Publications by authors named "Lihua Jiang"

150 Publications

Erratum: Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.

Am J Transl Res 2022 15;14(4):2767. Epub 2022 Apr 15.

Department of Endocrinology, Affiliated Hospital of Nantong University Nantong 226601, Jiangsu Province, China.

[This corrects the article on p. 11814 in vol. 13, PMID: 34786110.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091095PMC
April 2022

[Retracted] MicroRNA‑625 inhibits the progression of non‑small cell lung cancer by directly targeting HOXB5 and deactivating the Wnt/β‑catenin pathway.

Int J Mol Med 2022 Jun 19;49(6). Epub 2022 Apr 19.

Department of Pediatrics, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data shown in Fig. 2C and the images of tumors shown in Fig. 7B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. Independently of this investigation, the authors also requested a retraction of this article owing to the fact that the manuscript had been published without permission from one of the authors. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 44: 346‑356, 2019; DOI: 10.3892/ijmm.2019.4203].
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http://dx.doi.org/10.3892/ijmm.2022.5134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083848PMC
June 2022

IL-9 blockade attenuates inflammation in a murine model of mechanical ventilation-induced lung injury by inhibiting the NLRP3 inflammasome pathway.

Inflammopharmacology 2022 Mar 16. Epub 2022 Mar 16.

Department of Pediatric Orthopaedics, The Third Affiliated Hospital of Zhengzhou University, No. 7, Zhengzhou Kangfufront Street, Zhengzhou, 450052, Henan, China.

Objectives: Ventilation-induced lung injury (VILI) causes a huge economic and social burden, and its prevention and treatment have gained increasing attention in recent years. IL-9 is an important inflammatory factor, but its potential role in VILI remains unclear. This study intended to explore whether blocking IL-9 could alleviate VILI and explore its underlying mechanism.

Methods: Lung injury was induced by mechanical ventilation (MV) in C57BL/6 mice. Changes in inflammatory factors and NLRP3-related proteins were assessed using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Subsequently, Nlrp3 mice were used to further elucidate the underlying mechanism.

Results: The percentage of Th9 cells in the peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues of MV mice was increased compared to those of control mice. Treatment with anti-IL-9 mAb significantly alleviated the changes in lung histopathology, wet/dry lung proportion, total protein content, and neutrophil content in BALF induced by VILI. Additionally, administering anti-IL-9 mAb significantly downregulated the expression levels of inflammatory factors in BALF and lung tissues of mice with VILI. In addition, administering anti-IL-9 mAb inhibited NLRP3 inflammasome activation, as evidenced by the observed downregulation of NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Additionally, NLRP3-deficient mice had lower lung injury induced by VILI than wild-type mice. Furthermore, the anti-IL-9 mAb only partially inhibited VILI in Nlrp3 mice.

Conclusions: In MV mice, the anti-IL-9 mAb alleviated lung injury and reduced the secretion and expression of inflammatory factors partly by inhibiting the NLRP3 inflammasome pathway.
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http://dx.doi.org/10.1007/s10787-022-00947-7DOI Listing
March 2022

[Study on the effect of small alcohol on lipid hydration and liposome formation].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2022 Feb;39(1):112-119

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, P. R. China.

Liposomes with precisely controlled composition are usually used as membrane model systems to investigate the fundamental interactions of membrane components under well-defined conditions. Hydration method is the most common method for liposome formation which is found to be influenced by composition of the medium. In this paper, the effects of small alcohol (ethanol) on the hydration of lipid molecules and the formation of liposomes were investigated, as well as its coexistence with sodium chloride. It was found that ethanol showed the opposite effect to that of sodium chloride on the hydration of lipid molecules and the formation of liposomes. The presence of ethanol promoted the formation of liposomes within a certain range of ethanol content, but that of sodium chloride suppressed the liposome formation. By investigating the fluorescence intensity and continuity of the swelled membranes as a function of contents of ethanol and sodium chloride, it was found that sodium chloride and ethanol showed the additive effect on the hydration of lipid molecules when they coexisted in the medium. The results may provide some reference for the efficient preparation of liposomes.
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http://dx.doi.org/10.7507/1001-5515.202105060DOI Listing
February 2022

The Efficacy and Safety of Celecoxib for Pain Management After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Surg 2022 28;9:791513. Epub 2022 Jan 28.

Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China.

Background: This study aimed to determine the efficacy and safety of celecoxib for pain management after total knee arthroplasty (TKA).

Methods: PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify eligible randomized controlled trials (RCTs) that compared celecoxib with a placebo in term of pain control efficacy after TKA. Primary outcomes included pain scores at 24, 48, and 72 h after TKA. Secondary outcomes included the active range of motion (ROM) at 24, 48,72 h, and 7 days postoperatively, morphine consumption over 72 h after TKA, incidence of postoperative nausea and vomiting (PONV), and total blood loss after surgery. Data analysis was conducted using RevMan version 5.3.

Results: Five RCTs involving 593 participants were included in the study. Compared with a placebo, celecoxib significantly reduced visual analog scale (VAS) scores at rest at 24 h [mean difference (MD) = -0.72; 95% confidence interval (CI), -1.27 to -0.17; = 82%; = 0.01], 48 h (MD = -1.51; 95% CI, -2.07 to -0.95; = 0%; < 0.00001), and 72 h (MD = -1.30; 95% CI, -2.07 to -0.54; = 82%; = 0.0009) after TKA, decreased morphine consumption over postoperative 72 h (MD = -0.73; 95% CI, -0.96 to -0.51; = 96%; < 0.00001), and increased active ROM at 48 h (MD = 13.23; 95% CI, 7.79 to 18.67; = 0%; < 0.00001), 72 h (MD = 6.52; 95% CI, 4.95 to 8.10; = 68%; < 0.00001), and 7 days (MD = 7.98; 95% CI, 3.64 to 12.31; = 68%; = 0.0003) after the operation. No significant difference was found in the active ROM at 24 h (MD = 7.60; 95% CI, -6.14 to 21.34; = 94%; = 0.28) and the incidence of PONV after surgery [risk ratio (RR) = 0.66; 95% CI, 0.40 to 1.09; = 0%; = 0.11].

Conclusion: The administration of celecoxib is an effective and safe strategy for postoperative analgesia after TKA.
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http://dx.doi.org/10.3389/fsurg.2022.791513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831328PMC
January 2022

Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.

Am J Transl Res 2021 15;13(10):11814-11823. Epub 2021 Oct 15.

Department of Endocrinology, Affiliated Hospital of Nantong University Nantong 226601, Jiangsu Province, China.

Objective: To determine the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on cases with type 2 diabetes mellitus (T2DM) in terms of insulin dosage and blood glucose (BG) control.

Methods: A total of 180 patients with T2DM admitted to our hospital between March 2016 and March 2019 were selected and assigned to a GLP-1RA group (GLP-1 group, n=100) and a control group (control group, n=80). Patients in the GLP-1 group were treated with GLP-1RA combined with insulin, while those in the other group were treated with insulin alone. The following items of each patient were determined: Body weight, body mass index (BMI), waist circumference, blood pressure (BP), BG-related indexes, insulin dosage, insulin resistance index, cardiovascular function, serum lipid-related indexes, adverse reactions, total effective rate, and treatment satisfaction.

Results: Compared with the control group, the GLP-1 group showed a decrease in weight, BMI, waist circumference, BP, BG-related indexes, and insulin resistance index, consumed less insulin dosage, and also showed a decline in cardiovascular function, serum lipid-related indexes (total cholesterol (TC), triacylglycerol (TG), and low density lipoprotein cholesterol (LDL-C)), an increase in high density lipoprotein cholesterol (HDL-C), less adverse reactions, and higher total effective rate and treatment satisfaction.

Conclusion: GLP-1RA contributes to better BG control of patients with T2DM, and it reduces the insulin dosage required during operation for its stimulation to the production of insulin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581930PMC
October 2021

Enhanced growth of ginger plants by an eco- friendly nitrogen-fixing Pseudomonas protegens inoculant in glasshouse fields.

J Sci Food Agric 2022 May 26;102(7):3038-3046. Epub 2021 Nov 26.

Helmholtz International Laboratory for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.

Background: Excessive nitrogen (N) fertilization in glasshouse fields greatly increases N loss and fossil-fuel energy consumption resulting in serious environmental risks. Microbial inoculants are strongly emerging as potential alternatives to agrochemicals and offer an eco-friendly fertilization strategy to reduce our dependence on synthetic chemical fertilizers. Effects of a N-fixing strain Pseudomonas protegens CHA0-ΔretS-nif on ginger plant growth, yield, and nutrient uptake, and on earthworm biomass and the microbial community were investigated in glasshouse fields in Shandong Province, northern China.

Results: Application of CHA0-ΔretS-nif could promote ginger plant development, and significantly increased rhizome yields, by 12.93% and 7.09%, respectively, when compared to uninoculated plants and plants treated with the wild-type bacterial strain. Inoculation of CHA0-ΔretS-nif had little impact on plant phosphorus (P) acquisition, whereas it was associated with enhanced N and potassium (K) acquisition by ginger plants. Moreover, inoculation of CHA0-ΔretS-nif had positive effects on the bacteria population size and the number of earthworms in the rhizosphere. Similar enhanced performances were also found in CHA0-ΔretS-nif-inoculated ginger plants even when the N-fertilizer application rate was reduced by 15%. A chemical N input of 573.8 kg ha with a ginger rhizome yield of 1.31 × 10  kg ha was feasible.

Conclusions: The combined application of CHA0-ΔretS-nif and a reduced level of N-fertilizers can be employed in glasshouse ginger production for the purpose of achieving high yields while at the same time reducing the inorganic-N pollution from traditional farming practices. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11645DOI Listing
May 2022

A rare case of thoracic brucellosis misdiagnosed as malignant tumor and literature review.

Indian J Pathol Microbiol 2021 Oct-Dec;64(4):824-826

Department of Laboratory Medicine, Qingdao University Medical College affiliated Yantai Yuhuangding Hospital, Yantai, China.

Brucellosis remains a major public health problem worldwide. It is commonly found in most developed and developing countries, such as the Mediterranean region, the Middle East, and Latin America. In China, brucellosis is mainly distributed in some of the northern provinces and is relatively rare in Shandong province. Brucellosis has a variety of clinical manifestations, with fever, sweating, fatigue, and migratory joint pain being the most common. Because of the non-specific clinical symptoms, brucellosis is often misdiagnosed as other diseases. Here, we report a rare case of brucellosis of thoracic vertebrae misdiagnosed as thoracic malignant tumor and present a review of related literature.
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http://dx.doi.org/10.4103/IJPM.IJPM_592_20DOI Listing
January 2022

Chromatin accessibility associates with protein-RNA correlation in human cancer.

Nat Commun 2021 09 30;12(1):5732. Epub 2021 Sep 30.

Department of Genetics, Stanford University, Stanford, CA, USA.

Although alterations in chromatin structure are known to exist in tumors, how these alterations relate to molecular phenotypes in cancer remains to be demonstrated. Multi-omics profiling of human tumors can provide insight into how alterations in chromatin structure are propagated through the pathway of gene expression to result in malignant protein expression. We applied multi-omics profiling of chromatin accessibility, RNA abundance, and protein abundance to 36 human thyroid cancer primary tumors, metastases, and patient-match normal tissue. Through quantification of chromatin accessibility associated with active transcription units and global protein expression, we identify a local chromatin structure that is highly correlated with coordinated RNA and protein expression. In particular, we identify enhancers located within gene-bodies as predictive of correlated RNA and protein expression, that is independent of overall transcriptional activity. To demonstrate the generalizability of these findings we also identify similar results in an independent cohort of human breast cancers. Taken together, these analyses suggest that local enhancers, rather than distal enhancers, are likely most predictive of cancer gene expression phenotypes. This allows for identification of potential targets for cancer therapeutic approaches and reinforces the utility of multi-omics profiling as a methodology to understand human disease.
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http://dx.doi.org/10.1038/s41467-021-25872-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484618PMC
September 2021

Acrylamide induces intrinsic apoptosis and inhibits protective autophagy the ROS mediated mitochondrial dysfunction pathway in U87-MG cells.

Drug Chem Toxicol 2021 Sep 22:1-12. Epub 2021 Sep 22.

State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, China.

Acrylamide (ACR) is a potential neurotoxin commonly found in the environment, as well as in food repeatedly exposed heat processing, but the mechanism underpinning ACR-induced neurotoxicity remains unclear. This study investigated the potential association and underlying signal transduction of oxidative stress, apoptosis, and autophagy associated with ACR-triggered neurotoxicity. Therefore, U87-MG cells were treated with varying ACR concentrations, while the cell activity reduction depended on the specific dosage and time parameters. Biochemical analyses showed that ACR significantly increased the reactive oxygen species (ROS), malondialdehyde (MDA), and Ca levels while decreasing the glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), finally leading to a higher cell apoptotic rate. Moreover, ACR induced U87-MG cell apoptosis and autophagy ROS-triggered expression in the mitochondrial apoptosis pathway, NF-κB activation, and autophagosome accumulation. In addition, the autophagosome accumulation induced by ACR could probably be ascribed to blocked autophagic flux, inhibiting the autophagosomes from combining with lysosomes, while the inhibition of autophagy caused by ACR further promoted the initiation of apoptosis. In conclusion, the results indicated that the apoptotic and autophagic pathways responded to ACR-induced neurotoxicity. However, inhibited protective autophagy further promoted apoptotic progression. New insights may be derived from these cellular responses that can help develop diverse pathway strategies for assessing the risk posed by ACR.HIGHLIGHTSACR induced mitochondrial- and caspase-dependent apoptosis in U87-MG cells.ACR regulated the autophagic markers and blocked autophagic flux in U87-MG cells.ACR inhibited protective autophagy and promoted apoptotic initiation in U87-MG cells.
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http://dx.doi.org/10.1080/01480545.2021.1979030DOI Listing
September 2021

Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy.

Front Mol Neurosci 2021 19;14:699574. Epub 2021 Aug 19.

Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group ( < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (, , , , , , and ) with variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.
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http://dx.doi.org/10.3389/fnmol.2021.699574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417468PMC
August 2021

Whole-genome sequencing of endangered Zhoushan cattle suggests its origin and the association of MC1R with black coat colour.

Sci Rep 2021 08 30;11(1):17359. Epub 2021 Aug 30.

Genomic Diversity Laboratory, Graduate School of Bioscience, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga, 526-0829, Japan.

Zhoushan cattle are an endangered cattle breed in the Zhoushan islands in China. Since Zhoushan cattle have been bred in isolation, they show unique characteristics, such as dark black coat colour. However, no studies have been conducted on the genome of Zhoushan cattle. Here, we performed whole-genome sequencing of seven individuals of Zhoushan cattle and nine cattle in Wenling, geographically close to the Zhoushan islands. By integrating our data and publicly-available data, we found that Zhoushan cattle are genetically highly similar to Bos indicus cattle in south-eastern China. Furthermore, by identifying the genomic regions shared between Zhoushan cattle and Angus cattle, a Bos taurus breed, we found that the p.F195L mutation in melanocyte-stimulating hormone receptor (MC1R) could be associated with their dark black coat colour. Taken together, our results provide a valuable resource for characterising the uniqueness of Zhoushan cattle.
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http://dx.doi.org/10.1038/s41598-021-96896-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405626PMC
August 2021

Structured elements drive extensive circular RNA translation.

Mol Cell 2021 10 25;81(20):4300-4318.e13. Epub 2021 Aug 25.

Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Departments of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.
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http://dx.doi.org/10.1016/j.molcel.2021.07.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567535PMC
October 2021

AdaReg: data adaptive robust estimation in linear regression with application in GTEx gene expressions.

Stat Appl Genet Mol Biol 2021 07 13;20(2):51-71. Epub 2021 Jul 13.

Department of Genetics, Stanford University, Stanford, 94305, USA.

The Genotype-Tissue Expression (GTEx) project provides a valuable resource of large-scale gene expressions across multiple tissue types. Under various technical noise and unknown or unmeasured factors, how to robustly estimate the major tissue effect becomes challenging. Moreover, different genes exhibit heterogeneous expressions across different tissue types. Therefore, we need a robust method which adapts to the heterogeneities of gene expressions to improve the estimation for the tissue effect. We followed the approach of the robust estimation based on -density-power-weight in the works of Fujisawa, H. and Eguchi, S. (2008). Robust parameter estimation with a small bias against heavy contamination. . 99: 2053-2081 and Windham, M.P. (1995). Robustifying model fitting. : 599-609, where is the exponent of density weight which controls the balance between bias and variance. As far as we know, our work is the first to propose a procedure to tune the parameter to balance the bias-variance trade-off under the mixture models. We constructed a robust likelihood criterion based on weighted densities in the mixture model of Gaussian population distribution mixed with unknown outlier distribution, and developed a data-adaptive -selection procedure embedded into the robust estimation. We provided a heuristic analysis on the selection criterion and found that our practical selection trend under various 's in average performance has similar capability to capture minimizer as the inestimable mean squared error (MSE) trend from our simulation studies under a series of settings. Our data-adaptive robustifying procedure in the linear regression problem (AdaReg) showed a significant advantage in both simulation studies and real data application in estimating tissue effect of heart samples from the GTEx project, compared to the fixed procedure and other robust methods. At the end, the paper discussed some limitations on this method and future work.
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http://dx.doi.org/10.1515/sagmb-2020-0042DOI Listing
July 2021

Mechanism study of how lipid vesicle electroformation is suppressed by the presence of sodium chloride.

Colloids Surf B Biointerfaces 2021 Oct 29;206:111951. Epub 2021 Jun 29.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, China. Electronic address:

Giant lipid vesicles (GLVs) are usually adopted as models of cell membranes and electroformation is the most commonly used method for GLV formation. However, GLV electroformation are known to be suppressed by the presence of salt and the mechanism is not clear so far. In this paper, the lipid hydration and GLV electroformation were investigated as a function of the concentration of sodium chloride by depositing the lipids on the bottom substrates and top substrates. In addition, the electrohydrodynamic force generated by the electroosmotic flow (EOF) on the lipid phase was calculated with COMSOL Multiphysics. It was found that the mechanisms for the failure of GLV electroformation in salt solutions are: 1) the presence of sodium chloride decreases the membrane permeability to aqueous solution by accelerating the formation of well-packed membranes, suppressing the swelling and detachment of the lipid membranes; 2) the presence of sodium chloride decreased the electrohydrodynamic force by increasing the medium conductivity.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111951DOI Listing
October 2021

Disseminated Trichosporon asahii infection presenting as eosinophilia in an immunocompetent patient: A case report.

Indian J Med Microbiol 2021 Oct-Dec;39(4):552-555. Epub 2021 Jun 27.

Department of Laboratory Medicine, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Yantai, China. Electronic address:

Trichosporon are naturally found in external environments and are a part of the normal flora of the human skin, respiratory tract, and gastrointestinal tract. Disseminated Trichosporon infection occurs sporadically in patients with immunodeficiency, and is mainly manifested as blood, urine, catheter, and thorax/peritoneum infections, rarely as lymphatic, liver and spleen infections. Elevated blood eosinophil granulocyte from Trichosporon infection have rarely been reported. Here, we report a rare Case of eosinophilia associated with lymphatic and liver and spleen infections due to Trichosporon asahii in an immunocompetent patient. No reports of eosinophilia from Trichosporon infections other than lung, to our knowledge, have been published.
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http://dx.doi.org/10.1016/j.ijmmb.2021.05.021DOI Listing
December 2021

AdaTiSS: A Novel Data-Adaptive Robust Method for Identifying Tissue Specificity Scores.

Bioinformatics 2021 Jun 19. Epub 2021 Jun 19.

Department of Genetics, Stanford University, Stanford, 94305, CA, USA.

Motivation: Accurately detecting tissue specificity (TS) in genes helps researchers understand tissue functions at the molecular level. The Genotype-Tissue Expression project is one of the publicly available data resources, providing large-scale gene expressions across multiple tissue types. Multiple tissue comparisons and heterogeneous tissue expression make it challenging to accurately identify tissue specific gene expression. How to distinguish the inlier expression from the outlier expression becomes important to build the population level information and further quantify the TS. There still lacks a robust and data-adaptive TS method taking into account heterogeneities of the data.

Methods: We found that the key to identify tissue specific gene expression is to properly define a concept of expression population. In a linear regression problem, we developed a novel data-adaptive robust estimation based on density-power-weight under unknown outlier distribution and non-vanishing outlier proportion. The Gaussian-population mixture model was considered in the setting of identifying TS. We took into account heterogeneities of gene expression and applied the robust data-adaptive procedure to estimate the population parameters. With the well-estimated population parameters, we constructed the AdaTiSS algorithm.

Results: Our AdaTiSS profiled TS for each gene and each tissue, which standardized the gene expression in terms of TS. We provided a new robust and powerful tool to the literature of defining tissue specificity.

Availability: https://github.com/mwgrassgreen/AdaTiSS.
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http://dx.doi.org/10.1093/bioinformatics/btab460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652109PMC
June 2021

A Novel GH Family 20 β-N-acetylhexosaminidase With Both Chitosanase and Chitinase Activity From .

Front Mol Biosci 2021 19;8:684086. Epub 2021 May 19.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, China.

Aminooligosaccharides possess various biological activities and can exploit wide applications in food, pharmaceutical and cosmetic industries. Commercial aminooligosaccharides are often prepared by the hydrolysis of chitin and chitosan. In this study, a novel GH family 20 β-N-acetylhexosaminidases gene named AoNagase was cloned from and expressed in . The purified AoNagase had maximal activity at pH 5.5 and 65°C. It exhibited good pH stability in the range of pH 6.0-7.5 and at temperatures below 50°C. AoNagase was capable of hydrolyzing not only colloidal chitosan (508.26 U/mg) but also chitin (29.78 U/mg). The kinetic parameters ( and ) of AoNagase were 1.51 mM, 1106.02 U/mg for chitosan and 0.41 mM, 40.31 U/mg for colloidal chitin. To our knowledge, AoNagase is the first GH family 20 β-N-acetylhexosaminidase capable of hydrolyzing both chitosan and chitin. AoNagase is an endo-type β-N-acetylhexosaminidases and can potentially be used for the manufacturing of aminooligosaccharides.
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http://dx.doi.org/10.3389/fmolb.2021.684086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170477PMC
May 2021

Enhanced Electroluminescence Based on a -Conjugated Heptazine Derivative by Exploiting Thermally Activated Delayed Fluorescence.

Front Chem 2021 13;9:693813. Epub 2021 May 13.

College of Optoelectronic Technology, Chengdu University of Information Technology, Chengdu, China.

Heptazine derivatives have attracted much attention over the past decade by virtue of intriguing optical, photocatalytic as well as electronic properties in the fields of hydrogen evolution, organic optoelectronic technologies and so forth. Here, we report a simple -conjugated heptazine derivative (HAP-3DF) possessing an n→* transition character which exhibits enhanced electroluminescence by exploiting thermally activated delayed fluorescence (TADF). Green-emitting HAP-3DF shows relatively low photoluminescence quantum efficiencies ( ) of 0.08 in toluene and 0.16 in doped film with bis(2-(diphenylphosphino)phenyl) ether oxide (DPEPO) as the matrix. Interestingly, the organic light-emitting diode (OLED) incorporating 8 wt% HAP-3DF:DPEPO as an emitting layer achieved a high external quantum efficiency (EQE) of 3.0% in view of the fairly low of 0.16, indicating the presence of TADF stemming from n→* transitions. As the matrix changing from DPEPO to 1,3-di (9-carbazol-9-yl)benzene (mCP), a much higher of 0.56 was found in doped film accompanying yellow emission. More importantly, enhanced electroluminescence was observed from the OLED containing 8 wt% HAP-3DF:mCP as an emitting layer, and a rather high EQE of 10.8% along with a low roll-off was realized, which should be ascribed to the TADF process deriving from exciplex formation.
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http://dx.doi.org/10.3389/fchem.2021.693813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155250PMC
May 2021

Whole-genome resequencing of large yellow croaker (Larimichthys crocea) reveals the population structure and signatures of environmental adaptation.

Sci Rep 2021 05 27;11(1):11235. Epub 2021 May 27.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan, 316022, China.

Large yellow croaker is an economically important fish in China and East Asia. Despite its economic importance, genome-wide adaptions of domesticated large yellow croaker are largely unknown. Here, we performed whole-genome resequencing of 198 individuals of large yellow croaker obtained in the sea or from farmers in Zhoushan or Ningde. Population genomics analyses revealed the genetic population structure of our samples, reflecting the living environment. Each effective population size is estimated to be declining over generations. Moreover, we identified genetically differentiated genomic regions between the sea-captured population in the Zhoushan Sea area and that of the Ningde Sea area or between the sea-captured population and the farmed population in either area. Gene ontology analyses revealed the gene groups under selective sweep for the adaptation to the domesticated environment. All these results suggest that individuals of the large yellow croaker populations show genomic signatures of adaptation to different living environments.
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http://dx.doi.org/10.1038/s41598-021-90645-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159941PMC
May 2021

Decreased abundance of Akkermansia after adrenocorticotropic hormone therapy in patients with West syndrome.

BMC Microbiol 2021 04 23;21(1):126. Epub 2021 Apr 23.

Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310003, Zhejiang, China.

Background: Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic-pituitary-adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy.

Results: In this study, 29 infants with WS and 29 healthy infants aged 3-13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased.

Conclusion: The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.
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http://dx.doi.org/10.1186/s12866-021-02189-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063292PMC
April 2021

A genome-wide atlas of co-essential modules assigns function to uncharacterized genes.

Nat Genet 2021 05 15;53(5):638-649. Epub 2021 Apr 15.

Department of Genetics, Stanford University, Stanford, CA, USA.

A central question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into 'co-essential' pathways, but this approach has been limited by ubiquitous false positives. In the present study, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and protein complexes, and predicts the functions of 108 uncharacterized genes. Validating top predictions, we show that TMEM189 encodes plasmanylethanolamine desaturase, a key enzyme for plasmalogen synthesis. We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. Finally, we provide an interactive webtool for the community to explore our results, which establish co-essentiality profiling as a powerful resource for biological pathway identification and discovery of new gene functions.
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http://dx.doi.org/10.1038/s41588-021-00840-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763319PMC
May 2021

Functional and structural basis of extreme conservation in vertebrate 5' untranslated regions.

Nat Genet 2021 05 5;53(5):729-741. Epub 2021 Apr 5.

Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

The lack of knowledge about extreme conservation in genomes remains a major gap in our understanding of the evolution of gene regulation. Here, we reveal an unexpected role of extremely conserved 5' untranslated regions (UTRs) in noncanonical translational regulation that is linked to the emergence of essential developmental features in vertebrate species. Endogenous deletion of conserved elements within these 5' UTRs decreased gene expression, and extremely conserved 5' UTRs possess cis-regulatory elements that promote cell-type-specific regulation of translation. We further developed in-cell mutate-and-map (icM), a new methodology that maps RNA structure inside cells. Using icM, we determined that an extremely conserved 5' UTR encodes multiple alternative structures and that each single nucleotide within the conserved element maintains the balance of alternative structures important to control the dynamic range of protein expression. These results explain how extreme sequence conservation can lead to RNA-level biological functions encoded in the untranslated regions of vertebrate genomes.
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http://dx.doi.org/10.1038/s41588-021-00830-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825242PMC
May 2021

Risk Factors and Safety Analyses for Intrapartum Fever in Pregnant Women Receiving Epidural Analgesia During Labor.

Med Sci Monit 2021 Mar 15;27:e929283. Epub 2021 Mar 15.

Department of Anesthesiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).

BACKGROUND We aimed to explore the factors leading to epidural-related maternal fever and the influence of intrapartum fever on neonates. MATERIAL AND METHODS A retrospective analysis was performed on data from pregnant women who received epidural analgesia during labor. The primary aim was to determine the influence of epidural labor analgesia on the incidence of intrapartum fever in pregnant women. The secondary aim was to determine the influence of intrapartum fever on neonates. RESULTS Logistic regression analysis showed that premature rupture of membranes (OR=2.008, 95% CI: 1.551-2.600), vaginal examination performed more than 6 times (OR=1.681, 95% CI: 1.286-2.197), long duration of labor (OR=1.090, 95% CI: 1.063-1.118), and long time from rupture of membranes to delivery (OR=1.048, 95% CI: 1.010-1.087) were all risk factors for intrapartum fever in pregnant women with epidural labor analgesia. Regarding the secondary research outcome, the incidence of intrapartum fever was significantly associated with the number of neonates with Apgar score of 10 delivered from pregnant women with epidural labor analgesia (P<0.05). There was no statistically significant difference in the transfer rate of newborns to the Neonatal Intensive Care Unit (NICU) (P>0.05). CONCLUSIONS Premature rupture of membranes, vaginal examination performed more than 6 times, long duration of labor, and long time from rupture of membranes to delivery are all factors raising the risk of fever during epidural labor analgesia. Although intrapartum fever in the mothers had a significant influence on the number of neonates with Apgar score of 10, it did not affect the outcome of neonates in terms of NICU transfer rate.
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http://dx.doi.org/10.12659/MSM.929283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976662PMC
March 2021

Novel gene rearrangement in the mitochondrial genome of Muraenesox cinereus and the phylogenetic relationship of Anguilliformes.

Sci Rep 2021 01 28;11(1):2411. Epub 2021 Jan 28.

National Engineering Laboratory of Marine Germplasm Resources Exploration and Utilization, Zhejiang Ocean University, No. 1, Haida South Road, Zhoushan, Zhejiang, 316022, People's Republic of China.

The structure and gene sequence of the fish mitochondrial genome are generally considered to be conservative. However, two types of gene arrangements are found in the mitochondrial genome of Anguilliformes. In this paper, we report a complete mitogenome of Muraenesox cinereus (Anguilliformes: Muraenesocidae) with rearrangement phenomenon. The total length of the M. cinereus mitogenome was 17,673 bp, and it contained 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNA genes, and two identical control regions (CRs). The mitochondrial genome of M. cinereus was obviously rearranged compared with the mitochondria of typical vertebrates. The genes ND6 and the conjoint trnE were translocated to the location between trnT and trnP, and one of the duplicated CR was translocated to the upstream of the ND6. The tandem duplication and random loss is most suitable for explaining this mitochondrial gene rearrangement. The Anguilliformes phylogenetic tree constructed based on the whole mitochondrial genome well supports Congridae non-monophyly. These results provide a basis for the future Anguilliformes mitochondrial gene arrangement characteristics and further phylogenetic research.
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http://dx.doi.org/10.1038/s41598-021-81622-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844273PMC
January 2021

Characterization of the complete mitochondrial genome of Macrotocinclus affinis (Siluriformes; Loricariidae) and phylogenetic studies of Siluriformes.

Mol Biol Rep 2021 Jan 13;48(1):677-689. Epub 2021 Jan 13.

National engineering Laboratory of Marine Germplasm Resources Exploration and Utilization, Zhejiang Ocean University, Zhoushan, 316022, China.

The vertebrate mitochondrial genome is typically circular molecules made up of 14,000 to 16,000 bp, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (12 s rRNA and 16 s rRNA) and a control region. Compared with nuclear DNA, mitochondrial DNA has a higher mutation rate, so it is one of the most effective and reliable molecular markers in fish phylogeny. Macrotocinclus affinis was the only species in Macrotocinclus (it was classified as Otocinclus in the past) and currently lacks genetic information. Most of the current researches are based on the mitochondrial Cytb gene and RAG1 and RAG2 nuclear genes to study the phylogenetic analysis of Siluriformes. So, the study provides the characteristic features of the Macrotocinclus affinis mitochondrial genome and this is the first time that the phylogenetic relationship of Siluriformes has been reconstructed based on COI. We aimed to sequence the entire mitochondrial genome of Macrotocinclus affinis using conventional PCR techniques and to clarify its phylogenetic status in Siluriformes by using the COI sequence of mitochondria. In this study, we sequenced the whole mitochondrial genome of this species yielding a 16,632 bp circular assembly composed of the typical vertebrate mitochondrial features. It contains 13 protein-coding genes, two rRNA genes, 22 tRNA genes, a putative control region, and one origin of replication on the light-strand. The overall base composition includes A (30.07%), T (24.43%), C (29.43%) and G (16.01%). The genome composition is A + T biased (54.5%), and exhibits AT-skew (0.1036) and GC-skew (-0.2962). Moreover, the 13 PCGs encode 3850 amino acids in total. The result of the phylogenetic tree supports Macrotocinclus affinis has a closest relationship with Otocinclus cf. hoppei far. These results will help to understand the characteristics of the mitochondrial genome of Macrotocinclus affinis and provide molecular basis for the evolutionary relationship of Loricariidae.
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http://dx.doi.org/10.1007/s11033-020-06120-zDOI Listing
January 2021

Molecular Characterization and Evolution Analysis of Two Forms of TLR5 and TLR13 Genes Base on Genome Data.

Int J Genomics 2020 9;2020:4895037. Epub 2020 Dec 9.

National Engineering Research Center for Facilitated Marine Aquaculture, Zhejiang Ocean University, No. 1, South Haida Road, Dinghai District, Zhoushan, China.

TLRs (Toll-like receptors) are essential in host defense against pathogens. There are two types of TLR5, namely, membrane form of TLR5 (TLR5M) and soluble form of TLR5 (TLR5S), both of which perform a crucial role in flagellin response. TLR13 is a TLR that localizes to endosomes and recognizes nucleic acids released by internal microorganisms, including viruses, bacteria, and fungi. Here, the full-length coding sequence (CDS), protein structure, and immune response and subcellular localization of TLR5 (TLR5S) and TLR13 were characterized in large yellow croaker (). These TLRs share high sequence homology with other ichthyic TLRs, while also having their own characters; qtPCR was determined and the results found that the three genes were constitutively expressed in all examined tissues: TLR5M was highly expressed in the spleen and liver; TLR13 expression was high in the kidney, liver, and spleen. And TLRs were upregulated following stimulation with in the liver, spleen, and kidney. Immunofluorescence staining revealed that TLR5M were localized in the cytoplasm, while TLR5S and TLR13 were in the endosome. The evolutionary analysis has shown that TLR13 was clustered with TLR11, 19, 20, 21, and 22, while TLR5 and TLR3 were classified into a group; these results suggest that TLRs are vital in the defense of against bacterial infection and further increase our understanding of TLR function in innate immunity in teleosts.
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http://dx.doi.org/10.1155/2020/4895037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744196PMC
December 2020

Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma.

Front Genet 2020 9;11:602035. Epub 2020 Dec 9.

Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.

There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.
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http://dx.doi.org/10.3389/fgene.2020.602035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756030PMC
December 2020

RobNorm: model-based robust normalization method for labeled quantitative mass spectrometry proteomics data.

Bioinformatics 2021 05;37(6):815-821

Department of Genetics, Stanford University, Stanford, CA 94305, USA.

Motivation: Data normalization is an important step in processing proteomics data generated in mass spectrometry experiments, which aims to reduce sample-level variation and facilitate comparisons of samples. Previously published methods for normalization primarily depend on the assumption that the distribution of protein expression is similar across all samples. However, this assumption fails when the protein expression data is generated from heterogenous samples, such as from various tissue types. This led us to develop a novel data-driven method for improved normalization to correct the systematic bias meanwhile maintaining underlying biological heterogeneity.

Results: To robustly correct the systematic bias, we used the density-power-weight method to down-weigh outliers and extended the one-dimensional robust fitting method described in the previous work to our structured data. We then constructed a robustness criterion and developed a new normalization algorithm, called RobNorm.In simulation studies and analysis of real data from the genotype-tissue expression project, we compared and evaluated the performance of RobNorm against other normalization methods. We found that the RobNorm approach exhibits the greatest reduction in systematic bias while maintaining across-tissue variation, especially for datasets from highly heterogeneous samples.

Availabilityand Implementation: https://github.com/mwgrassgreen/RobNorm.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098025PMC
May 2021

A Quantitative Proteome Map of the Human Body.

Cell 2020 10 10;183(1):269-283.e19. Epub 2020 Sep 10.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of RNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. The tissue-specific distribution of proteins also provides an in-depth view of complex biological events that require the interplay of multiple tissues. Most importantly, our study demonstrated that protein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be obtained by transcript information alone. Overall, our results demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human diseases.
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http://dx.doi.org/10.1016/j.cell.2020.08.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575058PMC
October 2020
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