Publications by authors named "Jianxin Shi"

265 Publications

Cigarette Smoking and Opium Use in Relation to the Oral Microbiota in Iran.

Microbiol Spectr 2021 Sep 15:e0013821. Epub 2021 Sep 15.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institutegrid.48336.3a, Bethesda, Maryland, USA.

Cigarettes and opium contain chemicals and particulate matter that may modify the oral microbiota. This study aimed to investigate the association between cigarette and opium use with the oral microbiota. A total of 558 participants were recruited from Iran between 2011 and 2015. Individuals were categorized as never cigarette nor opium users, ever cigarette-only smokers, ever opium-only users, and ever both cigarette and opium users. Participants provided saliva samples for 16S rRNA gene sequencing. Logistic regression, microbiome regression-based kernel association test (MiRKAT), and zero-inflated beta regression models were calculated. For every increase in 10 observed amplicon sequence variants (ASVs), the odds for being a cigarette-only smoker, opium-only user, and both user compared to never users decreased by 9% (odds ratio [OR] = 0.91; 95% confidence interval [95% CI] = 0.86 to 0.97), 13% (OR = 0.87; 95% CI = 0.75 to 1.01), and 12% (OR = 0.88; 95% CI = 0.80 to 0.96), respectively. The microbial communities differed by cigarette and opium use as indicated by MiRKAT models testing the three beta-diversity matrices ( < 0.05 for all). Three genera were less likely and one genus was more likely to be detected in cigarette-only smokers or opium-only users than in never users. The relative abundance of the phylum (never, 14.78%; both, 21.20%) was higher and the phyla (never, 17.63%; both, 11.62%) and (never, 9.06%; both, 3.70%) were lower in users of both cigarettes and opium, while the phylum (never, 54.29%; opium, 65.49%) was higher in opium-only users. Cigarette and opium use was associated with lower alpha-diversity, overall oral microbiota community composition, and both the presence and relative abundance of multiple taxa. Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis, which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied across diverse populations. Additionally, the association of opium use with the oral microbiota has not been investigated to date. We conducted this study to investigate differences in the oral microbiota between ever users of cigarettes only, opium only, and both cigarettes and opium and never users of cigarettes and opium in Iran. Lower alpha-diversity, distinct overall oral microbial communities, and the presence and relative abundance of multiple taxa have been found for users of cigarettes and/or opium.
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http://dx.doi.org/10.1128/Spectrum.00138-21DOI Listing
September 2021

Genomic and evolutionary classification of lung cancer in never smokers.

Nat Genet 2021 Sep 6;53(9):1348-1359. Epub 2021 Sep 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.
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http://dx.doi.org/10.1038/s41588-021-00920-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432745PMC
September 2021

A penalized regression framework for building polygenic risk models based on summary statistics from genome-wide association studies and incorporating external information.

J Am Stat Assoc 2021 12;116(533):133-143. Epub 2020 Oct 12.

Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Maryland, United States of America, 9609 Medical Center Drive, RM 7E122, Bethesda, MD, 20892.

Large-scale genome-wide association (GWAS) studies provide opportunities for developing genetic risk prediction models that have the potential to improve disease prevention, intervention or treatment. The key step is to develop polygenic risk score (PRS) models with high predictive performance for a given disease, which typically requires a large training data set for selecting truly associated single nucleotide polymorphisms (SNPs) and estimating effect sizes accurately. Here, we develop a comprehensive penalized regression for fitting regularized regression models to GWAS summary statistics. We propose incorporating Pleiotropy and ANnotation information into PRS (PANPRS) development through suitable formulation of penalty functions and associated tuning parameters. Extensive simulations show that PANPRS performs equally well or better than existing PRS methods when no functional annotation or pleiotropy is incorporated. When functional annotation data and pleiotropy are informative, PANPRS substantially outperforms existing PRS methods in simulations. Finally, we applied our methods to build PRS for type 2 diabetes and melanoma and found that incorporating relevant functional annotations and GWAS of genetically related traits improved prediction of these two complex diseases.
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http://dx.doi.org/10.1080/01621459.2020.1764849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414872PMC
October 2020

Clinical Implications of Inter- and Intra-Tumor Heterogeneity of Immune Cell Markers in Lung Cancer.

J Natl Cancer Inst 2021 Aug 17. Epub 2021 Aug 17.

Integrative Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.

Background: Immune cell transcriptome signatures have been widely used to study the lung tumor microenvironment (TME). However, it is unclear to what extent the immune cell composition in the lung TME varies across histological and molecular subtypes (inter-tumor heterogeneity or Inter-TH) and within tumors (intratumor heterogeneity or ITH), and whether ITH has any prognostic relevance.

Methods: Using RNA sequencing in 269 tumor samples from 160 lung cancer patients we quantified the Inter-TH of immune gene expression and immune cell abundance and evaluated the association of median immune cell abundance with clinical/pathological features and overall survival. In 39 tumors with 132 multi-region samples, we also analyzed the ITH of immune cell abundance in relation to overall survival using a variance-weighted multivariate Cox model not biased by the number of samples per tumor.

Results: Substantial Inter-TH of 14 immune cell types was observed even within the same histological and molecular subtypes, but early-stage tumors had higher lymphocyte infiltration across all tumor types. In multi-region samples, an unbiased estimate of low ITH of overall immune cell composition (hazard ratio [HR] = 0.40, 95% confidence interval [CI] = 0.21 to 0.78; P = .007), dendritic cells (HR = 0.24, 95% CI = 0.096 to 0.58; P = .002) and macrophages (HR = 0.50, 95% CI = 0.30 to 0.84; P = .009) was strongly associated with poor survival. The ITH of three markers, including CD163 and CD68 (macrophages) and CCL13 (dendritic cells), was enough to characterize the ITH of the corresponding immune cell abundances and its association with overall survival.

Conclusion: This study suggests that lack of immune cell diversity may facilitate tumor evasion and progression. ITH inferred from CCL13, CD163 and CD68 could be used as a prognostic tool in clinical practice.
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http://dx.doi.org/10.1093/jnci/djab157DOI Listing
August 2021

Integrating GWAS and transcriptomics to identify genes involved in seed dormancy in rice.

Theor Appl Genet 2021 Jul 26. Epub 2021 Jul 26.

Joint International Research Laboratory of Metabolic and Developmental Sciences, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Key Message: Several QTLs and genes responsible for seed dormancy were detected and SNP candidates were shown to cause changes in seed germination. Seed dormancy is a key agricultural trait to prevent pre-harvest sprouting in crop plants such as rice (Oryza sativa L.), wheat (Triticum aestivum), and barley (Hordeum vulgare L.). However, our knowledge of seed dormancy is hampered by the complexities of studying a trait that changes over time after seed harvest, and is complicated by interactions between phytohormones, seed coat components and the environment. Here, we have conducted a genome-wide association study using a panel of 311 natural accessions of cultivated rice, examining a total of 519,158 single nucleotide polymorphisms (SNPs). Eight quantitative trait loci (QTLs) were found to associate with seed dormancy in the whole panel and five in the Japonica and Indica subpanel; expression of candidate genes within 100 kb of each QTL was examined in two published, germination-specific transcriptomic datasets. Ten candidate genes, differentially expressed within the first four days post-imbibition, were identified. Five of these genes had previously been associated with awn length, heading date, yield, and spikelet length phenotypes. Two candidates were validated using Quantitative Reverse Transcription (qRT)-PCR. In addition, previously identified genes involved in hormone signaling during germination were found to be differentially expressed between a japonica and an indica line; SNPs in the promoter of Os9BGlu33 were associated with germination index, with qRT-PCR validation. Collectively, our results are useful for future characterization of seed dormancy mechanism and crop improvement, and suggest haplotypes for further analysis that may be of use to boost PHS resistance in rice.
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http://dx.doi.org/10.1007/s00122-021-03911-1DOI Listing
July 2021

Cell-type-specific meQTLs extend melanoma GWAS annotation beyond eQTLs and inform melanocyte gene-regulatory mechanisms.

Am J Hum Genet 2021 09 21;108(9):1631-1646. Epub 2021 Jul 21.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address:

Although expression quantitative trait loci (eQTLs) have been powerful in identifying susceptibility genes from genome-wide association study (GWAS) findings, most trait-associated loci are not explained by eQTLs alone. Alternative QTLs, including DNA methylation QTLs (meQTLs), are emerging, but cell-type-specific meQTLs using cells of disease origin have been lacking. Here, we established an meQTL dataset by using primary melanocytes from 106 individuals and identified 1,497,502 significant cis-meQTLs. Multi-QTL colocalization with meQTLs, eQTLs, and mRNA splice-junction QTLs from the same individuals together with imputed methylome-wide and transcriptome-wide association studies identified candidate susceptibility genes at 63% of melanoma GWAS loci. Among the three molecular QTLs, meQTLs were the single largest contributor. To compare melanocyte meQTLs with those from malignant melanomas, we performed meQTL analysis on skin cutaneous melanomas from The Cancer Genome Atlas (n = 444). A substantial proportion of meQTL probes (45.9%) in primary melanocytes is preserved in melanomas, while a smaller fraction of eQTL genes is preserved (12.7%). Integration of melanocyte multi-QTLs and melanoma meQTLs identified candidate susceptibility genes at 72% of melanoma GWAS loci. Beyond GWAS annotation, meQTL-eQTL colocalization in melanocytes suggested that 841 unique genes potentially share a causal variant with a nearby methylation probe in melanocytes. Finally, melanocyte trans-meQTLs identified a hotspot for rs12203592, a cis-eQTL of a transcription factor, IRF4, with 131 candidate target CpGs. Motif enrichment and IRF4 ChIP-seq analysis demonstrated that these target CpGs are enriched in IRF4 binding sites, suggesting an IRF4-mediated regulatory network. Our study highlights the utility of cell-type-specific meQTLs.
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http://dx.doi.org/10.1016/j.ajhg.2021.06.018DOI Listing
September 2021

HSP70-16 and VDAC3 jointly inhibit seed germination under cold stress in Arabidopsis.

Plant Cell Environ 2021 Jun 25. Epub 2021 Jun 25.

Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Abscisic acid (ABA) transport plays a crucial role in seed germination under unfavourable conditions such as cold stress. Both heat shock protein 70 (HSP70) and voltage-dependent anion channel (VDAC) protein are involved in cold stress responses in Arabidopsis. However, their roles in seed germination with regard to ABA signaling remain unknown. Here we demonstrated that Arabidopsis HSP70-16 and VDAC3 jointly suppress seed germination under cold stress conditions. At 4°C, both HSP70-16 and VDAC3 facilitated the efflux of ABA from the endosperm to the embryo and thus inhibited seed germination. HSP70-16 interacted with VDAC3 on the plasma membrane and in the nucleus, and the interplay between HSP70-16 and VDAC3 activated the opening of the VDAC3 ion channel. Our work established a novel function of HSP70-16 in seed germination under cold stress and a possible association of VDAC3 activity with ABA transportation from endosperm to embryo under cold stress conditions. This study reveals that HSP70-16 interacts with VDAC3 and facilitates the opening of the VDAC3 ion channel, which influences ABA efflux from endosperm to embryo, thus negatively regulates seed germination under cold stress.
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http://dx.doi.org/10.1111/pce.14138DOI Listing
June 2021

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

Biol Psychiatry 2021 Mar 23. Epub 2021 Mar 23.

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois; Department of Psychiatry and Behavioral Sciences, North Shore University Health System, Evanston, Illinois.

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.

Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.

Results: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10; rs73033497, p = 8.8 × 10; rs7914279, p = 6.4 × 10), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).

Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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http://dx.doi.org/10.1016/j.biopsych.2021.02.972DOI Listing
March 2021

CRISPR/Cas systems: opportunities and challenges for crop breeding.

Plant Cell Rep 2021 Jun 11;40(6):979-998. Epub 2021 May 11.

Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Increasing crop production to meet the demands of a growing population depends largely on crop improvement through new plant-breeding techniques (NPBT) such as genome editing. CRISPR/Cas systems are NPBTs that enable efficient target-specific gene editing in crops, which is supposed to accelerate crop breeding in a way that is different from genetically modified (GM) technology. Herein, we review the applications of CRISPR/Cas systems in crop breeding focusing on crop domestication, heterosis, haploid induction, and synthetic biology, and summarize the screening methods of CRISPR/Cas-induced mutations in crops. We highlight the importance of molecular characterization of CRISPR/Cas-edited crops, and pay special attentions to emerging highly specific genome-editing tools such as base editors and prime editors. We also discuss future improvements of CRISPR/Cas systems for crop improvement.
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http://dx.doi.org/10.1007/s00299-021-02708-2DOI Listing
June 2021

PacBio Single-Molecule Long-Read Sequencing Reveals Genes Tolerating Manganese Stress in Saplings.

Front Genet 2021 6;12:635043. Epub 2021 Apr 6.

Department of Landscape Architecture, School of Design, Shanghai Jiao Tong University, Shanghai, China.

(Theaceae) is a subtropical evergreen tree and is used widely for forest firebreaks and gardening. It is a plant that tolerates salt and typically accumulates elevated amounts of manganese in the leaves. With large ecological amplitude, this tree species grows quickly. Due to its substantial biomass, it has a great potential for soil remediation. To evaluate the thorough framework of the mRNA, we employed PacBio sequencing technology for the first time to generate transcriptome. In this analysis, overall, 511,759 full length non-chimeric reads were acquired, and 163,834 high-quality full-length reads were obtained. Overall, 93,362 open reading frames were obtained, of which 78,255 were complete. In gene annotation analyses, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Genes (COG), Gene Ontology (GO), and Non-Redundant (Nr) databases were allocated 91,082, 71,839, 38,914, and 38,376 transcripts, respectively. To identify long non-coding RNAs (lncRNAs), we utilized four computational methods associated with protein families (Pfam), Cooperative Data Classification (CPC), Coding Assessing Potential Tool (CPAT), and Coding Non-Coding Index (CNCI) databases and observed 8,551, 9,174, 20,720, and 18,669 lncRNAs, respectively. Moreover, nine genes were randomly selected for the expression analysis, which showed the highest expression of Gene 6 (Na_Ca_ex gene), and CAX (CAX-interacting protein 4) was higher in manganese (Mn)-treated group. This work provided significant number of full-length transcripts and refined the annotation of the reference genome, which will ease advanced genetic analyses of
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http://dx.doi.org/10.3389/fgene.2021.635043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057201PMC
April 2021

The association between genetically determined ABO blood types and major depressive disorder.

Psychiatry Res 2021 05 24;299:113837. Epub 2021 Feb 24.

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.
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http://dx.doi.org/10.1016/j.psychres.2021.113837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071927PMC
May 2021

Tracing Lung Cancer Risk Factors Through Mutational Signatures in Never-Smokers.

Am J Epidemiol 2021 06;190(6):962-976

Epidemiologic studies often rely on questionnaire data, exposure measurement tools, and/or biomarkers to identify risk factors and the underlying carcinogenic processes. An emerging and promising complementary approach to investigate cancer etiology is the study of somatic "mutational signatures" that endogenous and exogenous processes imprint on the cellular genome. These signatures can be identified from a complex web of somatic mutations thanks to advances in DNA sequencing technology and analytical algorithms. This approach is at the core of the Sherlock-Lung study (2018-ongoing), a retrospective case-only study of over 2,000 lung cancers in never-smokers (LCINS), using different patterns of mutations observed within LCINS tumors to trace back possible exposures or endogenous processes. Whole genome and transcriptome sequencing, genome-wide methylation, microbiome, and other analyses are integrated with data from histological and radiological imaging, lifestyle, demographic characteristics, environmental and occupational exposures, and medical records to classify LCINS into subtypes that could reveal distinct risk factors. To date, we have received samples and data from 1,370 LCINS cases from 17 study sites worldwide and whole-genome sequencing has been completed on 1,257 samples. Here, we present the Sherlock-Lung study design and analytical strategy, also illustrating some empirical challenges and the potential for this approach in future epidemiologic studies.
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http://dx.doi.org/10.1093/aje/kwaa234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316614PMC
June 2021

Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival.

Nat Commun 2021 02 3;12(1):757. Epub 2021 Feb 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.
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http://dx.doi.org/10.1038/s41467-021-21026-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859411PMC
February 2021

Study of micro-trichome (mict) reveals novel connections between transcriptional regulation of multicellular trichome development and specific metabolism in cucumber.

Hortic Res 2021 Feb 1;8(1):21. Epub 2021 Feb 1.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Trichomes that cover the epidermis of aerial plant organs play multiple roles in plant protection. Compared with a unicellular trichome in model plants, the development mechanism of the multicellular trichome is largely unclear. Notably, variations in trichome development are often accompanied by defects in the biosynthesis of cuticle and secondary metabolites; however, major questions about the interactions between developmental differences in trichomes and defects in metabolic pathways remain unanswered. Here, we characterized the glabrous mutant mict/csgl1/cstbh via combined metabolomic and transcriptomic analyses to extend our limited knowledge regarding multicellular trichome development and metabolism in cucumber. Mict was found to be explicitly expressed within trichome cells. Transcriptomic analysis indicated that genes involved in flavonoid and cuticle metabolism are significantly downregulated in mict mutants. Further metabolomic analysis confirmed that flavonoids, lipids, and cuticle compositions are dramatically altered in mict mutants. Additional studies revealed that Mict regulates flavonoid, lipid, and cuticle biosynthesis by likely directly binding to downstream functional genes, such as CsTT4, CsFLS1, CsCER26, and CsMYB36. These findings suggest that specific metabolic pathways (e.g., flavonoids and cuticle components) are co-regulated by Mict and provide insights into transcriptional regulation mechanisms of multicellular trichome development and its specific metabolism in cucumber.
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http://dx.doi.org/10.1038/s41438-020-00456-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848009PMC
February 2021

Network Pharmacology-Based Analysis on the Mechanism of Action of Ephedrae Herba-Cinnamomi Ramulus Couplet Medicines in the Treatment for Psoriasis.

Med Sci Monit 2021 Jan 29;27:e927421. Epub 2021 Jan 29.

Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland).

BACKGROUND This study explored the mechanism of action of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) at the pharmacological level in the treatment of psoriasis. MATERIAL AND METHODS The active ingredients in MGCM were mined through literature retrieval and the BATMAN-TCM database, and potential targets were predicted. In addition, targets associated with psoriasis were acquired using multiple disease-related databases. Thereafter, an interaction network between candidate MGCM targets and the known psoriasis-associated targets was constructed based on the protein-protein interaction (PPI) data, using the STRING database. Then, the topological parameter degree was determined for mining the core targets for MGCM in the treatment of psoriasis, which also represented the major hubs within the PPI network. In addition, the core networks of targets and ingredients were constructed using Cytoscape software to apply MGCM in the treatment for psoriasis. These core targets were then analyzed for Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathway enrichment using OmicShare. RESULTS The ingredient-target core network of MGCM for treating psoriasis was constructed; it contained 52 active ingredients and corresponded to 19 core targets. In addition, based on enrichment analysis, these core targets were majorly enriched for several biological processes (immuno-inflammatory responses, leukocyte differentiation, energy metabolism, angiogenesis, and programmed cell death) together with the relevant pathways (Janus kinase-signal transducer and activator of transcription, toll-like receptors, nuclear factor kappaB, vascular endothelial growth factor, and peroxisome proliferator-activated receptor), thus identifying the possible mechanism of action of MGCM in treating psoriasis. CONCLUSIONS The present network pharmacology study indicated that MGCM alleviates various pathological factors of psoriasis through multiple compounds, multiple targets, and multiple pathways.
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http://dx.doi.org/10.12659/MSM.927421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852043PMC
January 2021

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

Int J Cancer 2021 06 26;148(11):2712-2723. Epub 2021 Feb 26.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; P < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.
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http://dx.doi.org/10.1002/ijc.33473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386185PMC
June 2021

Analysis of prevalence and prognosis of type 2 diabetes mellitus in patients with acute exacerbation of COPD.

BMC Pulm Med 2021 Jan 6;21(1). Epub 2021 Jan 6.

Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Disease, The First Hospital of China Medical University, No. 155 Nanjing Street, North, Shenyang, 110001, China.

Background: For patients with acute exacerbation of COPD (AECOPD), type 2 diabetes mellitus (T2DM) as comorbidity have poor outcomes. However, data on the impact of previously diagnosed and new- diagnosed T2DM in such a patient population is lacking.

Methods: Inpatients diagnosed with AECOPD in the department of Pulmonary and Critical Care Medicine of The First Hospital of China Medical University during 2011-2017 were enrolled. Data on demography, prevalence of type 2 DM, other comorbidities, hospital stays and laboratory tests (including arterial partial pressure of oxygen [PaO2]) results were recorded. Results were compared with AECOPD patients having previously diagnosed and new-diagnosed type 2 diabetes. Markers associated with development of type 2 DM and the prognosis of AECOPD patients were identified.

Results: Of the 196 patients enrolled in this study, the overall prevalence of T2DM was 26%. The PaO2 in the newly diagnosed T2DM group was considerably lower versus non-diabetic group. The T2DM group had a longer hospital stay and higher troponin level versus the non-diabetic group. AECOPD patients with T2DM were found to be correlated with hypertension. Age, need for assisted ventilation, increased troponin, and elevated fasting blood glucose on admission were risk factors for death in hospitalized AECOPD patients.

Conclusions: AECOPD patients had a higher prevalence of T2DM than the general population; T2DM comorbidity caused lower PaO2, longer hospital stays, and increased troponin. Poor blood glucose control may increase the risk of death in AECOPD patients.
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http://dx.doi.org/10.1186/s12890-020-01371-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788870PMC
January 2021

Promoting Human Nutrition and Health through Plant Metabolomics: Current Status and Challenges.

Biology (Basel) 2020 Dec 31;10(1). Epub 2020 Dec 31.

Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Plant metabolomics plays important roles in both basic and applied studies regarding all aspects of plant development and stress responses. With the improvement of living standards, people need high quality and safe food supplies. Thus, understanding the pathways involved in the biosynthesis of nutritionally and healthily associated metabolites in plants and the responses to plant-derived biohazards in humans is of equal importance to meet people's needs. For each, metabolomics has a vital role to play, which is discussed in detail in this review. In addition, the core elements of plant metabolomics are highlighted, researches on metabolomics-based crop improvement for nutrition and safety are summarized, metabolomics studies on plant natural products including traditional Chinese medicine (TCM) for health promotion are briefly presented. Challenges are discussed and future perspectives of metabolomics as one of the most important tools to promote human nutrition and health are proposed.
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http://dx.doi.org/10.3390/biology10010020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823625PMC
December 2020

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378844PMC
February 2021

DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Genes (Basel) 2020 12 24;12(1). Epub 2020 Dec 24.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas ( < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; -value = 9.4 × 10). DNA methylation was not associated with expression, but was inversely associated with expression after multiple comparison adjustment (-value = 0.04). Findings suggest that prostate tumor exon 3 hypomethylation is associated with increased aggressiveness.
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http://dx.doi.org/10.3390/genes12010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823928PMC
December 2020

Evaluation of Metal Tolerance of Fungal Strains Isolated from Contaminated Mining Soil of Nanjing, China.

Biology (Basel) 2020 Dec 15;9(12). Epub 2020 Dec 15.

Department of Landscape Architecture, School of Design, Shanghai Jiao Tong University, Shanghai 200240, China.

Rapidly increasing industry has resulted in greater discharge of hazardous chemicals in the soil. In the current study, soil samples were collected from Nanjing mine (32°09'19.29″ N 118°56'57.04″ E) and subjected to heavy metal analysis and microbe isolation. A total of 460 fungi were isolated, and five of these were yeast strains. Most of the strains exhibited tolerance to one metal. Five multimetal tolerant strains were selected and identified as , , , and . Isolated strains were grown in high concentrations of cadmium (Cd), chromium (Cr) and lead (Pb), for induced-tolerance training. The tolerance index (TI) revealed the highest Cd tolerance of novel strain at 5500 ppm (TI: 0.2). also displayed resistance at 4000 ppm against Cr (TI: 0.32) and Pb (TI: 0.32). In contrast, tolerance training for was not that successful. also displayed the highest bioaccumulation capacity for Cd (25.23 mg/g), Cu (21.63 mg/g), and Pb (20.63 mg/g) at 200 ppm. Scanning electron microscopy (SEM) explored the morphological changes in the mycelia of stressed fungi. Results of this study describe this delicate approach to be species and metal dependent and suggest a potential utilization of this fungal strain for the bioremediation of contaminated soils.
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http://dx.doi.org/10.3390/biology9120469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765179PMC
December 2020

Variation in oral microbiome is associated with future risk of lung cancer among never-smokers.

Thorax 2021 03 14;76(3):256-263. Epub 2020 Dec 14.

National Cancer Institute, Bethesda, Maryland, USA.

Objective: To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.

Design And Setting: A nested case-control study within two prospective cohort studies, the Shanghai Women's Health Study (n=74 941) and the Shanghai Men's Health Study (n=61 480).

Participants: Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).

Main Outcomes And Measures: Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.

Results: Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p=0.05; Simpson: p=0.04; Observed Species: p=0.64). No case-control differences were apparent for beta diversity (p=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR 1.00 (reference), OR 0.61 (95% CI 0.32 to 1.18), OR 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR 1.00 (reference), OR 0.66 (95% CI 0.35 to 1.25), OR 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (OR 1.00 (reference), OR 1.49 (95% CI 0.73 to 3.08), OR 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR 1.00 (reference), OR 2.15 (95% CI 1.03 to 4.47), OR 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.

Conclusions: Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215542DOI Listing
March 2021

Single-Crystal Red Phosphors and Their Core-Shell Structure for Improved Water-Resistance for Laser Diodes Applications.

Angew Chem Int Ed Engl 2021 Feb 28;60(8):3940-3945. Epub 2020 Dec 28.

School of Marine Sciences/and School of Chemistry, Sun Yat-Sen University, Zhuhai 519082, Guangzhou, 510275, P. R. China.

A solvent-vapor transport route produces centimeter-sized single-crystal red phosphors. The epitaxial growth route to yield its core-shell structure at ambient temperature was adopted. These red phosphors could be applied in all-inorganic WLED devices. Cs TiF :Mn (CTFM) single crystal provides enhancement of quantum efficiency, moisture resistance, and thermal stability compared to polycrystalline powders. The internal quantum efficiency can reach as high as 98.7 %. To further improve waterproof stability, the Cs TiF (CTF) shell with tunable thickness has been epitaxially grown on the CTFM single crystal surface and a unique three-step photoluminescence intensity evolution mechanism has been proposed. By combining as-prepared [email protected] core-shell structured single crystal, YAG:Ce single crystal and blue-chip, warm WLEDs with excellent color rendition (R =90, R =94), low correlated color temperature (CCT=3155 K), and high luminous efficacy were fabricated without any organic resins.
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http://dx.doi.org/10.1002/anie.202011022DOI Listing
February 2021

Comparison of the safety of brivaracetam at various doses among patients with epilepsy: A network meta-analysis of randomized controlled trials.

Exp Ther Med 2020 Dec 2;20(6):133. Epub 2020 Oct 2.

Department of Pharmacology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.

The present study aimed to compare the safety of brivaracetam (BRV) at various doses among patients with epilepsy through a network meta-analysis. Randomized controlled trials (RCTs) were retrieved from different databases, which were then pooled for a network analysis for calculating the odds ratios (ORs), together with the corresponding 95% confidence intervals (CIs) and surface under the cumulative ranking curve (SUCRA). A total of 9 RCTs were included in the final analysis. Compared with placebo, BRV at a dose of 50 mg daily led to a markedly increased risk of nervous system disorders (OR, 0.62; 95% CI, 0.43-0.90; P=0.01) and evidently increased the risk of psychiatric disorders (OR, 0.16; 95% CI, 0.04-0.64; P=0.022). However, BRV treatment was not associated with a statistically significant change in the prevalence of infectious diseases. SUCRA analysis suggested that treatment with BRV at 50 mg/day posed the highest risk of nervous system disorders and psychiatric disorders compared with placebo or other doses of BRV. In conclusion, BRV treatment at a dose of 50 mg/day may increase the risk of nervous system diseases and psychosis disorders compared with the placebo group. However, more high-quality clinical studies are warranted to validate these results.
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http://dx.doi.org/10.3892/etm.2020.9262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557724PMC
December 2020

Power of Microbiome Beta-Diversity Analyses Based on Standard Reference Samples.

Am J Epidemiol 2021 02;190(3):439-447

A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2 degrees-of-freedom (df) test) or additionally on squares and cross-product of mean distances (5-df test). We compared the power of 2-df and 5-df tests with the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2-df test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2-df test had slightly greater power than MiRKAT for Dirichlet multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5-df test yielded smaller P values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have power comparable to MiRKAT's (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.
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http://dx.doi.org/10.1093/aje/kwaa204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936037PMC
February 2021

Allele-specific open chromatin in human iPSC neurons elucidates functional disease variants.

Science 2020 07;369(6503):561-565

Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL 60201, USA.

Most neuropsychiatric disease risk variants are in noncoding sequences and lack functional interpretation. Because regulatory sequences often reside in open chromatin, we reasoned that neuropsychiatric disease risk variants may affect chromatin accessibility during neurodevelopment. Using human induced pluripotent stem cell (iPSC)-derived neurons that model developing brains, we identified thousands of genetic variants exhibiting allele-specific open chromatin (ASoC). These neuronal ASoCs were partially driven by altered transcription factor binding, overrepresented in brain gene enhancers and expression quantitative trait loci, and frequently associated with distal genes through chromatin contacts. ASoCs were enriched for genetic variants associated with brain disorders, enabling identification of functional schizophrenia risk variants and their cis-target genes. This study highlights ASoC as a functional mechanism of noncoding neuropsychiatric risk variants, providing a powerful framework for identifying disease causal variants and genes.
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http://dx.doi.org/10.1126/science.aay3983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773145PMC
July 2020

Progress of Clinical Application for Ex Vivo Lung Perfusion (EVLP) in Lung Transplantation.

Methods Mol Biol 2020 ;2204:217-224

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

In recent years, medical advances make lung transplantation become a standard treatment for terminal lung diseases (such as emphysema, pulmonary fibrosis, pulmonary cystic fibrosis, and pulmonary arterial hypertension) that cannot be cured by drugs or surgery (Lund et al., J Heart Lung Transplant 34:1244, 2015). However, the current number of donor lungs that meet the transplant criteria is no longer sufficient for transplanting, causing some patients to die while waiting for a suitable lung. Current methods for improving the situation of shortage of lung transplant donors include the use of donation after cardiac death (DCD) donors, smoker donors, and Ex Vivo Lung Perfusion (EVLP). Among them, EVLP is a technique for extending lung preservation time and repairing lung injury in the field of lung transplantation. By continuously assessing and improving the function of marginal donor lungs, EVLP increases the number of lungs that meet the transplant criteria and, to some extent, alleviates the current situation of shortage of donor lungs. This chapter reviews the clinical application and research progress of EVLP in the field of lung transplantation.
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http://dx.doi.org/10.1007/978-1-0716-0904-0_19DOI Listing
March 2021

ATP-Binding Cassette G Transporters SGE1 and MtABCG13 Control Stigma Exsertion.

Plant Physiol 2020 09 20;184(1):223-235. Epub 2020 Jul 20.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Stigma exsertion is an important agricultural trait that facilitates the application of heterosis in crop breeding. Although several quantitative trait loci associated with stigma exsertion have been fine-mapped or cloned, the underlying genetic basis, particularly in legumes, remains unclear. In this study, we identified and characterized the exserted stigma mutant () in the model legume The exserted stigma phenotype of is mainly caused by physical interaction between floral organs, in which normal petal and stamen elongation are inhibited due to flower cuticle defects. encodes an ATP-binding cassette G (ABCG) transporter that plays a critical role in regulating floral cutin and wax secretion in SGE1 physically interacts with another half-size transporter, MtABCG13, to form a functional heterodimer. Mutation of results in flower cuticle defects similar to those in as well as stigma exsertion, indicating that SGE1 and MtABCG13 are indispensable for flower cuticle secretion and collaboratively control stigma exsertion in Our findings reveal novel functions for ABCG transporters in determining stigma exsertion by affecting the physical interactions of floral organs, providing insight into the molecular mechanism underlying stigma exsertion in leguminous plants with complex zygomorphic flowers.
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http://dx.doi.org/10.1104/pp.20.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479885PMC
September 2020

Investigation of CRISPR/Cas9-induced SD1 rice mutants highlights the importance of molecular characterization in plant molecular breeding.

J Genet Genomics 2020 05 21;47(5):273-280. Epub 2020 May 21.

Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University-University of Adelaide Joint Centre for Agriculture and Health, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

Although Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has been widely used for basic research in model plants, its application for applied breeding in crops has faced strong regulatory obstacles, due mainly to a poor understanding of the authentic output of this system, particularly in higher generations. In this study, different from any previous studies, we investigated in detail the molecular characteristics and production performance of CRISPR/Cas9-generated SD1 (semi-dwarf 1) mutants from T to T generations, of which the selection of T and T was done only by visual phenotyping for semidwarf plants. Our data revealed not only on- and off-target mutations with small or lager indels but also exogenous elements in T plants. All indel mutants passed stably to T or T without additional modifications independent on the presence of Cas9, while some lines displayed unexpected hereditary patterns of Cas9 or some exogenous elements. In addition, effects of various SD1 alleles on rice height and yield differed depending on genetic backgrounds. Taken together, our data showed that the CRISPR/Cas9 system is effective in producing homozygous mutants for functional analysis, but it may be not as precise as expected in rice, and that early and accurate molecular characterization and screening must be carried out for generations before transitioning of the CRISPR/Cas9 system from laboratory to field.
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http://dx.doi.org/10.1016/j.jgg.2020.04.004DOI Listing
May 2020

Arabidopsis FAX1 mediated fatty acid export is required for the transcriptional regulation of anther development and pollen wall formation.

Plant Mol Biol 2020 Sep 17;104(1-2):187-201. Epub 2020 Jul 17.

Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Key Message: The mutation of FAX1 (Fatty Acid Export 1) disrupts ROS homeostasis and suppresses transcription activity of DYT1-TDF1-AMS-MS188 genetic network, leading to atypical tapetum PCD and defective pollen formation in Arabidopsis. Fatty acids (FAs) have multiple important biological functions and exert diverse cellular effects through modulating Reactive Oxygen Species (ROS) homeostasis. Arabidopsis FAX1 (Fatty Acid Export 1) mediates the export of de novo synthesized FA from chloroplast and loss of function of FAX1 impairs male fertility. However, mechanisms underlying the association of FAX1-mediated FA export with male sterility remain enigmatic. In this study, by using an integrated approach that included morphological, cytological, histological, and molecular analyses, we revealed that loss of function of FAX1 breaks cellular FA/lipid homeostasis, which disrupts ROS homeostasis and suppresses transcriptional activation of the DYT1-TDF1-AMS-MS188 genetic network of anther development, impairing tapetum development and pollen wall formation, and resulting in male sterility. This study provides new insights into the regulatory network for male reproduction in plants, highlighting an important role of FA export-mediated ROS homeostasis in the process.
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http://dx.doi.org/10.1007/s11103-020-01036-5DOI Listing
September 2020
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