Publications by authors named "Xiaoxia Yang"

188 Publications

Four-dimensional vibrational spectroscopy for nanoscale mapping of phonon dispersion in BN nanotubes.

Nat Commun 2021 Feb 19;12(1):1179. Epub 2021 Feb 19.

Electron Microscopy Laboratory, School of Physics, Peking University, Beijing, China.

Directly mapping local phonon dispersion in individual nanostructures can advance our understanding of their thermal, optical, and mechanical properties. However, this requires high detection sensitivity and combined spatial, energy and momentum resolutions, thus has been elusive. Here, we demonstrate a four-dimensional electron energy loss spectroscopy technique, and present position-dependent phonon dispersion measurements in individual boron nitride nanotubes. By scanning the electron beam in real space while monitoring both the energy loss and the momentum transfer, we are able to reveal position- and momentum-dependent lattice vibrations at nanometer scale. Our measurements show that the phonon dispersion of multi-walled nanotubes is locally close to hexagonal-boron nitride crystals. Interestingly, acoustic phonons are sensitive to defect scattering, while optical modes are insensitive to small voids. This work not only provides insights into vibrational properties of boron nitride nanotubes, but also demonstrates potential of the developed technique in nanoscale phonon dispersion measurements.
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http://dx.doi.org/10.1038/s41467-021-21452-5DOI Listing
February 2021

Fe-cation Doping in NiSe as an Effective Method of Electronic Structure Modulation towards High-Performance Lithium-Sulfur Batteries.

ChemSusChem 2021 Feb 17. Epub 2021 Feb 17.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan, Shandong, 250061, P. R. China.

The commercialization of Li-S batteries is hindered by the shuttling of lithium polysulfides (LiPSs), the sluggish sulfur redox kinetics as well as the low sulfur utilization during charge/discharge processes. Herein, a free-standing cathode material was developed, based on Fe-doped NiSe nanosheets grown on activated carbon cloth substrates (Fe-NiSe /ACC) for high-performance Li-S batteries. Fe-doping in NiSe plays a key role in the electronic structure modulation of NiSe , enabling improved charge transfer with the adsorbed LiPSs molecules, stronger interactions with the active sulfur species and higher electrical conductivity. Effective promotion of the sulfur redox kinetics and enhanced sulfur utilization were achieved under high areal sulfur loadings. The stronger interactions with LiPSs together with the unique 3D structure of Fe-NiSe /ACC also induced the transformation of Li S /Li S growth from conventional 2D films to 3D particles, significantly eliminating the barriers of solid nucleation and growth during the phase transition of liquid LiPSs to solid Li S /Li S. With a high sulfur loading of 9.9 mg cm , the Fe-NiSe /ACC cathode enabled a high area capacity of 9.14 mAh cm with a low average decay of 0.11 % per cycle over 200 cycles at 0.1 C.
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http://dx.doi.org/10.1002/cssc.202100216DOI Listing
February 2021

iT3SE-PX: Identification of Bacterial Type III Secreted Effectors Using PSSM Profiles and XGBoost Feature Selection.

Comput Math Methods Med 2021 6;2021:6690299. Epub 2021 Jan 6.

College of Information, Shanghai Ocean University, Shanghai 201306, China.

Identification of bacterial type III secreted effectors (T3SEs) has become a popular research topic in the field of bioinformatics due to its crucial role in understanding host-pathogen interaction and developing better therapeutic targets against the pathogens. However, the recognition of all effector proteins by using traditional experimental approaches is often time-consuming and laborious. Therefore, development of computational methods to accurately predict putative novel effectors is important in reducing the number of biological experiments for validation. In this study, we proposed a method, called iT3SE-PX, to identify T3SEs solely based on protein sequences. First, three kinds of features were extracted from the position-specific scoring matrix (PSSM) profiles to help train a machine learning (ML) model. Then, the extreme gradient boosting (XGBoost) algorithm was performed to rank these features based on their classification ability. Finally, the optimal features were selected as inputs to a support vector machine (SVM) classifier to predict T3SEs. Based on the two benchmark datasets, we conducted a 100-time randomized 5-fold cross validation (CV) and an independent test, respectively. The experimental results demonstrated that the proposed method achieved superior performance compared to most of the existing methods and could serve as a useful tool for identifying putative T3SEs, given only the sequence information.
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http://dx.doi.org/10.1155/2021/6690299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806399PMC
January 2021

Bicyclic Ligand-Biased Agonists of S1P: Exploring Side Chain Modifications to Modulate the PK, PD, and Safety Profiles.

J Med Chem 2021 Feb 25;64(3):1454-1480. Epub 2021 Jan 25.

Bristol Myers Squibb Research & Early Development, P.O. Box 4000, Princeton, New Jersey 08543-4000, United States.

Sphingosine-1-phosphate (S1P) binds to a family of sphingosine-1-phosphate G-protein-coupled receptors (S1P). The interaction of S1P with these S1P receptors has a fundamental role in many physiological processes in the vascular and immune systems. Agonist-induced functional antagonism of S1P has been shown to result in lymphopenia. As a result, agonists of this type hold promise as therapeutics for autoimmune disorders. The previously disclosed differentiated S1P modulator BMS-986104 () exhibited improved preclinical cardiovascular and pulmonary safety profiles as compared to earlier full agonists of S1P; however, it demonstrated a long pharmacokinetic half-life ( 18 days) in the clinic and limited formation of the desired active phosphate metabolite. Optimization of this series through incorporation of olefins, ethers, thioethers, and glycols into the alkyl side chain afforded an opportunity to reduce the projected human and improve the formation of the active phosphate metabolite while maintaining efficacy as well as the improved safety profile. These efforts led to the discovery of and , each of which are highly potent, biased agonists of S1P. These compounds not only exhibited shorter in vivo in multiple species but are also projected to have significantly shorter values in humans when compared to our first clinical candidate. In models of arthritis, treatment with and demonstrated robust efficacy.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01109DOI Listing
February 2021

Cataract-causing mutations L45P and Y46D impair the thermal stability of γC-crystallin.

Biochem Biophys Res Commun 2021 Feb 7;539:70-76. Epub 2021 Jan 7.

Eye Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China. Electronic address:

Crystallin gene mutations are responsible for about half of the congenital cataract caused by genetic disorders. L45P and Y46D mutations of γC-crystallin have been reported in patients with nuclear congenital cataract. In this study, we explored the thermal stability of wild type (WT), L45P, and Y46D mutants of γC-crystallin at low and high concentrations, as well as the effect of αA-crystallin on the thermal stability of mutants. Spectroscopic experiments were used to monitor the structural changes on temperature-gradient and time-course heating process. Intermediate morphologies were determined through cryo-electron microscopy. The thermal stability of WT and mutants at concentrations ranging up to hundreds of milligrams were assessed via the UNcle multifunctional protein stability analysis system. The results showed that L45P and Y46D mutations impaired the thermal stability of γC-crystallin at low (0.2 mg/mL) and high concentrations (up to 200 mg/mL). Notably, with increase in protein concentration, the thermal stability of L45P and Y46D mutants of γC-crystallin simultaneously decreased. Thermal stability of L45P and Y46D mutants could be rescued by αA-crystallin in a concentration-dependent manner. The dramatic decrease in thermal stability of γC-crystallin caused by L45P and Y46D mutations contributed to congenital cataract in the mature human lens.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.096DOI Listing
February 2021

Characterization of the complete chloroplast genome of (Gramineae), a native grass from the Qinghai-Tibetan Plateau.

Mitochondrial DNA B Resour 2020 Jan 31;5(1):949-950. Epub 2020 Jan 31.

Qinghai Academy of Animal and Veterinary Science, State Key Laboratory of Plateau Ecology and Agriculture in the Three River Head Waters Region, Qinghai University, Xining, Qinghai, China.

This study provides a chloroplast genome of . The complete cp genome was135,664 bp in length with typical quadripartite structure, containing a pair of inverted repeats (IR) of 21,552 bp each, a large single-copy (LSC) region of 79,790 bp, and a small single-copy (SSC) region of 12,770 bp. The overall G + C content of the cp genome was 38.30%, which encompassed 119 genes including 79 protein-coding genes,8 rRNA genes, and 32 tRNA genes. The phylogenetic analysis indicated that was closely related to cultivar KY-31in Gramineae. This study would contribute to enrich the L. cp genome resource and promote biological research.
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http://dx.doi.org/10.1080/23802359.2020.1719925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748791PMC
January 2020

Characterization of the complete chloroplast genome of L. cv. Qinghai (Gramineae).

Mitochondrial DNA B Resour 2020 Jan 14;5(1):532-533. Epub 2020 Jan 14.

State Key Laboratory of Plateau Ecology and Agriculture in the Three River Head Waters Region, Qinghai Academy of Animal and Veterinary Science, Qinghai University, Xining, Qinghai, China.

This study provides a chloroplast genome of L. cv. Qinghai. The complete genome is 135,606bp in length with a G+C content of 38.28%, which contains 32 tRNA genes, and 8 rRNA genes. The phylogenetic analysis indicated that L. cv. Qinghai is closely related to . These results contribute to explore the genetic evidence for adaptation to the Qinghai-Tibet Plateau.
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http://dx.doi.org/10.1080/23802359.2019.1710276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748860PMC
January 2020

VLA4-Targeted Nanoparticles Hijack Cell Adhesion-Mediated Drug Resistance to Target Refractory Myeloma Cells and Prolong Survival.

Clin Cancer Res 2020 Dec 22. Epub 2020 Dec 22.

Division of Cardiology, Washington University School of Medicine, St. Louis, Missouri.

Purpose: In multiple myeloma, drug-resistant cells underlie relapse or progression following chemotherapy. Cell adhesion-mediated drug resistance (CAM-DR) is an established mechanism used by myeloma cells (MMC) to survive chemotherapy and its markers are upregulated in residual disease. The integrin very late antigen 4 (VLA4; αβ) is a key mediator of CAM-DR and its expression affects drug sensitivity of MMCs. Rather than trying to inhibit its function, here, we hypothesized that upregulation of VLA4 by resistant MMCs could be exploited for targeted delivery of drugs, which would improve safety and efficacy of treatments.

Experimental Design: We synthetized 20 nm VLA4-targeted micellar nanoparticles (V-NP) carrying DiI for tracing or a novel camptothecin prodrug (V-CP). Human or murine MMCs, alone or with stroma, and immunocompetent mice with orthotopic multiple myeloma were used to track delivery of NPs and response to treatments.

Results: V-NPs selectively delivered their payload to MMCs and , and chemotherapy increased their uptake by surviving MMCs. V-CP, alone or in combination with melphalan, was well tolerated and prolonged survival in myeloma-bearing mice. V-CP also reduced the dose requirement for melphalan, reducing tumor burden in association with suboptimal dosing without increasing overall toxicity.

Conclusions: V-CP may be a safe and effective strategy to prevent or treat relapsing or refractory myeloma. V-NP targeting of resistant cells may suggest a new approach to environment-induced resistance in cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2839DOI Listing
December 2020

Identification and characterization of satellite DNAs in Poa L.

Mol Cytogenet 2020 Nov 16;13(1):47. Epub 2020 Nov 16.

State Key Laboratory of Plateau Ecology and Agriculture in the Three River Head Waters Region, Qinghai Academy of Animal and Veterinary Science, Xining, 810001, Qinghai Province, China.

Background: Poa L. is a large genus of grass in Gramineae, among which P. pratensis is widely cultivated as turf and forage. Satellite DNA is the main components of the plant genome. Information of satellites will helpful for dissection the genome composition and definition of the phylogeny relationship of these species. However, the knowledge about the satellites in genus Poa is still limited.

Results: Four satellite DNAs were identified using the Repeat Explorer pipeline in HiSeq Illumina reads from diploid plants in P. malaca (2n = 26). Two satellites showed high similarity with the previously identified PpTr-1 and PpTr-3, whereas two others are newly identified with the monomer of 326 bp (Poa-326) and 353 bp (Poa-353) respectively. The clone DNAs of PpTr-1 and PpTr-3, and oligonucleotides designed representing satellites Poa-326 and Poa-353 were probed to test on chromosomes across 13 Poa speceis with different polyploidy level by fluorescent in situ hybridization (FISH). PpTr-1, PpTr-3, and Poa-362 were stably positioned in the subtelomeric regions in nearly all species with the variation of hybridization sites number. However, Poa-353 showed different FISH patterns of multiple regions with the variation of hybridization intensity and distribution sites across species. In addition, 5S rDNA and 45S rDNA were used to characterize the genome of the Poa species. Four rDNA FISH patterns were revealed in the tested species.

Conclusion: Four identified satellite were high conservable across Poa species. Genome distribution of these satellites can be characterized by FISH. The variation of satellite DNAs and rDNA chromosomal distributions between species provide useful information for phylogenetic analysis in genus Poa.
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http://dx.doi.org/10.1186/s13039-020-00518-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670724PMC
November 2020

The responses of the growth, cytochrome P450 isoenzymes activities and the metabolomics in earthworms to sublethal doses of dichlorvos in soil.

Ecotoxicol Environ Saf 2021 Jan 30;207:111547. Epub 2020 Oct 30.

Institute of Agricultural Quality Standard and Testing Technology, Chongqing Academy of Agricultural Sciences, Chongqing 401329, People's Republic of China.

In this paper, earthworms (Eisenia fetida) were exposed to sublethal doses of dichlorvos (spiked concentration of 0.1, 1.0, 10 mg/kg) in soil for 14 days, the metabolomics and activities of cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9 and CYP3A4) of earthworms were analyzed aiming to identify sensitive biomarkers and reveal possible mode of toxic action. The results showed that CYP1A2 and CYP2C9 activity appeared to be more sensitive than CYP3A4 activity in response to dichlorvos, and that metabolic responses based on the metabolomics depended on both of the length of exposure and exposure dose. Malate, ornithine, glucose, inosine, myo-inositol and some amino acids (glutamine, tryptophan, phenylalanine, tyrosine, leucine, histidine, glutamate, lysine) and CYP isozenzymes may be biomarkers to reveal the toxic effect of dichlorvos on earthworms. Compared to controls, when dichlorvos dose reached 1.0 and 10 mg/kg on day 14, glucose and ornithine increased significantly, malate and some amino acids (glutamine, tryptophan, phenylalanine, tyrosine, leucine) decreased significantly, and activities of CYP1A2 and CYP2C9 were inhibited significantly. The current results suggested that 1.0 and 10 mg/kg dichlorvos for 14 days of exposure blocked energy metabolism, disordered Krebs cycle, interfered amino acids metabolism and evoked toxic effects on earthworms.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111547DOI Listing
January 2021

Efficacy of the combined use of donepezil with either quetiapine or sodium valproate in patients with Alzheimer's disease with behavioral and psychological symptoms of dementia, and their effects on vascular endothelial growth factors.

Exp Ther Med 2021 Jan 4;21(1):10. Epub 2020 Nov 4.

Mental Health Center, Second Provincial People's Hospital of Gansu, Gansu Mental Health Center, The Second Clinical Medical College of Northwest University for Nationalities, Lanzhou, Gansu 730000, P.R. China.

The present study aimed to compare the clinical efficacy of donepezil combined with quetiapine and with sodium valproate on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD), and to explore the changes and clinical value of vascular endothelial growth factor (VEGF). For this purpose, a total of 131 patients with AD admitted to the Infirmary of Shandong Agricultural University from January, 2017 to January, 2019 were included, of which 60 treated with donepezil combined with quetiapine were designated as group A, whereas 71 treated with donepezil combined with sodium valproate were designated as group B. The behavioral pathology in the AD rating scale (BEHAVE-AD) was used for the evaluation of the clinical efficacy, the brief psychiatric rating scale (BPRS) for the mental state assessment, and the mini-mental state examination (MMSE) for the assessment of cognitive performance. Any adverse reactions were recorded, and the treatment costs of the drugs were compared. According to the treatment efficacy, the patients were divided into the excellent efficacy group and the poor efficacy group. No significant differences were observed in clinical efficacy, or in the single and total adverse reactions between the 2 groups (P>0.05). The drug treatment costs in group A were significantly higher than those in group B (P<0.05). The expression of VEGF in the excellent efficacy group was significantly higher than that in the poor efficacy group (P<0.05). VEGF was found to negatively correlate with the BEHAVE-AD score before and after treatment (P<0.05). On the whole, the present study demonstrates that both quetiapine and sodium valproate combined with donepezil are effective in the treatment of patients with AD presenting with BPSD; the latter is relatively more cost-effective and thus may be worthy of clinical promotion. Moreover, VEGF negatively correlates with BEHAVE-AD score and can thus be used as a potential predictive marker for the treatment response of patients AD with BPSD.
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http://dx.doi.org/10.3892/etm.2020.9442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678612PMC
January 2021

Novel Cyclovirus Identified in Broiler Chickens With Transmissible Viral Proventriculitis in China.

Front Vet Sci 2020 29;7:569098. Epub 2020 Sep 29.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

In October 2018, an outbreak of transmissible viral proventriculitis (TVP) occurred in 30-day-old commercial broiler chickens on a farm in Weifang, China. TVP, an infectious viral disease characterized by runting and stunting, is associated with many viruses, and has a significant economic impact on the global poultry industry. TVP is diagnosed according to clinical symptoms, gross and histological lesions, and negative PCR results for pathogenic bacteria, avian leukosis virus subgroup J, Marek's disease virus, reticuloendotheliosis virus, infectious bursa disease virus, avian reovirus, chicken anemia virus, infectious bronchitis virus, chicken proventricular necrosis virus, gyrovirus 3 and chicken circovirus. To further detect the possible causative pathogens of TVP, we used PacBio third-generation sequencing to examine proventricular samples. A dominant abundance of the novel cyclovirus (CyCV), chCyCV-SDAU-1, was identified in broilers with TVP. The complete chCyCV-SDAU-1 genome was verified via inverse PCR, was 1936 bp long, and consisted of Rep, Cp, and two intergenic regions. Phylogenetic tree analysis showed that chCyCV-SDAU-1 formed an independent branch with other cycloviruses. The homology of chCyCV-SDAU-1 with 20 others known cycloviruses was < 40%. Retrospective investigation showed that the CyCV infection rate in the broilers with TVP was 80% (16/20), while no CyCV was found in healthy chickens. In conclusion, a novel CyCV was identified in chickens with TVP, though its role in this disease is unclear.
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http://dx.doi.org/10.3389/fvets.2020.569098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550471PMC
September 2020

Cellular and molecular imaging for stem cell tracking in neurological diseases.

Stroke Vasc Neurol 2020 Oct 29. Epub 2020 Oct 29.

China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing Tiantan Hospital, Beijing, China

Stem cells (SCs) are cells with strong proliferation ability, multilineage differentiation potential and self-renewal capacity. SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases, both in the preclinical experimental and clinical settings. Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally. Here we summarised the research progress of the main tracers, labelling methods and imaging technologies involved in current SC tracking technologies for various neurological diseases. Finally, the applications, challenges and unresolved problems of current SC tracing technologies were discussed.
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http://dx.doi.org/10.1136/svn-2020-000408DOI Listing
October 2020

tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke.

Circ Res 2021 Jan 19;128(1):62-75. Epub 2020 Oct 19.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, China (K.S., M.Z., D.-M.J., X.Y., Q.L., F.-D.S.).

Rationale: Hemorrhagic complications represent a major limitation of intravenous thrombolysis using tPA (tissue-type plasminogen activator) in patients with ischemic stroke. The expression of tPA receptors on immune cells raises the question of what effects tPA exerts on these cells and whether these effects contribute to thrombolysis-related hemorrhagic transformation.

Objective: We aim to determine the impact of tPA on immune cells and investigate the association between observed immune alteration with hemorrhagic transformation in ischemic stroke patients and in a rat model of embolic stroke.

Methods And Results: Paired blood samples were collected before and 1 hour after tPA infusion from 71 patients with ischemic stroke. Control blood samples were collected from 27 ischemic stroke patients without tPA treatment. A rat embolic middle cerebral artery occlusion model was adopted to investigate the underlying mechanisms of hemorrhagic transformation. We report that tPA induces a swift surge of circulating neutrophils and T cells with profoundly altered molecular features in ischemic stroke patients and a rat model of focal embolic stroke. tPA exacerbates endothelial injury, increases adhesion and migration of neutrophils and T cells, which are associated with brain hemorrhage in rats subjected to embolic stroke. Genetic ablation of annexin A2 in neutrophils and T cells diminishes the effect of tPA on these cells. Decoupling the interaction between mobilized neutrophils/T cells and the neurovascular unit, achieved via a S1PR (sphingosine-1-phosphate receptor) 1 modulator RP101075 and a CCL2 (C-C motif chemokine ligand 2) synthesis inhibitor bindarit, which block lymphocyte egress and myeloid cell recruitment, respectively, attenuates hemorrhagic transformation and improves neurological function after tPA thrombolysis.

Conclusions: Our findings suggest that immune invasion of the neurovascular unit represents a previously unrecognized mechanism underlying tPA-mediated brain hemorrhage, which can be overcome by precise immune modulation during thrombolytic therapy.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317596DOI Listing
January 2021

Reference values for plasma neurofilament light chain (NfL) in healthy Chinese.

Clin Chem Lab Med 2020 Oct 19. Epub 2020 Oct 19.

China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China.

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http://dx.doi.org/10.1515/cclm-2020-1030DOI Listing
October 2020

Effect of Goose Parvovirus and Duck Circovirus Coinfection in Ducks.

J Vet Res 2020 Sep 14;64(3):355-361. Epub 2020 Jul 14.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.

Introduction: Coinfection of goose parvovirus (GPV) and duck circovirus (DuCV) occurs commonly in field cases of short beak and dwarfism syndrome (SBDS). However, whether there is synergism between the two viruses in replication and pathogenicity remains undetermined.

Material And Methods: We established a coinfection model of GPV and DuCV in Cherry Valley ducks. Tissue samples were examined histopathologically. The viral loads in tissues were detected by qPCR, and the distribution of the virus in tissues was detected by immunohistochemistry (IHC).

Results: Coinfection of GPV and DuCV significantly inhibited growth and development of ducks, and caused atrophy and pallor of the immune organs and necrosis of the liver. GPV and DuCV synergistically amplified pathogenicity in coinfected ducks. In the early stage of infection, viral loads of both pathogens in coinfected ducks were significantly lower than those in monoinfected ducks (P < 0.05). With the development of the infection process, GPV and DuCV loads in coinfected ducks were significantly higher than those in monoinfected ducks (P < 0.05). Extended viral distribution in the liver, kidney, duodenum, spleen, and bursa of Fabricius was consistent with the viral load increases in GPV and DuCV coinfected ducks.

Conclusion: These results indicate that GPV and DuCV synergistically potentiate their replication and pathogenicity in coinfected ducks.
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http://dx.doi.org/10.2478/jvetres-2020-0048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497759PMC
September 2020

Correction to: MiR-96 promotes apoptosis of nucleus pulpous cells by targeting FRS2.

Hum Cell 2020 Oct;33(4):1335

Department of Spine, Beijing University of Chinese Medicine Third Affiliated Hospital, No.51 Xiaoguan Street, Outside, Andingmen, Beijing, 100029, China.

In the original publication of the.
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http://dx.doi.org/10.1007/s13577-020-00424-9DOI Listing
October 2020

Advance in study on 16S rRNA gene sequencing technology in oral microbial diversity.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Jul;45(7):849-855

Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.

The 16S rRNA gene is the most commonly used molecular marker for identifying microorganisms. It is used in sequencing technology, including the first-generation, the second-generation, and the third-generation sequencing technology. A large number of studies on the 16S rRNA gene have contributed to a deeper understanding of oral microbial diversity. In the healthy oral cavity, there is microbial diversity in time and space. With the occurrence or development of oral diseases such as caries, periodontal disease, or halitosis, the microbial diversity will be changed.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190236DOI Listing
July 2020

Direct observation of highly confined phonon polaritons in suspended monolayer hexagonal boron nitride.

Nat Mater 2021 Jan 17;20(1):43-48. Epub 2020 Aug 17.

International Center for Quantum Materials, Peking University, Beijing, China.

Phonon polaritons enable light confinement at deep subwavelength scales, with potential technological applications, such as subdiffraction imaging, sensing and engineering of spontaneous emission. However, the trade-off between the degree of confinement and the excitation efficiency of phonon polaritons prevents direct observation of these modes in monolayer hexagonal boron nitride (h-BN), where they are expected to reach ultrahigh confinement. Here, we use monochromatic electron energy-loss spectroscopy (about 7.5 meV energy resolution) in a scanning transmission electron microscope to measure phonon polaritons in monolayer h-BN, directly demonstrating the existence of these modes as the phonon Reststrahlen band (RS) disappears. We find phonon polaritons in monolayer h-BN to exhibit high confinement (>487 times smaller wavelength than that of light in free space) and ultraslow group velocity down to about 10c. The large momentum compensation provided by electron beams additionally allows us to excite phonon polaritons over nearly the entire RS band of multilayer h-BN. These results open up a broad range of opportunities for the engineering of metasurfaces and strongly enhanced light-matter interactions.
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http://dx.doi.org/10.1038/s41563-020-0763-zDOI Listing
January 2021

Avian leukosis virus subgroup J induces B cell anergy mediated by Lyn inhibited BCR signal transduction.

Vet Microbiol 2020 Aug 29;247:108781. Epub 2020 Jun 29.

College of Veterinary Medicine, Shandong Agricultural University, No 61, Daizong Street, Tai'an City, Shandong Province, 271018, China. Electronic address:

Immune tolerance induced by avian leukosis virus subgroup J (ALV-J) is a prerequisite for tumorigenesis. Although we had reported that B cell anergy induced by ALV-J was the main reason for immune tolerance, the molecular mechanism still remains unclear. Here, we found SU protein of ALV-J interacted with tyrosine kinase Lyn (a key protein in BCR signaling pathway) by confocal laser scanning microscopy and co-immunoprecipitation test, which suggested that Lyn might play an important role in B cell anergy induced by ALV-J. Correspondingly, the mRNA and protein level of Lyn was significantly up-regulated in B cells after ALV-J infection. Subsequently, the phosphorylated protein levels of Lyn at Tyr507 site were significantly up-regulated in ALV-J-infected B cells after BCR signal activation, but the phosphorylated protein level of Syk (a direct substrate of Lyn) at Tyr525/526 site, Ca flux, and NF-κB p65 protein level were significantly down-regulated. Interestingly, the phosphorylated protein level of Syk at Tyr525/526 site, Ca flux, and NF-κB p65 protein level were both significantly retrieved after the shLyn treatment in B cells infected by ALV-J. In summary, these results indicated that ALV-J activated the negative regulatory effect of phosphorylated Lyn protein at 507 site in BCR signal transduction pathway and then mediated B cell anergy, which will provide a new insight for revealing the pathogenesis of immune tolerance induced by ALV-J.
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http://dx.doi.org/10.1016/j.vetmic.2020.108781DOI Listing
August 2020

Relative contribution of environmental and nutritional variables to net primary production of in the riparian zone of a Three Gorges tributary.

Ecol Evol 2020 Jul 25;10(14):7073-7081. Epub 2020 May 25.

Institute of Quality Standard and Testing Technology Chongqing Academy of Agricultural Sciences Chongqing China.

Our knowledge of fundamental drivers of terrestrial net primary production (NPP) is crucial for improving the predictability of ecosystem stability under global climate change. However, the patterns and determinants of NPP are not fully understood, especially in the riparian zone ecosystem disturbed by periodic drought-rewetting (DRW) cycles. The environmental (flooding time, pH, moisture, and clay content) and nutritional properties (soil organic carbon, total nitrogen, total phosphorus, ammonium (NH-N), nitrate (NO-N), and C:N:P stoichiometry) were investigated in the riparian zone of Pengxi River-a typical tributary of Three Gorges Reservoir (TGR). Structure equation modeling was performed to evaluate the relative importance of environmental and nutritional properties on NPP of a dominating plant in the riparian zone of TGR. Our results indicated that NPP was much lower under much severe flooding stress. All of these variables could predict 46% of the NPP variance. Nutrient use efficiency (NUE) was one of the most critical predictor shaping the change of NPP. Specifically, flooding stress as a major driver had a direct positive effect on soil moisture and soil clay content. The soil clay content positively affects the soil C: N ratio, which further had an indirect negative impact on NPP by mediating NUE. Overall, our study provided a comprehensive analysis of the effects of the combined effect of environmental and nutrient factors on NPP and showed that continuous DRW cycles induced by hydrological regime stimulate the decrease of NPP of by changing NUE strategies. Further research is needed to explore the responses of NPP and NUE under different land use to DRW cycles and to investigate the DRW effects on the combined effect of environmental and nutrient factors by in situ experiments and long-term studies.
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http://dx.doi.org/10.1002/ece3.6409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391555PMC
July 2020

CNSA: a data repository for archiving omics data.

Database (Oxford) 2020 01;2020

China National GeneBank, Shenzhen 518120, China.

With the application and development of high-throughput sequencing technology in life and health sciences, massive multi-omics data brings the problem of efficient management and utilization. Database development and biocuration are the prerequisites for the reuse of these big data. Here, relying on China National GeneBank (CNGB), we present CNGB Sequence Archive (CNSA) for archiving omics data, including raw sequencing data and its further analyzed results which are organized into six objects, namely Project, Sample, Experiment, Run, Assembly and Variation at present. Moreover, CNSA has created a correlation model of living samples, sample information and analytical data on some projects. Both living samples and analytical data are directly correlated with the sample information. From either one, information or data of the other two can be obtained, so that all data can be traced throughout the life cycle from the living sample to the sample information to the analytical data. Complying with the data standards commonly used in the life sciences, CNSA is committed to building a comprehensive and curated data repository for storing, managing and sharing of omics data. We will continue to improve the data standards and provide free access to open-data resources for worldwide scientific communities to support academic research and the bio-industry. Database URL: https://db.cngb.org/cnsa/.
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http://dx.doi.org/10.1093/database/baaa055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377928PMC
January 2020

Nanotherapy delivery of c-myc inhibitor targets Protumor Macrophages and preserves Antitumor Macrophages in Breast Cancer.

Theranostics 2020 12;10(17):7510-7526. Epub 2020 Jun 12.

Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Tumor-associated macrophages (TAMs) enhance tumor growth in mice and are correlated with a worse prognosis for breast cancer patients. While early therapies sought to deplete all macrophages, current therapeutics aim to reprogram pro-tumor macrophages (M2) and preserve those necessary for anti-tumor immune responses (M1). Recent studies have shown that c-MYC (MYC) is induced in M2 macrophages and where it regulates the expression of tumor-promoting genes. In a myeloid lineage MYC KO mouse model, MYC had important roles in macrophage maturation and function leading to reduced tumor growth. We therefore hypothesized that targeted delivery of a MYC inhibitor to established M2 TAMs could reduce polarization toward an M2 phenotype in breast cancer models. In this study, we developed a MYC inhibitor prodrug (MI3-PD) for encapsulation within perfluorocarbon nanoparticles, which can deliver drugs directly to the cytosol of the target cell through a phagocytosis independent mechanism. We have previously shown that M2-like TAMs express significant levels of the vitronectin receptor, integrin β3, and targeting and therapeutic potential was evaluated using αvβ3 integrin targeted rhodamine-labeled nanoparticles (NP) or integrin αvβ3-MI3-PD nanoparticles. We observed that rhodamine, delivered by αvβ3-rhodamine NP, was incorporated into M2 tumor promoting macrophages through both phagocytosis-independent and dependent mechanisms, while NP uptake in tumor suppressing M1 macrophages was almost exclusively through phagocytosis. In a mouse model of breast cancer (4T1-GFP-FL), M2-like TAMs were significantly reduced with αvβ3-MI3-PD NP treatment. To validate this effect was independent of drug delivery to tumor cells and was specific to the MYC inhibitor, mice with integrin β3 knock out tumors (PyMT-Bo1 β3KO) were treated with αvβ3-NP or αvβ3-MI3-PD NP. M2 macrophages were significantly reduced with αvβ3-MI3-PD nanoparticle therapy but not αvβ3-NP treatment. These data suggest αvβ3-NP-mediated drug delivery of a c-MYC inhibitor can reduce protumor M2-like macrophages while preserving antitumor M1-like macrophages in breast cancer.
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http://dx.doi.org/10.7150/thno.44523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359087PMC
June 2020

The phenotypic and molecular characteristics of antimicrobial resistance of Salmonella enterica subsp. enterica serovar Typhimurium in Henan Province, China.

BMC Infect Dis 2020 Jul 15;20(1):511. Epub 2020 Jul 15.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Beijing, 100071, Fengtai District, China.

Background: Salmonella enterica subsp. enterica serovar Typhimurium infections continue to be a significant public health threat worldwide. The aim of this study was to investigate antibiotic resistance among 147 S. Typhimurium isolates collected from patients in Henan, China from 2006 to 2015.

Methods: 147 S. Typhimurium isolates were collected from March 2006 to November 2015 in Henan Province, China. Antimicrobial susceptibility testing was performed, and the resistant genes of ciprofloxacin, cephalosporins (ceftriaxone and cefoxitin) and azithromycin were detected and sequenced. Clonal relationships were assessed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).

Results: Of the 147 isolates, 91.1% were multidrug resistant (MDR), with 4.1% being resistant to all antibiotic classes tested. Of concern, 13 MDR isolates were co-resistant to the first-line treatments cephalosporins and ciprofloxacin, while three were also resistant to azithromycin. Seven PFGE patterns were identified among the 13 isolates. All of the isolates could be assigned to one of four main groups, with a similarity value of 89%. MLST assigned the 147 isolates into five STs, including two dominant STs (ST19 and ST34). Of the 43 ciprofloxacin-resistant isolates, 39 carried double gyrA mutations (Ser83Phe, Asp87Asn/Tyr/Gly) and a single parC (Ser80Arg) mutation, including 1 isolate with four mutations (gyrA: Ser83Phe, Asp87Gly; parC: Ser80Arg; parE: Ser458Pro). In addition, 12 isolates not only carried mutations in gyrA and parC but also had at least one plasmid-mediated quinolone resistance (PMQR) gene. Among the 32 cephalosporin-resistant isolates, the most common extended-spectrum β-lactamase (ESBL) gene was bla, followed by bla, bla, and bla. Moreover, the mphA gene was identified in 5 of the 15 azithromycin-resistant isolates. Four MDR isolates contained ESBL and PMQR genes, and one of them also carried mphA in addition.

Conclusion: The high level of antibiotic resistance observed in S. Typhimurium poses a great danger to public health, so continuous surveillance of changes in antibiotic resistance is necessary.
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http://dx.doi.org/10.1186/s12879-020-05203-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362628PMC
July 2020

Electrical Control of Interband Resonant Nonlinear Optics in Monolayer MoS.

ACS Nano 2020 Jul 7;14(7):8442-8448. Epub 2020 Jul 7.

Department of Electronics and Nanoengineering, Aalto University, Fi-00076 Aalto, Finland.

Monolayer transition-metal dichalcogenides show strong optical nonlinearity with great potential for various emerging applications. Here we demonstrate the gate-tunable interband resonant four-wave mixing and sum-frequency generation in monolayer MoS. Up to 80% modulation depth in four-wave mixing is achieved when the generated signal is resonant with the A exciton at room temperature, corresponding to an effective third-order optical nonlinearity |χ| tuning from (∼12.0 to 5.45) × 10 m/V. The tunability of the effective second-order optical nonlinearity |χ| at 440 nm C-exciton resonance wavelength is also demonstrated from (∼11.6 to 7.40) × 10 m/V with sum-frequency generation. Such a large tunability in optical nonlinearities arises from the strong excitonic charging effect in monolayer transition-metal dichalcogenides, which allows for the electrical control of the interband excitonic transitions and thus nonlinear optical responses for future on-chip nonlinear optoelectronics.
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http://dx.doi.org/10.1021/acsnano.0c02642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735744PMC
July 2020

MiR-96 promotes apoptosis of nucleus pulpous cells by targeting FRS2.

Hum Cell 2020 Oct 23;33(4):1017-1025. Epub 2020 Jun 23.

Department of Spine, Beijing University of Chinese Medicine Third Affiliated Hospital, No.51 Xiaoguan Street, Outside, Andingmen, Beijing, 100029, China.

This study aimed to investigate the molecular mechanism by which microRNA (miR)-96 regulates the progression of intervertebral disc degeneration (IDD). The expression of miR-96 in normal intervertebral discs and in IDD was detected by performing reverse transcription-quantitative PCR. CCK8 assay was applied to examine the proliferation of nucleus pulpous (NP) cells and flow cytometry was used to evaluate the cell apoptosis and cell cycle profile. In addition, the immunofluorescence analysis was employed to detect cell proliferation. The expressions of proteins were assessed by western blot analysis. TargetScan and miRDB were used to predict the target genes of miR-96. The results indicated that miR-96 expression was upregulated in IDD compared with normal intervertebral discs. Overexpression of miR-96 could significantly inhibit the proliferation of NP cells via inducing apoptosis and G1 arrest. In addition, fibroblast growth factor receptor substrate 2 (FRS2) was identified as the target of miR-96 and overexpression of FRS2 could revere the effect of miR-96 mimics in NP cells. Therefore, these findings demonstrated that miR-96 plays a critical role during the progression of IDD and miR-96 may serve as a target for the treatment of IDD.
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http://dx.doi.org/10.1007/s13577-020-00389-9DOI Listing
October 2020

Honeycombed Porous, Size-Matching Architecture for High-Performance Hybrid Direct Carbon Fuel Cell Anode.

ACS Appl Mater Interfaces 2020 Jul 26;12(27):30411-30419. Epub 2020 Jun 26.

Beijing Key Laboratory for Chemical Power Source and Green Catalysis, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, People's Republic of China.

Direct carbon fuel cells (DCFCs) demonstrate both superior electrical efficiency and fuel utilization compared to all other types of fuel cells, and it will be the most promising carbon utilization technology if the sluggish anode reaction kinetics that derives from the use of solid fuel can be addressed. Herein, the electrode morphology and fuel particle size are comprehensively considered to fabricate an efficient DCFC anode skeleton. A honeycombed and size-matching anode architecture with dual-scale porous structure is developed by water droplet templating, which demonstrates an efficient strategy to address the challenge of poor carbon reactivity and improve the electrochemical performance of DCFCs. Single cell with this designed anode framework demonstrates excellent performance, and the maximum power density is as high as 765 mW cm at 800 °C when using the matching carbon fuel. The size-matching between carbon fuel and anode framework shows a remarkable effect on the improvement of mass-transfer processes at the anodes. The significant contribution of the difficult electrochemical oxidation of carbon to the output performance is also demonstrated. These results represent a promising structural design strategy in developing high-performing fuel cells.
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http://dx.doi.org/10.1021/acsami.0c07350DOI Listing
July 2020

Renal survival and risk factors in IgA nephropathy with crescents.

Int Urol Nephrol 2020 Aug 12;52(8):1507-1516. Epub 2020 Jun 12.

Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, Shaanxi, China.

Purpose: The association between crescents and renal outcomes was inconsistent in a Chinese IgA nephropathy (IgAN) cohort, and limited research has investigated the prognosis of IgAN patients with crescents.

Methods: Between January 2008 and January 2013, 169 consecutive IgAN patients with crescents in the Xijing Hospital, who were matched to IgAN patients without crescents at a 1:1 ratio by sex, age, eGFR, and proteinuria were reviewed. Combined events were defined by either a ≥ 50% reduction in eGFR or ESRD.

Results: All patients were followed for a mean of 49.9 ± 26.0 months, and 41 (12.1%) patients had developed combined events. Five multivariate Cox regression models were created, and crescents was an independent risk factor for combined events. In model 5, crescents (HR = 2.216, 95% CI 1.040-4.345, P = 0.039) were notably associated with the risk of combined events after adjusting for age, sex, smoking, TA-P, persistent hematuria, and TA-MAP. Of the IgAN patients with crescents, 17.2% had developed combined events. In the baseline variables model, age, proteinuria, eGFR, E1, T1-T2, and RAAS had statistically significant associations with combined events in the multivariate Cox regression analyses. In the time varying variables model, TA-P, persistent hematuria, and TA-MAP were independent risk factors for combined events.

Conclusion: We validated that the presence of crescents was an independent predictor of combined events in Chinese IgAN patients. Age, proteinuria, eGFR, E1, T1-T2, RAAS, TA-P, persistent hematuria, and TA-MAP were independent risk factors for combined events in IgAN patients with crescents.
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http://dx.doi.org/10.1007/s11255-020-02457-3DOI Listing
August 2020

Mechanical loading induces HIF-1α expression in chondrocytes via YAP.

Biotechnol Lett 2020 Sep 25;42(9):1645-1654. Epub 2020 May 25.

Department of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, China.

Objectives: To investigate the role of YAP in cyclic mechanical stress induced up-regulation of HIF-1α in rat cartilage chondrocytes.

Results: Our in vitro and in vivo experiments demonstrated that cyclic mechanical stress promoted HIF-1α and YAP proteins expression in a magnitude dependent manner. Cyclic mechanical stress at 4000μ strain exhibited most significant effect in promoting HIF-1α and YAP up-regulation. Activation of YAP using LPA significantly promoted HIF-1α stabilization and expression, while YAP siRNA treatment suppressed the up-regulation of HIF-1α induced by cyclic mechanical stress.

Conclusion: Our results indicated that cyclic mechanical stress promoted HIF-1α stabilization and YAP is involved in mechanical stress induced HIF-1α up-regulation.
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http://dx.doi.org/10.1007/s10529-020-02910-4DOI Listing
September 2020

Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide.

J Nephrol 2020 Dec 23;33(6):1241-1250. Epub 2020 May 23.

Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, Shaanxi Province, China.

Background: The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial.

Methods: This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0 g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD.

Results: All patients were followed for a medial of 33.2 months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73 m per year. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups.

Conclusion: Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.
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http://dx.doi.org/10.1007/s40620-020-00752-xDOI Listing
December 2020