Publications by authors named "Zhen Tao"

156 Publications

Evaluation of the acute toxic effects of crude oil on intertidal mudskipper (Boleophthalmus pectinirostris) based on antioxidant enzyme activity and the integrated biomarker response.

Environ Pollut 2021 Oct 9;292(Pt A):118341. Epub 2021 Oct 9.

School of Marine Sciences, University of Maine, Orono, 04469, USA.

With the development of marine oil industry, oil spill accidents will inevitably occur, further polluting the intertidal zone and causing biological poisoning. The muddy intertidal zone and Boleophthalmus pectinirostris were selected as the research objects to conduct indoor acute exposure experiments within 48 h of crude oil pollution. Statistical analysis was used to reveal the activity changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in the gills and liver of mudskipper. Then, integrated biomarker response (IBR) indicators were established to comprehensively evaluate the biological toxicity. The results showed that the activities of SOD, CAT and GST in livers were higher than those in gills, and the maximum induction multipliers of SOD, CAT and GPx in livers appeared earlier than those in gills. Both SOD and GPx activities were induced at low pollutant concentrations and inhibited at high pollutant concentrations. For the dose-effect, the change trends of CAT and SOD were roughly inversed. There was substrate competition between GPx and CAT, with opposite trends over time. The activating mechanism of GST was similar to that of GPx, and the activation time was earlier than that of GPx. In terms of dose-effect trends, the IBR showed that the antioxidant enzymes activities in biological tissues were induced by low and inhibited by high pollutant concentrations. Overall, SOD and GPx in gills and CAT and GST in livers of the mudskippers were suitable as representative markers to comprehensively analyze and evaluate the biotoxicity effects of oil pollution in the intertidal zone. The star plots and IBR values obtained after data standardization were consistent with the enzyme activity differences, which can be used as valid supplementary indexes for biotoxicity evaluation. These research findings provide theoretical support for early indicators of biological toxicity after crude oil pollution in intertidal zones.
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http://dx.doi.org/10.1016/j.envpol.2021.118341DOI Listing
October 2021

sLOX-1: A Molecule for Evaluating the Prognosis of Recurrent Ischemic Stroke.

Neural Plast 2021 28;2021:6718184. Epub 2021 Aug 28.

Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100000, China.

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone ( = 0.3232, = 0.001). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204-1.842, < 0.0001). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.
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http://dx.doi.org/10.1155/2021/6718184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419492PMC
August 2021

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development.

Blood Adv 2021 Sep 7. Epub 2021 Sep 7.

NHGRI, NIH, Bethesda, Maryland, United States.

RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1 null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, even though zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multi-lineages, raising the possibility that HSCs can emerge without RUNX1. Here, using three new zebrafish runx1-/- lines we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-GFP+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1- /- embryos. Interestingly, genetic inactivation of both gata2b and its paralog, gata2a, did not affect hematopoiesis. However, knocking out runx1 and any three of the four alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as each other's safeguard.
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http://dx.doi.org/10.1182/bloodadvances.2020003969DOI Listing
September 2021

Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package.

J Chem Phys 2021 Aug;155(8):084801

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.
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http://dx.doi.org/10.1063/5.0055522DOI Listing
August 2021

The Incremental Prognostic Value of Hepatocyte Growth Factor in First-Ever Acute Ischemic Stroke: An Early Link Between Growth Factor and Interleukins.

Front Neurol 2021 4;12:691886. Epub 2021 Aug 4.

Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Hepatocyte growth factor (HGF) is a potential prognostic factor for acute ischemic stroke (AIS). In this study, we sought to validate its earlier predictive accuracy within 24 h for first-ever AIS. Moreover, as HGF interacts with interleukins, their associations may lead to novel immunomodulatory therapeutic strategies. Patients with first-ever AIS ( = 202) within 24 h were recruited. Plasma HGF and related interleukin concentrations were measured by multiplex immunoassays. The primary and secondary outcomes were major disability (modified Rankin scale score ≥3) at 3 months after AIS and death, respectively. Elastic net regression was applied to screen variables associated with stroke outcome; binary multivariable logistic analysis was then used to explore the relationship between HGF level and stroke outcome. After multivariate adjustment, upregulated HGF levels were associated with an increased risk of the primary outcome (odds ratio, 7.606; 95% confidence interval, 3.090-18.726; < 0.001). Adding HGF to conventional risk factors significantly improved the predictive power for unfavorable outcomes (continuous net reclassification improvement 37.13%, < 0.001; integrated discrimination improvement 8.71%, < 0.001). The area under the receiver operating characteristic curve value of the traditional model was 0.8896 and reached 0.9210 when HGF was introduced into the model. An elevated HGF level may also be a risk factor for mortality within 3 months poststroke. The HGF level was also positively correlated with IL-10 and IL-16 levels, and HGF before interaction with all interleukins was markedly negatively correlated with the lymphocyte/neutrophil ratio. HGF within 24 h may have prognostic potential for AIS. Our findings reinforce the link between HGF and interleukins.
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http://dx.doi.org/10.3389/fneur.2021.691886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371202PMC
August 2021

Analytical Gradients for Nuclear-Electronic Orbital Time-Dependent Density Functional Theory: Excited-State Geometry Optimizations and Adiabatic Excitation Energies.

J Chem Theory Comput 2021 Aug 14;17(8):5110-5122. Epub 2021 Jul 14.

Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States.

The computational investigation of photochemical processes often entails the calculation of excited-state geometries, energies, and energy gradients. The nuclear-electronic orbital (NEO) approach treats specified nuclei, typically protons, quantum mechanically on the same level as the electrons, thereby including the associated nuclear quantum effects and non-Born-Oppenheimer behavior into quantum chemistry calculations. The multicomponent density functional theory (NEO-DFT) and time-dependent DFT (NEO-TDDFT) methods allow efficient calculations of ground and excited states, respectively. Herein, the analytical gradients are derived and implemented for the NEO-TDDFT method and the associated Tamm-Dancoff approximation (NEO-TDA). The programmable equations for these analytical gradients as well as the NEO-DFT analytical Hessian are provided. The NEO approach includes the anharmonic zero-point energy (ZPE) and density delocalization associated with the quantum protons as well as vibronic mixing in geometry optimizations and energy calculations of ground and excited states. The harmonic ZPE associated with the other nuclei can be computed via the NEO Hessian. This approach is used to compute the 0-0 adiabatic excitation energies for a set of nine small molecules with all protons quantized, exhibiting slight improvement over the conventional electronic approach. Geometry optimizations of two excited-state intramolecular proton-transfer systems, [2,2'-bipyridyl]-3-ol and [2,2'-bipyridyl]-3,3'-diol, are performed with one and two quantized protons, respectively. The NEO calculations for these systems produce electronically excited-state geometries with stronger intramolecular hydrogen bonds and similar relative stabilities compared to conventional electronic methods. This work provides the foundation for nonadiabatic dynamics simulations of fundamental processes such as photoinduced proton transfer and proton-coupled electron transfer.
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http://dx.doi.org/10.1021/acs.jctc.1c00454DOI Listing
August 2021

Pathophysiological Significance of Neutrophilic Transfer RNA-Derived Small RNAs in Asymptomatic Moyamoya Disease.

Cells 2021 05 1;10(5). Epub 2021 May 1.

Department of Neurology, Institute of Cerebrovascular Diseases Research, Xuanwu Hospital, Capital Medical University, Beijing 100000, China.

Understanding asymptomatic moyamoya disease (aMMD), for which treatment options are currently limited, is key to the development of therapeutic strategies that will slow down the progression of this disease, as well as facilitate the discovery of therapeutic targets for symptomatic MMD. Newly found transfer RNA-derived small RNAs (tsRNAs) perform potential regulatory functions in neovascularization, which is a well-known pathological manifestation of MMD. In this study, the neutrophilic tsRNA transcriptome in aMMD was profiled using next-generation RNA sequencing in five patients and five matched healthy subjects. A negative binominal generalized log-linear regression was used to identify differentially expressed (DE)-tsRNAs in aMMD. Gene Ontology and functional pathway analyses were used to identify biological pathways involved with the targeted genes of the DE-tsRNAs. Four tsRNAs were selected and validated using quantitative reverse transcription polymerase chain reaction. In total, 186 tsRNAs were DE between the two groups. Pathophysiological events, including immune response, angiogenesis, axon guidance, and metabolism adjustment, were enriched for the DE-tsRNAs. The expression levels of the four DE-tsRNAs were consistent with those in the neutrophilic transcriptome. These aberrantly expressed tsRNAs and their targeted pathophysiological processes provide a basis for potential future interventions for aMMD.
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http://dx.doi.org/10.3390/cells10051086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147334PMC
May 2021

Flightless I Homolog Reverses Enzalutamide Resistance through PD-L1-Mediated Immune Evasion in Prostate Cancer.

Cancer Immunol Res 2021 Jul 19;9(7):838-852. Epub 2021 May 19.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tumor cells can evade immune surveillance and immune killing during the emergence of endocrine therapy resistance in prostate cancer, but the mechanisms underlying this phenomenon are still unclear. Flightless I homolog (FLII) is a coregulator for transcription factors in several malignancies. Here, we have demonstrated that endocrine therapy resistance can induce an immunosuppressive prostate tumor microenvironment and immune evasion through FLII downregulation, which leads to activation of the YBX1/PD-L1 signaling pathway. FLII expression negatively correlated with expression of PD-L1 in tumors. Mechanism studies demonstrated that FLII physically interacted with YBX1 to inhibit nuclear localization of YBX1 and thereby suppress transcription of in enzalutamide-resistant tumors. Restoration of FLII expression reversed enzalutamide resistance through activation of T-cell responses in the tumor microenvironment through inhibition of the YBX1/PD-L1 pathway. We also found that reversal of endocrine therapy resistance and immune evasion was mediated by proliferation of effector CD8 T cells and inhibition of tumor infiltration by regulatory T cells and myeloid-derived suppressor cells. Taken together, our results demonstrate a functional and biological interaction between endocrine therapy resistance and immune evasion mediated through the FLII/YBX1/PD-L1 cascade. Combination therapy with FLII expression and endocrine therapy may benefit patients with prostate cancer by preventing tumor immune evasion.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0729DOI Listing
July 2021

MiR-29a Knockout Aggravates Neurological Damage by Pre-polarizing M1 Microglia in Experimental Rat Models of Acute Stroke.

Front Genet 2021 15;12:642079. Epub 2021 Mar 15.

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Objective: By exploring the effects of miR-29a-5p knockout on neurological damage after acute ischemic stroke, we aim to deepen understanding of the molecular mechanisms of post-ischemic injury and thus provide new ideas for the treatment of ischemic brain injury.

Methods: miR-29a-5p knockout rats and wild-type SD rats were subjected to transient middle cerebral artery occlusion (MCAO). miR-29a levels in plasma, cortex, and basal ganglia of ischemic rats, and in plasma and neutrophils of ischemic stroke patients, as well as hypoxic glial cells were detected by real-time PCR. The infarct volume was detected by TTC staining and the activation of astrocytes and microglia was detected by western blotting.

Results: The expression of miR-29a-5p was decreased in parallel in blood and brain tissue of rat MCAO models. Besides, miR-29a-5p levels were reduced in the peripheral blood of acute stroke patients. Knockout of miR-29a enhanced infarct volume of the MCAO rat model, and miR-29a knockout showed M1 polarization of microglia in the MCAO rat brain. miR-29a knockout in rats after MCAO promoted astrocyte proliferation and increased glutamate release.

Conclusion: Knockout of miR-29a in rats promoted M1 microglial polarization and increased glutamate release, thereby aggravating neurological damage in experimental stroke rat models.
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http://dx.doi.org/10.3389/fgene.2021.642079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005650PMC
March 2021

Heparin-binding protein and procalcitonin in the diagnosis of pathogens causing community-acquired pneumonia in adult patients: a retrospective study.

PeerJ 2021 12;9:e11056. Epub 2021 Mar 12.

Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

The performance of inflammatory markers in community-acquired pneumonia (CAP) caused by different pathogens has not been fully studied. We sought to find the differences in the concentrations of procalcitonin (PCT) and heparin-binding protein (HBP) between patients with CAP caused by different pathogens. We enrolled 162 patients with CAP, divided into three groups on the basis of bacterial ( = 108), fungal ( = 21) and viral ( = 33) infection. Complete leukocyte counts and the concentration of HBP and PCT were measured, and the differences were compared with nonparametric tests. The receiver operating characteristic (ROC) curve was used to evaluate the significant differences in the sensitivity and specificity of the indicators. The leukocyte and neutrophils counts and the concentrations of HBP and PCT in the viral group were significantly lower than those in the other two groups ( < 0.001). The area under the ROC curve (AUC) of the concentration of HBP and PCT as well as leukocyte and neutrophils counts were 0.927, 0.892, 0.832 and 0.806 for distinguishing bacterial from viral infection, respectively. The best cut-off value was 20.05 ng/mL for HBP, with a sensitivity of 0.861 and specificity of 0.939. The best cut-off value was 0.195 ng/mL for PCT, with a sensitivity of 0.991 and specificity of 0.636. The best cut-off value was 5.195 × 10/L and 4.000 × 10/L for leukocyte and neutrophils counts, with sensitivity of 0.694 and 0.880 and specificity of 0.667 and 0.636, respectively. The AUC of HBP, PCT and leukocyte and neutrophil counts for distinguishing fungal from viral infection were 0.851, 0.883, 0.835 and 0.830, respectively. The best cut-off values were 29.950 ng/mL, 0.560 ng/mL, 5.265 × 10/L and 3.850 × 10/L, with sensitivity of 0.667, 0.714, 0.905 and 0.952 and specificity of 0.970, 0.879 0.667 and 0.606, respectively. There were no significant differences in the three indicators between the bacterial and fungal infection groups. The concentration of CRP showed no significant differences among the three groups. Consequently, the stronger immune response characterized by higher inflammation markers including HBP and PCT can help distinguish bacterial and fungal CAP from viral CAP.
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http://dx.doi.org/10.7717/peerj.11056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958890PMC
March 2021

Volatile DMNT directly protects plants against by disrupting the peritrophic matrix barrier in insect midgut.

Elife 2021 Feb 18;10. Epub 2021 Feb 18.

The National Key Engineering Lab of Crop Stress Resistance Breeding, the School of Life Sciences, Anhui Agricultural University, Hefei, China.

Insect pests negatively affect crop quality and yield; identifying new methods to protect crops against insects therefore has important agricultural applications. Our analysis of transgenic plants showed that overexpression of , encoding the key biosynthetic enzyme for the natural plant product (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), led to a significant resistance against a major insect pest, . DMNT treatment severely damaged the peritrophic matrix (PM), a physical barrier isolating food and pathogens from the midgut wall cells. DMNT repressed the expression of in midgut cells, and knocking down resulted in PM rupture and death. A 16S RNA survey revealed that DMNT significantly disrupted midgut microbiota populations and that midgut microbes were essential for DMNT-induced killing. Therefore, we propose that the midgut microbiota assists DMNT in killing . These findings may provide a novel approach for plant protection against .
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http://dx.doi.org/10.7554/eLife.63938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924945PMC
February 2021

Transition states, reaction paths, and thermochemistry using the nuclear-electronic orbital analytic Hessian.

J Chem Phys 2021 Feb;154(5):054108

Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.

The nuclear-electronic orbital (NEO) method is a multicomponent quantum chemistry theory that describes electronic and nuclear quantum effects simultaneously while avoiding the Born-Oppenheimer approximation for certain nuclei. Typically specified hydrogen nuclei are treated quantum mechanically at the same level as the electrons, and the NEO potential energy surface depends on the classical nuclear coordinates. This approach includes nuclear quantum effects such as zero-point energy and nuclear delocalization directly into the potential energy surface. An extended NEO potential energy surface depending on the expectation values of the quantum nuclei incorporates coupling between the quantum and classical nuclei. Herein, theoretical methodology is developed to optimize and characterize stationary points on the standard or extended NEO potential energy surface, to generate the NEO minimum energy path from a transition state down to the corresponding reactant and product, and to compute thermochemical properties. For this purpose, the analytic coordinate Hessian is developed and implemented at the NEO Hartree-Fock level of theory. These NEO Hessians are used to study the S2 reaction of ClCHCl and the hydride transfer of CH . For each system, analysis of the single imaginary mode at the transition state and the intrinsic reaction coordinate along the minimum energy path identifies the dominant nuclear motions driving the chemical reaction. Visualization of the electronic and protonic orbitals along the minimum energy path illustrates the coupled electronic and protonic motions beyond the Born-Oppenheimer approximation. This work provides the foundation for applying the NEO approach at various correlated levels of theory to a wide range of chemical reactions.
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http://dx.doi.org/10.1063/5.0033540DOI Listing
February 2021

Multicomponent Coupled Cluster Singles and Doubles with Density Fitting: Protonated Water Tetramers with Quantized Protons.

J Phys Chem Lett 2021 Feb 8;12(6):1631-1637. Epub 2021 Feb 8.

Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States.

Nuclear quantum effects such as zero-point energy are important for describing a wide range of chemical properties. The nuclear-electronic orbital (NEO) approach incorporates such effects into quantum chemistry calculations by treating specified nuclei, typically protons, quantum mechanically on the same level as electrons. Herein, both the traditional and -transformed NEO coupled cluster with singles and doubles (NEO-CCSD) methods are implemented with a density fitting (DF) scheme for approximating the four-center two-particle integrals. The enhanced computational efficiency enables calculations on larger molecules with multiple quantum protons. The NEO-DF-CCSD method predicts proton affinities within chemical accuracy. Its application to protonated water tetramers with all nine protons treated quantum mechanically produces the qualitatively correct ordering of the isomer energies, which are strongly influenced by the zero-point energy contributions inherently included in NEO energy calculations. This work showcases the capabilities of the NEO-DF-CCSD method and provides the foundation for future developments and applications.
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http://dx.doi.org/10.1021/acs.jpclett.0c03771DOI Listing
February 2021

Nuclear-electronic orbital Ehrenfest dynamics.

J Chem Phys 2020 Dec;153(22):224111

Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.

The recently developed real-time nuclear-electronic orbital (RT-NEO) approach provides an elegant framework for treating electrons and selected nuclei, typically protons, quantum mechanically in nonequilibrium dynamical processes. However, the RT-NEO approach neglects the motion of the other nuclei, preventing a complete description of the coupled nuclear-electronic dynamics and spectroscopy. In this work, the dynamical interactions between the other nuclei and the electron-proton subsystem are described with the mixed quantum-classical Ehrenfest dynamics method. The NEO-Ehrenfest approach propagates the electrons and quantum protons in a time-dependent variational framework, while the remaining nuclei move classically on the corresponding average electron-proton vibronic surface. This approach includes the non-Born-Oppenheimer effects between the electrons and the quantum protons with RT-NEO and between the classical nuclei and the electron-proton subsystem with Ehrenfest dynamics. Spectral features for vibrational modes involving both quantum and classical nuclei are resolved from the time-dependent dipole moments. This work shows that the NEO-Ehrenfest method is a powerful tool to study dynamical processes with coupled electronic and nuclear degrees of freedom.
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http://dx.doi.org/10.1063/5.0031019DOI Listing
December 2020

Mutant erythropoietin enhances white matter repair via the JAK2/STAT3 and C/EBPβ pathway in middle-aged mice following cerebral ischemia and reperfusion.

Exp Neurol 2021 03 9;337:113553. Epub 2020 Dec 9.

Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing 100053, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing 100053, China. Electronic address:

Previous studies have indicated that EPO maintains the M2 microglia phenotype that contributes to white matter repair after ischemic stroke in young mice (2 months old). However, the underlying mechanisms that regulate microglial polarization are poorly defined. This study investigated the neuroprotective effects of nonerythropoietic mutant EPO (MEPO) on white matter and the underlying mechanism in middle-aged (9-month-old) male mice following cerebral ischemia. Middle-aged male C57 BL/6 mice were treated with MEPO (5000 IU/kg) or vehicle after middle cerebral artery occlusion (MCAO) and reperfusion. The specific inhibitor AG490 was used to block the JAK2/STAT3 pathway. Neurological function was assessed by beam walking and adhesive removal tests. Immunofluorescence staining and western blotting were used to assess the severity of white matter injury, phenotypic changes in the microglia and the expression of the signaling molecules. MEPO significantly improved neurobehavioral outcomes, alleviated brain tissue loss, and ameliorated white matter injury after MCAO compared with the vehicle group. Moreover, MEPO promoted oligodendrogenesis by shifting microglia toward M2 polarization by promoting JAK2/STAT3 activation and inhibiting the expression of C/EBPβ at 14 days after cerebral ischemia-reperfusion. However, the MEPO's effect on microglial M2 polarization and oligodendrogenesis was largely suppressed by AG490 treatment. Collectively, these data indicate that MEPO treatment improves white matter integrity after cerebral ischemia, which may be partly explained by MEPO facilitating microglia toward the beneficial M2 phenotype to promote oligodendrogenesis via JAK2/STAT3 and the C/EBPβ signaling pathway. This study provides novel insight into MEPO treatment for ischemic stroke.
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http://dx.doi.org/10.1016/j.expneurol.2020.113553DOI Listing
March 2021

Molecular variation in a functionally divergent homolog of FCA regulates flowering time in Arabidopsis thaliana.

Nat Commun 2020 11 17;11(1):5830. Epub 2020 Nov 17.

The National Engineering Laboratory of Crop Resistance Breeding, School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.

The identification and functional characterization of natural variants in plants are essential for understanding phenotypic adaptation. Here we identify a molecular variation in At2g47310 that contributes to the natural variation in flowering time in Arabidopsis thaliana accessions. This gene, which we term SISTER of FCA (SSF), functions in an antagonistic manner to its close homolog FCA. Genome-wide association analysis screens two major haplotypes of SSF associated with the natural variation in FLC expression, and a single polymorphism, SSF-N414D, is identified as a main contributor. The SSF414N protein variant interacts more strongly with CUL1, a component of the E3 ubiquitination complex, than the SSF414D form, mediating differences in SSF protein degradation and FLC expression. FCA and SSF appear to have arisen through gene duplication after dicot-monocot divergence, with the SSF-N414D polymorphism emerging relatively recently within A. thaliana. This work provides a good example for deciphering the functional importance of natural polymorphisms in different organisms.
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http://dx.doi.org/10.1038/s41467-020-19666-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673134PMC
November 2020

Pit latrines may be a potential risk in rural China and low-income countries when dealing with COVID-19.

Sci Total Environ 2021 Mar 29;761:143283. Epub 2020 Oct 29.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

According to the latest reports, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused coronavirus disease 2019 (COVID-19), was successfully isolated from the excreta (stool and urine) of COVID-19 patients, suggesting SARS-CoV-2 could be transmitted through excreta contaminated water. As pit latrines and the use of untreated excreta as fertilizer were common in rural China, we surveyed 27 villages of Jiangxi and Hubei provinces and found that pit latrines could be a potential source of SARS-CoV-2 water pollution. Recently, bats have been widely recognized as the source of SARS-CoV-2. There were many possible intermediate hosts of SARS-CoV-2, including pangolin, snake, bird and fish, but which one was still not clear exactly. Here, we proposed a hypothesis to illustrate the mechanism that SARS-CoV-2 might spread from the excreta of infected humans in pit latrines to potential animal hosts, thus becoming a sustainable source of infection in rural China. Therefore, we believe that abolishing pit latrines and banning the use of untreated excreta as fertilizer can improve the local living environment and effectively prevent COVID-19 and other potential waterborne diseases that could emanate from the excreta of infected persons. Although this study focused on rural areas in China, the results could also be applied to low-income countries, especially in Africa.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598438PMC
March 2021

The value of percentile base on computed tomography histogram in differentiating the invasiveness of adenocarcinoma appearing as pure ground-glass nodules.

Medicine (Baltimore) 2020 Nov;99(45):e23114

Department of Radiology, the First Affiliated Hospital of Zhejiang Chinese Medical University.

To investigate the value of percentile base on computed tomography (CT) histogram analysis for distinguishing invasive adenocarcinoma (IA) from adenocarcinoma in situ (AIS) or micro invasive adenocarcinoma (MIA) appearing as pure ground-glass nodules.A total of 42 cases of pure ground-glass nodules that were surgically resected and pathologically confirmed as lung adenocarcinoma between January 2015 and May 2019 were included. Cases were divided into IA and AIS/MIA in the study. The percentile on CT histogram was compared between the 2 groups. Univariate and multivariate logistic regression were used to determine which factors demonstrated a significant effect on invasiveness. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the predictive ability of individual characteristics and the combined model.The 4 histogram parameters (25th percentile, 55th percentile, 95th percentile, 97.5th percentile) and the combined model all showed a certain diagnostic value. The combined model demonstrated the best diagnostic performance. The AUC values were as follows: 25th percentile = 0.693, 55th percentile = 0.706, 95th percentile = 0.713, 97.5th percentile = 0.710, and combined model = 0.837 (all P < .05).The percentile of histogram parameters help to improve the ability to radiologically determine the invasiveness of lung adenocarcinoma appearing as pure ground-glass nodules.
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http://dx.doi.org/10.1097/MD.0000000000023114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647573PMC
November 2020

Transcriptome profiling of genes involved in nutrient uptake regulated by phosphate-solubilizing bacteria in pepper (Capsicum annuum L.).

Plant Physiol Biochem 2020 Nov 9;156:611-626. Epub 2020 Oct 9.

Institute of Horticulture, Anhui Academy of Agricultural Sciences, Hefei, 230031, Anhui Province, China; Key Laboratory of Genetic Improvement and Ecophysiology of Horticultural Crops, Hefei, 230031, Anhui Province, China.

Improving nutrient absorption in pepper has become a vital prerequisite for growth to produce a sustainable yield. In this study, transcriptome gene expression in pepper inoculated with two types of phosphate-solubilizing bacteria (PSB) and grown under low and high nutrient levels (LN and HN) was analyzed. Results showed that the root length increased when pepper was grown under LN; however, the root structure was intensively tight under HN. Our data revealed that the roots preferred horizontal growth than longitudinal growth under HN. PSB strains 'M01' and 'N3' significantly (P < 0.01) increased the P uptake by 70.44% and 98.20%, respectively, but decreased the Ca content by 8.96% and 9.13%, respectively, compared with the control (L1). Although no remarkable difference was detected in the chlorophyll content, inoculation with the two PSB strains decreased the Fe content in pepper under HN. The total clean sequenced data from samples ranged between 5,923,659,118 and 9,955,045,953 bp. Transcriptome profiling revealed 320 upregulated and 449 downregulated genes in L3 versus L1 and 468 upregulated and 532 downregulated genes in L4 versus L1. Gene ontology analysis revealed that the biological processes, including response to stress and secondary metabolic process, were involved. Several pathways were subordinate to glycosphingolipid biosynthesis and linoleic acid and nitrogen metabolisms. Analysis of the eukaryotic orthologous group function revealed that most differential genes were attributed to RNA processing and modification, transcription, and signal transduction. Our results provided new insights into the molecular mechanism related to nutrient uptake in pepper inoculated with PSBs.
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http://dx.doi.org/10.1016/j.plaphy.2020.10.003DOI Listing
November 2020

An energy-stable mixed formulation for isogeometric analysis of incompressible hyper-elastodynamics.

Int J Numer Methods Eng 2019 Nov 5;120(8):937-963. Epub 2019 Jul 5.

Institute for Computational Engineering and Sciences, The University of Texas at Austin, 201 East 24th Street, 1 University Station C0200, Austin, TX 78712, USA.

We develop a mixed formulation for incompressible hyper-elastodynamics based on a continuum modeling framework recently developed in [41] and smooth generalizations of the Taylor-Hood element based on non-uniform rational B-splines (NURBS). This continuum formulation draws a link between computational fluid dynamics and computational solid dynamics. This link inspires an energy stability estimate for the spatial discretization, which favorably distinguishes the formulation from the conventional mixed formulations for finite elasticity. The inf-sup condition is utilized to provide a bound for the pressure field. The generalized- method is applied for temporal discretization, and a nested block preconditioner is invoked for the solution procedure [42]. The inf-sup stability for different pairs of NURBS elements is elucidated through numerical assessment. The convergence rate of the proposed formulation with various combinations of mixed elements is examined by the manufactured solution method. The numerical scheme is also examined under compressive and tensile loads for isotropic and anisotropic hyperelastic materials. Finally, a suite of dynamic problems is numerically studied to corroborate the stability and conservation properties.
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http://dx.doi.org/10.1002/nme.6165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517668PMC
November 2019

RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development.

Blood 2020 11;136(21):2373-2385

Oncogenesis and Development Section, National Human Genome Research Institute, and.

Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. It is generally considered that CBFβ-SMMHC, the fusion protein encoded by CBFB-MYH11, is a dominant negative repressor of RUNX1. However, recent findings challenge the RUNX1-repression model for CBFβ-SMMHC-mediated leukemogenesis. To definitively address the role of Runx1 in CBFB-MYH11-induced leukemia, we crossed conditional Runx1 knockout mice (Runx1f/f) with conditional Cbfb-MYH11 knockin mice (Cbfb+/56M). On Mx1-Cre activation in hematopoietic cells induced by poly (I:C) injection, all Mx1-CreCbfb+/56M mice developed leukemia in 5 months, whereas no leukemia developed in Runx1f/fMx1-CreCbfb+/56M mice, and this effect was cell autonomous. Importantly, the abnormal myeloid progenitors (AMPs), a leukemia-initiating cell population induced by Cbfb-MYH11 in the bone marrow, decreased and disappeared in Runx1f/fMx1-CreCbfb+/56M mice. RNA-seq analysis of AMP cells showed that genes associated with proliferation, differentiation blockage, and leukemia initiation were differentially expressed between Mx1-CreCbfb+/56M and Runx1f/fMx1-CreCbfb+/56M mice. In addition, with the chromatin immunocleavage sequencing assay, we observed a significant enrichment of RUNX1/CBFβ-SMMHC target genes in Runx1f/fMx1-CreCbfb+/56M cells, especially among downregulated genes, suggesting that RUNX1 and CBFβ-SMMHC mainly function together as activators of gene expression through direct target gene binding. These data indicate that Runx1 is indispensable for Cbfb-MYH11-induced leukemogenesis by working together with CBFβ-SMMHC to regulate critical genes associated with the generation of a functional AMP population.
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http://dx.doi.org/10.1182/blood.2020007747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685208PMC
November 2020

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke.

J Neuroinflammation 2020 Aug 14;17(1):237. Epub 2020 Aug 14.

Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, China.

Background: An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear.

Methods: A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses.

Results: Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p < 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p < 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%, p = 0.003; integrated discrimination improvement 5.78%, p = 0.0003).

Conclusions: sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.
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http://dx.doi.org/10.1186/s12974-020-01920-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427726PMC
August 2020

An Acceleration Based Fusion of Multiple Spatiotemporal Networks for Gait Phase Detection.

Int J Environ Res Public Health 2020 08 5;17(16). Epub 2020 Aug 5.

Artificial Intelligence Academy, Beijing Technology and Business University, Beijing 100048, China.

Human-gait-phase-recognition is an important technology in the field of exoskeleton robot control and medical rehabilitation. Inertial sensors with accelerometers and gyroscopes are easy to wear, inexpensive and have great potential for analyzing gait dynamics. However, current deep-learning methods extract spatial and temporal features in isolation-while ignoring the inherent correlation in high-dimensional spaces-which limits the accuracy of a single model. This paper proposes an effective hybrid deep-learning framework based on the fusion of multiple spatiotemporal networks (FMS-Net), which is used to detect asynchronous phases from IMU signals. More specifically, it first uses a gait-information acquisition system to collect IMU sensor data fixed on the lower leg. Through data preprocessing, the framework constructs a spatial feature extractor with CNN module and a temporal feature extractor, combined with LSTM module. Finally, a skip-connection structure and the two-layer fully connected layer fusion module are used to achieve the final gait recognition. Experimental results show that this method has better identification accuracy than other comparative methods with the macro-F1 reaching 96.7%.
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http://dx.doi.org/10.3390/ijerph17165633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460503PMC
August 2020

Wee1 kinase inhibitor AZD1775 potentiates CD8+ T cell-dependent antitumour activity via dendritic cell activation following a single high dose of irradiation.

Med Oncol 2020 Jul 21;37(8):66. Epub 2020 Jul 21.

Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

As standard treatments for cancer, DNA-damaging chemotherapeutic agents and irradiation therapy improve survival in patients with various cancers. Wee1, a kinase associated with the cell cycle, causes G2/M cell cycle arrest to allow repair of injured DNA in cancer cells, and a Wee1 inhibitor has been confirmed to lead to apoptosis in cancer cells. Recently, there has been renewed interest in exploring the immune environment which plays a significant role in tumour suppression. A Wee1 inhibitor combined with radiotherapy has been tested in lung, pancreatic, and prostate cancer and melanoma in vivo or in vitro. There is still no research evaluating the immunoregulatory effects of AZD1775 plus high-dose irradiation (IR) in vivo. T cell killing and CD8+ T cell depletion assays demonstrated that the combination of AZD1775 and IR delayed tumour growth in breast cancer mouse models. Additionally, combination treatment also suppressed the expression of PD-L1, a co-inhibitor, through the STAT3-IRF1 axis. The importance and originality of this study are that it explores the internal and external mechanisms of AZD1775 combined with a single high dose of IR and provides a rationale for applying the combination therapy described above in a clinical trial.
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http://dx.doi.org/10.1007/s12032-020-01390-wDOI Listing
July 2020

Frequency and Time Domain Nuclear-Electronic Orbital Equation-of-Motion Coupled Cluster Methods: Combination Bands and Electronic-Protonic Double Excitations.

J Phys Chem Lett 2020 Aug 28;11(15):6435-6442. Epub 2020 Jul 28.

Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520, United States.

The accurate description of excited vibronic states is important for modeling a wide range of photoinduced processes. The nuclear-electronic orbital (NEO) approach, which treats specified protons on the same level as the electrons, can describe excited electronic-protonic states. Herein the multicomponent equation-of-motion coupled cluster with singles and doubles (NEO-EOM-CCSD) method and its time-domain counterpart, TD-NEO-EOM-CCSD, are developed and implemented. The application of these methods to the HCN molecule highlights their capabilities. These methods predict qualitatively reasonable energies and intensities for a combination band corresponding to simultaneous excitation of two vibrational modes, as well as an overtone. These methods also describe states with double excitation character, such as excited electronic-protonic states corresponding to the simultaneous excitation of an electron and a proton. The ability of the NEO-EOM-CCSD method and its time-dependent counterpart to describe combination bands, overtones, and double excitations will enable a wide range of photochemical applications.
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http://dx.doi.org/10.1021/acs.jpclett.0c01891DOI Listing
August 2020

Metabolic Adjustments by LncRNAs in Peripheral Neutrophils Partly Account for the Complete Compensation of Asymptomatic MMD Patients.

CNS Neurol Disord Drug Targets 2020 ;19(4):306-317

Institute of Cerebrovascular Diseases Research, Department of Neurology, and Department of Neurosurgery of Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Due to the recent development of non-invasive examinations, more asymptomatic patients with Moyamoya Disease (MMD) have been diagnosed than ever. However, its underlying molecular mechanisms and clinical intervention guidelines are all still obscure.

Methods: Microarray was used to explore those differentially expressed mRNAs and lncRNAs in peripheral neutrophils of asymptomatic MMD patients. Then enrichment analyses based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for those differentially expressed mRNAs and lncRNA associated mRNAs were performed for underlying molecular mechanisms.

Results: Here, we identified a total of 2824 differentially expressed lncRNAs and 522 differentially expressed mRNAs (fold change > 2 and P<0.05) in peripheral neutrophils of asymptomatic MMD patients, compared with healthy controls. Then enrichment analyses based on GO and KEGG showed that the neighboring protein-coding mRNAs of those up-regulated and down-regulated lncRNAs were mainly involved in distinct metabolic processes respectively, which may act as a complementary response to insufficient blood supplies in MMD. Further enrichment analyses of those differentially expressed mRNAs preferentially listed essential physiological processes such as peptide cross-linking, chromatin assembly among others. Moreover, altered mRNAs also revealed to be enriched in renin secretion, platelet activation, inflammation and others.

Conclusion: We demonstrated for the first time that metabolic adjustments by dysregulated lncRNAs in peripheral neutrophils might partially account for the complete compensation of asymptomatic MMD patients. In addition, more attention should be paid on renin secretion and platelet activation in order to better understand the pathogenesis and guide clinical intervention for asymptomatic MMDs.
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http://dx.doi.org/10.2174/1871527319666200618150827DOI Listing
September 2021

Identification of a genomic region controlling thermotolerance at flowering in maize using a combination of whole genomic re-sequencing and bulked segregant analysis.

Theor Appl Genet 2020 Oct 13;133(10):2797-2810. Epub 2020 Jun 13.

The National Engineering Laboratory of Crop Resistance Breeding, School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.

Key Message: A novel genomic region controlling thermotolerance at flowering was identified by the combination of whole genomic re-sequencing and bulked segregant analysis in maize. The increasing frequency of extreme high temperature has brought a great threat to the development of maize throughout its life cycle, especially during the flowering phase. However, the genetic basis of thermotolerance at flowering in maize remains poorly understood. Here, we characterized a thermotolerant maize ecotype Abe2 and dissected its genetic basis using a F recombinant inbred line (RIL) population generated from a cross between Abe2 and B73. After continuous high temperature stress above 35 °C for 17 days, Abe2 and B73 show distinct leaf scorching phenotype under field conditions. To identify the genomic regions associated with the phenotypic variation, we applied a combination of whole genomic re-sequencing and bulked segregant analysis, and revealed 10,316,744 SNPs and 1,488,302 InDels between the two parental lines, and 2,693,054 SNPs and 313,757 InDels between the two DNA pools generated from the thermos-tolerant and the sensitive individuals of the RIL, of which, 108,655 and 17,853 SNPs may cause nonsynonymous variations. Finally, a 7.41 Mb genomic region on chromosome 1 was identified, and 7 candidate genes were annotated to participate in high temperature-related stress response. A candidate gene Zm00001d033339 encoding a serine/threonine protein kinase was proposed to be the most likely causative gene contributing to the thermotolerance at flowering by involving in stomatal movement (GO: 0010119) via Abscisic acid (ABA) pathway (KO04075). This work could provide an opportunity for gene cloning and pyramiding breeding to improve thermotolerance at flowering in maize.
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http://dx.doi.org/10.1007/s00122-020-03632-xDOI Listing
October 2020

Variation of biogeochemical cycle of riverine dissolved inorganic carbon and silicon with the cascade damming.

Environ Sci Pollut Res Int 2020 Aug 16;27(23):28840-28852. Epub 2020 May 16.

School of Geography and Planning, Guangdong Key Laboratory for Urbanization and Geosimulation, Sun Yat-sen University, Guangzhou, 510275, China.

To investigate the variation of the biogeochemical cycle of riverine dissolved inorganic carbon (DIC) and silicon (DSi) with the cascade damming, the bicarbonate ([Formula: see text]), dissolved silicon (DSi), and other environmental factors within the cascade reservoirs of the lower reaches of Yalongjiang River, passing through the southeastern Qinghai-Tibet Plateau, were systematically analyzed by collecting water samples during the wet season and dry season from 2018 to 2019, respectively. The results showed that the lower ratio of DSi to[Formula: see text] (0.044 ± 0.001) was mainly controlled by the domination of carbonate mineral in the sedimentary rock of the Yalongjiang River drainage basin. The DSi:[Formula: see text] ratio was positively correlated with discharge (P < 0.05), and negatively correlated with the water retention time (P < 0.01) and chlorophyll a, implying that the variations of DSi:[Formula: see text] ratio were mainly determined by the rock chemical weathering processes and the hydrologic process outside the reservoirs and the biological processes within the cascade reservoirs. The phytoplankton photosynthetic process stoichiometrically assimilated DSi and [Formula: see text], resulted in 3.46 × 10 t·Si a and 1.89 × 10 t·C a sequestering in the cascade reservoirs, respectively. Compared with the situation of dam-free in the lower reaches of Yalongjiang River, the export flux of [Formula: see text] and DSi at the mouth of Yalongjiang River was reduced by 11.87% and 62.50%, respectively; the ratio of DSi:[Formula: see text] decreased by 36.01% for only building the Ertan dam and 53.15% for the cascade damming, respectively. The water renewal time prolonged from 45 to 126.6 days due to the regulation of the cascade reservoirs in the mainstream. Ultimately, a conceptual model on migration-transformation of DIC and DSi within the cascade reservoirs in the lower reaches of Yalongjiang River was established. These findings demonstrated that riverine cascade damming could extend the biogeochemical coupling cycle of DIC and DSi within the inland aquatic ecosystems and ensure the ecological environment security in the hot-dry valley.
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http://dx.doi.org/10.1007/s11356-020-09174-5DOI Listing
August 2020

Single-Cell Transcriptome Analysis Reveals Intratumoral Heterogeneity in ccRCC, which Results in Different Clinical Outcomes.

Mol Ther 2020 07 29;28(7):1658-1672. Epub 2020 Apr 29.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, China. Electronic address:

Clear-cell renal cell carcinoma (ccRCC) is the most common histological type of RCC. To investigate the intratumoral heterogeneity of ccRCC, we analyzed single-cell RNA-sequencing data and identified 15 major cell types, along with 39 subgroups of cells derived from tumor or non-malignant tissues, and confirmed their presence by immunofluorescence staining in tissue chips. In this study, we verified that T cell exhaustion was the key factor responsible for the immunosuppressive property of ccRCC tissues, which was significantly related to poor prognosis. We also found that abnormal metabolic patterns occurred not only in cancer cells, but also in tumor-infiltrating stromal cells. Based on the fraction of each cell cluster detected by CIBERSORTx, 533 patients from The Cancer Genome Atlas (TCGA) KIRC dataset were divided into three groups. One group, which showed a lesser proportion of activated CD8 cells and greater proportion of exhausted CD8 cells, was associated with a poor prognosis. Hence, the blockade of immunosuppressive checkpoints, not only PD-1, but also LAG3, TIM-3, and other inhibitory checkpoints, could serve as a potential target for ccRCC immunotherapy. Our work will further the understanding of the heterogeneity among ccRCC tissues and provide novel strategies for treating ccRCC.
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http://dx.doi.org/10.1016/j.ymthe.2020.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335756PMC
July 2020

The Chinese herb aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats.

J Integr Neurosci 2020 Mar;19(1):21-29

Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 10053, P. R. China.

The neuroprotective role of in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.
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http://dx.doi.org/10.31083/j.jin.2020.01.1213DOI Listing
March 2020
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