. Multivariable Cox regression analysis revealed that the five-gene signature and tumor node metastasis (TNM) stage were independent prognostic factors for overall survival of HCC patients in GSE14520 and TCGA-LIHC. Combining TNM stage clinical pathological parameters and nomogram greatly improved the prognosis prediction of HCC. Further gene set enrichment analysis (GSEA) revealed enrichment of KEGG pathways related to cell cycle in the high-risk group and histidine metabolism in the low-risk group. Finally, all these five mRNAs are overexpressed between 12 pairs of HCC and adjacent normal tissues by quantitative real-time PCR validation. In brief, a five-gene prognostic signature and a nomogram were identified and constructed, respectively, and further validated for their HCC prognostic value. The five-gene risk score together with TNM stage models could aid in rationalizing customized therapies in HCC patients.
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http://dx.doi.org/10.1002/cam4.3900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178492PMC
June 2021

gen. nov., sp. nov., a novel member of the family isolated from pit clay used for making Chinese strong aroma-type liquor.

Int J Syst Evol Microbiol 2021 Apr;71(4)

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.

An anaerobic, Gram-stain-positive, rod-shaped, motile and spore-forming bacterium, designated strain LBM18003, was isolated from pit clay used for making Chinese strong aroma-type liquor. Growth occurred at 20-40 °C (optimum, 30-37 °C), pH 4.5-9.5 (optimum, pH 6.5-7.0) and in the presence of 0.0-1.0 % (w/v) sodium chloride (optimum, 0 %). The predominant fatty acids were C, C, C DMA and C 3-OH, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids and nine unidentified glycolipids. Phylogenetic analysis revealed that strain LBM18003 is a novel member of the family . The 16S rRNA gene sequence similarities of strain LBM18003 to its two most closely related species were less than 94.5 % for distinguishing genera, i.e. closely related to JCM 30532 (94.1 %) and DSM 107079 (93.2 %). The genome size of strain LBM18003 was 2 996 201 bp and its DNA G+C content was 48.48 mol%. Strain LBM18003 exhibited 67.8 and 68.1% pairwise-determined whole-genome average nucleotide identity values to JCM 30532 and DSM 107079, respectively; and showed 62.2 and 61.0 % the average amino acid identity values to JCM 30532 and DSM 107079, respectively; and demonstrated 46.1 and 41.5 % conserved genes to JCM 30532 and DSM 107079, respectively. The comparisons of 16S rRNA gene and genome sequences confirmed that strain LBM18003 represented a novel genus of the family . Based on morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, strain LBM18003 represents a novel species of a novel genus of the family , for which the name gen. nov., sp. nov. is proposed. The type strain is LBM18003 (=GDMCC 1.1626=JCM 33783).
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http://dx.doi.org/10.1099/ijsem.0.004789DOI Listing
April 2021

Lysine-specific demethylase 1 inhibition enhances autophagy and attenuates early-stage post-spinal cord injury apoptosis.

Cell Death Discov 2021 Apr 6;7(1):69. Epub 2021 Apr 6.

Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China.

Neuron death in spinal cords is caused primarily by apoptosis after spinal cord injury (SCI). Autophagy can act as a cellular response to maintain neuron homeostasis that can reduce apoptosis. Although more studies have shown that an epigenetic enzyme called Lysine-specific demethylase 1 (LSD1) can negatively regulate autophagy during cancer research, existing research does not focus on impacts related to LSD1 in nerve injury diseases. This study was designed to determine whether inhibiting LSD1 could enhance autophagy against apoptosis and provide effective neuroprotection in vitro and vivo after SCI. The results showed that LSD1 inhibition treatment significantly reduced spinal cord damage in SCI rat models and was characterized by upregulated autophagy and downregulated apoptosis. Further research demonstrated that using both pharmacological inhibition and gene knockdown could enhance autophagy and reduce apoptosis for in vitro simulation of SCI-caused damage models. Additionally, 3-methyladenine (3-MA) could partially eliminate the effect of autophagy enhancement and apoptosis suppression. These findings demonstrated that LSD1 inhibition could protect against SCI by activating autophagy and hindering apoptosis, suggesting a potential candidate for SCI therapy.
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http://dx.doi.org/10.1038/s41420-021-00455-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024310PMC
April 2021

Does spinal sagittal imbalance lead to future vertebral compression fractures in osteoporosis patients?

Spine J 2021 Mar 22. Epub 2021 Mar 22.

Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou 086-350001, China. Electronic address:

Background Context: Many risk factors for osteoporotic vertebral compression fractures (OVCFs) have been reported. However, there are few reports on the relationship between spine sagittal parameters in patients with osteoporosis.

Purpose: To explore whether: spinal sagittal imbalance is associated with future vertebral compression fractures in osteoporosis patients; spinal sagittal parameters in patients with osteoporosis can predict the occurrence of vertebral compression fractures.

Study Design: A retrospective cohort study.

Patient Sample: Patients with osteoporosis.

Outcome Measures: Occurrence of OVCFs during the follow-up period.

Methods: From January 2017 to October 2019, eligible patients with osteoporosis at the initial visit were enrolled. They were followed up to November 1, 2020. Based on whether OVCFs occurred during the follow-up, the patients were divided into two groups: the experimental group (vertebral compression fracture group) and the control group (no vertebral compression fracture group). Intragroup analysis was performed as follows: Pearson and Spearman correlation coefficients were used to calculate the correlation between each parameter. Intergroup analysis was performed as follows. For categorical variables, the chi-square test was used; for normally distributed continuous variables, an independent sample t-test was used; and for non-normally distributed variables, a two-sample nonparametric test was used. Binary logistic regression analysis and receiver operating characteristic (ROC) curves were used to determine independent risk factors and critical values, respectively.

Results: A total of 340 patients with osteoporosis were enrolled. The longest and shortest follow-up periods were 44 months and 12 months, respectively, with an average of 25.2±10.2 months. There were significant differences in age, bone mineral density (femur and lumbar), smoking history, medication treatment regularity, Thoracolumbar Kyphosis (TLK), Pelvic Tilt (PT), C7-S1 Sagittal Vertical Axis (C7-S1 SVA), and C2-7 Sagittal Vertical Axis (C2-7 SVA) between the experimental and control groups. There were no significant differences in sex, body mass index (BMI), alcohol consumption history, hypertension, diabetes, coronary heart disease, family history of osteoporosis, physical activity, Thoracic Kyphosis (TK), Lumbar Lordosis (LL), Pelvic Incidence (PI), Sacral Slope (SS), C2-C7 Cobb Angle (CL), T1 slope (T1S) or blood parameters. Through binary logistic regression analysis, we found that BMD, medication treatment regularity and C7-S1 SVA were independent risk factors for future vertebral compression fractures. According to the ROC curve, the prediction accuracy of C7-S1 SVA was the highest. Through the calculation of critical values, we found that when C7-S1 SVA was more than 3.81 cm, future OVCFs were more likely to occur, and for every 1cm increase in C7-S1 SVA, the incidence of future OVCFs would increase by 0.324 times (p<.001, OR=1.324). Through intragroup analysis, we further found that C7-S1 SVA was positively correlated with the percentage of vertebral body wedging.

Conclusions: For patients with osteoporosis, a C7-S1 SVA more than 3.81cm is significantly associated with a greater risk for vertebral compression fractures in the future.
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http://dx.doi.org/10.1016/j.spinee.2021.03.014DOI Listing
March 2021

Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride.

Nat Chem 2021 04 18;13(4):312-318. Epub 2021 Feb 18.

Department of Chemistry, University of California, Berkeley, CA, USA.

Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis.
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http://dx.doi.org/10.1038/s41557-020-00633-7DOI Listing
April 2021

Downregulation of miR-126-3p expression contributes to increased inflammatory response in placental trophoblasts in preeclampsia.

J Reprod Immunol 2021 04 1;144:103281. Epub 2021 Feb 1.

Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center - Shreveport, LA, 71103, United States. Electronic address:

MiR-126-3p is a prototype of an endothelial miRNA and has protective effects on endothelial cells. However, little is known about the effects of miR-126-3p on placental trophoblasts. In the present study, we tested the hypothesis that aberrant miR-126-3p expression is present in preeclamptic placenta which contributes to increased inflammatory response in trophoblasts. Placentas were obtained immediately after delivery from normotensive and preeclamptic pregnancies. Villous tissue was either fixed with formalin or used for trophoblast isolation. Trophoblast miR-126-3p expression was assessed by in situ hybridization of formalin-fixed tissue sections and by RT-PCR in cultured syncytiotrophoblasts. Culture medium was collected for measurement of IL-6, TNFα, and 8-Isoprostane production by ELISA and total cellular protein was collected for evaluation of HIF1α expression by Western blot. Effects of overexpression of miR-126-3p in trophoblasts on cytokine production were tested by transfection of pre-mir-126, a precursor of miR-126, into primary isolated trophoblasts. We found that downregulation of miR-126-3p expression was associated with increased IL-6 and TNFα production in trophoblasts from preeclamptic placentas vs. normal placentas. Moreover, transient overexpression of miR-126-3p significantly reduced IL-6 and TNFα production in trophoblasts from both normal and preeclamptic placentas. We further found that increase in miR-126-3p expression not only suppressed hypoxia-induced increases in IL-6 and TNFα production, but also attenuated hypoxia-induced increases in HIF1α expression and 8-Isoprostane production in trophoblasts cultured under hypoxic condition. These results provide plausible evidence that downregulation of miR-126-3p expression reduces anti-inflammatory and anti-oxidative stress activities in placental trophoblasts in preeclampsia.
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http://dx.doi.org/10.1016/j.jri.2021.103281DOI Listing
April 2021

Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria.

Nat Commun 2021 02 4;12(1):790. Epub 2021 Feb 4.

CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.

Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2-C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine.
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http://dx.doi.org/10.1038/s41467-021-20974-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862272PMC
February 2021

Brain Histopathology of Adult Decedents After Extracorporeal Membrane Oxygenation.

Neurology 2021 03 20;96(9):e1278-e1289. Epub 2021 Jan 20.

From the Department of Neurology (I.R.K., B.P.G.), Division of Neurocritical Care, and Department of Anesthesiology and Perioperative Medicine (Y.G.), University of Rochester Medical Center, NY; Department of Pathology (L.M., C.-Y.H.), University of Maryland Medical Center, Baltimore; Department of Pathology (K.S.C.), University of Michigan School of Medicine, Ann Arbor; Cardiac Surgery Research (F.F.), University of Maryland School of Medicine, Baltimore; College of Arts & Sciences (J.D., N.Q.), University of Rochester, NY; University of Maryland School of Medicine (A.R.); Program in Trauma and Critical Care (D.L.H.), Department of Medicine, and Program in Trauma (G.Y.P.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore; and Department of Pathology and Laboratory Medicine (M.D.J.), University of Rochester School of Medicine & Dentistry, NY.

Objective: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions.

Methods: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes.

Results: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, = 0.04); and those with infarction had lower peak Paco (53 vs 61 mm Hg, = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury.

Conclusion: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.
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http://dx.doi.org/10.1212/WNL.0000000000011525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055323PMC
March 2021

Gail Model Improves the Diagnostic Performance of the Fifth Edition of Ultrasound BI-RADS for Predicting Breast Cancer: A Multicenter Prospective Study.

Acad Radiol 2020 Dec 28. Epub 2020 Dec 28.

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuai Fu Yuan, Dong Cheng District, Beijing 100730, China. Electronic address:

Rationale And Objectives: The sonographic appearance of benign and malignant breast nodules overlaps to some extent, and we aimed to assess the performance of the Gail model as an adjunctive tool to ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) for predicting the malignancy of nodules.

Materials And Methods: From 2018 to 2019, 2607 patients were prospectively enrolled by 35 health care facilities. An individual breast cancer risk was assessed by the Gail model. Based on B-mode US, color Doppler, and elastography, all nodules were evaluated according to the fifth edition of BI-RADS, and these nodules were all confirmed later by pathology.

Results: We demonstrated that the Gail model, age, tumor size, tumor shape, growth orientation, margin, contour, acoustic shadowing, microcalcification, presence of duct ectasia, presence of architectural distortion, color Doppler flow, BI-RADS, and elastography score were significantly related to breast cancer (all p < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) for combining the Gail model with the BI-RADS category were 95.6%, 91.3%, 85.0%, 97.6%, 92.8%, and 0.98, respectively. Combining the Gail model with the BI-RADS showed better diagnostic efficiency than the BI-RADS and Gail model alone (AUC 0.98 vs 0.80, p < 0.001; AUC 0.98 vs 0.55, p < 0.001) and demonstrated a higher specificity than the BI-RADS (91.3% vs 59.4%, p < 0.001).

Conclusion: The Gail model could be used to differentiate malignant and benign breast lesions. Combined with the BI-RADS category, the Gail model was adjunctive to US for predicting breast lesions for malignancy. For the diagnosis of malignancy, more attention should be paid to high-risk patients with breast lesions.
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http://dx.doi.org/10.1016/j.acra.2020.12.002DOI Listing
December 2020

Implementation of a Lightweight Semantic Segmentation Algorithm in Road Obstacle Detection.

Sensors (Basel) 2020 Dec 10;20(24). Epub 2020 Dec 10.

School of Traffic and Transportation, Beijing Jiaotong University, Beijing 100044, China.

Due to deep learning's accurate cognition of the street environment, the convolutional neural network has achieved dramatic development in the application of street scenes. Considering the needs of autonomous driving and assisted driving, in a general way, computer vision technology is used to find obstacles to avoid collisions, which has made semantic segmentation a research priority in recent years. However, semantic segmentation has been constantly facing new challenges for quite a long time. Complex network depth information, large datasets, real-time requirements, etc., are typical problems that need to be solved urgently in the realization of autonomous driving technology. In order to address these problems, we propose an improved lightweight real-time semantic segmentation network, which is based on an efficient image cascading network (ICNet) architecture, using multi-scale branches and a cascaded feature fusion unit to extract rich multi-level features. In this paper, a spatial information network is designed to transmit more prior knowledge of spatial location and edge information. During the course of the training phase, we append an external loss function to enhance the learning process of the deep learning network system as well. This lightweight network can quickly perceive obstacles and detect roads in the drivable area from images to satisfy autonomous driving characteristics. The proposed model shows substantial performance on the Cityscapes dataset. With the premise of ensuring real-time performance, several sets of experimental comparisons illustrate that SP-ICNet enhances the accuracy of road obstacle detection and provides nearly ideal prediction outputs. Compared to the current popular semantic segmentation network, this study also demonstrates the effectiveness of our lightweight network for road obstacle detection in autonomous driving.
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http://dx.doi.org/10.3390/s20247089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763539PMC
December 2020

Development and Validation of a Preoperative Magnetic Resonance Imaging Radiomics-Based Signature to Predict Axillary Lymph Node Metastasis and Disease-Free Survival in Patients With Early-Stage Breast Cancer.

JAMA Netw Open 2020 12 1;3(12):e2028086. Epub 2020 Dec 1.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Centre, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Importance: Axillary lymph node metastasis (ALNM) status, typically estimated using an invasive procedure with a high false-negative rate, strongly affects the prognosis of recurrence in breast cancer. However, preoperative noninvasive tools to accurately predict ALNM status and disease-free survival (DFS) are lacking.

Objective: To develop and validate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of ALNM and to assess individual DFS in patients with early-stage breast cancer.

Design, Setting, And Participants: This retrospective prognostic study included patients with histologically confirmed early-stage breast cancer diagnosed at 4 hospitals in China from July 3, 2007, to September 21, 2019, randomly divided (7:3) into development and vaidation cohorts. All patients underwent preoperative MRI scans, were treated with surgery and sentinel lymph node biopsy or ALN dissection, and were pathologically examined to determine the ALNM status. Data analysis was conducted from February 15, 2019, to March 20, 2020.

Exposure: Clinical and DCE-MRI radiomic signatures.

Main Outcomes And Measures: The primary end points were ALNM and DFS.

Results: This study included 1214 women (median [IQR] age, 47 [42-55] years), split into development (849 [69.9%]) and validation (365 [30.1%]) cohorts. The radiomic signature identified ALNM in the development and validation cohorts with areas under the curve (AUCs) of 0.88 and 0.85, respectively, and the clinical-radiomic nomogram accurately predicted ALNM in the development and validation cohorts (AUC, 0.92 and 0.90, respectively) based on a least absolute shrinkage and selection operator (LASSO)-logistic regression model. The radiomic signature predicted 3-year DFS in the development and validation cohorts (AUC, 0.81 and 0.73, respectively), and the clinical-radiomic nomogram could discriminate high-risk from low-risk patients in the development cohort (hazard ratio [HR], 0.04; 95% CI, 0.01-0.11; P < .001) and the validation cohort (HR, 0.04; 95% CI, 0.004-0.32; P < .001) based on a random forest-Cox regression model. The clinical-radiomic nomogram was associated with 3-year DFS in the development and validation cohorts (AUC, 0.89 and 0.90, respectively). The decision curve analysis demonstrated that the clinical-radiomic nomogram displayed better clinical predictive usefulness than the clinical or radiomic signature alone.

Conclusions And Relevance: This study described the application of MRI-based machine learning in patients with breast cancer, presenting novel individualized clinical decision nomograms that could be used to predict ALNM status and DFS. The clinical-radiomic nomograms were useful in clinical decision-making associated with personalized selection of surgical interventions and therapeutic regimens for patients with early-stage breast cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.28086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724560PMC
December 2020

The Metabolism of in Phosphotransacetylase Negative Strains and Development of an Ethanologenic Strain.

Front Bioeng Biotechnol 2020 27;8:560726. Epub 2020 Oct 27.

National Renewable Energy Laboratory, Golden, CO, United States.

The sustainable production of chemicals from non-petrochemical sources is one of the greatest challenges of our time. CO release from industrial activity is not environmentally friendly yet provides an inexpensive feedstock for chemical production. One means of addressing this problem is using acetogenic bacteria to produce chemicals from CO, waste streams, or renewable resources. Acetogens are attractive hosts for chemical production for many reasons: they can utilize a variety of feedstocks that are renewable or currently waste streams, can capture waste carbon sources and covert them to products, and can produce a variety of chemicals with greater carbon efficiency over traditional fermentation technologies. Here we investigated the metabolism of , a model acetogen, to probe carbon and electron partitioning and understand what mechanisms drive product formation in this organism. We utilized CRISPR/Cas9 and an inducible riboswitch to target enzymes involved in fermentation product formation. We focused on the genes encoding phosphotransacetylase (), aldehyde ferredoxin oxidoreductases ( and ), and bifunctional alcohol/aldehyde dehydrogenases ( and ) and performed growth studies under a variety of conditions to probe the role of those enzymes in the metabolism. Finally, we demonstrated a switch from acetogenic to ethanologenic metabolism by these manipulations, providing an engineered bacterium with greater application potential in biorefinery industry.
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http://dx.doi.org/10.3389/fbioe.2020.560726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653027PMC
October 2020

Effects of Vitamin D3 on Intestinal Flora in a Mouse Model of Inflammatory Bowel Disease Treated with Rifaximin.

Med Sci Monit 2020 Nov 12;26:e925068. Epub 2020 Nov 12.

School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, China (mainland).

BACKGROUND Rifaximin is an antimicrobial agent used to treat inflammatory bowel disease (IBD). Vitamin D3 can control IBD due to its effects on inflammatory cytokines. The purpose of this study was to assess the effect of vitamin D3 on the intestinal flora of a dextran sulfate sodium (DSS)-induced mouse model treated with rifaximin. MATERIAL AND METHODS The mouse model of IBD was developed using DSS (4%) administered via the drinking water. Twenty-four male C57BL6 mice were divided into the control group with a normal diet (N=6), the DSS group with a normal diet (N=6), the DSS group with a normal diet treated with rifaximin (N=6), and the DSS group with a normal diet treated with rifaximin and vitamin D3 (N=6). After 14 days, the colonic tissue was studied histologically. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1ß (IL-1ß) and enzyme-linked immunosorbent assay (ELISA) were used to measure the level of IL-6 and P65, and phospho-p65 was measured by western blot. 16S rRNA gene sequencing was used to analyze fecal samples. RESULTS In the DSS mouse model of IBD, rifaximin reduced the inflammation severity of the colon and reduced the expression of phospho-p65, p65, TNF-alpha, and IL-6. In the DSS+rifaximin+vitamin D3 group, the therapeutic influences of rifaximin, in terms of weight loss and colonic disease activity, were significantly reduced, and the gut microbiota of the mice were completely changed in composition and diversity. CONCLUSIONS In a mouse model of IBD, treatment with vitamin D3 significantly increased the metabolism of rifaximin and reduced its therapeutic effects.
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http://dx.doi.org/10.12659/MSM.925068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670830PMC
November 2020

Erratum for Liu et al., "Ethanol Metabolism Dynamics in Grown on Carbon Monoxide".

Appl Environ Microbiol 2020 Nov 10;86(23). Epub 2020 Nov 10.

Shandong Provincial Key Laboratory of Synthetic Biology, Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, People's Republic of China

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http://dx.doi.org/10.1128/AEM.02376-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657638PMC
November 2020

Association of immune checkpoint inhibitor with survival in patients with cancers with protein tyrosine phosphatase receptor T mutation.

Clin Transl Med 2020 Oct;10(6):e214

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1002/ctm2.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591738PMC
October 2020

Synthetic yeast brews neuroactive compounds.

Authors:
Yang Gu Peng Xu

Nat Chem Biol 2021 01;17(1):8-9

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, USA.

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http://dx.doi.org/10.1038/s41589-020-00691-5DOI Listing
January 2021

High-throughput sequencing identification of differentially expressed microRNAs in metastatic ovarian cancer with experimental validations.

Cancer Cell Int 2020 21;20:517. Epub 2020 Oct 21.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004 Liaoning P. R. China.

Background: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments.

Methods: Differentially expressed miRNAs and mRNAs were screened from six pairs of primary OC tissues and metastatic tissues using a miRStar™ Human Cancer Focus miRNA and Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells.

Results: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities.

Conclusions: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.
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http://dx.doi.org/10.1186/s12935-020-01601-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579798PMC
October 2020
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