Publications by authors named "Fang Yan"

775 Publications

Study on the Strength Performance of Recycled Aggregate Concrete with Different Ages under Direct Shearing.

Materials (Basel) 2021 Apr 29;14(9). Epub 2021 Apr 29.

School of Civil and Architectural Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China.

In order to study the mechanical properties of recycled aggregate concrete (RAC) at different ages, 264 standard cubes were designed to test its direct shear strength and cube compressive strength while considering the parameters of age and recycled aggregate replacement ratio. The failure pattern and load-displacement curve of specimens at direct shearing were obtained; the direct shear strength and residual shear strength were extracted from the load-displacement curves. Experimental results indicate that the influence of the replacement ratio for the front and side cracks of RAC is insignificant, with the former being straight and the latter relatively convoluted. At the age of three days, the damaged interface between aggregate and mortar is almost completely responsible for concrete failure; in addition to the damage of coarse aggregates, aggregate failure is also an important factor in concrete failure at other ages. The load-displacement curve of RAC at direct shearing can be divided into elasticity, elastoplasticity, plasticity, and stabilization stages. The brittleness of concrete decreases with its age, which is reflected in the gradual shortening of the elastoplastic stage. At 28 days of age, the peak direct shear force increases with the replacement ratio, while the trend is opposite at ages of 3 days, 7 days, and 14 days, respectively. The residual strength of RAC decreases inversely to the replacement ratio, with the rate of decline growing over time. A two-parameter RAC direct shear strength calculation formula was established based on the analysis of age and replacement rate to peak shear force of RAC. The relationship between cube compressive strength and direct shear strength of recycled concrete at various ages was investigated.
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http://dx.doi.org/10.3390/ma14092312DOI Listing
April 2021

Identification of Metabolites of Aurantio-Obtusin in Rats Using Ultra-High-Performance Liquid Chromatography-Q-Exactive Orbitrap Mass Spectrometry with Parallel Reaction Monitoring.

J Anal Methods Chem 2021 15;2021:6630604. Epub 2021 Apr 15.

School of Pharmaceutical Sciences, Hunan Province Key Laboratory of Antiboby-Based Drug and Intelligent Delivery System, Hunan University of Medicine, Huaihua 418000, China.

Aurantio-obtusin (AO) is a major anthraquinone compound isolated from or , which possesses diverse pharmacological effects. Previous studies have shown that it has a good effect on lowering blood lipids and treating various diseases. A few studies have also reported about its metabolites. A rapid and reliable method using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry and multiple data-processing technologies was established to investigate the metabolites of AO in the plasma and various tissues of rats, including the heart, liver, spleen, lung, kidneys, and brain. Finally, a total of 36 metabolites were identified in the plasma of rats, which could be very beneficial for understanding the effective form of AO metabolites leading to new drug discovery. The result demonstrated that this strategy, especially parallel reaction monitoring, has shown a wide range of applications in the identification of metabolites.
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http://dx.doi.org/10.1155/2021/6630604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062173PMC
April 2021

A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment.

Ren Fail 2021 Dec;43(1):766-773

Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: This study aimed to explore the effectiveness of thiamin and folic acid supplementation on the improvement of the cognitive function in patients with maintenance hemodialysis.

Method: In the present study, we randomly assigned patients undergoing hemodialysis who had the Montreal Cognitive Assessment (MoCA) score lower than 26 to treatment group ( = 25, thiamin 90 mg/day combined with folic acid 30 mg/day) or control group ( = 25, nonintervention). All subjects were followed up for 96 weeks. The primary outcome was the improvement of the MoCA score. The secondary outcomes included homocysteine level, survival and safety.

Results: Patients in treatment group had an increase of the MoCA score from 21.95 ± 3.81 at baseline to 25.68 ± 1.96 at week 96 ( < 0.001, primary outcome), as compared with the MoCA score from 20.69 ± 3.40 to 19.62 ± 3.58 in control group. Thiamin combined with folic acid treatment also resulted in lower level of serum homocysteine in treatment group compare with control group at week 96 ( < 0.05, secondary outcome). 3 patients and 9 patients died during follow-up period in treatment and control group respectively ( = 0.048). The proportion of adverse events in treatment group was significantly lower than that in control group.

Conclusion: Hemodialysis patients with cognitive impairment treated with thiamin and folic acid had a significant improvement in MoCA score.
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http://dx.doi.org/10.1080/0886022X.2021.1914656DOI Listing
December 2021

High performance blue quantum light-emitting diodes by attaching diffraction wrinkle patterns.

Nanoscale 2021 Apr 26. Epub 2021 Apr 26.

Key Laboratory for Special Functional Materials of Ministry of Education, National & Local Joint Engineering Research Centre for High-efficiency Display and Lighting Technology, School of Materials and Engineering, Collaborative Innovation Centre of Nano Functional Materials and Applications, Henan University, Kaifeng 475004, China.

Highly efficient blue quantum-dot light-emitting diodes (QLEDs) are still challenging to use in displays and solid-state lighting. Enhancing light outcoupling is one of the most effective methods to improve the performance of blue QLEDs. Here, a strategy for a spectrally independent boost in light outcoupling of blue QLEDs is demonstrated by quasi-periodic wrinkles, which are successfully used as a diffraction grating for extracting trapped light at the substrate/air interface. The quasi-periodic wrinkles can be adjusted from nano-scale to micron-scale under the condition of a constant aspect ratio, and the optimized wrinkle device shows a maximum luminance of 11 769 cd m-2 and a peak EQE of 15.41%. The enhancement of EQE is 49.5% higher compared to that of the reference device. Furthermore, simulation and calculation also indicate that external micron-scattering wrinkle patterns are an attractive option for boosting the performances of blue QLEDs.
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http://dx.doi.org/10.1039/d1nr00082aDOI Listing
April 2021

A high-performance triboelectric-electromagnetic hybrid wind energy harvester based on rotational tapered rollers aiming at outdoor IoT applications.

iScience 2021 Apr 12;24(4):102300. Epub 2021 Mar 12.

Department of Electrical & Computer Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117576, Singapore.

This article proposed a high-performance triboelectric-electromagnetic hybrid wind energy harvester (WEH). By adopting the revolution and rotation movements of tapered rollers, which serve as both the rotor of the electromagnetic generator (EMG) part and freestanding layers of the triboelectric nanogenerator (TENG) part, the WEH can work as a sustainable power source and a self-powered wind speed sensor. When the wind speed is 12 m/s, super-high open-circuit voltage peaks of 47.4 and 683 V can be achieved by the EMG and TENG, respectively, corresponding to the high-power outputs of 62 and 1.8 mW. It was demonstrated that the WEH can easily light up over 600 red light-emitting diodes and even a 5-W globe light. A self-powered wireless temperature and humidity sensing network was also systematically demonstrated. In summary, the proposed WEH exhibits bright future toward IoT applications, such as in border detection, smart buildings, and so on.
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http://dx.doi.org/10.1016/j.isci.2021.102300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041867PMC
April 2021

Intercontinental transmission and local demographic expansion of SARS-CoV-2.

Epidemiol Infect 2021 04 13;149:e94. Epub 2021 Apr 13.

State Key Laboratory of Grassland Agro-Ecosystem, Institute of Innovation Ecology & School of Life Sciences, Lanzhou University, Lanzhou, China.

The global outbreak of coronavirus disease 2019 (COVID-19) is greatly threatening the public health in the world. We reconstructed global transmissions and potential demographic expansions of severe acute respiratory syndrome coronavirus 2 based on genomic information. We found that intercontinental transmissions were rare in January and early February but drastically increased since late February. After world-wide implements of travel restrictions, the transmission frequencies decreased to a low level in April. We identified a total of 88 potential demographic expansions over the world based on the star-radiative networks and 75 of them were found in Europe and North America. The expansion numbers peaked in March and quickly dropped since April. These findings are highly concordant with epidemic reports and modelling results and highlight the significance of quarantine validity on the global spread of COVID-19. Our analyses indicate that the travel restrictions and social distancing measures are effective in containing the spread of COVID-19.
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http://dx.doi.org/10.1017/S0950268821000777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060534PMC
April 2021

A novel metabolic gene signature-based nomogram to predict overall survival in breast cancer.

Ann Transl Med 2021 Mar;9(5):367

Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Breast cancer risk prediction is often based on clinicopathological characteristics despite the high heterogeneity derived from gene expression. Metabolic alteration is a hallmark of cancer, and thus, the integration of a metabolic signature with clinical parameters is necessary to predict disease outcomes in breast cancers.

Methods: Metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Genes with statistical significance in the univariate analysis were applied in the least absolute shrinkage and selection operator (LASSO) analysis to build a gene signature in the GSE20685 dataset. Clinicopathological characteristics and risk scores with prognostic significance were incorporated into the nomogram to predict the overall survival (OS) of patients. The Cancer Genome Atlas (TCGA) and GSE866166 datasets were used as the validation datasets. Time-dependent receiver operating characteristic (tROC) curves and calibration plots were used to assess the accuracy and discrimination of the model.

Results: A 55-gene metabolic gene signature (MGS) was constructed, and was significantly related to OS both in the discovery (P<0.001) and validation (P<0.001) datasets. The MGS was an independent prognostic factor and could divide patients into high- and low-risk groups regardless of their different prediction analysis of microarray 50 (PAM50) subtypes. Time-dependent ROC curves indicated that the risk scores based on the MGS [area under the ROC curve (AUC): 0.931] were superior to the those based on the American Joint Committee on Cancer (AJCC) stage (AUC: 0.781) and PAM50 (AUC: 0.675). A nomogram based on the AJCC stage and risk score could predict OS, and the calibration curves showed good agreement to the actual outcome, indicating that the nomogram may have practical utility. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis indicated that this MGS was primarily enriched in amino acid pathways.

Conclusions: Our results demonstrated that the MGS was superior to existing risk predictors such as PAM50 and AJCC stage. By combining clinical factors (AJCC stage) and the MGS, a nomogram was constructed and showed good predictive ability for OS in breast cancer.
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http://dx.doi.org/10.21037/atm-20-4813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033348PMC
March 2021

Isolation and initial characterization of a vasa homolog in Cynops cyanurus.

Gene Expr Patterns 2021 Mar 29;40:119180. Epub 2021 Mar 29.

School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan and Center for Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China. Electronic address:

The vasa mRNA encodes a putative RNA helicase that belongs to the DEAD-box protein family. Vasa protein is a conserved germ cell marker ranging from fruit fly to human. In this study, we cloned the full-length vasa cDNA from the ovary of newt Cynops cyanurus and examined its expression in embryos and adult tissues. The predictive C. cyanurus Vasa protein sequence shares eight conserved regions with Vasa proteins from other vertebrates. The C. cyanurus vasa mRNA expression is restricted to testis and ovary. During oogenesis, vasa mRNA shows highest expression in the early stages of oocytes. However, it rapidly down-regulates during embryogenesis. These findings suggest that Vasa may be involved in early germ cell specification/initiation in C. cyanurus.
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http://dx.doi.org/10.1016/j.gep.2021.119180DOI Listing
March 2021

Tomato SlBL4 plays an important role in fruit pedicel organogenesis and abscission.

Hortic Res 2021 Apr 1;8(1):78. Epub 2021 Apr 1.

Key Laboratory of Herbage & Endemic Crop Biotechnology, Ministry of Education, School of Life Science, Inner Mongolia University, Hohhot, 010021, China.

Abscission, a cell separation process, is an important trait that influences grain and fruit yield. We previously reported that BEL1-LIKE HOMEODOMAIN 4 (SlBL4) is involved in chloroplast development and cell wall metabolism in tomato fruit. In the present study, we showed that silencing SlBL4 resulted in the enlargement and pre-abscission of the tomato (Solanum lycopersicum cv. Micro-TOM) fruit pedicel. The anatomic analysis showed the presence of more epidermal cell layers and no obvious abscission zone (AZ) in the SlBL4 RNAi lines compared with the wild-type plants. RNA-seq analysis indicated that the regulation of abscission by SlBL4 was associated with the altered abundance of genes related to key meristems, auxin transporters, signaling components, and cell wall metabolism. Furthermore, SlBL4 positively affected the auxin concentration in the abscission zone. A dual-luciferase reporter assay revealed that SlBL4 activated the transcription of the JOINTLESS, OVATE, PIN1, and LAX3 genes. We reported a novel function of SlBL4, which plays key roles in fruit pedicel organogenesis and abscission in tomatoes.
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http://dx.doi.org/10.1038/s41438-021-00515-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012377PMC
April 2021

TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;

The induction of type I interferons through the transcription factor interferon regulatory factor 3 (IRF3) is considered a major outcome of stimulator of interferon genes (STING) activation that drives immune responses against DNA viruses and tumors. However, STING activation can also trigger other downstream pathways such as nuclear factor κB (NF-κB) signaling and autophagy, and the roles of interferon (IFN)-independent functions of STING in infectious diseases or cancer are not well understood. Here, we generated a STING mouse strain with a mutation (S365A) that disrupts IRF3 binding and therefore type I interferon induction but not NF-κB activation or autophagy induction. We also generated STING mice with mutations that disrupt the recruitment of TANK-binding kinase 1 (TBK1), which is important for both IRF3 and NF-κB activation but not autophagy induction (L373A or ∆CTT, which lacks the C-terminal tail). The STING-S365A mutant mice, but not L373A or ∆CTT mice, were still resistant to herpes simplex virus 1 (HSV-1) infections and mounted an antitumor response after cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) treatment despite the absence of STING-induced interferons. These results demonstrate that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.
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http://dx.doi.org/10.1073/pnas.2100225118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040795PMC
April 2021

A Critical Overview of Systematic Reviews of Shenfu Injection for Heart Failure.

Cardiovasc Ther 2021 6;2021:8816590. Epub 2021 Mar 6.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province 510515, China.

Objectives: Shenfu Injection (SFI) was widely used in the treatment of heart failure (HF) in China. A plethora of systematic reviews/meta-analyses (SRs/MAs) has been conducted in this research area, although with scattered results. The purpose of this overview was to conduct a comprehensive review to summarize and critically evaluate the existing evidence.

Methods: Digital databases were searched for SRs/MAs up to January 28, 2021. Two authors independently screened the reviews and assessed the methodological quality of included SRs/MAs using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2). Quality of evidence for outcomes evaluated within the reviews was appraised with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE).

Results: Thirteen SRs/MAs met the inclusion criteria. Based on AMSTAR-2, the quality of all SRs/MAs was critically low, because all of them have more than one critical domains that were unmet. Based on GRADE, the evidence quality of 24 outcome measures was low or very low, 27 outcome measures was moderate, and none outcome measure was high. Descriptive analysis showed that SFI was an effective and safe method for HF.

Conclusions: The use of SFI for the treatment of HF may be clinically effective and safe. However, this conclusion must be interpreted cautiously due to the generally low methodological quality and low evidence quality of the included SRs/MAs. More rigorously designed SRs/MAs and RCTs with high methodological quality are necessary for further proof.
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http://dx.doi.org/10.1155/2021/8816590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960068PMC
March 2021

The complete mitochondrial genome sequence of (Lepidoptera: Riodinidae).

Mitochondrial DNA B Resour 2021 Mar 11;6(3):816-818. Epub 2021 Mar 11.

Medical Plant Exploitation and Utilization Engineering Research Center, Sanming University, Sanming, PR China.

The complete mitochondrial genome (mitogenome) sequence of (Lepidoptera: Riodinidae) was determined and analyzed. The mitogenome is 15,680 bp in length with consisting of 13 protein-coding genes (PCGs), 22 transfer RNA () genes, two ribosomal genes ( and ), and one AT-rich region. The gene content, orientation, and order are identical to that of the majority of other lepidopteran insects. The mitogenome includes a gene with an atypical CGA(R) start codon and three genes (, , and ) exhibiting incomplete stop codons. All tRNAs have a typical secondary cloverleaf structure, except for which lacks the dihydrouridine (DHU) arm. The 825-bp long AT-rich region is the longest among sequenced riodinids, which range from 349 to 423 bp. The conclusion of phylogenetic analysis highly supported the monophyly of Riodinidae, which is standing as the sister of the family Lycaenidae.
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http://dx.doi.org/10.1080/23802359.2021.1884014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954486PMC
March 2021

Complete chloroplast genome sequence and phylogenetic analysis of winter oil rapeseed ( L.).

Mitochondrial DNA B Resour 2021 Mar 11;6(3):723-731. Epub 2021 Mar 11.

College of Agronomy, Gansu Agricultural University/Rapeseed Engineering Research Center of Gansu Province, Lanzhou, China.

Winter oil rapeseed '18 R-1' ( L.) is a new variety that can survive in northern China where the extreme low temperature is -20 °C to -32 °C. It is different from traditional and . In this study, the complete chloroplast (cp) genome of '18 R-1' was sequenced and analyzed to assess the genetic relationship. The size of cp genome is 153,494 bp, including one large single copy (LSC) region of 83,280 bp and one small single copy (SSC) region of 17,776 bp, separated by two inverted repeat (IR) regions of 26,219 bp. The GC content of the whole genome is 36.35%, while those of LSC, SSC, and IR are 34.12%, 29.20%, and 42.32%, respectively. The cp genome encodes 132 genes, including 87 protein-coding genes, eight rRNA genes, and 37 tRNA genes. In repeat structure analysis, 288 simple sequence repeats (SSRs) were identified. Cp genome of '18 R-1' was closely related to , and .
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http://dx.doi.org/10.1080/23802359.2020.1860697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954489PMC
March 2021

Establishment of a typing model for diffuse large B-cell lymphoma based on B-cell receptor repertoire sequencing.

BMC Cancer 2021 Mar 22;21(1):297. Epub 2021 Mar 22.

Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No.354 Beima Road, Hongqiao District, Tianjin, 300120, China.

Background: The purpose of this study was to construct a new typing model for diffuse large B-cell lymphoma (DLBCL) patients based on the B-cell receptor (BCR) and explore its potential molecular mechanism.

Methods: BCR repertoire sequencing and whole-exome sequencing were performed on formalin-fixed paraffin-embedded samples from 12 DLBCL patients. Subsequently, a typing model was built with cluster analysis, and prognostic indicators between the two groups were compared to verify the typing model. Then, mutation and bioinformatics analyses were conducted to investigate the potential biomarkers of prognostic differences between the two groups.

Results: Based on BCR sequencing data, we divided patients into two clusters (cluster 1 and cluster 2); this classification differed from the traditional typing method (GCB and non-GCB), in which cluster 1 included some non-GCB patients. The progression-free survival (PFS), overall survival (OS), metastasis and Shannon diversity index of IGH V-J and survival after chemotherapy were significantly different (P < 0.05) between the two clusters, but no statistical significance was found between the GCB and non-GCB groups. The mutation status of 248 genes was significantly different between cluster 1 and cluster 2. Among them, FTSJ3, MAGED2, and ODF3L2 were the specific mutated genes in all patients in cluster 2, and these genes could be considered critical to the different prognoses of the two clusters of DLBCL patients.

Conclusion: We constructed a new typing model of DLBCL based on BCR repertoire sequencing that can better predict the survival time after chemotherapy. FTSJ3, MAGED2, and ODF3L2 may represent key genes for the difference in prognosis between the two clusters.
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http://dx.doi.org/10.1186/s12885-021-08015-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986026PMC
March 2021

Inhaled nitric oxide reduces the intrapulmonary shunt to ameliorate severe hypoxemia after acute type A aortic dissection surgery.

Nitric Oxide 2021 05 3;109-110:26-32. Epub 2021 Mar 3.

Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China; Department of Critical Care Medicine, Xiamen Branch, Zhongshan Hospital Fudan University, No. 668 Jinghu Road, Huli District, Xiamen, 361015, China. Electronic address:

Background: To assess the relationship between the intrapulmonary shunt and PaO/FiO in severe hypoxemic patients after acute type A aortic dissection (ATAAD) surgery and to evaluate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunt.

Methods: Postoperative ATAAD patients with PaO/FiO ≤ 150 mmHg were enrolled. Intrapulmonary shunt was calculated from oxygen content of different sites (artery [CaO], mixed venous [CvO], and alveolar capillary [CcO]) using the Fick equation, where intrapulmonary shunt = (CcO-CaO)/(CcO-CvO). Related variables were measured at baseline (positive end expiratory pressure [PEEP] 5 cm HO), 30 min after increasing PEEP (PEEP 10 cm HO), 30 min after 5 ppm iNO therapy (PEEP 10 cm HO + iNO), and 30 min after decreasing PEEP (PEEP 5 cm HO + iNO).

Results: A total of 20 patients were enrolled between April 2019 and December 2019. Intrapulmonary shunt and PaO/FiO were correlated in severe hypoxemic, postoperative ATAAD patients (adjusted R = 0.467, p < 0.001). A mixed model for repeated measures revealed that iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt (by 15% at a PEEP of 5 cm HO and 16% at a PEEP of 10 cm HO, p < 0.001 each) and increased PaO/FiO (by 63% at a PEEP of 5 cm HO and 65% at a PEEP of 10 cm HO, p < 0.001 each). After iNO therapy, the decrement of intrapulmonary shunt and the increment of PaO/FiO were also correlated (adjusted R = 0.375, p < 0.001).

Conclusions: This study showed that intrapulmonary shunt and PaO/FiO were correlated in severe hypoxemic, postoperative ATAAD patients. Furthermore, iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt to improve severe hypoxemic conditions.
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http://dx.doi.org/10.1016/j.niox.2021.03.001DOI Listing
May 2021

[Bio-based molecules for biosynthesis of nano-metallic materials].

Sheng Wu Gong Cheng Xue Bao 2021 Feb;37(2):541-560

State Key Laboratory of Materials-Oriented Chemical Engineering, School of Pharmaceutical Sciences, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China.

Nano-metallic materials are playing an important role in the application of medicine, catalysis, antibacterial and anti-toxin due to their obvious advantages, including nanocrystalline strengthening effect, high photo-absorptivity, high surface energy and single magnetic region performance. In recent years, with the increasing consumption of global petrochemical resources and the aggravation of environmental pollution, nanomaterials based on bio-based molecules have aroused great concern. Bio-based molecules refer to small molecules and macromolecules directly or indirectly derived from biomass. They usually have good biocompatibility, low toxicity, degradability, wide source and low price. Besides, most bio-based molecules have unique physical, chemical properties and physiological activity, such as optical activity, acid/alkali amphoteric property, hydrophilic property and easy coordination with metal ions. Thus, the corresponding nano-materials based on bio-based molecules also have unique functions, such as anti-inflammatory, anti-cancer, anti-oxidation, antiviral fall blood sugar and blood fat etc. In this paper, we give a comprehensive overview of the preparation and application of nano-metallic materials based on bio-based molecules in recent years.
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http://dx.doi.org/10.13345/j.cjb.200336DOI Listing
February 2021

[Analysis and evaluation of mineral elements of Chrysanthemum morifolium for medicinal and tea use of different germplasm resources].

Zhongguo Zhong Yao Za Zhi 2021 Jan;46(2):272-280

Hubei Key Laboratory of Resource Science and Chemistry in Chinese Medicine, Hubei University of Chinese Medicine Hubei 430065, China.

In this study, 23 germplasm resources of Chrysanthemum morifolium used in medicine and tea were collected from Dabie Mountains and its surrounding producing areas, and the contents of 13 mineral elements were determined and compared. The thermal maps of correlation analysis, principal component analysis and cluster analysis were used for comprehensive evaluation. The results showed that the average content of each element in Ch. morifolium of different germplasm resources was: K>N>P>Mg>Ca>Fe>Mn>Zn>Cu>Ni>Cr>Pb>Cd, and the leaves were: K>N>Ca>Mg>P>Fe>Mn>Zn>Cr>Cu>Ni>Pb>Cd. There are rich contents of N, P, K, Ca, Mg and Fe in Ch. morifolium flowers and their leaves, among them, K element has the largest change range, while N, Ca, Fe, Mg and Zn elements have a larger change range. The absorption and accumulation of each element in the leaves of different germplasm resources varied greatly. The correlation analysis shows that there is a strong positive correlation between Ca element, Mg, Mn and Cd element.Principal component analysis in Ch. morifolium flowers characteristic elements for Mn, Cr, Cu, P, K, can be used as a Ch. morifolium resources to identify the characteristics of the elements, choose top five principal component(F1-F5) comprehensive evalua-tion of medicinal Ch. morifolium, scored in the top five varieties for Hangiu-Fuhuangju, Hangju-Xiaoyangju, Hangju-Sheyangju, Hangju-Dayanghua, Hangju-Subeiju,indicates that in terms of mineral elements, the five medicinal Ch. morifolium resources quality is better. The PCA score chart can divide 23 Ch. morifolium resources into 4 groups, and the cluster analysis heat map divides 23 Ch. morifolium resources into 5 groups. All the Ch. morifolium resources of the same type can be well clustered together, indicating that the difference in mineral element content of Ch. morifolium germplasm resources is closely related to genetic factors.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201023.101DOI Listing
January 2021

Effect and safety of Chinese herbal medicine granules in patients with severe coronavirus disease 2019 in Wuhan, China: a retrospective, single-center study with propensity score matching.

Phytomedicine 2021 May 5;85:153404. Epub 2020 Nov 5.

Department of Emergency, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Background: Chinese herbal medicine (CHM) has been used for severe illness caused by coronavirus disease 2019 (COVID-19), but its treatment effects and safety are unclear.

Purpose: This study reviews the effect and safety of CHM granules in the treatment of patients with severe COVID-19.

Methods: We conducteda single-center, retrospective study on patients with severe COVID-19 in a designated hospital in Wuhan from January 15, 2020 to March 30, 2020. The propensity score matching (PSM) was used to assess the effect and safety of the treatment using CHM granules. The ratio of patients who received treatment with CHM granules combined with usual care and those who received usual care alone was 1:1. The primary outcome was the time to clinical improvement within 28 days, defined as the time taken for the patients' health to show improvement by decline of two categories (from the baseline) on a modified six-category ordinal scale, or to be dischargedfrom the hospital before Day 28.

Results: Using PSM, 43 patients (45% male) aged 65.6 (57-70) yearsfrom each group were exactly matched. No significant difference was observed in clinical improvement of patients treated with CHM granules compared with those who received usual (p = 0.851). However, the use of CHM granules reduced the 28-day mortality (p = 0.049) and shortened the duration of fever (4 days vs. 7 days, p = 0.002). The differences in the duration of cough and dyspnea and the difference in lung lesion ratio on computerized tomography scans were not significant.Commonly,patients in the CHM group had an increased D-dimer level (p = 0.036).

Conclusion: Forpatients with severe COVID-19, CHM granules, combined with usual care, showed no improvement beyond usual care alone. However, the use of CHM granules reduced the 28-day mortality rate and the time to fever alleviation. Nevertheless, CHM granules may be associated with high risk of fibrinolysis.
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http://dx.doi.org/10.1016/j.phymed.2020.153404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642753PMC
May 2021

Thioredoxin-1 Rescues MPP/MPTP-Induced Ferroptosis by Increasing Glutathione Peroxidase 4.

Mol Neurobiol 2021 Feb 26. Epub 2021 Feb 26.

Laboratory of Molecular Neurobiology, Medical School, Kunming University of Science and Technology, No.727 Jingming South Road, Kunming, 650500, China.

Parkinson's disease (PD), a common neurodegenerative disease, is typically associated with the loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc). Ferroptosis is a newly identified cell death, which associated with iron accumulation, glutathione (GSH) depletion, lipid peroxidation formation, reactive oxygen species (ROS) accumulation, and glutathione peroxidase 4 (GPX4) reduction. It has been reported that ferroptosis is linked with PD.Thioredoxin-1 (Trx-1) is a redox regulating protein and plays various roles in regulating the activity of transcription factors and inhibiting apoptosis. However, whether Trx-1 plays the role in regulating ferroptosis involved in PD is still unknown. Our present study showed that 1-methyl-4-phenylpyridinium (MPP) decreased cell viability, GPX4, and Trx-1, which were reversed by Ferrostatin-1 (Fer-1) in PC 12 cells and SH-SY5Y cells. Moreover, the decreased GPX4 and GSH, and increased ROS were inhibited by Fer-1 and Trx-1 overexpression. We further repeated that behavior deficits resulted from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were improved in Trx-1 overexpression transgenic mice. Trx-1 reversed the decreases of GPX4 and tyrosine hydroxylase (TH) induced by MPTP in the substantia nigra pars compacta (SNpc). Our results suggest that Trx-1 inhibits ferroptosis in PD through regulating GPX4 and GSH.
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http://dx.doi.org/10.1007/s12035-021-02320-1DOI Listing
February 2021

Exosomal miR-128-3p Promotes Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells by Targeting FOXO4 via TGF-β/SMAD and JAK/STAT3 Signaling.

Front Cell Dev Biol 2021 9;9:568738. Epub 2021 Feb 9.

Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Epithelial-to-mesenchymal transition (EMT) is a key process that occurs during tumor metastasis, affecting a variety of malignancies including colorectal cancer (CRC). Exosomes mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including microRNAs (miRNAs). Exosomal delivery of miRNAs plays an important role in tumor initiation, development, and progression. In this study, we investigated the effect of exosomal transfer between CRC cells and aimed to identify specific miRNAs and downstream targets involved in EMT and metastasis in CRC cells. High expression of miR-128-3p was identified in exosomes derived from EMT-induced HCT-116 cells. Altered miR-128-3p expression in CRC cells led to distinct changes in proliferation, migration, invasion, and EMT. Mechanistically, miR-128-3p overexpression downregulated the expression of FOXO4 and induced the activation of TGF-β/SMAD and JAK/STAT3 signaling in CRC cells and xenografted tumors, which led to EMT. Clinically, high expression of miR-128-3p was significantly associated with perineural invasion, lymphovascular invasion, tumor stage, and CA 19-9 content in CRC patients. We revealed that exosomal miR-128-3p regulates EMT by directly suppressing its downstream target gene FOXO4 to activate TGF-β/SMAD and JAK/STAT3 signaling, and the properties of the miR-128-3p/FOXO4 axis were horizontally transferred via exosomal delivery. In turn, exosomal miR-128-3p could be considered as a new therapeutic vehicle for CRC.
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http://dx.doi.org/10.3389/fcell.2021.568738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900423PMC
February 2021

High-efficiency and multiplex adenine base editing in plants using new TadA variants.

Mol Plant 2021 May 22;14(5):722-731. Epub 2021 Feb 22.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; Scientific Observing and Experimental Station of Crop Pests in Guilin, Ministry of Agriculture and Rural Affairs, Guilin 541399, China. Electronic address:

Recently reported adenine base editors (ABEs) exhibit powerful potential for targeted gene correction as well as developing gain-of-function mutants and novel germplasms for both gene function studies and crop breeding. However, editing efficiency varies significantly among different target sites. Here, we investigated the activities of three evolved E. coli adenosine deaminase TadA variants (TadA8e, TadA8.17, and TadA8.20) side-by-side in transgenic rice. We found that TadA8e outperforms TadA8.17 and TadA8.20, and induces efficient A-to-G conversion at all tested sites in the rice genome, including those that were uneditable by ABE7.10 in our previous experiments. Furthermore, V82S/Q154R mutations were incorporated into TadA8e, resulting in a new variant that we named TadA9. Our data show that TadA9 is broadly compatible with CRISPR/SpCas9, CRISPR/SpCas9-NG, and CRISPR/SpRY, as well as CRISPR/ScCas9 nickase systems, achieving comparable or enhanced editing in a larger editing window at diverse PAM sites as compared with TadA8e. Finally, TadA9 was used to simultaneously install novel SNPs in four endogenous herbicide target genes in the commercial rice cultivar Nangeng 46 for potential field application in weed control. Collectively, we successfully generated a series of novel ABEs that can efficiently edit adenosines in the rice genome. Our findings suggest that TadA9 and TadA8e have great potentials in the development of plant base editors and crop molecular breeding.
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http://dx.doi.org/10.1016/j.molp.2021.02.007DOI Listing
May 2021

RNA sequencing-based exploration of the effects of far-red light on lncRNAs involved in the shade-avoidance response of .

PeerJ 2021 12;9:e10769. Epub 2021 Feb 12.

College of Resources and Chemical Engineering, Sanming University, Sanming, China.

() is a valuable medicinal plant with a low natural survival rate, and its shade-avoidance response to far-red light is as an important strategy used by the plant to improve its production efficiency. However, the lncRNAs that play roles in the shade-avoidance response of have not yet been investigated. This study found that an appropriate proportion of far-red light can have several effects, including increasing the leaf area and accelerating stem elongation, in . The effects of different far-red light treatments on were analysed by RNA sequencing technology, and a total of 69 and 78 lncRNAs were differentially expressed in experimental group 1 (FR1) versus the control group (CK) (FR1-CK) and in experimental group 4 (FR4) versus the CK (FR4-CK), respectively. According to GO and KEGG analyses, most of the differentially expressed lncRNA targets are involved in the membrane, some metabolic pathways, hormone signal transduction, and O-methyltransferase activity, among other functions. Physiological and biochemical analyses showed that far-red light promoted the accumulation of flavonoids, alkaloids, carotenoids and polysaccharides in . The effect of far-red light on might be closely related to the cell membrane and Ca transduction. Based on a Cytoscape analysis and previous research, this study also found that MSTRG.38867.1, MSTRG.69319.1, and MSTRG.66273.1, among other components, might participate in the far-red light signalling network through their targets and thus regulate the shade-avoidance response of . These findings will provide new insights into the shade-avoidance response of .
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http://dx.doi.org/10.7717/peerj.10769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883695PMC
February 2021

Association of β-arrestin1 and p53-Mdm2 signaling in the development of missed abortion.

J Obstet Gynaecol Res 2021 May 21;47(5):1675-1685. Epub 2021 Feb 21.

Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Background: Missed abortion is a peculiar form of spontaneous abortion before 20 weeks' gestation. The definite etiology and pathogenesis are not fully understood. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R may be closely related to G-protein-coupled receptor kinases (GRK)/β-arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding β-arrestin1 in missed abortion.

Methods: The mRNA levels of β-arrestin1 in villous samples of 30 missed abortion patients and 31 healthy controls were determined by real-time quantitative polymerase chain reaction (PCR). Immunohistochemistry was used to explore the expression and location of β-arrestin1, p53, Mdm2, VEGF and HIF-lα in trophoblasts. Transwell assays were performed to examine the influences of β-arrestin1 expression on cell invasion. Furthermore, we tested the effect of β-arrestin1 on the expression of p53, Mdm2, ERK, AKT and NF-κB.

Results: The expression of β-arrestin1 in the villous samples of missed abortion group was dramatically lower than control group by quantitative real-time-PCR and immunohistochemistry. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2, HIF-lα and lower level of VEGF than healthy controls by immunohistochemistry. Functional studies showed that suppression of β-arrestin1 in HTR-8 cells inhibited cell invasion. The protein expressions of ERK and AKT in HTR-8 cells were significantly downregulated by reducing the expression of β-arrestin1, while the expressions of p53, Mdm2, NF-κB were enhanced. Overexpression of β-arrestin1 exhibited the adverse effect.

Conclusion: Our data indicated that β-arrestin1 play an important role in maintaining the maternal-fetal tolerance, the decreased expression of β-arrestin1 in the villous samples may be related with the development of missed abortion.
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http://dx.doi.org/10.1111/jog.14643DOI Listing
May 2021

Research progress on hosts and carriers, prevalence, virulence of infectious hypodermal and hematopoietic necrosis virus (IHHNV).

J Invertebr Pathol 2021 Feb 14;183:107556. Epub 2021 Feb 14.

School of Agriculture, Ludong University, Yantai, PR China. Electronic address:

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is one of the major viral pathogens of penaeid shrimp and it has spread worldwide. IHHNV causes substantial economic loss to the shrimp farming industry and has been listed as a notifiable crustacean disease pathogen by the World Organization for Animal Health (OIE). In this paper, we reviewed studies on the hosts and carriers, prevalence, genotypes and virulence of IHHNV. The pathogenesis mechanisms of IHHNV and the viral interference between IHHNV and white spot syndrome virus (WSSV) were also discussed. The mechanism of IHHNV infection and its virulence difference in different hosts and different developmental stages have not been fully studied yet. The mechanisms underlying viral interference between IHHNV and WSSV are not yet fully understood. Further studies are needed to elucidate the precise molecular mechanisms underlying IHHNV infection and to apply the insights gained from such studies for the effective control and prevention of IHHNV disease.
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http://dx.doi.org/10.1016/j.jip.2021.107556DOI Listing
February 2021

Physiological responses of the diatoms Thalassiosira weissflogii and Thalassiosira pseudonana to nitrogen starvation and high light.

Mar Environ Res 2021 Apr 5;166:105276. Epub 2021 Feb 5.

School of Life Science, Ludong University, Yantai, 264025, China; Key Laboratory of Marine Biotechnology in Universities of Shandong, Ludong University,Yantai, 264025, China. Electronic address:

As oceans warm, the depth of the upper mixed layer is predicted to decrease, resulting in insufficient nutrient supply and higher solar radiation for phytoplankton. In order to understand the photophysiological responses of the key eukaryotic phytoplankton diatoms to high light and nutrient limitation, we grew two diatoms, Thalassiosira weissflogii and Thalassiosira pseudonana under N starvation conditions and exposed them to high visible light. It showed that the large-sized diatom T. weissflogii can maintain photosynthetic activity for a longer period of time under nitrogen starvation as compared with the small-sized diatom T. pseudonana. The electron transfer reaction was inhibited in both diatoms and the fast closing of reaction centers promoted the development of Q non-reducing PSII centers, thus facilitated the rapid induction of NPQ, however, the induction of NPQ depended on the degree of N starvation. N starvation exacerbated the photoinhibition caused by high light. The smaller-sized T. pseudonana had a higher σi value and was more sensitive to high-light, but its PSII repair rate was also higher. In contrast, T. weissflogii was more tolerant to high light with a lower σi value, but the tolerance was severely reduced under N-starvation. This study provides helpful insight into how climate change variables impact diatom's photosynthetic physiology.
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http://dx.doi.org/10.1016/j.marenvres.2021.105276DOI Listing
April 2021

Cdc42 Facilitates Axonogenesis by Enhancing Microtubule Stabilization in Primary Hippocampal Neurons.

Cell Mol Neurobiol 2021 Feb 11. Epub 2021 Feb 11.

Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

The establishment of polarity is an essential process in early neuronal development. Cdc42, a GTPase of the Rho family, is a key regulator of cytoskeletal dynamics and neuronal polarity. However, the mechanisms underlying the action of cdc42 in regulating axonogenesis have not been elucidated. Here, we expressed wild-type cdc42, a constitutively active cdc42 mutant (cdc42F28L) and a dominant negative cdc42 mutant (cdc42N17), respectively, in the primary hippocampal neurons to alter the activity of cdc42. We found that cdc42 activities were paralleled with the capacities to promote axonogenesis in the cultured neurons. Cdc42 also enhanced microtubule stability in the cultured neurons. Pharmacologically stabilizing microtubules significantly abrogated the defective axonogenesis induced by cdc42 inhibition. Moreover, cdc42 promoted the dephosphorylation of collapsing response mediator protein-2 (CRMP-2) at Thr514 by increasing GSK-3β phosphorylation at Ser9 in the cultured neurons. These findings suggest that cdc42 may facilitate axonogenesis by promoting microtubule stabilization in rat primary hippocampal neurons.
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http://dx.doi.org/10.1007/s10571-021-01051-0DOI Listing
February 2021

Pulmonary Artery Catheter in Patients with Severe Acute Pancreatitis: A Single-Center Retrospective Study.

Dig Dis Sci 2021 Feb 11. Epub 2021 Feb 11.

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.

Objective: It is still uncertain what effects pulmonary artery catheter (PAC)-guided resuscitation has on outcomes for patients with severe acute pancreatitis (SAP). Therefore, we aimed to investigate the effect of PAC on hospital mortality in patients with SAP.

Methods: We collected the data of patients with a diagnosis of SAP from January 10, 2017, to July 30, 2019. Patients were divided into a PAC group and a control group. The primary outcome measured was the day-28 mortality. Secondary outcomes included day-90 mortality, duration of ICU and hospital stay, ventilation days, usage of renal support and vasoactive agents, incidences of acute abdominal compartment syndrome, infusion volumes, and fluid balance and hemodynamic characteristics measured by the PAC. Kaplan-Meier analysis was applied to estimate survival outcomes. Complications related to PAC were also analyzed.

Results: There was no significant difference between the PAC group and the control group for day-28 mortality (22.7% vs. 30%, odds ratio, 0.69; 95% CI 0.31-1.52; P = 0.35). The duration of ICU stay in the PAC group was shorter (P = 0.00), and the rate of dependence on renal support treatment was lower in the PAC group than in the control group (P = 0.03). There was no difference in other secondary outcomes and no significant difference in the survival curve between the two groups (log-rank P = 0.72, X = 0.13). However, SAP patients inserted PAC within 24 h ICU admission showed that duration of renal support therapy in PAC patients within 24 h ICU admission (mean days, 1.60; standard deviation, 0.14) was shorter than those with 24-72 h ICU admission (mean days, 2.94; standard deviation, 0.73; P = 0.03). The organ failure rates (1 organ, 2 organs and 3 organs) were all lower in PAC patients within 24 h ICU admission than with 24-72 h ICU admission (P = 0.02, P = 0.02, P = 0.048, respectively).

Conclusion: In patients with severe acute pancreatitis, PAC-guided fluid resuscitation shortened the duration of ICU stay, and patients in the PAC group had a lower rate of dependence on renal support, while no benefit in terms of mortality was observed. However, SAP patients inserted PAC within 24 h ICU admission showed shorter duration of renal support therapy and lower organ failure rates than those with 24-72 h ICU admission, indicating that early use of PAC, especially within 24 h, might be better for SAP patients.
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http://dx.doi.org/10.1007/s10620-021-06881-yDOI Listing
February 2021

Identification of differentially expressed genes involved in amino acid and lipid accumulation of winter turnip rape (Brassica rapa L.) in response to cold stress.

PLoS One 2021 8;16(2):e0245494. Epub 2021 Feb 8.

Gansu Provincial Key Laboratory of Aridland Crop Science, Lanzhou, China.

Winter turnip rape (Brassica rapa L.) is an important overwintering oil crop that is widely planted in northwestern China. It considered to be a good genetic resource for cold-tolerant research because its roots can survive harsh winter conditions. Here, we performed comparative transcriptomics analysis of the roots of two winter turnip rape varieties, Longyou7 (L7, strong cold tolerance) and Tianyou2 (T2, low cold tolerance), under normal condition (CK) and cold stress (CT) condition. A total of 8,366 differentially expressed genes (DEGs) were detected between the two L7 root groups (L7CK_VS_L7CT), and 8,106 DEGs were detected for T2CK_VS_T2CT. Among the DEGs, two ω-3 fatty acid desaturase (FAD3), two delta-9 acyl-lipid desaturase 2 (ADS2), one diacylglycerol kinase (DGK), and one 3-ketoacyl-CoA synthase 2 (KCS2) were differentially expressed in the two varieties and identified to be related to fatty acid synthesis. Four glutamine synthetase cytosolic isozymes (GLN), serine acetyltransferase 1 (SAT1), and serine acetyltransferase 3 (SAT3) were down-regulated under cold stress, while S-adenosylmethionine decarboxylase proenzyme 1 (AMD1) had an up-regulation tendency in response to cold stress in the two samples. Moreover, the delta-1-pyrroline-5-carboxylate synthase (P5CS), δ-ornithine aminotransferase (δ-OAT), alanine-glyoxylate transaminase (AGXT), branched-chain-amino-acid transaminase (ilvE), alpha-aminoadipic semialdehyde synthase (AASS), Tyrosine aminotransferase (TAT) and arginine decarboxylase related to amino acid metabolism were identified in two cultivars variously expressed under cold stress. The above DEGs related to amino acid metabolism were suspected to the reason for amino acids content change. The RNA-seq data were validated by real-time quantitative RT-PCR of 19 randomly selected genes. The findings of our study provide the gene expression profile between two varieties of winter turnip rape, which lay the foundation for a deeper understanding of the highly complex regulatory mechanisms in plants during cold treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870078PMC
February 2021

Evidence-based Chinese medicine for the response to public health emergencies: The Guangzhou declaration.

J Evid Based Med 2021 Feb 7;14(1):3-4. Epub 2021 Feb 7.

Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China.

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http://dx.doi.org/10.1111/jebm.12422DOI Listing
February 2021