Publications by authors named "Deng Pan"

262 Publications

Heterotrophic nitrification and related functional gene expression characteristics of Alcaligenes faecalis SDU20 with the potential use in swine wastewater treatment.

Bioprocess Biosyst Eng 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Microbial Technology, Microbial Technology Institute, Shandong University, Qingdao, 266237, People's Republic of China.

A new heterotrophic nitrifying bacterium was isolated from the compost of swine manure and rice husk and identified as Alcaligenes faecalis SDU20. Strain SDU20 had heterotrophic nitrification potential and could remove 99.7% of the initial NH-N. Nitrogen balance analysis revealed that 15.9 and 12.3% of the NH-N were converted into biological nitrogen and nitrate nitrogen, respectively. The remaining 71.44% could be converted into N or NO. Single-factor experiments showed that the optimal conditions for ammonium removal were the carbon source of sodium succinate, C/N ratio 10, initial pH 8.0, and temperature 30 °C. Nitrification genes were determined to be upregulated when sodium succinate was used as the carbon source analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Strain SDU20 could tolerate 4% salinity and show resistance to some heavy metal ions. Strain SDU20 removed 72.6% high concentrated NH-N of 2000 mg/L within 216 h. In a batch experiment, the highest NH-N removal efficiency of 98.7% and COD removal efficiency of 93.7% were obtained in the treatment of unsterilized swine wastewater. Strain SDU20 is promising in high-ammonium wastewater treatment.
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http://dx.doi.org/10.1007/s00449-021-02581-zDOI Listing
May 2021

One-pot pyrolysis of a typical invasive plant into nitrogen-doped biochars for efficient sorption of phthalate esters from aqueous solution.

Chemosphere 2021 May 3;280:130712. Epub 2021 May 3.

Co-Innovation Center for the Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Nanjing, 210037, PR China; National Positioning Observation Station of Hung-tse Lake Wetland Ecosystem in Jiangsu Province, Huaian, Jiangsu, 223100, PR China. Electronic address:

Invasive plants pose a significant threat to natural ecosystems because of their high adaptability, rapid propagation and spreading ability in the environment. In this study, a typical aquatic invasive plant, Pistia stratiotes, was chosen as a novel feedstock for the preparation of nitrogen-doped biochars (NBs) for the first time, and the NBs were used as efficient sorbents to remove phthalate esters (PAEs) from aqueous solution. Characterization results showed that NBs possess great pore structure (up to 126.72 m g), high nitrogen (2.02%-2.66%) and ash (24.7%-34.1%) content, abundant surface functional groups, hydrophobicity and a graphene structure. Batch sorption experiments were performed to investigate the sorption performance, processes and mechanisms. The capacities for PAEs sorption onto NBs were high, especially with NBs pyrolyzed at 700 °C, ranging up to 161.7 mg g for diethyl phthalate and 85.4 mg g for dibutyl phthalate; these levels were better than many reported for other sorbents. With kinetic and isotherm results, Pseudo-second order and Freundlich models fit the sorption data well, and chemical interactions involving hydrogen bonding, Lewis acid-base interaction, functional group interaction, cation-π interaction and π-π stacking interaction were identified as possible rate-limited steps. Moreover, Intra-particle diffusion and Dubinin-Radushkevich models indicated that multiple pore filling and partitioning dominated the process of PAEs sorption onto NBs. This study opens the door for new methods of pollution control with waste treatment, since invasive plant biomass resources were converted into advanced biochars for efficient environmental remediation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130712DOI Listing
May 2021

Clinical characteristics and gene mutation analysis of clear cell tumor of the lung.

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):362-368

Department of Radiation Oncology, Lihuili Hospital, Ningbo Medical Center, Ningbo, China.

There were rare clinical reports on clear cell tumor of the lung (CCTL). The clinical characteristics and underlying genetic mutation status of CCTL are poorly understood. From 2012 to 2017, patients pathologically diagnosed with CCTL in our hospital were investigated and analyzed based on clinical manifestations, pathological characteristics, prognosis and full gene mutation status through next generation sequencing (NGS) technology. During a 6-year period, four eligible patients were diagnosed with CCTL through surgical resection and were included in this study. All patients showed solitary nodules or lumps located in the left lung. The average maximum diameter of lesions was 2.5 ± 1.1 cm. Computed tomography (CT) imaging characteristics of these nodules/lumps demonstrated the features of benign tumors. The hematoxylin-eosin (HE) morphology and immunohistochemistry were consistent with the histopathological features of benign CCTL. Subsequent NGS analysis showed frame shift mutations of F2421/E2419, K1466E mutation, and p. 1450_1456 deletion mutation in mTOR gene in two of four patient samples and amplifications of MCL1 were observed in three of four samples. CCTL is a rare type of primary pulmonary mesenchymal tumor with good prognosis. Preliminary diagnosis on CT is usually sclerosing pneumocytoma. It is still unclear whether the occurrence and development of the disease are related to specific gene mutation. In this study, the genomic findings of frame shift mutation of mTOR genes and amplification of MCL1 gene in CCTL suggest that these mutations might play a role in proliferation of CCTL.
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http://dx.doi.org/10.4103/IJPM.IJPM_65_19DOI Listing
April 2021

Hydrochemical characterization and quality assessment of groundwater in the hilly area of the Taihang Mountains in Henan Province, China.

Environ Sci Pollut Res Int 2021 Apr 10. Epub 2021 Apr 10.

Henan Institute of Geological Environment Monitoring, Zhengzhou, 450016, China.

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley's ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca and HCO, respectively, and the principal hydrochemical facies was Ca-Mg-HCO. In terms of pH, total dissolved solids, Na, Cl, F, and SO, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.
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http://dx.doi.org/10.1007/s11356-021-13579-1DOI Listing
April 2021

Untargeted Stable Isotope Probing of the Gut Microbiota Metabolome Using C-Labeled Dietary Fibers.

J Proteome Res 2021 May 8;20(5):2904-2913. Epub 2021 Apr 8.

Superfund Research Center, University of Kentucky, Lexington 40536, Kentucky, United States.

The gut microbiome generates numerous metabolites that exert local effects and enter the circulation to affect the functions of many organs. Despite extensive sequencing-based characterization of the gut microbiome, there remains a lack of understanding of microbial metabolism. Here, we developed an untargeted stable isotope-resolved metabolomics (SIRM) approach for the holistic study of gut microbial metabolites. Viable microbial cells were extracted from fresh mice feces and incubated anaerobically with C-labeled dietary fibers including inulin or cellulose. High-resolution mass spectrometry was used to monitor C enrichment in metabolites associated with glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleotide synthesis, and pyruvate catabolism in both microbial cells and the culture medium. We observed the differential use of inulin and cellulose as substrates for biosynthesis of essential and non-essential amino acids, neurotransmitters, vitamin B5, and other coenzymes. Specifically, the use of inulin for these biosynthetic pathways was markedly more efficient than the use of cellulose, reflecting distinct metabolic pathways of dietary fibers in the gut microbiome, which could be related with host effects. This technology facilitates deeper and holistic insights into the metabolic function of the gut microbiome (Metabolomic Workbench Study ID: ST001651).
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http://dx.doi.org/10.1021/acs.jproteome.1c00124DOI Listing
May 2021

Neuroanatomy of melanocortin-4 receptor pathway in the mouse brain.

Open Life Sci 2020 13;15(1):580-587. Epub 2020 Aug 13.

College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China.

Objective: Melanocortin-4 receptors (MC4Rs) are key regulators of energy homeostasis and adipose deposition in the central nervous system. Considering that MC4R expression regions and function-related research mainly focus on the paraventricular nucleus (PVN), little is known about their distribution throughout the mouse brain, although its messenger RNA distribution has been analyzed in the rat. Therefore, MC4R protein localization in mouse neurons was the focus of this study.

Methods: MC4R protein distribution was assessed in mice through immunofluorescence and Western blotting.

Results: MC4R was differentially expressed throughout the arcuate nucleus (ARC), nucleus of the solitary tract (NTS), raphe pallidus (RPa), medial cerebellar nucleus, intermediolateral nucleus, and brainstem. The highest MC4R protein levels were found in the ARC and ventromedial hypothalamic nucleus, while they were significantly lower in the parabrachial nucleus and NTS. The lowest MC4R protein levels were found in the PVN; there was no difference in the protein levels between the area postrema and RPa.

Conclusions: These data provide a basic characterization of MC4R-expressing neurons and protein distribution in the mouse brain and may aid further research on its role in energy homeostasis.
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http://dx.doi.org/10.1515/biol-2020-0063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874588PMC
August 2020

Controllable double-helical microstructures by photonic orbital angular momentum for chiroptical response.

Opt Lett 2021 Mar;46(6):1401-1404

Three-dimensional helical microstructures are abundant in nature and can be applied as chiral metamaterials for advanced nanophotonics. Here we report a flexible method to fabricate double-helical microstructures with single exposure by recording the chirality of incident optical vortices. Two coaxial optical vortices can interfere to generate a helical optical field, confirmed by the numerical simulation. The diameters of double-helical microstructures can be tailored by the magnitude of topological charges. This fast manufacturing strategy provides the opportunity to efficiently yield helical microstructures. Finally, the chirality of double-helical microstructures can be reversibly read by optical vortices, demonstrating a strong chiroptical response.
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http://dx.doi.org/10.1364/OL.419798DOI Listing
March 2021

Dilatancy, shear jamming, and a generalized jamming phase diagram of frictionless sphere packings.

Soft Matter 2021 Mar 18;17(11):3121-3127. Epub 2021 Feb 18.

Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur Campus, Bengaluru 560064, India.

Granular packings display the remarkable phenomenon of dilatancy, wherein their volume increases upon shear deformation. Conventional wisdom and previous results suggest that dilatancy, also being the related phenomenon of shear-induced jamming, requires frictional interactions. Here, we show that the occurrence of isotropic jamming densities φ above the minimal density (or the J-point density) φ leads both to the emergence of shear-induced jamming and dilatancy in frictionless packings. Under constant pressure shear, the system evolves into a steady-state at sufficiently large strains, whose density only depends on the pressure and is insensitive to the initial jamming density φ. In the limit of vanishing pressure, the steady-state exhibits critical behavior at φ. While packings with different φ values display equivalent scaling properties under compression, they exhibit striking differences in rheological behaviour under shear. The yield stress under constant volume shear increases discontinuously with density when φ > φ, contrary to the continuous behaviour in generic packings that jam at φ. Our results thus lead to a more coherent, generalised picture of jamming in frictionless packings, which also have important implications on how dilatancy is understood in the context of frictional granular matter.
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http://dx.doi.org/10.1039/d0sm02186eDOI Listing
March 2021

Rotational Doppler cooling and heating.

Sci Adv 2021 Jan 6;7(2). Epub 2021 Jan 6.

ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels, Barcelona, Spain.

Doppler cooling is a widely used technique to laser cool atoms, molecules, and nanoparticles by exploiting the Doppler shift associated with translational motion. The rotational Doppler effect arising from rotational coordinate transformation should similarly enable optical manipulation of the rotational motion of nanosystems. Here, we show that rotational Doppler cooling and heating (RDC and RDH) effects embody rich and unexplored physics, including an unexpected strong dependence on particle morphology. For geometrically constrained particles, cooling and heating are observed at red- or blue-detuned laser frequencies relative to particle resonances. In contrast, for nanosystems that can be modeled as solid particles, RDH appears close to resonant illumination, while detuned frequencies produce cooling of rotation. We further predict that RDH can lead to optomechanical spontaneous chiral symmetry breaking, where an achiral particle under linearly polarized illumination starts spontaneously rotating. Our results open up new exciting possibilities to control the rotational motion of nanosystems.
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http://dx.doi.org/10.1126/sciadv.abd6705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787484PMC
January 2021

Characterization of Feedback Neurons in the High-Level Visual Cortical Areas That Project Directly to the Primary Visual Cortex in the Cat.

Front Neuroanat 2020 8;14:616465. Epub 2021 Jan 8.

College of Life Sciences, Anhui Normal University, Wuhu, China.

Previous studies indicate that top-down influence plays a critical role in visual information processing and perceptual detection. However, the substrate that carries top-down influence remains poorly understood. Using a combined technique of retrograde neuronal tracing and immunofluorescent double labeling, we characterized the distribution and cell type of feedback neurons in cat's high-level visual cortical areas that send direct connections to the primary visual cortex (V1: area 17). Our results showed: (1) the high-level visual cortex of area 21a at the ventral stream and PMLS area at the dorsal stream have a similar proportion of feedback neurons back projecting to the V1 area, (2) the distribution of feedback neurons in the higher-order visual area 21a and PMLS was significantly denser than in the intermediate visual cortex of area 19 and 18, (3) feedback neurons in all observed high-level visual cortex were found in layer II-III, IV, V, and VI, with a higher proportion in layer II-III, V, and VI than in layer IV, and (4) most feedback neurons were CaMKII-positive excitatory neurons, and few of them were identified as inhibitory GABAergic neurons. These results may argue against the segregation of ventral and dorsal streams during visual information processing, and support "reverse hierarchy theory" or interactive model proposing that recurrent connections between V1 and higher-order visual areas constitute the functional circuits that mediate visual perception. Also, the corticocortical feedback neurons from high-level visual cortical areas to the V1 area are mostly excitatory in nature.
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http://dx.doi.org/10.3389/fnana.2020.616465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820340PMC
January 2021

Continuous and Patterned Conducting Polymer Coatings on Diverse Substrates: Rapid Fabrication by Oxidant-Intermediated Surface Polymerization and Application in Flexible Devices.

ACS Appl Mater Interfaces 2021 Feb 21;13(4):5583-5591. Epub 2021 Jan 21.

College of Materials, Xiamen University, Xiamen 361005, P. R. China.

Conducting polymer coatings and patterns are the most important forms of these materials for many practical applications, but a simple and efficient approach to these forms remains challenging. Herein, we report a universal oxidant-intermediated surface polymerization (OISP) for the fabrication of conducting polymer coatings and patterns on various substrates. A coating or pattern composed of densely packed colloidal VO·HO nanowires is deposited on the substrate spin coating, dip coating, or printing, which is converted into a conducting polymer one after oxidation polymerization. The polymerization occurs selectively on the VO·HO coatings, and high-quality polypyrrole, polyaniline, and poly(3,4-ethylenedioxythiophene) coatings and patterns on planar and curved polymeric, metallic, and ceramic substrates are obtained in a fast reaction rate similar to the electrochemical polymerization. The mechanistic study reveals that the method relies on the excellent processability and formability of VO·HO nanowires, which is further explained by their large aspect ratio and surface activity. A flexible gas sensor array comprising three individual sensors made of different conducting polymers is fabricated using oxidant-intermediated surface polymerization, and it is successfully used to distinguish various analyte vapors. The method developed here will provide a powerful tool for the fabrication of conducting polymer-based devices.
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http://dx.doi.org/10.1021/acsami.0c20159DOI Listing
February 2021

The advanced paraffin-section preparation technique based on multiple cumulus-oocyte complexes rather than ovaries in ovine.

Reprod Biol 2021 Mar 26;21(1):100473. Epub 2020 Dec 26.

College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, PR China; Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agricultural University, Hohhot, 010018, PR China. Electronic address:

Immunohistochemical staining is the important method for the identification of protein expression in mammal ovaries, in particular in the follicles with the potential to develop into cumulus-oocyte complexes (COCs), which are able to support oocyte maturation regardless of in vivo or in vitro. Here, we reported an advanced immunohistochemical method based on an artificial structure gathering multiple COCs by paraffin embedding for rapid and highly sensitive detection of co-expressed proteins in ovine COCs rather than ovaries. Compared with the conventional immunohistochemistry on ovine ovaries, the advanced COC paraffin sectioning technique showed the better immunostaining effect and featured the higher generation rate for COCs, the distincter cumulus layers, and the more simplified procedures. These results indicate that the COC paraffin sectioning technique is highly effectively applied for identification of protein expression in ovine COC.
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http://dx.doi.org/10.1016/j.repbio.2020.100473DOI Listing
March 2021

The complete chloroplast genome sequence of purple mullein ( L.).

Mitochondrial DNA B Resour 2020 Jan 24;5(1):819-820. Epub 2020 Jan 24.

Key laboratory of Plant Stress Biology, School of Life Sciences, Henan University, Kaifeng, China.

, known as purple mullein or temptress purple, is a species native to Central Europe, Central Asia, and Western China. In the present study, the chloroplast (cp) genome of was assembled using genome skimming sequencing. The cp genome of is 153,348 bp in length comprising two copies of inverted regions (IR, 25,430 bp) separated by the large single-copy (LSC, 84,601 bp) and small single copy (SSC, 17,887 bp) regions. It encodes 114 unique genes, consisting of 80 protein-coding genes, 30 tRNA genes, and 4 rRNA genes, with 20 duplicated genes in the IR regions. Phylogenetic analysis indicates that exhibits a closer relationship with rather than .
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http://dx.doi.org/10.1080/23802359.2020.1715880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748468PMC
January 2020

Complete chloroplast genome of and its phylogenetic implication in Rosales.

Mitochondrial DNA B Resour 2020 Jan 21;5(1):758-759. Epub 2020 Jan 21.

Key Laboratory of Plant Stress Biology, School of Life Sciences, Henan University, Kaifeng, China.

, which belongs to Moraceae, is a tree species lived in a humid climate at low and middle altitudes. The complete chloroplast (cp) genome of was sequenced and assembled in this study. The cp genome is 161,445 bp in length with comprising two copies of inverted region (IR, 25,894 bp) separated by the large single copy (LSC, 89,633 bp) and small single copy (SSC, 20,024 bp) regions. It encodes 111 unique genes, consisting of 77 protein-coding genes, 30 tRNA genes, and four rRNA genes, with 19 duplicated genes in the IR regions. Phylogenetic analysis indicates that is sister to in Moraceae family.
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http://dx.doi.org/10.1080/23802359.2020.1715304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748527PMC
January 2020

Top-down influence affects the response adaptation of V1 neurons in cats.

Brain Res Bull 2021 Feb 14;167:89-98. Epub 2020 Dec 14.

College of Life Sciences, Anhui Normal University, Wuhu, Anhui, 241000, China. Electronic address:

The visual system lowers its perceptual sensitivity to a prolonged presentation of the same visual signal. This brain plasticity, called visual adaptation, is generally attributed to the response adaptation of neurons in the visual cortex. Although well-studied in the neurons of the primary visual cortex (V1), the contribution of high-level visual cortical regions to the response adaptation of V1 neurons is unclear. In the present study, we measured the response adaptation strength of V1 neurons before and after the top-down influence of the area 21a (A21a), a higher-order visual cortex homologous to the primate V4 area, was modulated with a noninvasive tool of transcranial direct current stimulation (tDCS). Our results showed that the response adaptation of V1 neurons enhanced significantly after applying anode (a-) tDCS in A21a when compared with that before a-tDCS, whereas the response adaptation of V1 neurons weakened after cathode (c-) tDCS relative to before c-tDCS in A21a. By contrast, sham (s-) tDCS in A21a had no significant impact on the response adaptation of V1 neurons. Further analysis indicated that a-tDCS in A21a significantly increased both the initial response (IR) of V1 neurons to the first several (five) trails of visual stimulation and the plateau response (PR) to the prolonged visual stimulation; the increase in PR was lower than in IR, which caused an enhancement in response adaptation. Conversely, c-tDCS significantly decreased both IR and PR of V1 neurons; the reduction in PR was smaller than in IR, which resulted in a weakness in response adaptation. Furthermore, the tDCS-induced changes of V1 neurons in response and response adaptation could recover after tDCS effect vanished, but did not occur after the neuronal activity in A21a was silenced by electrolytic lesions. These results suggest that the top-down influence of A21a may alter the response adaptation of V1 neurons through activation of local inhibitory circuitry, which enhances network inhibition in the V1 area upon an increased top-down input, weakens inhibition upon a decreased top-down input, and thus maintains homeostasis of V1 neurons in response to the long-presenting visual signals.
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http://dx.doi.org/10.1016/j.brainresbull.2020.12.007DOI Listing
February 2021

Joint analysis of mixed types of outcomes with latent variables.

Stat Med 2021 Feb 9;40(5):1272-1284. Epub 2020 Dec 9.

Department of Statistics, The Chinese University of Hong Kong, Shatin, Hong Kong.

We propose a joint modeling approach to investigating the observed and latent risk factors of mixed types of outcomes. The proposed model comprises three parts. The first part is an exploratory factor analysis model that summarizes latent factors through multiple observed variables. The second part is a proportional hazards model that examines the observed and latent risk factors of multivariate time-to-event outcomes. The third part is a linear regression model that investigates the determinants of a continuous outcome. We develop a Bayesian approach coupled with MCMC methods to determine the number of latent factors, the association between latent and observed variables, and the important risk factors of different types of outcomes. A modified stochastic search item selection algorithm, which introduces normal-mixture-inverse gamma priors to factor loadings and regression coefficients, is developed for simultaneous model selection and parameter estimation. The proposed method is subjected to simulation studies for empirical performance assessment and then applied to a study concerning the risk factors of type 2 diabetes and the associated complications.
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http://dx.doi.org/10.1002/sim.8840DOI Listing
February 2021

Corrigendum to "Special Staining of the Liquid-Based Cytopathology Test in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients".

Can Respir J 2020 6;2020:7893513. Epub 2020 Nov 6.

Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Medical School of Ningbo University, 247 Renmin Road, Ningbo, Zhejiang 315020, China.

[This corrects the article DOI: 10.1155/2020/8243473.].
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http://dx.doi.org/10.1155/2020/7893513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669353PMC
November 2020

Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury.

J Neurosci 2020 12 6;40(50):9602-9616. Epub 2020 Nov 6.

Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1093

Functional recovery in the end target muscle is a determinant of outcome after peripheral nerve injury. The neuromuscular junction (NMJ) provides the interface between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs). After nerve injury, tSCs extend cytoplasmic processes between NMJs to guide axon growth and NMJ reinnervation. The mechanisms related to NMJ reinnervation are not known. We used multiple mouse models to investigate the mechanisms of NMJ reinnervation in both sexes, specifically whether macrophage-derived vascular endothelial growth factor-A (Vegf-A) is crucial to establishing NMJ reinnervation at the end target muscle. Both macrophage number and Vegf-A expression increased in end target muscles after nerve injury and repair. In mice with impaired recruitment of macrophages and monocytes (-/- mice), the absence of CD68+ cells (macrophages) in the muscle resulted in diminished muscle function. Using a Vegf-receptor 2 (VegfR2) inhibitor (cabozantinib; CBZ) via oral gavage in wild-type (WT) mice resulted in reduced tSC cytoplasmic process extension and decreased NMJ reinnervation compared with saline controls. Mice with Vegf-A conditionally knocked out in macrophages ( mice) demonstrated a more prolonged detrimental effect on NMJ reinnervation and worse functional muscle recovery. Together, these results show that contributions of the immune system are integral for NMJ reinnervation and functional muscle recovery after nerve injury. This work demonstrates beneficial contributions of a macrophage-mediated response for neuromuscular junction (NMJ) reinnervation following nerve injury and repair. Macrophage recruitment occurred at the NMJ, distant from the nerve injury site, to support functional recovery at the muscle. We have shown hindered terminal Schwann cell (tSC) injury response and NMJ recovery with inhibition of: (1) macrophage recruitment after injury; (2) vascular endothelial growth factor receptor 2 (VegfR2) signaling; and (3) Vegf secretion from macrophages. We conclude that macrophage-derived Vegf is a key component of NMJ recovery after injury. Determining the mechanisms active at the end target muscle after motor nerve injury reveals new therapeutic targets that may translate to improve motor recovery following nerve injury.
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http://dx.doi.org/10.1523/JNEUROSCI.1736-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726545PMC
December 2020

Anomalous Thermodiffusion of Electrons in Graphene.

Phys Rev Lett 2020 Oct;125(17):176802

ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.

We reveal a dramatic departure of electron thermodiffusion in solids relative to the commonly accepted picture of the ideal free-electron gas model. In particular, we show that the interaction with the lattice and impurities, combined with a strong material dependence of the electron dispersion relation, leads to counterintuitive diffusion behavior, which we identify by comparing a two-dimensional electron gas (2DEG) and single-layer graphene. When subject to a temperature gradient ∇T, thermodiffusion of massless Dirac fermions in graphene exhibits an anomalous behavior with electrons moving along ∇T and accumulating in hot regions, in contrast to normal electron diffusion in a 2DEG with parabolic dispersion, where net motion against ∇T is observed, accompanied by electron depletion in hot regions. These findings bear fundamental importance for the understanding of the spatial electron dynamics in emerging materials, establishing close relations with other branches of physics dealing with electron systems under nonuniform temperature conditions.
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http://dx.doi.org/10.1103/PhysRevLett.125.176802DOI Listing
October 2020

Berberine for diarrhea in children and adults: a systematic review and meta-analysis.

Therap Adv Gastroenterol 2020 23;13:1756284820961299. Epub 2020 Oct 23.

Researcher, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, School of Traditional Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, China.

Background: Diarrhea is a ubiquitous digestive system disease, leading to loss of fluid and electrolytes, and may be life-threatening, especially in children and adults who are immunosuppressed or malnourished. Berberine has a broad-spectrum antibiotic activity and is very widely used to treat diarrhea in China. No systematic review has been carried out to evaluate the evidence presented in clinical trials. The aim of this study was to assess the effectiveness and safety of berberine in diarrhea treatment among children and adults.

Methods: Seven databases and two clinical trial registries were searched on 1 September 2019. Randomized controlled trials were included, where participants were diagnosed (first diagnosed) as having diarrhea according to clear diagnostic criteria. Berberine alone or in combination with Western medication as intervention were included. Subgroup analyses were conducted based on children or adults, acute or persistent diarrhea, infectious or noninfectious and treatment courses. Primary outcomes were clinical cure rate and duration of diarrhea. The GRADE tool was used to assess the quality of evidence.

Results: A total of 38 randomized controlled trials were included involving 3948 participants (including 27 trials on 2702 children) were included. Compared with antibiotics, berberine plus antibiotics showed better results in both adults and in children in general, especially when given for 7 days or 3 days in acute infectious diarrhea of children. Compared with the control groups, using berberine alone or in combination with montmorillonite, probiotics, and vitamin B increased the clinical cure rate of diarrhea. The use of berberine alone or berberine combined with montmorillonite reduced the duration of hospitalization. Using berberine had significantly better laboratory indicators (isoenzyme, inflammatory factors, myocardial enzyme, and fecal trait) and fewer systemic symptoms than the no berberine groups. Overall, 22 of 27 trials on children used berberine as an enema. No deaths and serious adverse events were reported. The quality of evidence of included trials was moderate to low or very low. The impact of different dosages, frequencies and treatment durations on the outcomes was not evaluated due to insufficient number of trials.

Conclusion: This review demonstrated that berberine was generally effective in improving clinical cure rates and shortening the duration of diarrhea compared with control groups. No severe adverse event was reported. However, there is still a lack of high-quality evidence for evaluating the efficacy and safety of berberine.

Trial Registration: PROSPERO CRD42020151001 (available from http://www.crd.york.ac.uk/PROSPERO/).
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http://dx.doi.org/10.1177/1756284820961299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586028PMC
October 2020

Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice.

Toxicol Appl Pharmacol 2020 12 20;409:115301. Epub 2020 Oct 20.

Superfund Research Center, University of Kentucky, Lexington, KY 40536, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536, USA. Electronic address:

Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.taap.2020.115301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725976PMC
December 2020

An antibody-drug conjugate targeting a GSTA glycosite-signature epitope of MUC1 expressed by non-small cell lung cancer.

Cancer Med 2020 12 20;9(24):9529-9540. Epub 2020 Oct 20.

Tongji University School of Medicine, Shanghai, China.

Antibodies targeting aberrantly glycosylated proteins are ineffective in treating cancer. Antibody-drug conjugates have emerged as effective alternatives, facilitating tumor-specific drug delivery. Previous studies have assessed the aberrantly glycosylated tandem repeat region of MUC1 glycoprotein as three site-specific glycosylated neoantigen peptide motifs (PDTR, GSTA, and GVTS) for binding with a monoclonal antibody. This study aimed to develop an antibody-drug conjugate for cancer treatment based on monoclonal antibodies against the aforementioned three neoantigen peptide motifs. Internalization of monoclonal antibodies was assessed via immunofluorescence staining and colocalization with lysosomal markers in live cells. Antibody positivity in tumor and peritumoral tissue samples was assessed via immunohistochemistry. The efficacy of anti-MUC1 ADCs was evaluated using various cancer cell lines and a mouse tumor xenograft model. An anti-MUC1 ADC was synthesized by conjugating GSTA neoantigen-specific 16A with monomethyl auristatin E (MMAE), which displayed potent antitumoral efficacy with an IC ranging 0.2-49.4 nM toward various cancer cells. In vivo, 16A-MMAE inhibited tumor growth in a dose-dependent manner in a mouse xenograft model established using the NCI-H838 NSCLC cell line, at a minimum effective dose of 1 mg/kg. At 3 mg/kg, 16A-MMAE did not cause significant toxicity in a transgenic mouse expressing human MUC1. The high antitumoral efficacy of 16A-MMAE suggests that aberrant glycosylated MUC1 neoantigen is a potential target for the development of ADCs for treating various cancers. Personalized therapy may be achieved through such glycosite-specific ADCs.
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http://dx.doi.org/10.1002/cam4.3554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774737PMC
December 2020

Liposomes embedded within fibrin gels facilitate localized macrophage manipulations within nerve.

J Neurosci Methods 2021 01 17;348:108981. Epub 2020 Oct 17.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA. Electronic address:

Background: Understanding the role of macrophages at discrete spatial locations during nerve regeneration after injury is important. But, methodologies that systemically manipulate macrophages can obscure their roles within discrete spatial locations within nerve.

New Method: Liposomes were embedded within fibrin gels to construct a delivery system that facilitated macrophage-specific manipulations at a sole spatial region, as macrophages accumulated within the fibrin. Clodronate liposomes were characterized for their toxicity to specific cells composing nerve in vitro, then tested for macrophage-specific depletion in vivo. This delivery system using clodronate liposomes was used to repair a mouse sciatic nerve gap to evaluate its efficacy and effects.

Result: Clodronate liposomes showed specific toxicity to macrophages without affecting dorsal root ganglia (DRG)-derived neurons, endothelial cells, or Schwann cells in culture. The delivery system demonstrated sustained release of liposomes for more than 7 days while still retaining liposomes within the fibrin. In vivo, the delivery system demonstrated macrophages were targeted by liposomes, and the use of clodronate liposomes minimized macrophage accumulation within fibrin, while not affecting macrophage accumulation within DRG. Nerve regeneration across the nerve gap repaired using this delivery system was associated with decreased angiogenesis, Schwann cell accumulation, axon growth, and reinnervation of affected muscle.

Comparison With Existing Methods: This delivery system allowed specific perturbation of macrophages locally in nerve. This method could be applicable across species without the need for genetic manipulations or systemic pharmaceuticals.

Conclusion: Liposomes embedded within fibrin gels locally target macrophages at the site of nerve injury, which enables greater precision in conclusions regarding their roles in nerve.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108981DOI Listing
January 2021

Healthful nutrition as a prevention and intervention paradigm to decrease the vulnerability to environmental toxicity or stressors and associated inflammatory disease risks.

Food Front 2020 Mar 26;1(1):13-14. Epub 2020 Mar 26.

University of Kentucky Superfund Research Center, University of Kentucky, Lexington, KY, USA.

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http://dx.doi.org/10.1002/fft2.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566652PMC
March 2020

Inhibitory effect of central ghrelin on steroid synthesis affecting reproductive health in female mice.

J Steroid Biochem Mol Biol 2020 11 10;204:105750. Epub 2020 Sep 10.

College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China; Inner Mongolia Key Laboratory of Basic Veterinary Science, Hohhot, 010018, China; Vocational and Technical College, Inner Mongolia Agricultural University, Baotou, 014109, China. Electronic address:

Ghrelin is a 28-amino acid peptide hormone that regulates ovarian steroid hormone synthesis; however, there is limited evidence regarding the regulation of this pathway by ghrelin in mice ovary. Thus, we aimed to investigate whether central ghrelin action plays a role in murine reproductive health by inhibiting steroid synthesis. Further, we sought to examine the mechanism of central ghrelin action in ovarian steroid hormone synthesis. After the administration of intracerebroventricular ghrelin (1 nmol), we found reduced serum concentrations of oestradiol and progesterone and reduced secretion of follicle-stimulating hormone and luteinising hormone. Although ghrelin reduced 3β-hydroxysteroid dehydrogenase mRNA and protein levels in the hypothalamus, it did not affect the expression of steroidogenic acute regulatory protein and cytochrome P450 17A1. In the ovary, central ghrelin regulation indirectly inhibited the mRNA and protein levels of steroidogenic acute regulatory protein, cytochrome P450 17A1, and 3β-hydroxysteroid dehydrogenase. Moreover, no changes were observed in the expression of proliferating cell nuclear antigen and phosphorylation of extracellular signal-regulated kinase. We hypothesised that central ghrelin regulation suppressed serum oestradiol and progesterone levels by indirectly inhibiting the expression of steroidogenic acute regulatory protein, cytochrome P450 17A1, and 3β-hydroxysteroid dehydrogenase in the ovary. In this regulation, the suppressed secretion of the follicle-stimulating hormone and luteinising hormone in the pituitary by ghrelin could be involved. Furthermore, hypothalamic 3β-hydroxysteroid dehydrogenase expression is reduced by ghrelin injection.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105750DOI Listing
November 2020

Effects of proximal fibular osteotomy on stress changes in mild knee osteoarthritis with varus deformity: a finite element analysis.

J Orthop Surg Res 2020 Sep 3;15(1):375. Epub 2020 Sep 3.

The Lab of Orthopaedics of Chinese Medicine of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.

Background: Many previous studies lack sufficient quantitative evidences about changes in biomechanical properties of the knee in response to proximal fibular osteotomy (PFO). Therefore, the aim of this study was to compare the preoperative and postoperative effects of PFO on mechanical stresses in the knee joint and provide with a biomechanical basis for PFO in the treatment of mild knee osteoarthritis (KOA) with varus deformity.

Methods: A total of 10 patients suffering mild KOA with varus deformity were enrolled in this study. Their image data from computerized tomography (CT) and magnetic resonance imaging (MRI) were used for finite element models, and PFO models were established. Static structural analysis was carried out using ABAQUS to compare the von Mises stress distribution and values of the maximal von Mises stress of femoral cartilage, meniscuses, tibial cartilages, and tibial plateau before and after surgery.

Results: The stress distribution in the cortical bone of the tibial plateau showed that stresses were transferred from the anterior medial area to the posterior medial area after PFO. Values of the maximal von Mises stress in femoral cartilage, medial meniscus, medial tibial cartilage, and tibial plateau after surgery were significantly lower than the preoperative values, with statistically significant differences (P < 0.05). Postoperative values of the maximal von Mises stress of lateral meniscus and lateral tibial cartilage were significantly higher than the preoperative ones, with statistically significant differences (P < 0.05).

Conclusion: PFO could reduce the stresses in the medial compartment of the knee joint with stress pathways transferring from the anterior medial area to the posterior medial area of the tibial plateau. Therefore, PFO is recommended for the treatment of mild KOA with varus deformity featuring favorably pain-relieving effects.
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http://dx.doi.org/10.1186/s13018-020-01894-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469409PMC
September 2020

A Predicting Nomogram for Mortality in Patients With COVID-19.

Front Public Health 2020 11;8:461. Epub 2020 Aug 11.

Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Qingdao University, Qingdao, China.

The global COVID-19 epidemic remains severe, with the cumulative global death toll reaching more than 207,170 as of May 2, 2020 (1). Our research objective is to establish a reliable nomogram to predict mortality in COVID-19 patients. The nomogram can help us distinguish between patients who are at high risk of death and need close attention. For the single-center retrospective study, we collected 21 cases of patients who died in the critical illness area of the Optical Valley Branch of Tongji Hospital, Huazhong University of Science and Technology, from February 9 to March 10. Additionally, we selected 99 patients discharged during this period for analysis. The nomogram was constructed to predict the mortality for COVID-19 patients using the primary group of 120 patients and was validated using an independent cohort of 84 patients. We used multivariable logistic regression analysis to construct the prediction model. The nomogram was evaluated for calibration, differentiation, and clinical usefulness. The predictors included in the nomogram were c-reactive protein, PaO/FiO, and cTnI. The areas under the curves of the nomogram were 0.988 (95% CI: 0.972-1.000) and 0.956 (95% CI, 0.874-1.000) in the primary and validation groups, respectively. Decision curve analysis suggests that the nomogram may have clinical usefulness. This study provides a nomogram containing c-reactive protein, PaO/FiO, and cTnI that can be conveniently used to predict individual mortality in COVID-19 patients. Next, we will collect as many cases as possible from multiple centers to build a more reliable nomogram to predict mortality for COVID-19 patients.
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http://dx.doi.org/10.3389/fpubh.2020.00461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432145PMC
May 2021

COCO enhances the efficiency of photoreceptor precursor differentiation in early human embryonic stem cell-derived retinal organoids.

Stem Cell Res Ther 2020 08 24;11(1):366. Epub 2020 Aug 24.

Laboratory of Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, Division of Ophthalmic Genetics, The Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.

Background: Significant progress has been made in cell replacement therapy for neural retinal diseases using retinal cells differentiated from human pluripotent stem cells. Low tumorigenicity and the ability to mature to form synaptic junctions make precursor cells a promising donor source. Here, we attempted to improve the yield of photoreceptor precursor cells in three-dimensional retinal organoids from human embryonic stem cells (hESCs).

Methods: A CRX-tdTomato-tagged hESC line was generated to track retinal precursors in 3D retinal organoids. COCO, a multifunctional antagonist of the Wnt, TGF-β, and BMP pathways, was employed to 3D organoid differentiation schemes for enhanced photoreceptor precursor cells. Organoid fluorescence intensity measurement was used to monitor retinalization tendency with the number of precursors further checked by flow cytometry. Signature gene expression during organoid differentiation were assessed by qPCR and immunocytochemistry after COCO supplementation.

Results: CRX-positive cells can be spatiotemporally tracked by tdTomato without affecting retinalization during retinal organoid differentiation. Fluorescence intensity of organoids, which turned out highly consistent with flow cytometry measurement, allowed us to determine the differentiation efficiency of precursors during organoid culturing directly. Using COCO as an auxiliary supplement, rather than alone, can yield an increased number of photoreceptor precursors in the early stage of organoid differentiation. Over a longer time-frame, photoreceptor precursors enhanced their fate of cones and decreased fate of rods after treatment with COCO.

Conclusions: Tracing with the CRX-reporter system showed that in retinal organoids derived from human pluripotent stem cells, COCO increased the differentiation efficiency of photoreceptor precursors and cones.
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http://dx.doi.org/10.1186/s13287-020-01883-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444242PMC
August 2020

Multiplexed end-point microfluidic chemotaxis assay using centrifugal alignment.

Lab Chip 2020 08;20(17):3096-3103

School of Biomedical Engineering, University of British Columbia, Canada. and Centre for Blood Research, University of British Columbia, Canada and Department of Mechanical Engineering, University of British Columbia, Canada and Department of Urologic Sciences, University of British Columbia, Canada.

A fundamental challenge to multiplexing microfluidic chemotaxis assays at scale is the requirement for time-lapse imaging to continuously track migrating cells. Drug testing and drug screening applications require the ability to perform hundreds of experiments in parallel, which is not feasible for assays that require continuous imaging. To address this limitation, end-point chemotaxis assays have been developed using fluid flow to align cells in traps or sieves prior to cell migration. However, these methods require precisely controlled fluid flow to transport cells to the correct location without undesirable mechanical stress, which introduce significant set up time and design complexity. Here, we describe a microfluidic device that eliminates the need for precise flow control by using centrifugation to align cells at a common starting point. A chemoattractant gradient is then formed using passive diffusion prior to chemotaxis in an incubated environment. This approach provides a simple and scalable approach to multiplexed chemotaxis assays. Centrifugal alignment is also insensitive to cell geometry, enabling this approach to be compatible with primary cell samples that are often heterogeneous. We demonstrate the capability of this approach by assessing chemotaxis of primary neutrophils in response to an fMLP (N-formyl-met-leu-phe) gradient. Our results show that cell alignment by centrifugation offers a potential avenue to develop scalable end-point multiplexed microfluidic chemotaxis assays.
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http://dx.doi.org/10.1039/d0lc00311eDOI Listing
August 2020

Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors.

Clin Cancer Res 2020 Nov 28;26(22):5990-6002. Epub 2020 Jul 28.

Department of Data Science, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Purpose: Immune checkpoint blockade has shown remarkable efficacy, but in only a minority of patients with cancer, suggesting the need to develop additional treatment strategies. Aberrant glycosylation in tumors, resulting from the dysregulated expression of key enzymes in glycan biosynthesis, modulates the immune response. However, the role of glycan biosynthesis enzymes in antitumor immunity is poorly understood. We aimed to study the immunomodulatory effects of these enzymes.

Experimental Design: We integrated transcriptional profiles of treatment-naïve human tumors and functional CRISPR screens to identify glycometabolism genes with immunomodulatory effects. We further validated our findings using coculture and syngeneic tumor growth assays.

Results: We identified , encoding an enzyme in N-glycan maturation, as a key immunomodulatory gene. Analyses of public immune checkpoint blockade trial data also suggested a synergy between MAN2A1 inhibition and anti-PD-L1 treatment. Loss of in cancer cells increased their sensitivity to T-cell-mediated killing. knockout enhanced response to anti-PD-L1 treatment and facilitated higher cytotoxic T-cell infiltration in tumors under anti-PD-L1 treatment. Furthermore, a pharmacologic inhibitor of MAN2A1, swainsonine, synergized with anti-PD-L1 in syngeneic melanoma and lung cancer models, whereas each treatment alone had little effect.

Conclusions: loss renders cancer cells more susceptible to T-cell-mediated killing. Swainsonine synergizes with anti-PD-L1 in suppressing tumor growth. In light of the limited efficacy of anti-PD-L1 and failed phase II clinical trial on swainsonine, our study reveals a potential therapy combining the two to overcome tumor immune evasion..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0778DOI Listing
November 2020