Publications by authors named "Wenxiao Zhang"

46 Publications

Direct and Inverse Reduced-Form Models for Reciprocal Calculation of BC Emissions and Atmospheric Concentrations.

Environ Sci Technol 2021 08 23;55(15):10300-10309. Epub 2021 Jul 23.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing 100871, China.

Atmospheric black carbon (BC) concentrations are governed by both emissions and meteorological conditions. Distinguishing these effects enables quantification of the effectiveness of emission mitigation actions by excluding meteorological effects. Here, we develop reduced-form models in both direct (RFDMs) and inverse (RFIMs) modes to estimate ambient BC concentrations. The models were developed based on outputs from multiyear simulations under three conditional scenarios with realistic or fixed emissions and meteorological conditions. We established a set of probabilistic functions (PFs) to quantify the meteorological influences. A significant two-way linear relationship between multiyear annual emissions and mean ambient BC concentrations was revealed at the grid cell scale. The correlation between them was more significant at grid cells with high emission densities. The concentrations and emissions at a given grid cell are also significantly correlated with emissions and concentrations of the surrounding areas, respectively, although to a lesser extent. These dependences are anisotropic depending on the prevailing winds and source regions. The meteorologically induced variation at the monthly scale was significantly higher than that at the annual scale. Of the major meteorological parameters, wind vectors, temperature, and relative humidity were found to most significantly affect variation in ambient BC concentrations.
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http://dx.doi.org/10.1021/acs.est.1c02174DOI Listing
August 2021

High Reliability Graphene-Wrapped Nanoprobes for Scanning Probe Microscopy.

Nanotechnology 2021 Jul 20. Epub 2021 Jul 20.

Changchun University of Science and Technology, Weixing Road No.7089, Changchun, 130022, CHINA.

Nanoprobe is a powerful tool in scanning probe microscopy (SPM) to explore various fields of nanoscience. However, the tips can wear out very fast due to the low stability of conventional probes, especially after some measurements of high currents or lateral frictions, which results in image distortion and test imprecision. Herein, a novel functional nanoprobe is presented using the graphene sheets in high quality graphene solution to wrap on a plasma treated conventional Pt-Ir coated nanoprobe, which shows highly stability and resistant to degradation, leading to significantly increased lifetime. Furthermore, we show that the graphene-wrapped nanoprobes have the advantages of enhanced electrical conductivity and reduced tip-sample friction, compared with Pt-Ir coated nanoprobes. The simplicity and low cost of this method make it valuable to various functional graphene-wrapped nanoprobes and applications.
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http://dx.doi.org/10.1088/1361-6528/ac1630DOI Listing
July 2021

Highly Efficient Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization.

Chemistry 2021 Sep 22;27(50):12758-12762. Epub 2021 Jul 22.

The province and ministry co-sponsored collaborative innovation center for medical epigenetics Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy, Tianjin Medical University, Tianjin, 300070, P. R. China.

Dynamic nuclear polarization (DNP) is a powerful method to enhance the sensitivity of solid-state magnetic nuclear resonance (ssNMR) spectroscopy. However, its biomolecular applications at high magnetic fields (preferably>14 T) have so far been limited by the intrinsically low efficiency of polarizing agents and sample preparation aspects. Herein, we report a new class of trityl-nitroxide biradicals, dubbed SNAPols that combine high DNP efficiency with greatly enhanced hydrophilicity. SNAPol-1, the best compound in the series, shows DNP enhancement factors at 18.8 T of more than 100 in small molecules and globular proteins and also exhibits strong DNP enhancements in membrane proteins and cellular preparations. By integrating optimal sensitivity and high resolution, we expect widespread applications of this new polarizing agent in high-field DNP/ssNMR spectroscopy, especially for complex biomolecules.
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http://dx.doi.org/10.1002/chem.202102253DOI Listing
September 2021

Investigation of the mechanical effects of targeted drugs on cancerous cells based on atomic force microscopy.

Anal Methods 2021 07 22;13(28):3136-3146. Epub 2021 Jun 22.

School of Engineering, University of Warwick, Coventry, CV4 7AL, UK.

Cancer is currently drawing more and more attention as the leading factor in death worldwide. However, little research has been directed towards investigating the micro/nanoscale mechanical properties of cancer cells treated by targeted drugs to evaluate the model systems of targeted drugs using atomic force microscopy (AFM) nano-indentation, especially in light of the multiple drugs targeting various cancerous cells. This paper aims to compare the mechanical effects of sorafenib tosylate and osimertinib mesylate on hepatoma carcinoma cells and lung cancerous cells using atomic force microscopy from the perspective of a model system based on nano-indentation at the micro/nanoscale, which has rarely been investigated. The Sneddon model is applied to fit the force-distance curves, and the mechanical properties, i.e., Young's moduli, can then be calculated. For the SMMC-7721 cells, osimertinib mesylate is a more effective inhibitor than sorafenib tosylate. For the A549 cells, osimertinib mesylate and sorafenib tosylate both have an obvious inhibitory effect. The experimental results may make possible contributions to the diagnosis and treatment of early-stage cancers.
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http://dx.doi.org/10.1039/d1ay00649eDOI Listing
July 2021

Effective Surface Treatment for High-Performance Inverted CsPbIBr Perovskite Solar Cells with Efficiency of 15.92.

Nanomicro Lett 2020 Aug 19;12(1):170. Epub 2020 Aug 19.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, People's Republic of China.

Highlights: A simple and multifunctional surface treatment strategy is proposed to address the inferior-performance inverted CsPbIBr perovskite solar cells (PSCs). The induced-ions exchange can align energy levels, passivate both GBs and surface, and gift the solid protection from external erosions. The inverted CsPbIBr PSCs reveal a champion efficiency of 15.92% and superior stability after moisture, operational, and thermal ages. Developing high-efficiency and stable inverted CsPbIBr perovskite solar cells is vitally urgent for their unique advantages of removing adverse dopants and compatible process with tandem cells in comparison with the regular. However, relatively low opening circuit voltage (V) and limited moisture stability have lagged their progress far from the regular. Here, we propose an effective surface treatment strategy with high-temperature FABr treatment to address these issues. The induced ions exchange can not only adjust energy level, but also gift effective passivation. Meanwhile, the gradient distribution of FA can accelerate the carriers transport to further suppress bulk recombination. Besides, the Br-rich surface and FA substitution can isolate moisture erosions. As a result, the optimized devices show champion efficiency of 15.92% with V of 1.223 V. In addition, the tolerance of humidity and operation get significant promotion: maintaining 91.7% efficiency after aged at RH 20% ambient condition for 1300 h and 81.8% via maximum power point tracking at 45 °C for 500 h in N. Furthermore, the unpackaged devices realize the rare reported air operational stability and, respectively, remain almost efficiency (98.9%) after operated under RH 35% for 600 min and 91.2% under RH 50% for 300 min.
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http://dx.doi.org/10.1007/s40820-020-00509-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770732PMC
August 2020

Electrical conductivity measurement of λ DNA molecules by conductive atomic force microscopy.

Nanotechnology 2021 Jun 16. Epub 2021 Jun 16.

Changchun University of Science and Technology, 7089, , 130022, CHINA.

Conductive atomic force microscopy (C-AFM) is a powerful tool used in the microelectronics analysis by applying a certain bias voltage between the conducting probe and the sample and obtaining the electrical information of sample. In this work, the surface morphological information and current images of the lambda DNA (λ DNA) molecules with different distributions were obtained by C-AFM. The 1 ng/μl and 10 ng/μl DNA solutions were dripped onto mica sheets for making randomly distributed DNA and DNA network samples, and another 1 ng/μl DNA sample was placed in a DC electric field with a voltage of 2 V before being dried for stretching the DNA sample. The results show that the current flowing through DNA networks was significantly higher than the stretched and random distribution of DNA in the experiment. The I-V curve of DNA networks was obtained by changing the bias voltage of C-AFM from -9 V to 9 V. The currents flowing through stretched DNA at different pH values were studied. When the pH was 7, the current was the smallest, and the current was gradually increased as the solution became acidic or alkaline.
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http://dx.doi.org/10.1088/1361-6528/ac0be6DOI Listing
June 2021

TIGIT modulates sepsis-induced immune dysregulation in mice with preexisting malignancy.

JCI Insight 2021 Jun 8;6(11). Epub 2021 Jun 8.

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

TIGIT is a recently identified coinhibitory receptor that is upregulated in the setting of cancer and functionally contributes to the impairment of antitumor immunity. However, its role during sepsis is unknown. Because patients with cancer are 10 times more likely to die of sepsis than previously healthy (PH) patients with sepsis, we interrogated the role of TIGIT during sepsis in the context of preexistent malignancy. PH mice or cancer (CA) mice inoculated with lung carcinoma cells were made septic by cecal ligation and puncture (CLP). We found that sepsis induced TIGIT upregulation predominantly on Tregs and NK cells in both PH and CA mice. Anti-TIGIT Ab improved the 7-d survival of CA septic mice but not PH mice after CLP. Treatment of CA septic animals but not PH septic animals with anti-TIGIT mAb significantly reversed sepsis-induced loss of CD4+ T cells, CD8+ T cells, Foxp3+ Treg, and CD19+ B cells in the spleen, which was the result of decreased caspase-3+ apoptotic cells. In sum, we found that anti-TIGIT Ab reversed sepsis-induced T cell apoptosis in CA septic mice and led to a significant survival benefit, suggesting its use as a potential immunotherapy to improve outcomes in septic patients with cancer.
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http://dx.doi.org/10.1172/jci.insight.139823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262279PMC
June 2021

Updated Global Black Carbon Emissions from 1960 to 2017: Improvements, Trends, and Drivers.

Environ Sci Technol 2021 06 7;55(12):7869-7879. Epub 2021 Jun 7.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing 100871, China.

Accurate estimation of black carbon (BC) emissions is essential for assessing the health and climate impact of this pollutant. Past emission inventories were associated with high uncertainty due to data limitations, and recent information has provided a unique updating opportunity. Moreover, understanding the drivers that cause temporal emission changes is of research value. Here, we update the global BC emission estimates using new data on the activities and emission factors (EFs). The new inventory covers 73 detailed sources at 0.1° × 0.1° spatial resolution and monthly temporal resolution from 1960 to 2017. The estimated annual emissions were 32% higher than the average of several previous inventories, which was primarily due to field-measured EFs for residential stoves and differentiated EFs for motor vehicles. In addition, the updated emissions show an inverse U-shaped temporal trend, which was mainly driven by the interaction between the positive effects of population growth, per capita energy consumption, and vehicle fleet and the negative effects of residential energy switching, stove upgrading, phasing out of beehive coke ovens, and reduced EFs for vehicles and industrial processes. Urbanization caused a significant increase in urban emissions accompanied by a more significant decline in rural emissions.
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http://dx.doi.org/10.1021/acs.est.1c03117DOI Listing
June 2021

Coal Is Dirty, but Where It Is Burned Especially Matters.

Environ Sci Technol 2021 06 12;55(11):7316-7326. Epub 2021 May 12.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing 100871, China.

Coal abatement actions for pollution reduction often target total coal consumption. The health impacts of coal uses, however, vary extensively among sectors. Here, we modeled the sectorial contributions of coal uses to emissions, outdoor and indoor PM (particulate matter with an aerodynamic diameter of less than 2.5 mm) concentrations, exposures, and health outcomes in China from 1970 to 2014. We show that in 2014, residential coal accounted for 2.9% of total energy use but 34% of premature deaths associated with PM exposure, showing that effects were magnified substantially along the causal path. The number of premature deaths attributed to unit coal consumption in the residential sector was 40 times higher than that in the power and industrial sectors. Emissions of primary PM were more important than secondary aerosol precursors in terms of health consequences, and indoor exposure accounted for 97% and 91% of total premature deaths attributable to PM from coal combustion in 1974 and 2014, respectively. Our assessment raises a critical challenge in the switching of residential coal uses to effectively mitigate PM exposure in the Chinese population.
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http://dx.doi.org/10.1021/acs.est.1c01148DOI Listing
June 2021

Tumor-Specific T Cells Exacerbate Mortality and Immune Dysregulation during Sepsis.

J Immunol 2021 05 28;206(10):2412-2419. Epub 2021 Apr 28.

Department of Surgery, Emory University School of Medicine, Atlanta, GA

Sepsis induces significant immune dysregulation characterized by lymphocyte apoptosis and alterations in the cytokine milieu. Because cancer patients exhibit a 10-fold greater risk of developing sepsis compared with the general population, we aimed to understand how pre-existing malignancy alters sepsis-induced immune dysregulation. To address this question, we assessed the impact of tumor-specific CD8 T cells on the immune response in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. Tumor-bearing animals containing Thy1.1 tumor-specific CD8 T cells were subjected to CLP, and groups of animals received anti-Thy1.1 mAb to deplete tumor-specific CD8 T cells or isotype control. Results indicated that depleting tumor-specific T cells significantly improved mortality from sepsis. The presence of tumor-specific CD8 T cells resulted in increased expression of the 2B4 coinhibitory receptor and increased apoptosis of endogenous CD8 T cells. Moreover, tumor-specific T cells were not reduced in number in the tumors during sepsis but did exhibit impaired IFN-γ production in the tumor, tumor draining lymph node, and spleen 24 h after CLP. Our research provides novel insight into the mechanisms by which pre-existing malignancy contributes to increased mortality during sepsis.
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http://dx.doi.org/10.4049/jimmunol.2000865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121248PMC
May 2021

Chemical anti-corrosion strategy for stable inverted perovskite solar cells.

Sci Adv 2020 Dec 16;6(51). Epub 2020 Dec 16.

School of Physics and Electronic Science, Engineering Research Center of Nanophotonics and Advanced Instrument, Ministry of Education, East China Normal University, Shanghai 200062, China.

One big challenge for long-lived inverted perovskite solar cells (PSCs) is that commonly used metal electrodes react with perovskite layer, inducing electrode corrosion and device degradation. Motivated by the idea of metal anticorrosion, here, we propose a chemical anticorrosion strategy to fabricate stable inverted PSCs through introducing a typical organic corrosion inhibitor of benzotriazole (BTA) before Cu electrode deposition. BTA molecules chemically coordinate to the Cu electrode and form an insoluble and polymeric film of [BTA-Cu], suppressing the electrochemical corrosion and reaction between perovskite and the Cu electrode. PSCs with BTA/Cu show excellent air stability, retaining 92.8 ± 1.9% of initial efficiency after aging for 2500 hours. In addition, >90% of initial efficiency is retained after 85°C aging for over 1000 hours. PSCs with BTA/Cu also exhibit good operational stability, and 88.6 ± 2.6% of initial efficiency is retained after continuous maximum power point tracking for 1000 hours.
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http://dx.doi.org/10.1126/sciadv.abd1580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744079PMC
December 2020

Differentiated-Rate Clean Heating Strategy with Superior Environmental and Health Benefits in Northern China.

Environ Sci Technol 2020 Oct 23. Epub 2020 Oct 23.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing 100871, China.

Residential heating using solid fuels contributes significantly to air pollution and has subsequent health impacts in China. To mitigate emissions, a clean heating campaign (CHC-1) covering 28 municipalities has been implemented. Although only a single penetration rate was initially planned by CHC-1 for all municipalities, outcomes in the different municipalities varied considerably. Recently, a second phase (CHC-2) has been launched for the remaining 128 municipalities in northern China with once again a fixed penetration rate set. Here, we quantified factors that affected the penetration rates of CHC-1, developed an intervention scheme with differentiated targets for CHC-2, and compared the environmental and health benefits of the fixed- and differentiated-rate strategies. We found that the penetration rates of CHC-1 depended on per capita income, terrain slope, and population density and that such relationships could be quantified using a piecewise regression model. This model was applied to develop a differentiated-rate strategy for CHC-2. It clearly evidenced that a differentiated scheme would be more environmentally beneficial. Although the same number of rural households can achieve clean heating under both intervention scenarios, the proposed differentiated strategy can prevent 30 000 (23 000-34 000) premature deaths associated with residential heating annually compared to the 26 000 (21 000-31 000) premature deaths prevented under the fixed-rate scheme. Differences among gender and age groups and the effects of urbanization and aging are also discussed.
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http://dx.doi.org/10.1021/acs.est.0c04019DOI Listing
October 2020

Postmodification via Thiol-Click Chemistry Yields Hydrophilic Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization.

J Phys Chem B 2020 10 6;124(41):9047-9060. Epub 2020 Oct 6.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China.

Dynamic nuclear polarization (DNP) is a powerful method to enhance nuclear magnetic resonance (NMR) signal intensities, enabling unprecedented applications in life and material science. An ultimate goal is to expand the use of DNP-enhanced solid-state NMR to ultrahigh magnetic fields where optimal spectral resolution and sensitivity are integrated. Trityl-nitroxide (TN) biradicals have attracted significant interest in high-field DNP, but their application to complex (bio)molecules has so far been limited. Here we report a novel postmodification strategy for synthesis of hydrophilic TN biradicals in order to improve their use in biomolecular applications. Initially, three TN biradicals (referred to as NATriPols 1-3) with amino-acid linkers were synthesized. EPR studies showed that the α-position of the amino-acid linkers is an ideal modification site for these biradicals since their electron-electron magnetic interactions are marginally affected by the substituents at this position. On the basis of this finding, we synthesized NATriPol-4 with pyridine disulfide appended at the α-position. Postmodification of NATriPol-4 via thiol-click chemistry resulted in various TN biradicals including hydrophilic NATriPol-5 in a quantitative manner. Interestingly, DNP enhancements at 18.8 T of NATriPols for C,N-proline in a glycerol/water matrix are inversely correlated with their hydrophobicity. Importantly, applications of hydrophilic NATriPol-5 and NATriPol-3 to biomolecules including a globular soluble protein and a membrane targeting peptide reveal significantly improved performance compared to TEMTriPol-1 and AMUPol. Our work provides an efficient approach for one-step synthesis of new polarizing agents with tunable physicochemical properties, thus expediting optimization of new biradicals for biomolecular applications at ultrahigh magnetic fields.
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http://dx.doi.org/10.1021/acs.jpcb.0c08321DOI Listing
October 2020

A novel model for regional indoor PM quantification with both external and internal contributions included.

Environ Int 2020 12 17;145:106124. Epub 2020 Sep 17.

College of Urban and Environmental Sciences, Laboratory for Earth Surface Processes, Sino-French Institute for Earth System Science, Peking University, Beijing 100871, China. Electronic address:

PM (particulate matter with an aerodynamic size ≤ 2.5 μm) of indoor origins is a dominant contributor to the overall air pollution exposure. Although some sophisticated models have been developed to simulate indoor air quality for individual households, it is still challenging to quantify indoor PM on a regional scale, which is critical for health impact assessments. In this study, a new model was developed to predict indoor PM concentrations by quantifying the external penetration, as well as the internal contributions. The model was parameterized based on a set of simultaneously measured indoor and outdoor PM concentrations at five-second temporal resolution for 53 households in Beijing. This study found that indoor PM concentrations were significantly correlated with those in the outdoor environment with an approximately 1-h lag-time on average. Outdoor-to-indoor penetration dominated the contribution to indoor PM during polluted hours with relatively high ambient PM concentrations, while the indoor PM, during clean hours, was contributed by internal sources, including smoking, cooking, incense burning, and human disturbance. The influence of windows, house area, and air purifier use was addressed in the new model. The model was applied to evaluate indoor PM concentrations in six urban districts of Beijing via an uncertainty analysis. The model was developed based on and applied to households using clean residential energy, and it would be interesting also important to evaluate it in households using solid fuels.
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http://dx.doi.org/10.1016/j.envint.2020.106124DOI Listing
December 2020

Fibrin-associate diffuse large B-Cell lymphoma arising in a left atrial myxoma: A case report and literature review.

Cardiovasc Pathol 2020 Nov - Dec;49:107264. Epub 2020 Jul 22.

Department of Pathology, Binzhou Medical University Hospital, Binzhou 256603, China. Electronic address:

We report a 60-year-old male with fibrin-associated diffuse large B-cell lymphoma (fa-DLBCL) in left atrial myxoma. Echocardiography showed a mass (63 mm × 33 mm) in the left atrium. Histological inspection indicated fa-DLBCL on the surface of atrial myxoma incidentally, together with extensive fibrinous like exudation on myxoma surface. Malignant cells were localized in solid sheets and nests at the peripheral area of the fibrinous exudation which were positive for B-lineage markers (CD20+, CD79a+, PAX-5+) and in situ hybridization of EBV-encoded RNA (EBER). PCR amplification showed clonal rearrangement of immunoglobulin heavy chain (IgH) genes. The patient was still alive with no recurrence in the 35-month follow-up after surgery. We also did a detailed clinicopathological analysis and literature review, which indicated that fa-DLBCL was a heterogeneous entity.
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http://dx.doi.org/10.1016/j.carpath.2020.107264DOI Listing
October 2020

Effect of AFM Nanoindentation Loading Rate on the Characterization of Mechanical Properties of Vascular Endothelial Cell.

Micromachines (Basel) 2020 May 31;11(6). Epub 2020 May 31.

School of Engineering, University of Warwick, Coventry CV4 7AL, UK.

Vascular endothelial cells form a barrier that blocks the delivery of drugs entering into brain tissue for central nervous system disease treatment. The mechanical responses of vascular endothelial cells play a key role in the progress of drugs passing through the blood-brain barrier. Although nanoindentation experiment by using AFM (Atomic Force Microscopy) has been widely used to investigate the mechanical properties of cells, the particular mechanism that determines the mechanical response of vascular endothelial cells is still poorly understood. In order to overcome this limitation, nanoindentation experiments were performed at different loading rates during the ramp stage to investigate the loading rate effect on the characterization of the mechanical properties of bEnd.3 cells (mouse brain endothelial cell line). Inverse finite element analysis was implemented to determine the mechanical properties of bEnd.3 cells. The loading rate effect appears to be more significant in short-term peak force than that in long-term force. A higher loading rate results in a larger value of elastic modulus of bEnd.3 cells, while some mechanical parameters show ambiguous regulation to the variation of indentation rate. This study provides new insights into the mechanical responses of vascular endothelial cells, which is important for a deeper understanding of the cell mechanobiological mechanism in the blood-brain barrier.
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http://dx.doi.org/10.3390/mi11060562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345843PMC
May 2020

Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis.

J Leukoc Biol 2020 03 27;107(3):485-495. Epub 2020 Jan 27.

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

Patients with cancer are at an increased risk of developing and dying from sepsis. We previously reported that blockade of the chemokine receptor CXCR4 resulted in decreased CD4 T cell exhaustion and improved survival in a model of polymicrobial sepsis in previously healthy mice. Here, we sought to determine whether CXCR4 blockade could improve mortality and immune dysregulation during sepsis complicated with malignancy. Results in animals inoculated with a lung cancer cell line and subjected to CLP 3 weeks later indicated that CXCR4 was up-regulated on naïve and central memory T cells following sepsis. Of note, and in contrast to results in previously healthy mice, CXCR4 blockade failed to improve survival in cancer septic animals; instead, it actually significantly worsened survival. In the setting of cancer, CXCR4 blockade failed to result in T cell egress from the bone marrow, reverse lymphopenia in the spleen, or reverse T cell exhaustion. Mechanistically, elevated expression of CD69 on naïve T cells in the bone marrow of cancer septic animals was associated with their inability to egress from the bone marrow in the setting of CXCR4 blockade. In conclusion, these results illuminate the differential impact of CXCR4 blockade on sepsis pathophysiology in the setting of cancer and highlight the need for personalized therapy during sepsis.
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http://dx.doi.org/10.1002/JLB.3A1019-502RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262428PMC
March 2020

The salt-induced transcription factor GmMYB84 confers salinity tolerance in soybean.

Plant Sci 2020 Feb 5;291:110326. Epub 2019 Nov 5.

The Key Laboratory of the Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China. Electronic address:

Transcription factor activation and DNA methylation are important plant responses to abiotic stress. Here, we established that the salinity stress-induced expression of the soybean (Glycine max) transcription factor-encoding gene GmMYB84 relies on DNA methylation. The level of DNA methylation at sequences 690 nt to 950 nt upstream of the GmMYB84 transcription initiation codon was markedly reduced in plants exposed to salinity stress, resulting in a higher abundance of transcripts. When challenged with salinity stress, plants constitutively expressing GmMYB84 outperformed untransformed plants with respect to their germination rate, primary root elongation, proline accumulation, antioxidant enzyme activity, membrane integrity, and K levels. Arabidopsis thaliana plants heterologously expressing GmMYB84 were more tolerant to salt stress and exhibited higher germination rates than the wild type. Electrophoretic mobility shift assays revealed that GmMYB84 binds to the cis-regulatory sequences of GmAKT1, the homolog of ARABIDOPSIS K TRANSPORTER 1 (AKT1). Thus, DNA methylation modulates the salinity stress-induced expression of the soybean transcription factor-encoding gene GmMYB84 and thereby confers salinity stress tolerance.
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http://dx.doi.org/10.1016/j.plantsci.2019.110326DOI Listing
February 2020

Determination of viscohyperelastic properties of tubule epithelial cells by an approach combined with AFM nanoindentation and finite element analysis.

Micron 2020 Feb 13;129:102779. Epub 2019 Nov 13.

School of Engineering, University of Warwick, Coventry, CV4 7AL, United Kingdom.

Tubule epithelial cell is a complex element that not only exhibits elasticity behaviour, but also presents nonlinear and time-dependent behaviour during any stage of its life cycle. Responses of tubule epithelial cells to physical stimuli are influenced by their mechanical properties. However, accurately constitution of their mechanical properties is still a challenge and the characterisation mechanism is far from sophisticated. In addition, the particular mechanism that determines the mechanical response is still unclear. In order to overcome this limit, an approach combined with AFM nanoindentation experiment and computation modelling by a viscohyperelastic model is developed to describe the complex behaviour in the current study. Viscohyperelastic parameters of tubule epithelial cells treated and untreated with drug Cytochalasin D are obtained by the optimization algorithm applied in this approach. The comparison between treated and untreated results indicate that larger amount of relaxation was observed due to the disruption of cytoskeleton when using drug Cytochalasin D. Our results demonstrate the feasibility of this approach to monitor the variation of these viscohyperelastic parameters, which can be used as an effective index for renal disease diagnosed and drug evaluation.
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http://dx.doi.org/10.1016/j.micron.2019.102779DOI Listing
February 2020

A disulfiram-loaded electrospun poly(vinylidene fluoride) nanofibrous scaffold for cancer treatment.

Nanotechnology 2020 Mar 25;31(11):115101. Epub 2019 Nov 25.

International Research Centre for Nano Handing and Manufacturing of China (CNM), Changchun University of Science and Technology, Changchun 130022, People's Republic of China.

Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, has shown its effectiveness against diverse cancer types. Thus, we developed a disulfiram-loaded scaffold using the electrospinning method to enhance the stability of DSF and to facilitate its appropriate distribution to tumor tissues. The drug release profile of the disulfiram-loaded scaffold was examined by high-performance liquid chromatography. We obtained mechanical and morphological characterizations of A549 cells treated with different scaffolds by various techniques to evaluate its antitumor properties. This work revealed that the cells after the treatment with the disulfiram-loaded scaffold exhibited a lower height and a larger elastic modulus compared with the untreated cells and those treated with the neat electrospun fibers. The changes were the indicators of cell apoptosis. Taken collectively, the results indicate that DSF was successfully incorporated into the electrospun fibers, and the disulfiram-loaded scaffold has great potential for inhibiting the regional recurrence of cancer.
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http://dx.doi.org/10.1088/1361-6528/ab5b35DOI Listing
March 2020

2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy.

JCI Insight 2019 11 14;4(22). Epub 2019 Nov 14.

Department of Surgery, Emory University, Atlanta, Georgia, USA.

In addition to its well-known beneficial effects for the treatment of several types of cancer, PD-1 blockade has shown encouraging results in preclinical models of sepsis and in a recent clinical trial in sepsis. Because cancer is the most common comorbidity in septic patients, here we aimed to determine the efficacy of PD-1 checkpoint blockade in the setting of sepsis complicated with preexisting malignancy. In a model of established lung cancer followed by cecal ligation and puncture-induced (CLP-induced) sepsis, PD-1 blockade exhibited no therapeutic effect on sepsis survival. This diminished efficacy of PD-1 blockade in cancer septic animals (septic animals with cancer) was characterized by a reduction in both the quality and quantity of PD-1+ responder cells. Specifically, CD8+ T cells isolated from cancer septic animals exhibited decreased CD28 expression and a reduction in the CXCR5+PD-1+ subset. In addition, flow cytometric analysis of T cells isolated from cancer septic animals revealed 2B4 as another possible checkpoint under these conditions. Administration of anti-2B4 to cancer septic animals significantly improved sepsis survival and was associated with increased T cell costimulatory receptor expression and decreased coinhibitory receptor expression. These results illustrate functions of coinhibitory receptors in the setting of sepsis complicated with cancer.
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http://dx.doi.org/10.1172/jci.insight.127867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948854PMC
November 2019

The gut microbiome alters immunophenotype and survival from sepsis.

FASEB J 2019 10 15;33(10):11258-11269. Epub 2019 Jul 15.

Department of Surgery, Emory Critical Care Center, Atlanta, Georgia, USA.

The microbiome is increasingly implicated in immune regulation and mortality from sepsis. Mice with identical genetic backgrounds but distinct microbiomes were obtained from different vendors and analyzed following cecal ligation and puncture (CLP). β diversity of the microbiome measured from feces demonstrated significant differences between The Jackson Laboratory (Jax; Bar Harbor, ME, USA) and Charles River Laboratories (CR; Wilmington, MA, USA) C57/B6 mice. Jax mice had 7-d mortality of 90% following CLP, whereas CR mice had a mortality of 53%. Differences in vendor were associated with altered immunophenotype with increased splenic IFN-γCD4 T cells, effector memory CD4 T cells, and central memory CD4 T cells and increased Peyer's patch effector memory CD4 T cells in septic CR mice. To determine whether differences in the microbiome were responsible for these differences, Jax and CR mice were cohoused for 3 wk, after which they assumed a similar microbiota composition. Cohoused mice had improved survival following CLP compared to Jax mice and had similar survival regardless of their vendor of origin. All differences in immunophenotype between septic Jax and CR mice disappeared following cohousing. These findings suggest that the microbiome plays a crucial role in survival and the host immune response from sepsis and represents a potential target for therapeutic intervention.-Fay, K. T., Klingensmith, N. J., Chen, C.-W., Zhang, W., Sun, Y., Morrow, K. N., Liang, Z., Burd, E. M., Ford, M. L., Coopersmith, C. M. The gut microbiome alters immunophenotype and survival from sepsis.
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http://dx.doi.org/10.1096/fj.201802188RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766641PMC
October 2019

A GmSIN1/GmNCED3s/GmRbohBs Feed-Forward Loop Acts as a Signal Amplifier That Regulates Root Growth in Soybean Exposed to Salt Stress.

Plant Cell 2019 09 21;31(9):2107-2130. Epub 2019 Jun 21.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao 266237, People's Republic China

Abscisic acid (ABA) and reactive oxygen species (ROS) act as key signaling molecules in the plant response to salt stress; however, how these signals are transduced and amplified remains unclear. Here, a soybean () salinity-induced NAM/ATAF1/2/CUC2 (NAC) transcription factor encoded by () was shown to be a key component of this process. Overexpression of in soybean promoted root growth and salt tolerance and increased yield under salt stress; RNA interference-mediated knockdown of had the opposite effect. The rapid induction of in response to salinity required ABA and ROS, and the effect of on root elongation and salt tolerance was achieved by boosting cellular ABA and ROS contents. GmSIN1 upregulated 9--epoxycarotenoid dioxygenase coding genes in soybean (, associated with ABA synthesis) and genes in soybean (, associated with ROS generation) by binding to their promoters at a site that has not been described to date. Together, , , and constitute a positive feed-forward system that enables the rapid accumulation of ABA and ROS, effectively amplifying the initial salt stress signal. These findings suggest that the combined modulation of ABA and ROS contents enhances soybean salt tolerance.
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http://dx.doi.org/10.1105/tpc.18.00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751118PMC
September 2019

Correlation analysis between ultrasonography and mammography with other risk factors related to breast cancer.

Oncol Lett 2019 Jun 12;17(6):5511-5516. Epub 2019 Apr 12.

Department of Ultrasound Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China.

Value and correlation analysis between ultrasound and mammography in the diagnosis and other risk factors related to breast cancer were explored. A total of 1,473 patients who underwent breast color ultrasonography and molybdenum target X-ray examination in Binzhou Medical University Hospital from March 2017 to August 2018 were collected, and the patient's ultrasound and mammography results were compared, also the pathological biopsy was used as the reference golden criteria to calculate the value of both test methods and the value of combined diagnosis in breast cancer. The risk factors associated with breast cancer were analyzed. Among the 1,473 patients, 387 breast cancer patients were detected by ultrasonography, 351 by mammography and 339 cases by combined diagnosis. A total of 314 cases were diagnosed as breast cancer after pathological biopsy. However, there were significant differences in tumor size, stages, and BI-RADS grades (P<0.05). There was no significant difference in the diagnostic efficacy between ultrasonography and mammography (P>0.05), however, the diagnostic efficacy of ultrasonography combined with mammography was significantly better than the two single tests (P<0.05). After logistic regression analysis, there was no significant correlation between residence address, height, blood type, ethnicity, or education with breast cancer (P>0.05). However, age, fertility status, and BMI were all risk factors related to breast cancer (OR>1; P<0.05). In conclusion, ultrasonography combined with mammography can effectively improve the early diagnosis rate of breast cancer, however, the patient's age, birth status, and BMI may affect the results of ultrasonography and mammography. In clinical practice, it is necessary to determine the imaging results in combination with the actual situation of the patients to improve the diagnosis rate of breast cancer.
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http://dx.doi.org/10.3892/ol.2019.10246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507439PMC
June 2019

Efficient light harvesting with a nanostructured organic electron-transporting layer in perovskite solar cells.

Nanoscale 2019 May;11(19):9281-9286

Key Laboratory of Graphene Technologies and Applications of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.

Nanostructures have proved to be advantageous in light harvesting, improving the power conversion efficiency (PCE) of photovoltaic devices. However, the reported light-harvesting nanostructures all require extra processing beyond that for device fabrication, with multiple steps for nano-patterned structures or plasmonic nano-particles. Here we synthesized a conjugated polymer PFPDI which could simply form a nanostructured film on perovskite by spin coating. PFPDI possesses a perylene diimide-based backbone and phosphite ester pendants, which makes it a robust electron-transporting material (ETM) in perovskite solar cells. Furthermore, the perovskite solar cells with PFPDI as the electron-transporting layer (ETL) exhibited a higher light-harvesting efficiency compared to the standard phenyl-C61-butyric acid methyl ester (PCBM) devices. The JSC of the PFPDI device was enhanced from 19.71 mA cm-2 to 23.43 mA cm-2. SEM images and reflectance spectra confirmed that the PFPDI formed ditch-like nanostructures on perovskite film and induced a better light-harvesting efficiency. Further research indicated that the interaction of P[double bond, length as m-dash]O with Pb was essential to the formation of the nanostructures of PFPDI on perovskite. Therefore, our work not only offers an efficient organic ETM, but also opens up new horizons for simply constructing nanostructures with light-harvesting ability in photovoltaic devices.
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http://dx.doi.org/10.1039/c9nr03030aDOI Listing
May 2019

Increased attrition of memory T cells during sepsis requires 2B4.

JCI Insight 2019 05 2;4(9). Epub 2019 May 2.

Department of Surgery, and.

Recent seminal studies have revealed that laboratory mice differ from adult humans with regard to the frequency, number, and distribution of memory T cells. Because our data show that memory T cells are more susceptible to sepsis-induced death than naive T cells, in this study we developed a model in which mice possess a memory T cell compartment more similar to that of adult humans, to better study immune responses during sepsis in the more physiologically relevant context of high frequencies of memory T cells. Using this model, we found that CD44hi memory T cells significantly upregulated the coinhibitory molecule 2B4 during sepsis, and 2B4+ memory T cells coexpressed markers of both activation and exhaustion. Genetic deficiency in 2B4 resulted in decreased mortality during sepsis. Mechanistically, this decreased mortality was associated with reduced caspase-3/7+ apoptotic T cells in 2B4-/- relative to WT, septic hosts. These results were corroborated by analysis of PBMCs isolated from human patients with sepsis, which showed increased frequencies of caspase-3/7+ apoptotic cells among 2B4+ relative to 2B4- T cells. Thus, 2B4 plays a critical role in sepsis-induced apoptosis in both murine memory T cells and those isolated from human patients with sepsis.
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http://dx.doi.org/10.1172/jci.insight.126030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538360PMC
May 2019

Sepsis erodes CD8 memory T cell-protective immunity against an EBV homolog in a 2B4-dependent manner.

J Leukoc Biol 2019 03 9;105(3):565-575. Epub 2019 Jan 9.

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

Epstein-Barr virus (EBV) reactivation commonly occurs following sepsis, but the mechanisms underlying this are unknown. We utilized a murine EBV homolog (gHV) and the cecal ligation and puncture model of polymicrobial sepsis to study the impact of sepsis on gHV reactivation and CD8 T cell immune surveillance following a septic insult. We observed a significant increase in the frequency of gHV-infected germinal center B cells on day 7 following sepsis. This increase in viral load was associated with a concomitant significant decrease in the frequencies of gHV-specific CD8 T cells, as measured by class I MHC tetramers corresponding to the immunodominant viral epitopes. Phenotypic analysis revealed an increased frequency of gHV-specific CD8 T cells expressing the 2B4 coinhibitory receptor in septic animals compared with sham controls. We sought to interrogate the role of 2B4 in modulating the gHV-specific CD8 T cell response during sepsis. Results indicated that in the absence of 2B4, gHV-specific CD8 T cell populations were maintained during sepsis, and gHV viral load was unchanged in 2B4 septic animals relative to 2B4 sham controls. WT CD8 T cells upregulated PD-1 during sepsis, whereas 2B4 CD8 T cells did not. Finally, adoptive transfer studies revealed a T cell-intrinsic effect of 2B4 coinhibition on virus-specific CD8 T cells and gHV viral load during sepsis. These data demonstrate that sepsis-induced immune dysregulation erodes antigen-specific CD8 responses against a latent viral infection and suggest that blockade of 2B4 may better maintain protective immunity against EBV in the context of sepsis.
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http://dx.doi.org/10.1002/JLB.4A0718-292RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094871PMC
March 2019

In-situ cross-linking strategy for efficient and operationally stable methylammoniun lead iodide solar cells.

Nat Commun 2018 09 18;9(1):3806. Epub 2018 Sep 18.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.

Long-term operational stability is the foremost issue delaying the commercialization of perovskite solar cells (PSCs). Here we demonstrate an in-situ cross-linking strategy for operationally stable inverted MAPbI PSCs through the incorporation of a cross-linkable organic small molecule additive trimethylolpropane triacrylate (TMTA) into perovskite films. TMTA can chemically anchor to grain boundaries and then in-situ cross-link to a robust continuous network polymer after thermal treatment, thus enhancing the thermal, water-resisting and light-resisting properties of organic/perovskite films. As a result, the cross-linked PSCs exhibit 590-fold improvement in operational stability, retaining nearly 80% of their initial efficiency after continuous power output for 400 h at maximum power point under full-sun AM 1.5 G illumination of Xenon lamp without any UV-filter. In addition, under moisture or thermal (85 °C) conditions, cross-linked TMTA-based PSCs also show excellent stability with over 90% of their initial or post burn-in efficiency after aging for over 1000 h.
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http://dx.doi.org/10.1038/s41467-018-06204-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143610PMC
September 2018

Recent Advance in Solution-Processed Organic Interlayers for High-Performance Planar Perovskite Solar Cells.

Adv Sci (Weinh) 2018 Jul 8;5(7):1800159. Epub 2018 May 8.

Key Laboratory of Graphene Technologies and Applications of Zhejiang Province Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences Ningbo 315201 China.

Planar heterojunction perovskite solar cells (PSCs) provide great potential for fabricating high-efficiency, low-cost, large-area, and flexible photovoltaic devices. In planar PSCs, a perovskite absorber is sandwiched between hole and electron transport materials. The charge-transporting interlayers play an important role in enhancing charge extraction, transport, and collection. Organic interlayers including small molecules and polymers offer great advantages for their tunable chemical/electronic structures and low-temperature solution processibility. Here, recent progress of organic interlayers in planar heterojunction PSCs is discussed, and the effect of chemical structures on device performance is also illuminated. Finally, the main challenges in developing planar heterojunction PSCs based on organic interlayers are identified, and strategies for enhancing the device performance are also proposed.
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http://dx.doi.org/10.1002/advs.201800159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051387PMC
July 2018

Murine Pancreatic Cancer Alters T Cell Activation and Apoptosis and Worsens Survival After Cecal Ligation and Puncture.

Shock 2019 06;51(6):731-739

Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia.

Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation. These results cannot distinguish the individual roles of cancer versus sepsis since different models of each were used. We therefore created a new cancer/sepsis model to standardize each variable. Mice were injected with a pancreatic cancer cell line and 3 weeks later cancer mice and healthy mice were subjected to CLP. Cancer septic mice had a significantly higher 10-day mortality than previously healthy septic mice. Cancer septic mice had increased CD4 T cells and CD8 T cells, associated with decreased CD4 T cell apoptosis 24 h after CLP. Further, splenic CD8+ T cell activation was decreased in cancer septic mice. In contrast, no differences were noted in intestinal apoptosis, proliferation, or permeability, nor were changes noted in local bacterial burden, renal, liver, or pulmonary injury. Cancer septic mice thus have consistently reduced survival compared with previously healthy septic mice, independent of the cancer or sepsis model utilized. Changes in lymphocyte apoptosis are common to cancer model and independent of sepsis model, whereas gut apoptosis is common to sepsis model and independent of cancer model. The host response to the combination of cancer and sepsis is dependent, at least in part, on both chronic comorbidity and acute illness.
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http://dx.doi.org/10.1097/SHK.0000000000001203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309343PMC
June 2019
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