Publications by authors named "Weiguo Zhang"

378 Publications

MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.

J Neuroinflammation 2020 Aug 31;17(1):256. Epub 2020 Aug 31.

Department of Anesthesiology, Center for Perioperative Organ Protection, Duke University Medical Center, Durham, NC, USA.

Background: Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One key component of post-CA syndrome is sterile inflammation, which affects various organs including the brain. A major effector of sterile inflammation is activated NLRP3 inflammasome, which leads to increased release of interleukin (IL)-1β. However, how NLRP3 inflammasome impacts neuroinflammation and neurologic outcome after CA is largely undefined.

Methods: Mice were subjected to a potassium-based murine CA and cardiopulmonary resuscitation (CPR) model. MCC950 was used to suppress activation of NLRP3 inflammasome after CA/CPR. Levels of protein and mRNA were examined by Western blotting and quantitative PCR, respectively. Immunologic changes were assessed by measuring cytokine expression and immune cell compositions. CA outcomes, including neurologic deficits, bacterial load in the lung, and survival rate, were evaluated.

Results: Using our CA/CPR model, we found that NLRP3 inflammasome was activated in the post-CA brain, and that pro-inflammatory cytokine levels, including IL-1β, were increased. After treatment with MCC950, a potent and selective NLRP3 inflammasome inhibitor, mice exhibited improved functional recovery and survival rate during the 14-day observational period after CA/CPR. In line with these findings, IL-1β mRNA levels in the post-CA brain were significantly suppressed after MCC950 treatment. Interestingly, we also found that in MCC950- vs. vehicle-treated CA mice, immune homeostasis in the spleen was better preserved and bacterial load in the lung was significantly reduced.

Conclusions: Our data demonstrate that activation of NLRP3 inflammasome could be a key event shaping the post-CA immuno- and neuro-pathology, and identify this pathway as a unique and promising therapeutic target to improve outcomes after CA/CPR.
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http://dx.doi.org/10.1186/s12974-020-01933-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457538PMC
August 2020

Accelerated Green Process of 2,5-Dimethylpyrazine Production from Glucose by Genetically Modified .

ACS Synth Biol 2020 09 4;9(9):2576-2587. Epub 2020 Sep 4.

The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800# Lihu Road, WuXi 214122, People's Republic of China.

2,5-Dimethylpyrazine (2,5-DMP) is an indispensable additive for flavoring in the food industry and an important substrate for producing hypoglycemic and antilipolytic drugs. However, 2,5-DMP is produced by chemical synthesis in industry. Herein, a "green" strategy to produce 2,5-DMP has been reported for the first time. To do this, we rewrote the 2,5-DMP biosynthesis pathway and substrate transmembrane transport in an l-threonine high-yielding strain to promote highly efficient 2,5-DMP production from glucose by submerged fermentation. The final strain T6-47-7 could produce 1.43 ± 0.07 g/L of 2,5-DMP with a carbon yield of 6.78% and productivity of 0.715 g/(L·d) in shake-flask fermentation using a phase-wise manner of hypoxia-inducible expression. The design-based strategy for constructing the 2,5-DMP high-yielding strain reported here could serve as a general concept for breeding high-yielding strains that produce some other type of alkylpyrazine.
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http://dx.doi.org/10.1021/acssynbio.0c00329DOI Listing
September 2020

Duodenal mucinous cystadenoma.

J Gastrointestin Liver Dis 2020 Sep 9;29(3):301. Epub 2020 Sep 9.

Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.

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http://dx.doi.org/10.15403/jgld-2497DOI Listing
September 2020

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

J Cereb Blood Flow Metab 2021 05 12;41(5):1091-1102. Epub 2020 Aug 12.

Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.
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http://dx.doi.org/10.1177/0271678X20948612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054717PMC
May 2021

Downregulation of miR-1225-5p is pivotal for proliferation, invasion, and migration of HCC cells through NFκB regulation.

J Clin Lab Anal 2020 Nov 28;34(11):e23474. Epub 2020 Jul 28.

Department of Hepatolibiary Surgery, Jining No.1 People's Hospital, Jining, China.

Background: As one of the most frequently seen malignancies, hepatocellular carcinoma (HCC) serves as the second largest contributor to malignancy-specific mortality worldwide. MicroRNA-1225-5p (miR-1225) exerts an essential impact on the growth and metastasis of many malignancies. However, the contribution of miR-125 to HCC and the molecular mechanism of cancer cell viability and apoptosis are still unclear. We focused our research on exploring the function and molecular mechanism of miR-1225 in regulating HCC cell growth, migration, and invasion.

Material: Quantitative PCR data showed that miR-1225 expression was repressed in HCC cell lines and in the tissues of HCC patients, compared to that in normal human hepatic cells and tissues. Transfection of a miR-1225 mimic inhibited cell viability and proliferation as indicated by CCK-8 staining and MTT assay. Transwell invasion, wound healing assay, and Western blotting were performed to assess whether miR-1225 repressed the metastasis and invasion of HCC cells, and decreased matrix metalloproteinase 9 (MMP9) expression. Further bioinformatic prediction and dual-luciferase reporter assay suggested that miR-1225 targeted the 3'-UTR of NFκB p65.

Results: Overexpression of p65 protein counteracted the repressive impact of miR-1225 on invasion, migration, and proliferation of HCC cells.

Conclusion: This research provided new evidences that miR-1225 inhibits the viability, migration, and invasion of HCC cells by downregulation of p65.
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http://dx.doi.org/10.1002/jcla.23474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676203PMC
November 2020

Dual inhibition of PFKFB3 and VEGF normalizes tumor vasculature, reduces lactate production, and improves chemotherapy in glioblastoma: insights from protein expression profiling and MRI.

Theranostics 2020 5;10(16):7245-7259. Epub 2020 Jun 5.

Department of Radiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.

Tumor vascular normalization (TVN) is emerging to enhance the efficacy of anticancer treatment in many cancers including glioblastoma (GBM). However, a common and severe challenge being currently faced is the transient TVN effect, hampering the sustained administration of anticancer therapy during TVN window. Additionally, the lack of non-contrast agent-based imaging biomarkers to monitor TVN process postpones the clinical translation of TVN strategy. In this study, we investigated whether dual inhibition of VEGF and the glycolytic activator PFKFB3 could reinforce the TVN effect in GBM. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM)-MRI were performed to monitor TVN process and to identify whether IVIM-MRI is a candidate or complementary imaging biomarker for monitoring TVN window without exogenous contrast agent administration. Patient-derived orthotopic GBM xenografts in mice were established and treated with bevacizumab (BEV), 3PO (PFKFB3 inhibitor), BEV+3PO dual therapy, or saline. The vascular morphology, tumor hypoxia, and lactate level were evaluated before and at different time points after treatments. Doxorubicin was used to evaluate chemotherapeutic efficacy and drug delivery. Microarray of angiogenesis cytokines and western blotting were conducted to characterize post-treatment molecular profiling. TVN process was monitored by DCE- and IVIM-MRI. Correlation analysis of pathological indicators and MRI parameters was further analyzed. Dual therapy extended survival and delayed tumor growth over each therapy alone, concomitant with a decrease of cell proliferation and an increase of cell apoptosis. The dual therapy reinforces TVN effect, thereby alleviating tumor hypoxia, reducing lactate production, and improving the efficacy and delivery of doxorubicin. Mechanistically, several angiogenic cytokines and pathways were downregulated after dual therapy. Notably, dual therapy inhibited Tie1 expression, the key regulator of TVN, in both endothelial cells and tumor cells. DCE- and IVIM-MRI data showed that dual therapy induced a more homogenous and prominent TVN effect characterized by improved vascular function in tumor core and tumor rim. Correlation analysis revealed that IVIM-MRI parameter had better correlations with TVN pathological indicators compared with the DCE-MRI parameter . Our results propose a rationale to overcome the current limitation of BEV monotherapy by integrating the synergistic effects of VEGF and PFKFB3 blockade to enhance chemotherapy efficacy through a sustained TVN effect. Moreover, we unveil IVIM-MRI parameter has much potential as a complementary imaging biomarker to monitor TVN window more precisely without exogenous contrast agent injection.
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http://dx.doi.org/10.7150/thno.44427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330843PMC
May 2021

Polymorphism and Molten Nitrate Salt-Assisted Single Crystal to Single Crystal Ion Exchange in the Cesium Ferrogermanate Zeotype: CsFeGeO.

Inorg Chem 2020 Jul 2;59(14):9699-9709. Epub 2020 Jul 2.

Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.

Two polymorphs of a new cesium ferrogermanate zeotype, CsFeGeO, were synthesized using the molten CsCl-CsF flux growth approach at 900 °C. The orthorhombic polymorph, referred to as (), crystallizes in the centrosymmetric nonpolar space group. The compound exhibits a three-dimensional porous framework structure composed of disordered (Fe/Ge)O corner-sharing tetrahedra that generate large eight-sided channels running down the -axis. These channels are occupied by Cs ions that provide charge balance to the anionic framework. Minor modifications in the reaction conditions lead to the synthesis of a monoclinic polymorph of CsFeGeO, referred to as (), crystallizing in the noncentrosymmetric polar space group 2 and exhibiting an identical framework structure to (), albeit featuring ordered FeO and GeO tetrahedra. Solid state synthesis of CsFeGeO produces a polycrystalline mixture of () and (), referred to as (). Polarization-electric field (P-E) measurements of () indicate that the material is not ferroelectric. Powder second harmonic generation (SHG) measurements of () and () revealed them to be SHG active with intensities of 1.5 and 0.2 times that of α-SiO, respectively. The temperature dependent magnetic susceptibility of () exhibits a downturn at = 2.6 K, indicative of antiferromagnetic ordering. First-principles calculations in the form of density functional theory showed that () and () differ in stability by only 1.3 meV/atom, with () being the thermodynamically stabilized phase. Additional calculations for (), using molten nitrate as reference, predicted the formation of energetically favorable phases, KFeGeO () and RbFeGeO (). They were subsequently prepared via a molten nitrate salt bath treatment of () to replace Cs with K and Rb, affording () and () as single-crystal to single-crystal ion exchange products. Structure determination and property measurements for a pyroxene phase, CsFeGeO, referred to as (), are also reported. This compound crystallized as a side product in the flux synthesis of CsFeGeO.
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http://dx.doi.org/10.1021/acs.inorgchem.0c00936DOI Listing
July 2020

Is Death Taboo for Older Chinese Immigrants?

Authors:
Weiguo Zhang

Omega (Westport) 2020 May 27:30222820927883. Epub 2020 May 27.

Department of Sociology, University of Toronto, Canada.

Much of the scholarly literature sees death as a taboo topic for Chinese. To test this assumption, this study held seven focus groups in the Greater Toronto Area in 2017. It found that the majority of the older Chinese immigrant participants talked about death freely using either the word or a euphemism. They talked about various issues including medical treatment and end-of-life care, medical assistance in dying, death preparation, and so on. A small number did not talk about death, but it seemed their reluctance was related to anxiety or discomfort or simply reflected a choice of words. The study concludes death as taboo could be a myth, at least for older Chinese immigrants.
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http://dx.doi.org/10.1177/0030222820927883DOI Listing
May 2020

Deciphering the crucial roles of AraC-type transcriptional regulator Cgl2680 on NADPH metabolism and L-lysine production in Corynebacterium glutamicum.

World J Microbiol Biotechnol 2020 May 26;36(6):82. Epub 2020 May 26.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800# Lihu Road, WuXi, 214122, People's Republic of China.

Lysine is widely used in food, medical and feed industries. The biosynthesis of L-lysine is closely related to NADPH level, but the regulation mechanism between the biosynthesis of L-lysine in C. glutamicum and the cofactor NADPH is still not clear. Here, a high intracellular NADPH level strain C. glutamicum XQ-5Δpgi::(zwf-gnd) was constructed by blocking the glycolytic pathway and overexpressing the pentose phosphate pathway in the lysine-producing strain C. glutamicum XQ-5, and the intracellular NADPH level in strain XQ-5Δpgi::(zwf-gnd) was increased from 3.57 × 10 nmol/(10 cells) to 1.8 × 10 nmol/(10 cell). Transcriptome analyses pointed to Cgl2680 as an important regulator of NADPH levels and L-lysine biosynthesis in C. glutamicum. By knocking out the gene Cgl2680, the intracellular NADPH level of the recombinant C. glutamicum lysC ΔCgl2680 was raised from 7.95 × 10 nmol/(10 cells) to 2.04 × 10 nmol/(10 cells), consequently leading to a 2.3-fold increase in the NADPH/NADP ratio. These results indicated that the regulator Cgl2680 showed the negative regulation for NADPH regeneration. In addition, Cgl2680-deficient strain C. glutamicum lysC ΔCgl2680 showed the increase of yield of both L-lysine and L-leucine as well as the increase of HO tolerance. Collectively, our data demonstrated that Cgl2680 plays an important role in negatively regulating NADPH regeneration, and these results provides new insights for breeding L-lysine or L-leucine high-yielding strain.
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http://dx.doi.org/10.1007/s11274-020-02861-yDOI Listing
May 2020

A Nonlinear Double Model for Multisensor-Integrated Navigation Using the Federated EKF Algorithm for Small UAVs.

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

School of Automation, Northwestern Polytechnical University, Xi'an 710129, China.

Aimed at improving upon the disadvantages of the single centralized Kalman filter for integrated navigation, including its fragile robustness and low solution accuracy, a nonlinear double model based on the improved decentralized federated extended Kalman filter (EKF) for integrated navigation is proposed. The multisensor error model is established and simplified in this paper according to the near-ground short distance navigation applications of small unmanned aerial vehicles (UAVs). In order to overcome the centralized Kalman filter that is used in the linear Gaussian system, the improved federated EKF is designed for multisensor-integrated navigation. Subsequently, because of the navigation requirements of UAVs, especially for the attitude solution accuracy, this paper presents a nonlinear double model that consists of the nonlinear attitude heading reference system (AHRS) model and nonlinear strapdown inertial navigation system (SINS)/GPS-integrated navigation model. Moreover, the common state parameters of the nonlinear double model are optimized by the federated filter to obtain a better attitude. The proposed algorithm is compared with multisensor complementary filtering (MSCF) and multisensor EKF (MSEKF) using collected flight sensors data. The simulation and experimental tests demonstrate that the proposed algorithm has a good robustness and state estimation solution accuracy.
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http://dx.doi.org/10.3390/s20102974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288117PMC
May 2020

Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome-Similar Coronavirus.

J Infect Dis 2020 06;222(2):223-233

Zhengzhou University College of Public Health, Zhengzhou, China.

Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002-2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.
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http://dx.doi.org/10.1093/infdis/jiaa278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313917PMC
June 2020

Effects of BMPER, CXCL10, and HOXA9 on Neovascularization During Early-Growth Stage of Primary High-Grade Glioma and Their Corresponding MRI Biomarkers.

Front Oncol 2020 5;10:711. Epub 2020 May 5.

Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.

Neovascularization is required in high-grade glioma (HGG). The objective of this study was to explore neovascularization-related genes and their corresponding MRI biomarkers during the early-growth stage of HGG. Tumor tissues from 30 HGG patients underwent perfusion MRI scanning prior to surgery were used to establish orthotopic xenograft models, pathologically analyze the tumor vasculature and perform transcriptome sequencing. The cases were divided into two groups based on whether the xenograft was successfully established. Microvascular density and BMPER, CXCL10, and HOXA9 expression of surgical specimens in the xenograft-forming group was significantly elevated and the microvascular diameter was significantly reduced, inhibition of BMPER, CXCL10, or HOXA9 in the glioma stem cell significantly suppressed its tube formation abilities. The experiment showed that BMPER was highly expressed in the early tumor growth phase (20 days), CXCL10 and HOXA9 expression was elevated with tumor progress, and spatially associated with tumor vasculature. Perfusion weighted MRI (PWI-MRI) derived parameters, rCBV, rCBF, K, and V, were also increased in the xenograft-forming group. In conclusion BMPER, CXCL10, and HOXA9 promote early tumor growth and progression by stimulating neovascularization of primary HGG. The rCBV, rCBF, K, and V can be used as imaging biomarkers to predict the expression statuses of these genes.
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http://dx.doi.org/10.3389/fonc.2020.00711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214627PMC
May 2020

Carcinoma of unknown primary detected by whole-body diffusion-weighted imaging: A case report and review of the literature.

Radiol Case Rep 2020 Jul 12;15(7):983-987. Epub 2020 May 12.

Department of Radiology, Daping hospital, Army medical university, Chongqing 400042, China.

Carcinoma of unknown primary accounts for 2%-5% of all head and neck tumors. Identification of the primary site is challenging. We present a case report of a 43-year-old man with metastatic cervical lymphadenopathy for 3 year, and the primary tumor was unknown after routine examinations, including positron emission tomography/computed tomography. Whole-body diffusion-weighted imaging was performed to detect small lesions in the nasopharynx, and a biopsy confirmed the lesions as squamous cell carcinoma. Therefore, the primary tumor site was found in a patient with carcinoma of unknown primary, suggesting that whole-body diffusion-weighted imaging can be very helpful in detecting small occult cancer.
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http://dx.doi.org/10.1016/j.radcr.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225598PMC
July 2020

Emergency trauma care during the outbreak of corona virus disease 2019 (COVID-19) in China.

World J Emerg Surg 2020 05 15;15(1):33. Epub 2020 May 15.

State Key Laboratory of Trauma, Burns and Combined Injuries, Medical Center of Trauma and War injury, Daping Hospital, Army Medical University, Chongqing, 400042, China.

Background: A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan.

Main Body: The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period.

Conclusions: The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19.
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http://dx.doi.org/10.1186/s13017-020-00312-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226718PMC
May 2020

MicroRNA-628-5p Facilitates Enterovirus 71 Infection by Suppressing TRAF3 Signaling.

Cell Mol Immunol 2021 May 12;18(5):1320-1322. Epub 2020 May 12.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.

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http://dx.doi.org/10.1038/s41423-020-0453-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093227PMC
May 2021

Patient‑derived orthotopic xenograft glioma models fail to replicate the magnetic resonance imaging features of the original patient tumor.

Oncol Rep 2020 May 9;43(5):1619-1629. Epub 2020 Mar 9.

Department of Radiology, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China.

Patient‑derived orthotopic glioma xenograft models are important platforms used for pre‑clinical research of glioma. In the present study, the diagnostic ability of magnetic resonance imaging (MRI) was examined with regard to the identification of biomarkers obtained from patient‑derived glioma xenografts and human tumors. Conventional MRI, diffusion weighted imaging and dynamic contrast‑enhanced (DCE)‑MRI were used to analyze seven pairs of high grade gliomas with their corresponding xenografts obtained from non‑obese diabetic‑severe‑combined immunodeficiency nude mice. Tumor samples were collected for transcriptome sequencing and histopathological staining, and differentially expressed genes were screened between the original tumors and the corresponding xenografts. Gene Ontology (GO) analysis was performed to predict the functions of these genes. In 6 cases of xenografts with diffuse growth, the degree of enhancement was significantly lower compared with the original tumors. Histopathological staining indicated that the microvascular area and microvascular diameter of the xenografts were significantly lower compared with the original tumors (P=0.009 and P=0.007, respectively). In one case, there was evidence of nodular tumor growth in the mouse. Both MRI and histopathological staining showed a clear demarcation between the transplanted tumors and the normal brain tissues. The relative apparent diffusion coefficient values of the 7 cases examined were significantly higher compared with the corresponding original tumors (P=0.001) and transfer coefficient values derived from DCE‑MRI of the tumor area was significantly lower compared with the original tumors (P=0.016). GO analysis indicated that the expression levels of extracellular matrix‑associated genes, angiogenesis‑associated genes and immune function‑associated genes in the original tumors were higher compared with the corresponding xenografts. In conclusion, the data demonstrated that the MRI features of patient‑derived xenograft glioma models in mice were different compared with those of the original patient tumors. Differential gene expression may underlie the differences noted in the MRI features between original tumors and corresponding xenografts. The results of the present study highlight the precautions that should be taken when extrapolating data from patient‑derived xenograft studies, and their applicability to humans.
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http://dx.doi.org/10.3892/or.2020.7538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107810PMC
May 2020

Antisense targeting of decoy exons can reduce intron retention and increase protein expression in human erythroblasts.

RNA 2020 08 20;26(8):996-1005. Epub 2020 Apr 20.

Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

The decoy exon model has been proposed to regulate a subset of intron retention (IR) events involving predominantly larger introns (>1 kb). Splicing reporter studies have shown that decoy splice sites are essential for activity, suggesting that decoys act by engaging intron-terminal splice sites and competing with cross-intron interactions required for intron excision. The decoy model predicts that antisense oligonucleotides may be able to block decoy splice sites in endogenous pre-mRNA, thereby reducing IR and increasing productive gene expression. Indeed, we now demonstrate that targeting a decoy 5' splice site in the O-GlcNAc transferase () gene reduced IR from ∼80% to ∼20% in primary human erythroblasts, accompanied by increases in spliced RNA and OGT protein expression. The remaining IR was refractory to antisense treatment and might be mediated by independent mechanism(s). In contrast, other retained introns were strongly dependent on decoy function, since antisense targeting of decoy 5' splice sites greatly reduced () or nearly eliminated () IR in two widely expressed splicing factors, and also greatly reduced IR in transcripts encoding the erythroid-specific structural protein, α-spectrin (). These results show that modulating decoy exon function can dramatically alter IR and suggest that dynamic regulation of decoy exons could be a mechanism to fine-tune gene expression post-transcriptionally in many cell types.
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http://dx.doi.org/10.1261/rna.075028.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373989PMC
August 2020

Melanin-Like Nanomaterials for Advanced Biomedical Applications: A Versatile Platform with Extraordinary Promise.

Adv Sci (Weinh) 2020 Apr 7;7(7):1903129. Epub 2020 Feb 7.

Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China.

Developing efficient, sustainable, and biocompatible high-tech nanoplatforms derived from naturally existing components in living organisms is highly beneficial for diverse advanced biomedical applications. Melanins are nontoxic natural biopolymers owning widespread distribution in various biosystems, possessing fascinating physicochemical properties and playing significant physiological roles. The multifunctionality together with intrinsic biocompatibility renders bioinspired melanin-like nanomaterials considerably promising as a versatile and powerful nanoplatform with broad bioapplication prospects. This panoramic Review starts with an overview of the fundamental physicochemical properties, preparation methods, and polymerization mechanisms of melanins. A systematical and well-bedded description of recent advancements of melanin-like nanomaterials regarding diverse biomedical applications is then given, mainly focusing on biological imaging, photothermal therapy, drug delivery for tumor treatment, and other emerging biomedicine-related implementations. Finally, current challenges toward clinical translation with an emphasis on innovative design strategies and future striving directions are rationally discussed. This comprehensive and detailed Review provides a deep understanding of the current research status of melanin-like nanomaterials and is expected to motivate further optimization of the design of novel tailorable and marketable multifunctional nanoplatforms in biomedicine.
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http://dx.doi.org/10.1002/advs.201903129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141020PMC
April 2020

Thirdhand smoke exposure causes replication stress and impaired transcription in human lung cells.

Environ Mol Mutagen 2020 07 16;61(6):635-646. Epub 2020 Apr 16.

Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to the development of diseases. However, THS exposure-induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here, we found that THS exposure increased the percentage of cells in S-phase, suggesting impaired S-phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1, and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double-strand break induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS-exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription-blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. Loss of nucleotide excision repair exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases.
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http://dx.doi.org/10.1002/em.22372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363442PMC
July 2020

lncRNA MIAT promotes cell invasion and migration in esophageal cancer.

Exp Ther Med 2020 May 9;19(5):3267-3274. Epub 2020 Mar 9.

Department of Surgical Oncology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

Long non-coding RNAs (lncRNAs) serve crucial roles in carcinogenesis. Myocardial infarction-associated transcript (MIAT), originally isolated as a candidate gene for myocardial infarction, has been revealed to serve as an oncogene in chronic lymphocytic leukaemias and neuroendocrine prostate cancer. However, little is known about its expression pattern, biological function and underlying mechanism in esophageal cancer. Cell lines of esophageal cancer were used in the current study. The results of the present study revealed that MIAT knockdown decreased cell viability, migration, invasion and cell cycle arrest in the G1 phase. Mechanistic assessment revealed that MIAT interacts with histone methyltransferase mixed-lineage leukemia (MLL). The relative proteins expressions were measured by western blotting assay. MIAT knockdown suppressed cell invasion and migration by regulation MMP-2/9 protein expressions. The results of the current study indicated that MIAT expression was associated with esophageal cancer and may serve as a critical target in the progression and metastasis in esophageal cancer.
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http://dx.doi.org/10.3892/etm.2020.8588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132222PMC
May 2020

Co-production of lipid, exopolysaccharide and single-cell protein by Sporidiobolus pararoseus under ammonia nitrogen-limited conditions.

Bioprocess Biosyst Eng 2020 Aug 3;43(8):1403-1414. Epub 2020 Apr 3.

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

With the rapid depletion of crude resources, microorganism lipids have started attracting increasing attention because of their renewable qualities. However, their production is limited by high costs. In this study, we aimed to reduce the production cost of Sporidiobolus pararoseus JD-2 lipid by co-producing extracellular polysaccharide (EPS) and single-cell protein (SCP). In batch fermentation, the yields of lipid, EPS and SCP under ammonia nitrogen limitation increased by 20.3%, 32.0% and 43.7%, respectively, compared with the yields in the control group (without NH). Next, fed-batch fermentation was performed under different ammonia nitrogen levels. The yield, productivity and coefficient of lipid reached 47.1 ± 1.1 g/L, 0.66 g/L/h and 0.250 g/g, respectively, under an ammonia nitrogen level of 20 g/L (NH)SO. In the same process, 14.3 ± 1.6 g/L EPS and 12.7 ± 0.8 g/L SCP were also obtained. Nutrient analysis of the product revealed that NH affected the proportion of pigments in the carotenoids and increased the content of unsaturated fatty acids in the lipid; EPS mainly comprised galactose, glucose, mannose and fucose, at a ratio of approximately 45:37:2:1; and the essential amino acid content in SCP accounted for 48% of the product. Thus, this study provided a new strategy for improving S. pararoseus JD-2 lipid production at a lower cost.
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http://dx.doi.org/10.1007/s00449-020-02335-3DOI Listing
August 2020

Virology, Epidemiology, Pathogenesis, and Control of COVID-19.

Viruses 2020 03 27;12(4). Epub 2020 Mar 27.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review.
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http://dx.doi.org/10.3390/v12040372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232198PMC
March 2020

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration.

Cell Transplant 2020 Jan-Dec;29:963689720908500

Department of Orthopaedics, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, Chin.

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.
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http://dx.doi.org/10.1177/0963689720908500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444208PMC
June 2021

Synthesis and Characterization of Two New Second Harmonic Generation Active Iodates: KSc(IO) and KSc(IO)Cl.

ACS Omega 2020 Mar 4;5(10):5235-5240. Epub 2020 Mar 4.

Department of Materials and Environmental Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden.

Transparent single crystals of two new iodates KSc(IO) and KSc(IO)Cl have been synthesized hydrothermally. Single-crystal X-ray diffraction was used to determine their crystal structures. Both compounds crystallize in non-centrosymmetric space groups. The compound KSc(IO) crystallizes in the orthorhombic space group 2. The crystal structure is made up of [ScO] octahedra, [IO] trigonal pyramids, and [KO] distorted cubes. The compound KSc(IO)Cl crystallizes in the trigonal space group 3. The building blocks are [ScO] octahedra, [KO] polyhedra, and [IO] trigonal pyramids. The Cl ions act as counter ions and reside in tunnels in the crystal structure. The second harmonic generation (SHG) measurements at room temperature, using 1064 nm radiation, on polycrystalline samples show that the SHG intensities of KSc(IO) and KSc(IO)Cl are around 2.8 and 2.5 times that of KHPO (KDP), respectively. In addition, KSc(IO) and KSc(IO)Cl are phase-matchable at the fundamental wavelength of 1064 nm. The large anharmonicity in the optical response of both compounds is further supported by an anomalous temperature dependence of optical phonon frequencies as well as their enlarged intensities in Raman scattering. The latter corresponds to a very large electronic polarizability.
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http://dx.doi.org/10.1021/acsomega.9b04288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081421PMC
March 2020

Periodic Tendril Perversion and Helices in the AMoOF (A = K, Rb, NH, Tl) Family.

J Am Chem Soc 2020 04 19;142(13):6375-6380. Epub 2020 Mar 19.

Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.

Although compounds of the formula AMoOF (A = K, Rb, Cs, NH, Tl) have been known for decades, crystal structures have only been reported for CsMoOF and NHMoOF. The three compounds (Rb/NH/Tl)MoOF are isostructural and crystallize in the centrosymmetric space group 2 (No. 15). The compounds contain the MoOF anionic chain, composed of corner-sharing MoOF octahedra, with Mo coordinated by two bridging fluoride anions that are to terminal oxide anions. The MoOF chain has a very unusual and complex chain structure; a single chain contains alternating zigzag and helical sections. These helical regions alternate in chirality along the chain, and thus the chains exhibit periodic tendril perversion. To the best of the authors' knowledge, no other materials with a similar chain structure have been reported. On the other hand, KMoOF is noncentrosymmetric and chiral, crystallizing in the enantiomorphic space group 222 (No. 19). KMoOF also contains the MoOF anionic chain. However, the chain is helical, with only one enantiomer present, resulting in a chiral, noncentrosymmetric structure.
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http://dx.doi.org/10.1021/jacs.0c01218DOI Listing
April 2020

The Rice Gene Confers Resistance to pv. in the Model Rice Kitaake Genetic Background.

Front Plant Sci 2020 6;11:49. Epub 2020 Feb 6.

Department of Plant Pathology and the Genome Center, University of California, Davis, Davis, CA, United States.

The rice XA21 and XA3 pattern receptor kinases, derived from and an cultivar Wase Aikoku 3, respectively, confer resistance to strains of the Gram-negative bacterium pv. (), the causal agent of rice bacterial blight disease. Previously, we showed that transfer of to the model rice cultivar Kitaake enhances resistance to . In this manuscript we demonstrate that Kitaake expressing confers resistance to strain PXO79 and that the stress-related marker genes and are upregulated in -infected rice leaves. We also show that rice somatic embryogenesis receptor kinase 2 (OsSERK2) positively regulates XA3-mediated immunity in Kitaake. We found that overexpression of XA21 binding protein 15 (XB15) and XB24, two negative regulators of XA21-mediated immunity, do not affect XA3-mediated immunity in the Kitaake genetic background. Our results indicate that the rice immune receptors XA21 and XA3 employ both shared and distinct signaling components in their response to . The results are important to further understand pathogen-associated molecular pattern (PAMP)-triggered immunity in rice. Furthermore, the presence of Kitaake rice carrying will facilitate genetic research to study the XA3-mediated immunity.
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http://dx.doi.org/10.3389/fpls.2020.00049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017783PMC
February 2020

Vascular habitat analysis based on dynamic susceptibility contrast perfusion MRI predicts IDH mutation status and prognosis in high-grade gliomas.

Eur Radiol 2020 Jun 20;30(6):3254-3265. Epub 2020 Feb 20.

Department of Radiology, Army Medical Center of PLA, Army Medical University, 10# Changjiangzhilu, Chongqing, 400042, People's Republic of China.

Objective: The current study aimed to evaluate the clinical practice for hemodynamic tissue signature (HTS) method in IDH genotype prediction in three groups derived from high-grade gliomas.

Methods: Preoperative MRI examinations of 44 patients with known grade and IDH genotype were assigned into three study groups: glioblastoma multiforme, grade III, and high-grade gliomas. Perfusion parameters were analyzed and were used to automatically draw the four reproducible habitats (high-angiogenic enhancing tumor habitats, low-angiogenic enhancing tumor habitats, infiltrated peripheral edema habitats, vasogenic peripheral edema habitats) related to vascular heterogeneity. These four habitats were then compared between inter-patient with IDH mutation and their wild-type counterparts at these three groups, respectively. The discriminating potential for HTS in assessing IDH mutation status prediction was assessed by ROC curves.

Results: Compared with IDH wild type, IDH mutation had significantly decreased relative cerebral blood volume (rCBV) at the high-angiogenic enhancing tumor habitats and low-angiogenic enhancing tumor habitats. ROC analysis revealed that the rCBVs in habitats had great ability to discriminate IDH mutation from their wild type in all groups. In addition, the Kaplan-Meier survival analysis yielded significant differences for the survival times observed from the populations dichotomized by low (< 4.31) and high (> 4.31) rCBV in the low-angiogenic enhancing tumor habitat.

Conclusions: The HTS method has been proven to have high prediction capabilities for IDH mutation status in high-grade glioma patients, providing a set of quantifiable habitats associated with tumor vascular heterogeneity.

Key Points: • The HTS method has a high accuracy for molecular stratification prediction for all subsets of HGG. • The HTS method can give IDH mutation-related hemodynamic information of tumor-infiltrated and vasogenic edema. • IDH-relevant rCBV difference in habitats will be a great prognosis factor in HGG.
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http://dx.doi.org/10.1007/s00330-020-06702-2DOI Listing
June 2020

Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis.

Nature 2020 02 19;578(7796):577-581. Epub 2020 Feb 19.

Department of Horticulture, Foshan University, Foshan, China.

Hydrogen peroxide (HO) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues. HO enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for HO also exist on the cell surface remains unknown. In plant cells, HO triggers an influx of Ca ions, which is thought to be involved in HO sensing and signalling. Here, by using forward genetic screens based on Ca imaging, we isolated hydrogen-peroxide-induced Ca increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by HO via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates HO-induced activation of Ca channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular HO is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.
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http://dx.doi.org/10.1038/s41586-020-2032-3DOI Listing
February 2020

Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of L-lysine production from mixed sugar.

Microb Cell Fact 2020 Feb 18;19(1):39. Epub 2020 Feb 18.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800# Lihu Road, Wuxi, 214122, China.

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTS and PTS) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.
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http://dx.doi.org/10.1186/s12934-020-1294-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029506PMC
February 2020

Comprehensive understanding of Saccharomyces cerevisiae phenotypes with whole-cell model WM_S288C.

Biotechnol Bioeng 2020 05 13;117(5):1562-1574. Epub 2020 Feb 13.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.

Biological network construction for Saccharomyces cerevisiae is a widely used approach for simulating phenotypes and designing cell factories. However, due to a complicated regulatory mechanism governing the translation of genotype to phenotype, precise prediction of phenotypes remains challenging. Here, we present WM_S288C, a computational whole-cell model that includes 15 cellular states and 26 cellular processes and which enables integrated analyses of physiological functions of Saccharomyces cerevisiae. Using WM_S288C to predict phenotypes of S. cerevisiae, the functions of 1140 essential genes were characterized and linked to phenotypes at five levels. During the cell cycle, the dynamic allocation of intracellular molecules could be tracked in real-time to simulate cell activities. Additionally, one-third of non-essential genes were identified to affect cell growth via regulating nucleotide concentrations. These results demonstrated the value of WM_S288C as a tool for understanding and investigating the phenotypes of S. cerevisiae.
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http://dx.doi.org/10.1002/bit.27298DOI Listing
May 2020
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