Publications by authors named "Miao Tang"

78 Publications

[Size Distribution of Aerosol Hygroscopic Growth Factors in Winter in Tianjin].

Huan Jing Ke Xue 2021 Feb;42(2):574-583

China Meteorological Administration-Nankai University Cooperative Laboratory for Atmospheric Environment-Health Research, State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.

Aerosol hygroscopic growth factors[(RH)] are key for evaluating aerosol light extinction and direct radiative forcing. The hygroscopic tandem differential mobility analyzer (HTDMA) was utilized to measure the size-resolved (RH) under different polluted conditions in winter in Tianjin. Furthermore, based on the size distribution of aerosol water-soluble ions, the (RH) across a wide size range (60 nm to 9.8 μm) was estimated using the -Köhler theory, which provides a basis for the estimation of aerosol optical parameters and direct radiative forcing under ambient conditions. Under clean conditions, ultrafine particles (<100 nm) were more hygroscopic and (RH=80%) was higher than 1.30 due to the active photolysis reaction. However, under severely polluted conditions, the proportion of water-soluble ions in aerosols increased with the increasing size; (RH) increased with particle size, where (RH=80%) and (RH=85%) for 300 nm particles was 1.39 and 1.46, respectively. For a wide size range (60 nm to 9.8 μm), the aerosols in the accumulation mode were more hygroscopic and aerosols in the Aitken mode were less hygroscopic, with coarse mode aerosols being the least hygroscopic. During the polluted period, the particulate size notably increased, and the mass fraction of NO and SO in the accumulation mode aerosols was significantly higher than during the clean period. Accordingly, the hygroscopicity of accumulation mode aerosols was strongly enhanced during the polluted period[(RH)=1.3-1.4] and aerosols in the 0.18-3.1 μm size range all had a strong hygroscopicity. On polluted days, the synergistic effect of the increase in particle size, water-soluble ions, and aerosol hygroscopicity results in the considerable deterioration of visibility.
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http://dx.doi.org/10.13227/j.hjkx.202007273DOI Listing
February 2021

Pure arterial malformation with associated aneurysmal subarachnoid hemorrhage: Two case reports and literature review.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Feb;46(2):200-206

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.

In recent years, in the absence of venous component, dilated, overlapping, and tortuous arteries forming a mass of arterial loops with a coil-like appearance have been defined as pure arterial malformation (PAM). It is extremely rare, and its etiology and treatment have not yet been fully elucidated. Here, we reported 2 cases of PAM with associated aneurysmal subarachnoid hemorrhage in this paper. Both patients had severe headache as the first symptom. Subarachnoid hemorrhage was found by CT and computed tomography angiography (CTA) and PAM with associated aneurysm was found by digital subtraction angiography (DSA). In view of the distribution of blood and the location of aneurysms, the aneurysm rupture was the most likely to be considered. Based on the involvement of the lesion in the distal blood supply, only the aneurysm was clamped during the operation. It used to be consider that PAM is safety, because of the presentation and natural history of previously reported cases. Through the cases we reported, we have doubted about "the benign natural history" and discussed its treatment. PAM can promote the formation of aneurysms and should be reviewed regularly. The surgical indications for PAM patients with aneurysm formation need to be further clarified. Management of PAM patients with ruptured aneurysm is the same as that of ruptured aneurysm. Whether there are indications needed to treat simple arterial malformations remains to be further elucidated with the multicenter, randomized controlled studies on this disease.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190673DOI Listing
February 2021

Screening of chemical linkers for development of pullulan bioconjugates for intravitreal ocular applications.

Eur J Pharm Sci 2021 Mar 2;161:105785. Epub 2021 Mar 2.

University of Padova, Department of Pharmaceutical and Pharmacological Sciences, Via F. Marzolo 5, 35131 Padova, Italy. Electronic address:

The treatment of posterior segment disorders of the eye requires therapeutic strategies to achieve drug effects over prolonged times. Innovative colloidal delivery systems can be designed to deliver drugs to the retina and prolong their intravitreal permanence. In order to exploit pullulan (Pull) as polymeric drug carrier for intravitreal drug delivery, derivatives of hydrophobic model molecule rhodamine B (RhB) were conjugated to the pullulan backbone through linkers with different stability, namely ether (Et), hydrazone (Hy) or ester (Es) bond to obtain Pull-Et-RhB, Pull-Hy-RhB and Pull-Es-RhB, respectively. Dynamic light scattering and transmission electron microscopy analyses showed that the polymer conjugates self-assembled into 20-25 nm particles. Pull-Et-RhB was fairly stable at all tested pH values. At the vitreal pH of 7.4, 50% of RhB was released from Pull-Hy-RhB and Pull-Es-RhB in 11 and 6 days, respectively. At endosomal pH (5.5), 50% of RhB was released from Pull-Hy-RhB and Pull-Es-RhB in 4 and 1 days, respectively. Multiple particle tracking analyses in ex vivo porcine eye model showed that the diffusivity of the bioconjugates in the vitreous was about 10 times lower than in water. Flow cytometry and confocal microscopy analyses showed that bioconjugates are remarkably taken up by the retinal RPE cells. In vivo studies showed that after intravitreal injection to mice, the bioconjugates localize in the ganglion cell layer and in the inner and outer plexiform layers. Pull-Hy-RhB particles were detected also inside the retinal blood vessels. These results demonstrate that pullulan with tailored linkers for drug conjugation is a promising vehicle for long-acting intravitreal injectables that are capable to permeate to the retina.
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http://dx.doi.org/10.1016/j.ejps.2021.105785DOI Listing
March 2021

N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerization.

Nat Commun 2021 03 2;12(1):1379. Epub 2021 Mar 2.

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Many immune responses depend upon activation of NF-κB, an important transcription factor in the elicitation of a cytokine response. Here we show that N4BP1 inhibits TLR-dependent activation of NF-κB by interacting with the NF-κB signaling essential modulator (NEMO, also known as IκB kinase γ) to attenuate NEMO-NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like (ubiquitin conjugation to ER degradation-like) domains in N4BP1 mediate interaction with the NEMO COZI domain. Both in vitro and in mice, N4bp1 deficiency specifically enhances TRIF-independent (TLR2, TLR7, or TLR9-mediated) but not TRIF-dependent (TLR3 or TLR4-mediated) NF-κB activation, leading to increased production of proinflammatory cytokines. In response to TLR4 or TLR3 activation, TRIF causes activation of caspase-8, which cleaves N4BP1 distal to residues D424 and D490 and abolishes its inhibitory effect. N4bp1 mice also have diminished numbers of T cells in the peripheral blood. Our work identifies N4BP1 as an inhibitory checkpoint protein that must be overcome to activate NF-κB, and a TRIF-initiated caspase-8-dependent mechanism by which this is accomplished.
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http://dx.doi.org/10.1038/s41467-021-21711-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925594PMC
March 2021

An Integrated Design of a Polypseudorotaxane-Based Sea Cucumber Mimic.

Angew Chem Int Ed Engl 2021 Feb 19. Epub 2021 Feb 19.

Department of Chemistry, Dartmouth College, Hanover, NH, 03755, USA.

The development of integrated systems that mimic the multi-stage stiffness change of marine animals such as the sea cucumber requires the design of molecularly tailored structures. Herein, we used an integrated biomimicry design to fabricate a sea cucumber mimic using sidechain polypseudorotaxanes with tunable nano-to-macroscale properties. A series of polyethylene glycol (PEG)-based sidechain copolymers were synthesized to form sidechain polypseudorotaxanes with α-cyclodextrins (α-CDs). By tailoring the copolymers' molecular weights and their PEG grafting densities, we rationally tuned the sizes of the formed polypseudorotaxanes crystalline domain and the physical crosslinking density of the hydrogels, which facilitated 3D printing and the mechanical adaptability to these hydrogels. After 3D printing and photo-crosslinking, the obtained hydrogels exhibited large tensile strain and broad elastic-to-plastic variations upon α-CD (de)threading. These discoveries enabled a successful fabrication of a sea cucumber mimic, demonstrating multi-stage stiffness changes.
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http://dx.doi.org/10.1002/anie.202017019DOI Listing
February 2021

[Characterization and Source Apportionment of Atmospheric VOCs in Tianjin in 2019].

Huan Jing Ke Xue 2021 Jan;42(1):55-64

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

The characterization and source apportionment of atmospheric volatile organic compounds (VOCs) in Tianjin in 2019 were investigated based on high-resolution online monitoring data observed at an urban site in Tianjin. The results showed that the average annual concentration of VOCs was 48.9 μg·m, and seasonal concentrations followed with winter (66.9 μg·m) > autumn (47.9 μg·m) > summer (42.0 μg·m) > spring (34.6 μg·m). The chemical compositions of the VOCs were alkanes, aromatics, alkenes, and alkynes, which accounted for 65.0%, 17.4%, 14.6%, and 3.0% of the VOCs concentrations on average, respectively. The proportion of alkanes, aromatics, and alkynes was the highest in autumn, summer, and winter, respectively, while a higher alkenes proportion was observed in summer and winter. The ozone formation potential contribution of alkanes, alkenes, aromatics, and alkynes in spring and summer was 16.9%, 48.6%, 33.5%, and 1.0%, respectively, and the species with higher contributions were ethene, propylene, ,-xylene, 1,2,3-trimethylbenzene, toluene, isoprene, trans-2-butene, cis-2-pentene, -xylene, and -ethyltoluene. During autumn and winter, the aromatics contributed as much as 91.5% to the secondary organic aerosol (SOA) formation potential, and -xylene, toluene, ,-xylene, ethylbenzene, -ethyltoluene, and benzene were the main contributing species. Positive matrix factorization was applied to estimate VOCs source contributions, and automobile exhaust, liquefied petroleum gas/natural gas (LPG/NG) and gasoline evaporation, solvent usage, petrochemical industrial emissions, combustion, and natural sources were identified as major sources of VOCs in spring and summer, accounting for 29.2%, 19.9%, 16.4%, 10.3%, 7.3%, and 6.6%, respectively. While in autumn and winter, the contributions of LPG/NG and gasoline evaporation, automobile exhaust, combustion, solvent usage, and petrochemical industrial emissions were 32.4%, 21.9%, 18.5%, 13.3%, and 8.4%, respectively. Compared to the source contributions in spring and summer, a significant increase was observed for LPG/NG and combustion emission of 62.8% and 153.4%, respectively, and other sources decreased by 18.4%-25.0% in autumn and winter. Source composition spectrums showed that the petrochemical industry and solvent usage were the main emission sources of alkenes and aromatics in spring and summer, and combustion and solvent usage were the main emission sources of aromatics in autumn and winter. Thus, focus should be played on the petrochemical industry and solvent usage in spring and summer and on combustion and solvent usage in autumn and winter to further prevent and control ozone and SOA in Tianjin.
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http://dx.doi.org/10.13227/j.hjkx.202006257DOI Listing
January 2021

The critical role of superoxide anion radicals on delaying tetrachlorohydroquinone autooxidation by penicillamine.

Free Radic Biol Med 2021 Feb 19;163:369-378. Epub 2020 Dec 19.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Beijing, Hong Kong, PR China. Electronic address:

We have recently found that penicillamine, a classic copper-chelating thiol-drug for Wilson's disease, can delay tetrachlorohydroquinone (TCHQ) autooxidation via a previously unrecognized redox-activity. However, its underlying molecular mechanism remains not fully understood. In this study, we found, interestingly and unexpectedly, that superoxide dismutase (SOD) can significantly shorten the delay of TCHQ autooxidation by penicillamine, but not by ascorbate; SOD can also markedly increase the yields of the oxidized form of penicillamine. Similar effects were observed with a recently-developed specific and sensitive superoxide anion radical (O) probe CT-02H, which was also employed to successfully measure O generated from both TCHQ and TCHQ/penicillamine systems for the first time. More importantly, addition of extra O (KO/18-crown-6) can further prolong the delaying effects by penicillamine and slow down penicillamine consumption. Taken together, an unexpected critical role of O in TCHQ/penicillamine interaction was proposed: O may regenerate penicillamine, thereby continuously reducing TCSQ to TCHQ and finally delaying TCHQ autooxidation; In contrast, if O were eliminated, which can not only markedly change the reaction equilibrium, accelerate the rate of interaction, and ultimately shorten the delay of TCHQ autooxidation by penicillamine, but can also accelerate penicillamine oxidation to form its corresponding disulfide solely via redox reaction without any minor nucleophilic reaction. These findings not only further support our previously-proposed redox mechanism for the protection against TCHQ-induced cytotoxicity by penicillamine, but also reveal a new mode of action for O in the inhibition of haloquinoids-induced toxicity by thiol antioxidants.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.014DOI Listing
February 2021

mutations identified in autism spectrum disorder using forward genetics.

Elife 2020 12 22;9. Epub 2020 Dec 22.

Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, United States.

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental disorders with high phenotypic and genetic heterogeneity, complicating the discovery of causative genes. Through a forward genetics approach selecting for defective vocalization in mice, we identified as a candidate ASD gene. To validate our discovery, we generated a knockout mouse model () and confirmed that inactivating disrupts vocalization. In addition, mice displayed repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis. Loss of KDM5A also resulted in dysregulation of the hippocampal transcriptome. To determine if mutations cause ASD in humans, we screened whole exome sequencing and microarray data from a clinical cohort. We identified pathogenic variants in nine patients with ASD and lack of speech. Our findings illustrate the power and efficacy of forward genetics in identifying ASD genes and highlight the importance of KDM5A in normal brain development and function.
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http://dx.doi.org/10.7554/eLife.56883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755391PMC
December 2020

Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration.

J Neuroinflammation 2020 Nov 25;17(1):355. Epub 2020 Nov 25.

The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.

Background: Macular fibrosis causes irreparable vision loss in neovascular age-related macular degeneration (nAMD) even with anti-vascular endothelial growth factor (VEGF) therapy. Inflammation is known to play an important role in macular fibrosis although the underlying mechanism remains poorly defined. The aim of this study was to understand how infiltrating macrophages and complement proteins may contribute to macular fibrosis.

Methods: Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser protocol developed by our group. The eyes were collected at 10, 20, 30 and 40 days after the second laser and processed for immunohistochemistry for infiltrating macrophages (F4/80 and Iba-1), complement components (C3a and C3aR) and fibrovascular lesions (collagen-1, Isolectin B4 and α-SMA). Human retinal sections with macular fibrosis were also used in the study. Bone marrow-derived macrophages (BMDMs) from C57BL/6J mice were treated with recombinant C3a, C5a or TGF-β for 48 and 96 h. qPCR, Western blot and immunohistochemistry were used to examine the expression of myofibroblast markers. The involvement of C3a-C3aR pathway in macrophage to myofibroblast transition (MMT) and subretinal fibrosis was further investigated using a C3aR antagonist (C3aRA) and a C3a blocking antibody in vitro and in vivo.

Results: Approximately 20~30% of F4/80 (or Iba-1) infiltrating macrophages co-expressed α-SMA in subretinal fibrotic lesions both in human nAMD eyes and in the mouse model. TGF-β and C3a, but not C5a treatment, significantly upregulated expression of α-SMA, fibronectin and collagen-1 in BMDMs. C3a-induced upregulation of α-SMA, fibronectin and collagen-1 in BMDMs was prevented by C3aRA treatment. In the two-stage laser model of induced subretinal fibrosis, treatment with C3a blocking antibody but not C3aRA significantly reduced vascular leakage and Isolectin B4 lesions. The treatment did not significantly alter collagen-1 fibrotic lesions.

Conclusions: MMT plays a role in macular fibrosis secondary to nAMD. MMT can be induced by TGF-β and C3a but not C5a. Further research is required to fully understand the role of MMT in macular fibrosis. Macrophage to myofibroblast transition (MMT) contributes to subretinal fibrosis. Subretinal fibrosis lesions contain various cell types, including macrophages and myofibroblasts, and are fibrovascular. Myofibroblasts are key cells driving pathogenic fibrosis, and they do so by producing excessive amount of extracellular matrix proteins. We have found that infiltrating macrophages can transdifferentiate into myofibroblasts, a phenomenon termed macrophage to myofibroblast transition (MMT) in macular fibrosis. In addition to TGF-β1, C3a generated during complement activation in CNV can also induce MMT contributing to macular fibrosis. RPE = retinal pigment epithelium. BM = Bruch's membrane. MMT = macrophage to myofibroblast transition. TGFB = transforming growth factor β. a-SMA = alpha smooth muscle actin. C3a = complement C3a.
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http://dx.doi.org/10.1186/s12974-020-02033-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690191PMC
November 2020

Unexpected reversible and controllable nuclear uptake and efflux of the DNA "light-switching" Ru(ii)-polypyridyl complex in living cells via ion-pairing with chlorophenolate counter-anions.

J Mater Chem B 2020 12 10;8(45):10327-10336. Epub 2020 Nov 10.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, China. and Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Beijing, Hong Kong, China.

An in-depth understanding of the mechanisms of cellular uptake and efflux would facilitate the design of metal complexes with not only better functionality and targeted theranostic efficiency, but also with controlled toxicity. Here we find, unexpectedly, that the DNA "light-switching" Ru(ii)-polypyridyl complex [Ru(phen)(dppz)] already delivered to the nucleus via ion-pairing with chlorophenolate counter-anions can gradually efflux to the cytoplasm when the cells were washed and incubated with fresh culture-medium. Interestingly, [Ru(phen)(dppz)] effluxed to the cytoplasm can be redirected back to the nucleus when the chlorophenolate counter-anions were added again. The efflux of nuclear [Ru(phen)(dppz)] was found to be mediated mainly via ATP-binding cassette (ABC) transporter proteins. Analogous reversible, but enantio-selective nuclear uptake and efflux were observed with the two pure chiral forms of [Ru(phen)(dppz)]Cl. This represents the first report of reversible and controllable nuclear uptake and efflux of a DNA "light-switching" Ru(ii)-complex in living-cells via ion-pairing, which should provide novel insights for future research on using ion-pairing as an effective approach to control the cellular uptake and redistribution of other potential theranostic metal complexes.
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http://dx.doi.org/10.1039/d0tb00821dDOI Listing
December 2020

[Characterization and Source Apportionment of PM Based on the Online Observation in Tianjin].

Huan Jing Ke Xue 2020 Oct;41(10):4355-4363

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

To study the characterization and source apportionment of PM in Tianjin, based on high-resolution online monitoring data from 2017 to 2019, the concentrations and its chemical compositions and sources of PM were analyzed. The results showed that the average concentration of PM was 61 μg ·m. The primary chemical compositions of PM were nitrate, organic carbon (OC), ammonium, sulfate, elemental carbon (EC), and Cl and their corresponding mass percentages to PM were 17.7%, 12.6%, 11.5%, 10.7%, 3.4%, and 3.1%, respectively. From 2017 to 2019, the concentrations of PM and its main chemical compositions exhibited a decreasing trend; the mass ratios of NO and NH to PM exhibited an increasing trend, while the mass ratios of SO, OC, and EC to PM exhibited a decreasing trend; further, the mass ratio of Cl exhibited a slight increasing trend. The concentrations of K, Ca, and Na and their mass percentages to PM increased. The concentrations of PM and its primary components were relatively higher during heating season, and relatively lower during non-heating season. High values of SOR and NOR indicated that the secondary transformation of nitrate and sulfate played an important role during summer and autumn, which resulted in higher mass percentages of secondary inorganic ions (NO, SO, and NH) to PM during summer and autumn. When the PM concentrations were at excellent levels, the mass ratios of the secondary inorganic ions to PM were relatively lower, the mass ratios of OC, Ca, and Na to PM were relatively higher, and secondary organic carbon (SOC) was high. When the PM concentrations were between light pollution to heavy pollution levels, as the pollution levels increased, the mass percentages of secondary inorganic ions, OC, EC, and Cl, and other components (K, Ca, and Na) showed a significant increasing trend, relatively stable level, slightly increasing trend, and decreasing trend, respectively. When PM concentrations were between moderate pollution to heavy pollution levels, the influence of vehicle emission increased significantly. The source apportionment of PM were analyzed using the positive matrix factorization model. The major sources of PM in Tianjin were secondary source, vehicle exhaust, industrial and coal combustion emissions, and crustal dust. From 2017 to 2019, the contribution of vehicle exhaust increased, and the contribution of secondary source and crustal dust showed a slight increasing trend, while the contribution of industrial and coal combustion emissions decreased. For Tianjin, vehicle exhaust and industrial and coal combustion emissions were the primary sources of PM. The adjustment of industrial and energy structure and management and control of vehicle exhaust are the main directions for air pollution control in Tianjin.
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http://dx.doi.org/10.13227/j.hjkx.202001185DOI Listing
October 2020

[Characteristics of Secondary Organic Particles and the Potential Formation of SOA from VOCs During Wintertime Heavy Pollution Episodes in Tianjin].

Huan Jing Ke Xue 2020 Aug;41(8):3492-3499

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

The characteristics of secondary organic reactions were studied based on supersite monitoring data from January to March, 2019, in Tianjin. During heavy pollution episodes, SOC (secondary organic carbon) accounted for between 3.1% and 3.8% of PM, and the growth rate of SOC was obviously higher than that of PM, thus indicating that secondary organic reactions had a considerable effect on PM. The growth rate of VOCs (volatile organic compounds) was lower than that of PM, which was probably due to the fact that VOCs were consumed as precursors to secondary particles. The ratio of ethane to acetylene was higher than 2.0 during heavy pollution episodes indicating that air masses were old, and the ratio was lower than clean air days showing that the reaction activities were higher than before. During the heavy pollution episodes, the potential formation of SOA (secondary organic aerosol) from VOCs ranged from 0.49 to 1.21 μg·m. Among the species, aromatic hydrocarbons contributed the most, whereby the highest contribution exceeded 90%, and their growth rates were also the highest; hence, aromatic hydrocarbons were the VOCs species that had the greatest effect on SOA.
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http://dx.doi.org/10.13227/j.hjkx.202001116DOI Listing
August 2020

[Characterization of Two Heavy Pollution Episodes in Tianjin in 2020].

Huan Jing Ke Xue 2020 Sep;41(9):3879-3888

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

High-resolution online monitoring data from January to February in 2020 was used to study the characterization of two heavy pollution episodes in Tianjin in 2020; the heavy pollution episode that lasted from January 16 to 18, 2020 (referred to as episode Ⅰ) and that from February 9 to 10, 2020 (referred to as episode Ⅱ) were analyzed. The results showed that two heavy pollution episodes were influenced by regional transportation in the early stage and local adverse meteorological conditions in the later stage. During these episodes, the average wind speed was low, the average relative humidity was close to 70%, and relative humidity approached the saturated, the boundary layer heights were below 300 m, and the horizontal and vertical diffusion conditions were poor. Compared to episode Ⅰ, the concentration of pollutants decreased during episode Ⅱ, especially for the concentration of NO. During the episode Ⅱ, the concentrations of PM and CO were higher in the north of Tianjin. The chemical component concentrations and their mass ratios to PM changed significantly in both episodes; the concentrations of secondary inorganic ions (NO, SO, and NH), elemental carbon (EC) and Cawere higher in episode Ⅰ, the concentrations of organic carbon (OC) and Cl slightly increased in episode Ⅱ; and the concentrations of Kwere higher in episode Ⅱ. Compared to episode Ⅰ, because of the increase in the combustion sources and significant reductions in the number of vehicles, the mass ratios of SO, OC, and K to PM increased while the mass ratios of NO and EC to PM decreased in episode Ⅱ; the mass ratios of NH and Cl to PM were relatively higher due to the continuity of the industrial production processes; the mass ratios of Ca to PM were lower in two heavy pollution episodes because construction activities were halted. Source apportionment of PM was performed using the positive matrix factorization (PMF) model. In episode Ⅰ, the major sources of PM in Tianjin were secondary sources, industrial and coal combustion, vehicle exhaust, crustal dust, fireworks and biomass burning, with contributions of 53.8%, 20.2%, 18.6%, 6.3%, and 1.1%, respectively. In episode Ⅱ, the same sources were identified in the PMF analysis with contributions of 48.3%, 28.2%, 8.7%, 2.6%, and 12.2%, respectively. Compared to episode Ⅰ, the contributions of industrial and coal combustion, fireworks and biomass burning increased, and the contributions of secondary sources, vehicle exhaust, and crustal dust decreased in episode Ⅱ; contributions of vehicle exhaust and crustal dust decreased by 53.2% and 58.7%, respectively.
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http://dx.doi.org/10.13227/j.hjkx.202003109DOI Listing
September 2020

First Direct and Unequivocal Electron Spin Resonance Spin-Trapping Evidence for pH-Dependent Production of Hydroxyl Radicals from Sulfate Radicals.

Environ Sci Technol 2020 11 16;54(21):14046-14056. Epub 2020 Oct 16.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.

Recently, the sulfate radical (SO) has been found to exhibit broad application prospects in various research fields such as chemical, biomedical, and environmental sciences. It has been suggested that SO could be transformed into a more reactive hydroxyl radical (OH); however, no direct and unequivocal experimental evidence has been reported yet. In this study, using an electron spin resonance (ESR) secondary radical spin-trapping method coupled with the classic spin-trapping agent 5,5-dimethyl-1-pyrroline -oxide (DMPO) and the typical OH-scavenging agent dimethyl sulfoxide (DMSO), we found that OH can be produced from three SO-generating systems from weakly acidic (pH = 5.5) to alkaline conditions (optimal at pH = 13.0), while SO is the predominant radical species at pH < 5.5. A comparative study with three typical OH-generating systems strongly supports the above conclusion. This is the first direct and unequivocal ESR spin-trapping evidence for OH formation from SO over a wide pH range, which is of great significance to understand and study the mechanism of many SO-related reactions and processes. This study also provides an effective and direct method for unequivocally distinguishing OH from SO.
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http://dx.doi.org/10.1021/acs.est.0c04410DOI Listing
November 2020

Early Molecular Events during Onset of Diapause in Silkworm Eggs Revealed by Transcriptome Analysis.

Int J Mol Sci 2020 Aug 27;21(17). Epub 2020 Aug 27.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

Diapause is a form of dormancy, and silkworm embryos are ideal models for studying diapause in insects. However, molecular events in eggs during the onset of diapause remain unclear. In this study, transcriptome analyses were performed on silkworm diapause eggs via RNA sequencing at 20 and 48 h after oviposition. A total of 6402 differentially expressed genes (DEGs) were detected in diapause eggs at 48 h versus that at 20 h after oviposition. Gene ontology enrichment analysis showed that DEGs in diapause eggs at 48 h versus that at 20 h after oviposition were involved in ribosome-related metabolism and hydrogen transport. Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched biological pathways, namely the oxidative phosphorylation, Forkhead box protein O3 (FoxO) signaling, ribosome, endoplasmic reticular protein processing, and autophagy pathways. Fifteen DEGs from the FoxO signaling pathway were selected, and their expression profiles were consistent with the transcriptome results from real-time quantitative reverse transcription polymerase chain reaction. Our results can improve understanding of the diapause mechanism in silkworm eggs and identified key pathways for future studies.
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http://dx.doi.org/10.3390/ijms21176180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503879PMC
August 2020

A Two-Stage Laser-Induced Mouse Model of Subretinal Fibrosis Secondary to Choroidal Neovascularization.

Transl Vis Sci Technol 2020 03 9;9(4). Epub 2020 Mar 9.

The Welcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.

Purpose: To develop a model that can recapitulate key features of macular fibrosis in neovascular age-related macular degeneration (nAMD).

Methods: Adult C57BL/6J mice received three laser burns/eye to induce choroidal neovascularization (CNV). Seven days later, a second laser burn was directed to each of the neovascular lesions. Traditional laser-induced CNV was used as a control. Lesions were monitored at 10, 20, 30, and 40 days post-laser (p.l) treatment by fundus imaging, fundus fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. The expression of collagen-1 (COL-1), fibronectin, α-smooth muscle actin, F4/80, complement factor B (CFB), Complement component 3 (C3), transforming growth factor-β (TGF-β), and fibroblast growth factor 2 (FGF2) in retina and retinal pigment epithelium/choroid was examined by immunofluorescence and reverse transcription polymerase chain reaction.

Results: The two-stage laser protocol induced significantly larger lesions than the traditional laser-CNV by OCT and immunohistochemistry at all time points. Confocal microscopy detected COL-1 fibers and IBA1/CD31 blood vessels in lesions from the two-stage laser protocol 30 to 40 days p.l. Lesions from traditional laser-CNV contain only COL-1 fibers but not blood vessels at this time point. Higher levels of proinflammatory (inducible nitric oxide synthase (iNOS), C3, CFB) and profibrotic (TGF-β, FGF2, and vascular endothelial growth factor) genes were detected in the retinas from the two-stage laser-induced lesions compared with the traditional laser-CNV lesion. Higher number of infiltrating F4/80 macrophages was also observed in and around the two-stage laser-induced fibrotic lesion.

Conclusions: The two-stage laser treatment induced subretinal fibrovascular membranes that persist over 40 days.

Translational Relevance: The model is a useful tool to study the mechanism of macular fibrosis in nAMD and test antifibrotic drugs.
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http://dx.doi.org/10.1167/tvst.9.4.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396176PMC
March 2020

Dominant atopy risk mutations identified by mouse forward genetic analysis.

Allergy 2021 Apr 20;76(4):1095-1108. Epub 2020 Sep 20.

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background: Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice.

Methods: We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation.

Results: Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations.

Conclusions: Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.
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http://dx.doi.org/10.1111/all.14564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889751PMC
April 2021

In situ continuous hourly observations of wintertime nitrate, sulfate and ammonium in a megacity in the North China plain from 2014 to 2019: Temporal variation, chemical formation and regional transport.

Chemosphere 2021 Jan 25;262:127745. Epub 2020 Jul 25.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, 100083, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Nitrate (NO), sulfate (SO) and ammonium (NH) in airborne fine particles (PM) play a vital role in the formation of heavy air pollution in northern China. In particular, the increasing contribution of NO to PM has attracted worldwide attention. In this study, a highly time-resolved analyzer was used to measure water-soluble inorganic ions in PM in one of the fastest-developing megacities, Tianjin, China, from November 15 to March 15 (wintertime heating period) in 2014-2019. Severe PM pollution episodes markedly decreased during the heating period from 2014 to 2019. The highest concentrations of NO and SO were recorded in the heating period of 2015/2016. Afterwards, NO decreased from 2015/2016 (20.2 ± 23.8 μg/m) to 2017/2018 (11.6 ± 14.8 μg/m) but increased with increasing NO concentrations during the heating period of 2018/2019. A continuous decrease in the SO concentration led to a decrease in SO from 2015/2016 (16.8 ± 21.8 μg/m) to 2018/2019 (6.5 ± 8.9 μg/m). The NO and SO concentrations increased as the air quality deteriorated. However, the proportion of NO and SO in PM slightly increased when the air quality deteriorated from moderate pollution (MP) to severe pollution (SP) levels. The average molar ratios of NH to [NO+2 × (SO)] were 1.7, 0.9, 1.2, 1.2 and 1.5 for the heating periods of 2014/2015, 2015/2016, 2016/2017, 2017/2018 and 2018/2019, respectively, most of which were higher than 1.0, thus revealing an overall excess of NH during the heating periods. However, the molar equivalent ratios of [NH] to [NO+2 × (SO)] were less than 1 under increasing PM pollution. The molar equivalent ratios of [NO]/[SO] were positively correlated with those of [NH]/[SO]. When the molar equivalent ratios of [NH]/[SO] were more than 1.5, those of [NO]/[SO] increased from close to 1 to higher values, indicating that the dominance of NO formation played an important role. The results of nonparametric wind regression exhibited distinct hot spots of NO, SO and NH (higher concentrations) in the wind sectors between NE and SE at wind speeds of approximately 6-21 km/h. The southern areas in the North China Plain and parts of the western areas of China contributed more NO, SO and NH than other areas to the study site. The abovementioned areas were also characterized by a higher contribution of NO than of SO to the study site and by NH-rich conditions. In summary, more efforts should be made to reduce NO in the Beijing-Tianjin-Hebei region. This study provides observational evidence of the increasingly important role of nitrate as well as scientific support for formulating effective control strategies for regional haze in China.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127745DOI Listing
January 2021

Adenosine monophosphate deaminase 3 null mutation causes reduction of naive T cells in mouse peripheral blood.

Blood Adv 2020 08;4(15):3594-3605

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX.

Adenosine monophosphate deaminase 3 (Ampd3) encodes the erythrocyte isoform of the adenosine monophosphate (AMP) deaminase gene family. Mutations in this gene have been reported in humans, leading to autosomal-recessive erythrocyte AMP deaminase deficiency. However, the mutation is considered clinically asymptomatic. Using N-ethyl-N-nitrosourea mutagenesis to find mutations that affect peripheral lymphocyte populations, we identified 5 Ampd3 mutations (Ampd3guangdong, Ampd3carson, Ampd3penasco, Ampd3taos, and Ampd3commanche) that strongly correlated with a reduction in naive CD4+ T and naive CD8+ T-cell populations. Causation was confirmed by targeted ablation of Ampd3. Knockout mice had reduced frequencies of CD62LhiCD44lo CD4+ naive and CD8+ naive T cells. Interestingly, these phenotypes were restricted to T cells circulating in peripheral blood and were not seen in T cells from secondary lymphoid organs (lymph nodes and spleen). We found that reduction of naive T cells in the peripheral blood of Ampd3-/- mice was caused by T-cell-extrinsic factor(s), which we hypothesize to be elevated levels of adenosine triphosphate released by Ampd3-deficient erythrocytes. These findings provide an example in which disruption of an erythrocyte-specific protein can affect the physiological status of lymphocytes in peripheral blood.
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http://dx.doi.org/10.1182/bloodadvances.2020001762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422112PMC
August 2020

Forward genetic analysis using OCT screening identifies mutations leading to progressive outer retinal degeneration in mice.

Proc Natl Acad Sci U S A 2020 06 26;117(23):12931-12942. Epub 2020 May 26.

Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Retinal disease and loss of vision can result from any disruption of the complex pathways controlling retinal development and homeostasis. Forward genetics provides an excellent tool to find, in an unbiased manner, genes that are essential to these processes. Using -ethyl--nitrosourea mutagenesis in mice in combination with a screening protocol using optical coherence tomography (OCT) and automated meiotic mapping, we identified 11 mutations presumably causative of retinal phenotypes in genes previously known to be essential for retinal integrity. In addition, we found multiple statistically significant gene-phenotype associations that have not been reported previously and decided to target one of these genes, (encoding sideroflexin-3), using CRISPR/Cas9 technology. We demonstrate, using OCT, light microscopy, and electroretinography, that two mouse lines developed progressive and severe outer retinal degeneration. Electron microscopy showed thinning of the retinal pigment epithelium and disruption of the external limiting membrane. Using single-cell RNA sequencing of retinal cells isolated from C57BL/6J mice, we demonstrate that is expressed in several bipolar cell subtypes, retinal ganglion cells, and some amacrine cell subtypes but not significantly in Müller cells or photoreceptors. In situ hybridization confirmed these findings. Furthermore, pathway analysis suggests that Sfxn3 may be associated with synaptic homeostasis. Importantly, electron microscopy analysis showed disruption of synapses and synaptic ribbons in the outer plexiform layer of mice. Our work describes a previously unknown requirement for in retinal function.
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http://dx.doi.org/10.1073/pnas.1921224117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293615PMC
June 2020

Genetic and structural studies of RABL3 reveal an essential role in lymphoid development and function.

Proc Natl Acad Sci U S A 2020 04 27;117(15):8563-8572. Epub 2020 Mar 27.

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390-8505;

The small GTPase RABL3 is an oncogene of unknown physiological function. Homozygous knockout alleles of mouse were embryonic lethal, but a viable hypomorphic allele ( []) causing in-frame deletion of four amino acids from the interswitch region resulted in profound defects in lymphopoiesis. Impaired lymphoid progenitor development led to deficiencies of B cells, T cells, and natural killer (NK) cells in mice. T cells and NK cells exhibited impaired cytolytic activity, and mice infected with mouse cytomegalovirus (MCMV) displayed elevated titers in the spleen. Myeloid cells were normal in number and function. Biophysical and crystallographic studies demonstrated that RABL3 formed a homodimer in solution via interactions between the effector binding surfaces on each subunit; monomers adopted a typical small G protein fold. RABL3 displayed a large compensatory alteration in switch I, which adopted a β-strand configuration normally provided by the deleted interswitch residues, thereby permitting homodimer formation. Dysregulated effector binding due to conformational changes in the switch I-interswitch-switch II module likely underlies the phenotype. One such effector may be GPR89, putatively an ion channel or G protein-coupled receptor (GPCR). RABL3, but not RABL3, strongly associated with and stabilized GPR89, and an -ethyl--nitrosourea (ENU)-induced mutation () in phenocopied .
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http://dx.doi.org/10.1073/pnas.2000703117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165429PMC
April 2020

Single-cell RNA sequencing study of retinal immune regulators identified CD47 and CD59a expression in photoreceptors-Implications in subretinal immune regulation.

J Neurosci Res 2020 07 12;98(7):1498-1513. Epub 2020 Mar 12.

Aier Eye Institute, Aier School of Ophthalmology, Central South University, Changsha, P.R. China.

The neuroretina is protected by its own defense system, that is microglia and the complement system. Under normal physiological conditions, microglial activation is tightly regulated by the neurons although the underlying mechanism remains elusive. Using published single-cell RNA sequencing data sets, we found that immune regulatory molecules including CD200, CD47, CX3CL1, TGFβ, and complement inhibitor CD59a are expressed by various retinal neurons. Importantly, we found that photoreceptors express higher levels of CD47 and CD59a, which was further confirmed in cultured 661W cells, WERI-Rb1 cells, and microdissected photoreceptors from human eyes. The expression of CD59a mRNA in 661W cells was upregulated by TNFα and hypoxia, whereas LPS, hypoxia, and IL-4 upregulated CD47 mRNA expression in 661W cells. Immunofluorescence staining detected strong CD59a immunoreactivity in the outer nuclear layer, inner/outer segments, and discrete staining in ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer. The expression of CD59a in photoreceptors was increased in the detached retina, but decreased in retinas from experimental autoimmune uveoretinitis (EAU) mice. In EAU retina, CD59a was highly expressed by active immune cells. CD47 was detected in GCL, IPL, and inner nuclear layer and some photoreceptors. The expression of CD47 in photoreceptors was also increased in the detached retina but decreased in EAU retina. In a coculture system, 661W enhanced arginase-1 and reduced IL-6 mRNA expression in BV2 microglial cells. Our results suggest that photoreceptors express immune regulatory molecules and may have the potential to regulate immune activation in the outer retina/subretinal space under pathophysiological conditions.
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http://dx.doi.org/10.1002/jnr.24618DOI Listing
July 2020

Quantitative Analyses of the Interfacial Properties of Current Collectors at the Mesoscopic Level in Lithium Ion Batteries by Using Hierarchical Graphene.

Nano Lett 2020 Mar 28;20(3):2175-2182. Epub 2020 Feb 28.

Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People's Republic of China.

At the mesoscopic level of commercial lithium ion battery (LIB), it is widely believed that the poor contacts between current collector (CC) and electrode materials (EM) lead to weak adhesions and large interfacial electric resistances. However, systematic quantitative analyses of the influence of the interfacial properties of CC are still scarce. Here, we built a model interface between CC and electrode materials by directly growing hierarchical graphene films on commercial Al foil CC, and we performed systematic quantitative studies of the interfacial properties therein. Our results show that the interfacial electric resistance dominates, i.e. ∼2 orders of magnitude higher than that of electrode materials. The interfacial resistance could be eliminated by hierarchical graphene interlayer. Cathode on CC with eliminated interfacial resistance could deliver much improved power density outputs. Our work quantifies the mesoscopic factors influencing the battery performance and offers practical guidelines of boosting the performance of LIBs and beyond.
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http://dx.doi.org/10.1021/acs.nanolett.0c00348DOI Listing
March 2020

Essential requirement for nicastrin in marginal zone and B-1 B cell development.

Proc Natl Acad Sci U S A 2020 03 18;117(9):4894-4901. Epub 2020 Feb 18.

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;

γ-secretase is an intramembrane protease complex that catalyzes the proteolytic cleavage of amyloid precursor protein and Notch. Impaired γ-secretase function is associated with the development of Alzheimer's disease and familial acne inversa in humans. In a forward genetic screen of mice with -ethyl--nitrosourea-induced mutations for defects in adaptive immunity, we identified animals within a single pedigree exhibiting both hypopigmentation of the fur and diminished T cell-independent (TI) antibody responses. The causative mutation was in , an essential gene encoding the protein nicastrin (NCSTN), a member of the γ-secretase complex that functions to recruit substrates for proteolysis. The missense mutation severely limits the glycosylation of NCSTN to its mature form and impairs the integrity of the γ-secretase complex as well as its catalytic activity toward its substrate Notch, a critical regulator of B cell and T cell development. Strikingly, however, this missense mutation affects B cell development but not thymocyte or T cell development. The allele uncovered in these studies reveals an essential requirement for NCSTN during the type 2 transitional-marginal zone precursor stage and peritoneal B-1 B cell development, the TI antibody response, fur pigmentation, and intestinal homeostasis in mice.
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http://dx.doi.org/10.1073/pnas.1916645117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060662PMC
March 2020

Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development.

J Exp Med 2020 Apr;217(4)

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX.

In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell-independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells.
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http://dx.doi.org/10.1084/jem.20190006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144532PMC
April 2020

Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation.

Sci Immunol 2020 01;5(43)

Center for the Genetics of Host Defense, UT Southwestern Medical Center, Dallas, TX 75390, USA.

T follicular helper cells (T) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in , encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies in mice with a targeted null mutation of demonstrated polyclonal hypergammaglobulinemia of IgE, IgG1, and IgA isotypes, which was exacerbated by the T cell-dependent humoral response to immunization. GC formation and GC B cells were increased in spleens. These effects were the result of excessive cell-autonomous T development caused by unrestricted Bcl6 nuclear translocation in CD4 T cells. Prkd2 directly binds to Bcl6, and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting T development. In response to immunization, Bcl6 repressed expression in CD4 T cells, thereby committing them to T development. Thus, Prkd2 and Bcl6 form a mutually inhibitory positive feedback loop that controls the stable transition from naïve CD4 T cells to T during the adaptive immune response.
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http://dx.doi.org/10.1126/sciimmunol.aaz0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278039PMC
January 2020

Chiral Os(II) Polypyridyl Complexes as Enantioselective Nuclear DNA Imaging Agents Especially Suitable for Correlative High-Resolution Light and Electron Microscopy Studies.

ACS Appl Mater Interfaces 2020 Jan 8;12(3):3465-3473. Epub 2020 Jan 8.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences , Chinese Academy of Sciences , Beijing 100085 , P. R. China.

The high-resolution technique transmission electron microscopy (TEM), with OsO as the traditional fixative, is an essential tool for cell biology and medicine. Although OsO has been extensively used, it is far from perfect because of its high volatility and toxicity. Os(II) polypyridyl complexes like [Os(phen)(dppz)] (phen = 1,10-phenanthroline; dppz = dipyridophenazine) are not only the well-known molecular DNA "light-switches" but also the potential ideal candidates for TEM studies. Here, we report that the cell-impermeable cationic [Os(phen)(dppz)] can be preferentially delivered into the live-cell nucleus through ion-pairing with chlorophenolate counter-anions, where it functions as an unparalleled enantioselective nuclear DNA imaging reagent especially suitable for correlative light and electron microscopy (CLEM) studies in both living and fixed cells, which can clearly visualize chromosome aggregation and decondensation during mitosis simultaneously. We propose that the chiral Os(II) polypyridyl complexes can be used as a distinctive group of enantioselective high-resolution CLEM imaging probes for live-cell nuclear DNA studies.
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http://dx.doi.org/10.1021/acsami.9b19776DOI Listing
January 2020

[Vertical Distribution and Transport of PM During Heavy Pollution Events in the Jing-Jin-Ji Region].

Huan Jing Ke Xue 2019 Oct;40(10):4303-4309

Tianjin Eco-Environmental Monitoring Center, Tianjin 300191, China.

Based on vehicle-borne tethered balloon measurements, the vertical distribution of particulate matter (PM) concentrations were observed in Gaocun in the Wuqing District of Tianjin from December 17 to 19, 2016, during a period of heavy pollution. Using observational data, the transport flux of PM in the Jing-Jin-Ji region was calculated. The results showed that the mixed layer was low at only 200 m during the heavy pollution period. The vertical distribution of PM concentrations was closely associated with the heights of mixed layer whereby, below the mixed layer, PM concentrations were higher. Vertical variation was insignificant, forming a district pollution layer. Above the mixed layer, PM concentrations rapidly decreased and stabilized at low levels. During the observation period, higher concentrations of PM were found with particle sizes of less than 1.0 μm, and lower concentrations were observed for particle sizes larger than 2.2 μm. The size profiles of PM tallied with relative humidity and the height of the mixed layer. The size distribution was wider during periods of high humidity and with a lower mixed layer height. The greatest PM transport flux was from the southwest, accounting for 63.3% of the total flux; the highest fluxes occurred at the heights of 46-156 m and 156-296 m. The dominant transport direction was southwest below 300 m, while the dominant transport direction was dispersed over 300 m.
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http://dx.doi.org/10.13227/j.hjkx.201903111DOI Listing
October 2019

Atmospheric Low-Temperature Plasma-Induced Changes in the Structure of the Lignin Macromolecule: An Experimental and Theoretical Investigation.

J Agric Food Chem 2020 Jan 3;68(2):451-460. Epub 2020 Jan 3.

College of Materials Science and Engineering , Nanjing Forestry University , Nanjing 210037 , China.

Atmospheric low-temperature plasma has emerged as a promising pretreatment for lignocellulose to improve bio-refining. Herein, we investigated plasma-induced changes in the chemical structure of lignin to obtain a fundamental understanding of the plasma-lignocellulose interaction. Based on the results, plasma possesses a strong capacity to cleave C-C covalent bonds in the aliphatic region of lignin, accompanied by oxidation. Plasma treatment leads to the degradation and fragmentation of lignin. Pronounced deconstruction of β-O-4 aryl ether is observed in plasma. The relative content of β-O-4 aryl ether was reduced from the initial value of 65.1/100Ar to 58.7/100Ar for lignin from corncob and from the initial value of 72.5/100Ar to 63.8/100Ar for lignin from poplar after plasma treatment, respectively. According to the density functional theory analysis, the oxygen atom of β-O-4 aryl ether is the most likely potential reaction site and the C-O covalent bond exhibits the lowest decomposition free energy (50.5 kcal mol), which will easily be cleaved in plasma. The dominant reaction pathway of lignin degradation is the cleavage of the C-O covalent bond followed by the cleavage of the C-C bond. We propose that this investigation is beneficial to optimize and expand the applications of plasma treatment in pretreatment of lignocellulose.
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http://dx.doi.org/10.1021/acs.jafc.9b05604DOI Listing
January 2020

Targeted live-cell nuclear delivery of the DNA 'light-switching' Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes.

Nucleic Acids Res 2019 11;47(20):10520-10528

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, P. R. China.

We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets.
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http://dx.doi.org/10.1093/nar/gkz152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847114PMC
November 2019