Publications by authors named "Gao Fei"

1,808 Publications

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pH/ROS dual-sensitive and chondroitin sulfate wrapped poly (β-amino ester)-SA-PAPE copolymer nanoparticles for macrophage-targeted oral therapy for ulcerative colitis.

Nanomedicine 2021 Sep 22:102461. Epub 2021 Sep 22.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China. Electronic address:

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.
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http://dx.doi.org/10.1016/j.nano.2021.102461DOI Listing
September 2021

Species and Individual Differences and Connectional Asymmetry of Broca's Area in Humans and Macaques.

Neuroimage 2021 Sep 22:118583. Epub 2021 Sep 22.

Centre for Cognitive and Brain Sciences, University of Macau, Taipa, Macau SAR, China; Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China. Electronic address:

To reveal the connectional specialization of the Broca's area (or its homologue), voxel-wise inter-species and individual differences, and inter-hemispheric asymmetry were respectively inspected in humans and macaques at both whole-brain connectivity and single tract levels. It was discovered that the developed connectivity blueprint approach is able to localize connectionally comparable voxels between the two species in Broca's area, whereas the quantitative differences between blueprints of locationally or connectionally corresponding voxels enable us to generate inter-hemispheric, inter-subject, and inter-species connectional variabilities, respectively. More importantly, the inter-species and inter-subject variabilities exhibited positive correlation in both two primates, and relatively higher variabilities were detected in the anatomically defined pars triangularis. By contrast, negative relationship was identified between the inter-species variability and hemispheric asymmetry in human brain. In particular, relatively higher asymmetry was revealed in the anatomically defined pars opercularis. Therefore, our novel findings demonstrated that pars triangularis, as compared to pars opercularis, might be a more active area during primate evolution, in which the brain connectivity and possible functions of pars triangularis show relatively higher degree in species specialization, yet lower in hemispheric specialization. Meanwhile, brain connectivity and possible functions of pars opercularis manifested an opposite pattern. At the tract level, functional roles related to the ventral stream in speech comprehension were relatively conservative and bilaterally organized, while those related to the dorsal stream in speech production show relatively higher species and hemispheric specializations.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118583DOI Listing
September 2021

β-1,3-d-Glucan based yeast cell wall system loaded emodin with dual-targeting layers for ulcerative colitis treatment.

Carbohydr Polym 2021 Dec 27;273:118612. Epub 2021 Aug 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China. Electronic address:

Herein, a β-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC.
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http://dx.doi.org/10.1016/j.carbpol.2021.118612DOI Listing
December 2021

A single nucleotide polymorphism in the gene is associated with Behcet's disease in a Chinese Han population.

Int J Ophthalmol 2021 18;14(9):1315-1320. Epub 2021 Sep 18.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Aim: To explore the association of single nucleotide polymorphisms (SNPs) in the gene region with the susceptibility to Behcet's disease (BD) in a Chinese Han population.

Methods: A total of eight SNPs in the candidate gene region (rs11792633, rs7025417, rs10975519 and rs1048274 in ; rs2310220, rs12712142, rs13424006 and rs3821204 in ) were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array iPLEX platform.

Results: A statistically significant association was observed between rs12712142 and BD patients. The frequency of rs12712142 variant allele A was significantly lower in BD patients than that in controls (OR=0.8, 95%CI: 0.69-0.94, =0.039); the genotype distribution (=0.043) and additive and dominant genetic model analyses (OR=0.8, 95%CI: 0.69-0.94, =0.040 and OR=0.72, 95%CI: 0.58-0.88, =0.011) also indicated a strong association between rs12712142 and BD patients.

Conclusion: This is the first study to reveal the association between rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population, indicating a protective role of in the pathogenesis of BD.
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http://dx.doi.org/10.18240/ijo.2021.09.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403853PMC
September 2021

Boosting the photothermal performance of vacancy-rich MoSe nanoflowers for photoacoustic imaging guided tumor chemo-photothermal therapy.

Nanoscale 2021 Sep 17;13(35):14960-14972. Epub 2021 Sep 17.

Key Laboratory of Advanced Materials of Ministry of Education of China, Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science & Engineering, Tsinghua University, Beijing 100084, China.

Due to the relatively low photo-thermal conversion efficiency and poor tumor targeting capacity, phototheranostic nanoagents encounter some challenges in cancer photothermal therapy. To address this problem, in the current research we developed vacancy-rich MoSe (0 ≤ ≤ 1) nanoflowers (MNFs) with molecular 2-deoxy-D-glucose (2-DG) as the activity target, which could be used as a novel phototheranostic nanoagent in the photoacoustic imaging guided chemo-photothermal synergistic therapy. This selenium-deficient structure endows MNFs with high photothermal conversion efficiency (41.7%) due to the strong localized surface plasmon resonances. Besides, the surface linked 2-DG molecules and the flower-like morphology in the nanoagents promoted the targeting effect (active and passive), thus facilitating the efficient concentration of the nanoagents within the tumor site. Both and anti-tumor experiments have demonstrated the high synergistic efficacy promoted by MNFs and complete tumor eradication with lower administration dosages could be achieved. This rational design of nanoparticles not only provided the paradigm of high therapeutic efficacy of a chemo-photothermal protocol for precise cancer theranostics, but also expanded the scope of nanomedical applications using semiconductor-based nanoplatforms through well-defined designing of their microstructures and physiochemical properties.
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http://dx.doi.org/10.1039/d1nr03306aDOI Listing
September 2021

Lentinan-Based Oral Nanoparticle Loaded Budesonide With Macrophage-Targeting Ability for Treatment of Ulcerative Colitis.

Front Bioeng Biotechnol 2021 27;9:702173. Epub 2021 Aug 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Ulcerative colitis (UC) is a global, chronic, and refractory disease. Corticosteroids are first-line drugs for the treatment of UC but also cause adverse side effects. Budesonide (BUD), a corticosteroid with relatively low side effects, has been approved by the Food and Drug Administration for use as enteric capsules (Entocort EC) for the treatment of inflammatory bowel disease (IBD). However, this formulation lacks specific targeting ability to UC lesions. Herein, we describe the development of an advanced macrophage-targeted oral lentinan (LNT)-based nanoparticles (NPs) loaded BUD for treatment of UC. Briefly, LNT was used as a food source and natural carrier to load BUD by a simple solvent evaporation method to form LNT/BUD-NPs. LNT showed good loading capacity with high encapsulation and loading efficiencies to BUD of approximately 92.19 and 9.58%, respectively. Evaluation of the gastric stability of LNT/BUD-NPs indicated that LNT could effectively protect BUD from gastric acid and digestive enzymes. The release behavior and transmission electron microscopy image of LNT/BUD-NPs in the intestinal content of mice confirmed that intestinal flora can promote BUD release from LNT. Moreover, evaluation of cellular uptake showed that LNT/BUD-NPs could specifically target macrophages and enhance their uptake rate the Dectin-1 receptor. In biodistribution studies, LNT/BUD-NPs were able to efficiently accumulate in the inflamed colon of mice. As expected, LNT/BUD-NPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, LNT/BUD-NPs have the advantages of good gastric stability, release mediated by mouse intestinal content, macrophage-targeting, and anti-UC effects. These advantages indicate LNT-based NPs are a promising oral drug delivery system for UC therapy.
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http://dx.doi.org/10.3389/fbioe.2021.702173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429481PMC
August 2021

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography.

Lipids Health Dis 2021 Sep 12;20(1):106. Epub 2021 Sep 12.

Department of Cardiology, An Zhen Hospital, Capital Medical University, Anzhenli avenue, Chao Yang district, Beijing, 100029, China.

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited.

Methods: In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up.

Results: LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8-29.2] μm vs 13.2 [7.4-18.6] μm; P = 0.029), greater increases in minimum lumen area (0.20[0.10-0.33] mm vs 0.13 [0.12-0.24] mm; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8-24.5] vs. 8.4̊ [2.0-10.5]; P = 0.008).

Conclusions: The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype.

Trial Registration: ClinicalTrials.gov Identifier: NCT04851769 . Registered 2 Mar 2019.
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http://dx.doi.org/10.1186/s12944-021-01528-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436513PMC
September 2021

Discussion on "Causal mediation of semicompeting risks" by Yen-Tsung Huang.

Biometrics 2021 Sep 12. Epub 2021 Sep 12.

Department of Epidemiology, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1111/biom.13520DOI Listing
September 2021

Constitutive Descriptions and Restoration Mechanisms of a Fe-17Cr Alloy during Deformation at Temperatures of 700-1000 °C.

Materials (Basel) 2021 Sep 3;14(17). Epub 2021 Sep 3.

State Key Laboratory of Rolling and Automation, Northeastern University, Shenyang 110819, China.

The deformation behavior for highly purified Fe-17Cr alloy was investigated at 700~1000 °C and 0.5~10 s. The microstructure evolution and corresponding mechanism during deformation were studied in-depth, using electron backscattering diffraction, transmission electron microscopy and precession electron diffraction. During deformation, dynamic recrystallization (DRX) occurred, along with extensive dynamic recovery, and the active DRX mechanism depended on deformation conditions. At higher Zener-Hollomon parameter ( ≥ 5.93 × 10 s), the development of the shear band was promoted, and then continuous DRX was induced by the formation and intersection shear band. At lower Zener-Hollomon parameter ( ≤ 3.10 × 10 s), the nucleation of the new grain was attributed to the combination of continuous DRX by uniform increase in misorientation between subgrains and discontinuous DRX by grain boundary bulging, and with increasing temperature, the effect of the former became weaker, whereas the effect of the latter became stronger. The DRX grain size increased with the temperature. For alleviating ridging, it seems advantageous to activate the continuous DRX induced by shear band through hot deformation with higher . In addition, the modified Johnson-Cook and Arrhenius-type models by conventional way were developed, and the modified Johnson-Cook model was developed, using the proposed way, by considering strain dependency of the material parameters. The Arrhenius-type model was also modified by using the proposed way, through distinguishing stress levels for acquiring partial parameter and through employing peak stress to determine the activation energy and considering strain dependency of only other parameters for compensating strain. According to our comparative analyses, the modified Arrhenius-type model by the proposed approach, which is suggested to model hot-deformation behavior for metals having only ferrite, could offer a more accurate prediction of flow behavior as compared to other developed models.
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http://dx.doi.org/10.3390/ma14175022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434333PMC
September 2021

Transformation of Highly Stable Pt Single Sites on Defect Engineered Ceria into Robust Pt Clusters for Vehicle Emission Control.

Environ Sci Technol 2021 Sep 8;55(18):12607-12618. Epub 2021 Sep 8.

Department of Civil, Environmental, and Construction Engineering, Catalysis Cluster for Renewable Energy and Chemical Transformations (REACT), NanoScience Technology Center (NSTC), University of Central Florida, Orlando, Florida 32816, United States.

Engineering surface defects on metal oxide supports could help promote the dispersion of active sites and catalytic performance of supported catalysts. Herein, a strategy of ZrO doping was proposed to create rich surface defects on CeO (CZO) and, with these defects, to improve Pt dispersion and enhance its affinity as single sites to the CZO support (Pt/CZO). The strongly anchored Pt single sites on CZO support were initially not efficient for catalytic oxidation of CO/CH. However, after a simple activation by H reduction, the catalytic oxidation performance over Pt/CZO catalyst was significantly boosted and better than Pt/CeO. Pt/CZO catalyst also exhibited much higher thermal stability. The structural evolution of Pt active sites by H treatment was systematically investigated on aged Pt/CZO and Pt/CeO catalysts. With H reduction, ionic Pt single sites were transformed into active Pt clusters. Much smaller Pt clusters were created on CZO ( 1.2 nm) than on CeO ( 1.8 nm) due to stronger Pt-CeO interaction on aged Pt/CZO. Consequently, more exposed active Pt sites were obtained on the smaller clusters surrounded by more oxygen defects and Ce species, which directly translated to the higher catalytic oxidation performance of activated Pt/CZO catalyst in vehicle emission control applications.
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http://dx.doi.org/10.1021/acs.est.1c02853DOI Listing
September 2021

Revealing the effect of paired redox-acid sites on metal oxide catalysts for efficient NO removal by NH-SCR.

J Hazard Mater 2021 Aug 24;416:125826. Epub 2021 Apr 24.

Department of Civil, Environmental, and Construction Engineering, Catalysis Cluster for Renewable Energy and Chemical Transformations (REACT), NanoScience Technology Center (NSTC), University of Central Florida, Orlando, FL 32816, United States. Electronic address:

Understanding the nature of active sites on metal oxide catalysts in the selective catalytic reduction (SCR) of NO by NH (NH-SCR) is a crucial prerequisite for the development of novel efficient NH-SCR catalysts. In this work, two CeO-based SCR catalyst systems with diverse acidic metal oxides-CeO interfaces, i.e., NbO-CeO (NbO/CeO and CeO/NbO) and WO-CeO (WO/CeO and CeO/WO), were prepared and used to reveal the relationship between NH-SCR activity and surface acidity/redox properties. In combination with the results of the NH-SCR activity test and various characterizations, it was found that the NH-SCR performance of NbO-CeO and WO-CeO catalysts was highly dependent on the strong interactions between the redox component (CeO) and acidic component (NbO or WO), as well as the amount of paired redox-acid sites. From a quantitative perspective, an activity-surface acidity/redox property relationship was proposed. For both NbO-CeO and WO-CeO catalysts systems operated at the more concerned low-temperature range (200 °C), the NH-SCR activity in low NO conversion region (< 40%) was mainly dominated by the surface acidity of catalysts, while the NH-SCR activity in high NO conversion region (> 40%) was more determined by redox properties.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125826DOI Listing
August 2021

Discussion on "Estimating vaccine efficacy over time after a randomized study is unblinded" by Anastasios A. Tsiatis and Marie Davidian.

Biometrics 2021 Sep 7. Epub 2021 Sep 7.

Department of Statistics, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1111/biom.13542DOI Listing
September 2021

The in-situ Calibration Method for Ambient dose Equivalent Dosemeters.

Radiat Prot Dosimetry 2021 Sep 8. Epub 2021 Sep 8.

Radiation Metrology Center of China Institute of Atomic Energy 102413.

Ambient dose equivalent dosemeters are widely distributed in nuclear facilities for routine continuous monitoring or nuclear accident emergency monitoring, they are inconvenient to be disassembled and sent to the metrology laboratory for calibration. To ensure the accuracy of such dosemeters, the research of in-situ calibration method has been carried out. Ambient dose equivalent secondary standard ionization chamber and portable gamma ray irradiation facility have been designed for in-situ calibration. The experiments of in-situ calibration were carried out in five typical sites located in China Institute of Atomic Energy, results showed that the relative deviation between in-situ calibration factors and metrology laboratory calibration factors are within 5%.The combined standard uncertainty of the in-situ calibration factor is 2.8%, and the expanded uncertainty is 5.6% (k=2).The in-situ calibration method can meet the calibration requirements of the fixed ambient dose equivalent dosemeters.
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http://dx.doi.org/10.1093/rpd/ncab130DOI Listing
September 2021

E2A ablation enhances proportion of nodal-like cardiomyocytes in cardiac-specific differentiation of human embryonic stem cells.

EBioMedicine 2021 Sep 3;71:103575. Epub 2021 Sep 3.

Department of Physiology and Pathophysiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

Background: Human sinoatrial cardiomyocytes are essential building blocks for cell therapies of conduction system disorders. However, current differentiation protocols for deriving nodal cardiomyocytes from human pluripotent stem cells (hPSCs) are very inefficient.

Methods: By employing the hPSCs to cardiomyocyte (CM) in vitro differentiation system and generating E2A-knockout hESCs using CRISPR/Cas9 gene editing technology, we analyze the functions of E2A in CM differentiation.

Findings: We found that knockout of the transcription factor E2A substantially increased the proportion of nodal-like cells in hESC-derived CMs. The E2A ablated CMs displayed smaller cell size, increased beating rates, weaker contractile force, and other functional characteristics similar to sinoatrial node (SAN) cells. Transcriptomic analyses indicated that ion channel-encoding genes were up-regulated in E2A ablated CMs. E2A directly bounded to the promoters of genes key to SAN development via conserved E-box motif, and promoted their expression. Unexpect enhanced activity of NOTCH pathway after E2A ablation could also facilate to induct ventricle workingtype CMs reprogramming into SAN-like cells.

Interpretation: Our study revealed a new role for E2A during directed cardiac differentiation of hESCs and may provide new clues for enhancing induction efficiency of SAN-like cardiomyocytes from hPSCs in the future.

Funding: This work was supported by the NSFC (No.82070391, N.S.; No.81870175 and 81922006, P.L.), the National Key R&D Program of China (2018YFC2000202, N.S.; 2017YFA0103700, P.L.), the Haiju program of National Children's Medical Center EK1125180102, and Innovative research team of high-level local universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005).
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http://dx.doi.org/10.1016/j.ebiom.2021.103575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426208PMC
September 2021

Deficiency in WDFY4 reduces the number of CD8 T cells via reactive oxygen species-induced apoptosis.

Mol Immunol 2021 Sep 2;139:131-138. Epub 2021 Sep 2.

Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:

WDFY4 (WD repeat and FYVE domain-containing 4) is a susceptibility gene involved in several autoimmune diseases and plays an important role in the immune system. However, it is not clear how WDFY4 affects T cells. We have generated a Wdfy4-knockout mouse and found that selective deficiency of Wdfy4 in T cells led to a reduction in the number of CD8 T cells in the periphery, thus promoting tumor growth when mice were challenged with a transplantable tumor. Moreover, conditional ablation of Wdfy4 in T cells enhanced the apoptosis of CD8 T cells and increased the intracellular levels of reactive oxygen species accompanied by the upregulation of Nox2. Mechanistically, the decrease in the CD8 T-cell numbers in Wdfy4-knockout mice was associated with activation of the p53 pathway and inhibition of the extracellular signal-regulated kinase pathway. In addition, WDFY4 participated in cell proliferation. In conclusion, our results elucidate the biological role of WDFY4 in apoptosis and establish a link between WDFY4 and T cells.
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http://dx.doi.org/10.1016/j.molimm.2021.08.022DOI Listing
September 2021

Increased serum level of interleukin-33 in Vogt-Koyanagi-Harada correlates with disease activity.

Clin Immunol 2021 Aug 31;231:108846. Epub 2021 Aug 31.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address:

Objectives: To measure the serum level of IL-33 in patients with Vogt-Koyanagi-Harada disease (VKH) and Behçet's uveitis (BU) in the Chinese Han population and investigate its associations with disease activity and clinical parameters.

Methods: Serum was collected from 41 VKH patients (16 active and 25 inactive patients), 60 BU patients (24 active and 36 inactive patients), and 36 healthy controls. The serum level of IL-33 was measured using the enzyme-linked immunosorbent assay (ELISA) method. Demographic features, clinical manifestations, and intraocular inflammation activity scores (anterior chamber cells score, anterior chamber flare score, and vitreal haze score) were recorded.

Results: The serum level of IL-33 significantly increased in all VKH patients, active VKH patients, and inactive VKH patients, as compared to healthy controls (p < 0.001, p < 0.001, and p = 0.002, respectively), and was higher in the active VKH than in the inactive VKH patients (p = 0.049). The serum level of IL-33 positively correlated with the anterior chamber cells score, vitreal haze score, and the annualized number of relapses in VKH patients (Rho = 0.359, p = 0.021; Rho = 0.344, p = 0.028; Rho = 0.537, p < 0.001, respectively). Serum IL-33 level was significantly associated with the annualized number of relapses in patients with BU (Rho = 0.361, p = 0.005).

Conclusion: Serum IL-33 level is significantly increased in VKH patients in the Chinese Han population. IL-33 level is in positive correlation with the activity and relapses of VKH. Increased IL-33 might contribute to the pathogenesis of VKH and serve as a potential biomarker for VKH disease.
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http://dx.doi.org/10.1016/j.clim.2021.108846DOI Listing
August 2021

Spinal Cord Stimulation Reduces Ventricular Arrhythmias by Attenuating Reactive Gliosis and Activation of Spinal Interneurons.

JACC Clin Electrophysiol 2021 Aug 17. Epub 2021 Aug 17.

Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. Electronic address:

Objectives: This study investigated spinal cord neuronal and glial cell activation during cardiac ischemia-reperfusion (IR)-triggered ventricular arrhythmias and neuromodulation therapy by spinal cord stimulation (SCS).

Background: Myocardial ischemia induces changes in cardiospinal neural networks leading to sudden cardiac death. Neuromodulation with SCS decreases cardiac sympathoexcitation; however, the molecular mechanisms remain unknown.

Methods: Yorkshire pigs (n = 16) were randomized to Control, IR, or IR+SCS groups. A 4-pole SCS lead was placed in the T1-T4 epidural space with stimulation for 30 minutes before IR (50 Hz, 0.4-ms duration, 90% motor threshold). Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were recorded. Immunohistochemistry of thoracic spinal sections was used to map and identify Fos-positive neuronal and glial cell types during IR with and without SCS.

Results: IR increased cardiac sympathoexcitation and arrhythmias (VAS = 6.2 ± 0.9) that were attenuated in IR + SCS (VAS = 2.8 ± 0.5, P = 0.017). IR increased spinal cellular Fos expression (#Fos+ cells Control = 23 ± 2 vs IR = 88 ± 5, P < 0.0001) in T1-T4, with the greatest increase localized to T3, and the greatest %Fos+ cells being microglia and astrocytes. Fos expression was attenuated by IR + SCS (62 ± 4, P < 0.01), primarily though a reduction in Fos+ microglia and astrocytes, as SCS also led to increase in Fos+ neurons in deep dorsal laminae.

Conclusions: In a porcine model, cardiac IR was associated with astrocyte and microglial cell activation. Our results suggest that preemptive thoracic SCS decreased IR-induced cardiac sympathoexcitation and ventricular arrhythmias through attenuation of reactive gliosis and activation of inhibitory interneurons in the dorsal horn of spinal cord.
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http://dx.doi.org/10.1016/j.jacep.2021.05.016DOI Listing
August 2021

PRMT5>regulates ovarian follicle development by facilitating translation.

Elife 2021 Aug 27;10. Epub 2021 Aug 27.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Protein arginine methyltransferase 5 () is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of in granulosa cells resulted in aberrant follicle development and female infertility. In knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in -deficient granulosa cells was repressed by overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducing expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.
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http://dx.doi.org/10.7554/eLife.68930DOI Listing
August 2021

Divergence in the Aquilegia ecalcarata complex is correlated with geography and climate oscillations: Evidence from plastid genome data.

Mol Ecol 2021 Aug 26. Epub 2021 Aug 26.

College of Life Sciences, Shaanxi Normal University, Xi'an, China.

Quaternary climate oscillations and geographical heterogeneity play important roles in determining species and genetic diversity distribution patterns, but how these factors affect the migration and differentiation of East Asian plants species at the population level remains poorly understood. The Aquilegia ecalcarata complex, a group that originated in the Late Tertiary and is widely distributed throughout East Asia, displays high genetic variation that is suitable for studying elaborate phylogeographic patterns and demographic history related to the impact of Quaternary climate and geography. We used plastid genome data from 322 individuals in 60 populations of the A. ecalcarata complex to thoroughly explore the impact of Quaternary climate oscillations and geography on the phylogeographic patterns and demographic history of the A. ecalcarata complex through a series of phylogenetic, divergence time estimation, and demographic history analyses. The dry, cold climate and frequent climate oscillations that occurred during the early Pleistocene and the Mid-Pleistocene transition led to the differentiation of the A. ecalcarata complex, which was isolated in various areas. Geographically, the A. ecalcarata complex can be divided into Eastern and Western Clades and five subclades, which conform to the divergence of the East Asian flora. Our results clearly show the impact of Quaternary climate and geography on evolutionary history at the population level. These findings promote the understanding of the relationship between plant genetic differentiation and climate and geographical factors of East Asia at the population level.
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http://dx.doi.org/10.1111/mec.16151DOI Listing
August 2021

Active Surveillance, Drug Resistance, and Genotypic Profiling of Among School-Age Children in China.

Front Med (Lausanne) 2021 10;8:701494. Epub 2021 Aug 10.

Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) nasal colonization predisposes individuals for endogenous infections and is a major threat to children. Recently, oxacillin/cefoxitin-susceptible -positive (OS-MRSA) has been reported worldwide. Herein, a prospective, cross-sectional study was conducted across five schools, representing three educational stages, in Guangzhou, China. Nasal swabs from 2,375 students were cultured for and all isolates were subjected to antibiotic susceptibility testing phenotypically and confirmed by and genetic detection; all the isolates were classified as MSSA, MRSA, or OS-MRSA. All strains were also analyzed by multi-locus sequence typing. Among the 2,375 swabs, was detected in 744 children (31.3%, 95% CI: 25.9-36.7%), of whom 72 had MRSA (3.0%, 95% CI: 0.6-5.4%) and 4 had OS-MRSA (0.2%, 95% CI: 0.1-0.3%), of which an oxacillin- and cefoxitin-susceptible MRSA strain was identified. The prevalence of and MRSA was higher in younger children. The highest percentage of drug resistance of the isolates ( = 744) was to penicillin (85.5%), followed by erythromycin (43.3%) and clidamycin (41.0%). The most prevalent sequence types (STs) were ST30, ST45, and ST188 in MSSA, accounting for 38.7% of the total isolates, whereas ST45, ST59, and ST338 accounted for 74.6% of the MRSA isolates and ST338 accounted for 50.0% of the OS-MRSA isolates. The MRSA and OS-MRSA isolates ( = 76) were grouped into three clades and one singleton, with clonal complex (CC) 45 as the most predominant linkage. The top nine multi-locus sequence typing-based CCs (CC30, CC45, CC5, CC1, CC15, CC944, CC398, CC59, CC7) represented 86.7% of all isolates. All CC30 isolates were resistant to erythromycin and clidamycin, and almost all these isolates were also resistant to penicillin (99.2%). The CC45 and CC59 isolates exhibited high resistance rates to oxacillin at 31.5 and 59.0%, respectively. This study provides updated data valuable for designing effective control strategies to mitigate the burden of disease and to improve the adequacy of empirical antimicrobial treatments for potentially harmful infections.
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http://dx.doi.org/10.3389/fmed.2021.701494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382981PMC
August 2021

Correction: FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation.

Cell Death Dis 2021 Aug 26;12(9):808. Epub 2021 Aug 26.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

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http://dx.doi.org/10.1038/s41419-021-04096-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390478PMC
August 2021

Transcriptomic Analysis of Long Noncoding RNA and mRNA Expression Profiles in the Amygdala of Rats with Bone Cancer Pain-Depression Comorbidity.

Life (Basel) 2021 Aug 14;11(8). Epub 2021 Aug 14.

Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.

Bone cancer pain (BCP)-depression comorbidity has become a complex clinical problem during cancer treatment; however, its underlying molecular mechanisms have not been clarified. Several long noncoding RNAs (lncRNAs) have been demonstrated to be promising therapeutic targets in depression, but research on the role of lncRNAs in BCP-depression comorbidity has been limited. Therefore, high-throughput RNA sequencing was performed to detect differentially expressed profiles in the amygdala of a BCP-depression rat model in this study. We detected 330 differentially expressed mRNAs (DEmRNAs) and 78 differentially expressed lncRNAs (DElncRNAs) in the BCP-depression comorbidity model and then verified the expression of six DEmRNAs and six DElncRNAs with the greatest degrees of difference by RT-qPCR. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that differentially expressed genes were strongly enriched in inflammatory and immunologic systemic responses. Then the nuclear factor kappa B (NF-κB) signaling pathway and the Th17 differentiation pathway showed significant differences, as determined by Western blot analysis. Finally, we constructed a protein-protein interaction (PPI) network to explore the potential regulatory mechanism of DEmRNAs. In conclusion, our study reveals a new resource for the understanding of dysregulated lncRNAs and mRNAs in BCP-depression comorbidity and provides novel potential therapeutic targets for further approaches.
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http://dx.doi.org/10.3390/life11080834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400935PMC
August 2021

Liraglutide inhibits the progression of prediabetes in rats by reducing Raf-1 kinase inhibitor protein.

Ann Transl Med 2021 Jul;9(14):1157

Beijing Hengfeng Mingcheng Biotechnology Co., Ltd., Beijing, China.

Background: The cleavage product of Raf-1 kinase inhibitor protein (RKIP), hippocampal cholinergic neurostimulating peptide (HCNP) is involved in the promotion of insulin secretion. Studies have shown that liraglutide can inhibit the progression of prediabetes. This study aims to investigate whether the above effects of liraglutide are related to RKIP and HCNP.

Methods: Insulin-1 (INS-1) cells were divided into control group (CON), HCNP group, and HCNP + darifenacin group (H-DAR). The three groups were cultured with Roswell Park Memorial Institute (RPMI) 1640, synthetic HCNP (50 pg/mL) and RPMI 1640, and HCNP + RPMI 1640 + darifenacin respectively. Subsequently, twelve 12- to 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into 2 groups: the placebo group (PBO) and the liraglutide treatment group (LIRA). Six Long Evans Tokushima Otsuka (LETO) rats were used as the control group (CON). The LIRA group was given liraglutide 200 µg/kg intraperitoneally twice a day. After 12 weeks, body weight, fasting blood glucose, 2 hours postprandial blood glucose, and insulin resistance index were recorded. Western blot was used to detect expression level of C-RKIP, N-RKIP, and extracellular signal-regulated kinase of phosphorylation (p-ERK). Real-time quantitative polymerase chain reaction (qRT-PCR) to detect pancreatic tissue choline acetyltransferase () and M3 cholinergic receptor (M3R) gene expression levels.

Results: At glucose concentrations of 5.6 and 16.7 mmol/L, the insulin content in the HCNP group was higher than that in the CON and H-DAR groups (all P<0.01). The body weight and fasting serum insulin (FINS) of rats in the PBO group were higher than those in the LIRA group and the CON group (P<0.01). The relative content of C-RKIP protein in the PBO group was higher than that in the LIRA and CON groups (P<0.01). The relative content of N-RKIP protein and p-ERK protein was lower than that in the LIRA and CON group (P<0.05 and P<0.01, respectively). and gene expression levels in PBO group were lower than those in LIRA and CON group (P<0.01).

Conclusions: Liraglutide promotes the production of HCNP, can increase activity, activate M3R, and further promote the secretion of insulin.
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http://dx.doi.org/10.21037/atm-21-3094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350642PMC
July 2021

Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation.

Int Arch Allergy Immunol 2021 Aug 23:1-8. Epub 2021 Aug 23.

Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. WDFY4 (WDFY family member 4) is a susceptibility gene in several autoimmune diseases.

Objective: In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated.

Methods: Naïve CD4+ T cells were isolated from wild-type and WDFY4-deficient mice and induced to differentiate in vitro. Subsequently, a mouse model of asthma was established by sensitization with ovalbumin.

Results: Study results showed that WDFY4 deficiency could promote the differentiation of Th2 cells and the production of Th2 cytokines. WDFY4-deficient asthmatic mice showed higher levels of Th2 cytokines in the lungs and bronchoalveolar lavage fluid than wild-type mice. Moreover, infiltration of inflammatory cells, hyperplasia of goblet cells, production of mucus, and deposition of collagen were enhanced in WDFY4-deficient asthmatic mice.

Conclusions: Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.
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http://dx.doi.org/10.1159/000516970DOI Listing
August 2021

Successful treatment of refractory pure red cell aplasia with eltrombopag after ABO-incompatible allogeneic hematopoietic stem cell transplantation.

J Zhejiang Univ Sci B 2021 Aug;22(8):695-700

Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Pure red cell aplasia (PRCA) is a well-recognized complication of ABO major mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence of 10%-20% (Zhidong et al., 2012; Busca et al., 2018). It is clinically characterized by anemia, reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy (Shahan and Hildebrandt, 2015). The mechanism for PRCA has been presumed to be persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which can interfere with the engraftment of donor erythroid cells (Zhidong et al., 2012). Several risk factors of PRCA at presentation are known, such as presence of anti-A isoagglutinins before transplantation, reduced intensity conditioning, absence of acute graft-versus-host disease (GVHD), sibling donors, and cyclosporin A (CsA) as GVHD prophylaxis (Hirokawa et al., 2013). PRCA is not considered to be a barrier to HSCT, as some patients can recover spontaneously or benefit from various approaches including high-dose steroids, erythropoietin (EPO), plasma exchange, immunoadsorption, donor lymphocyte infusion (DLI), treatment with rituximab, bortezomib, or daratumumab, and tapering or discontinuation of immunosuppression (Hirokawa et al., 2013; Bathini et al., 2019). However, there are still some patients who fail to respond even to aggressive treatment; they become red cell transfusion-dependent and iron-overloaded, and their life quality is impaired.
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http://dx.doi.org/10.1631/jzus.B2000532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377576PMC
August 2021

Immune efficacy of a candidate porcine reproductive and respiratory syndrome vaccine rHN-NP49 administered by a Needle-free intradermal delivery system in comparison with intramuscular injection.

Vaccine 2021 Sep 16;39(39):5557-5562. Epub 2021 Aug 16.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis Yangzhou University, Yangzhou 225009, PR China. Electronic address:

Porcine reproductive and respiratory syndrome (PRRS) is one of the major drivers of economic loss in the swine industry worldwide. In commercial pig production, vaccination is the first option in an attempt to control infectious diseases. Pigs are therefore often immunized with different vaccines, and almost all of them are delivered via the intramuscular (IM) route. However, the IM injection may result in physical damage, stress reactions, and is labor demanding. An alternative route is urgently needed to reduce the disadvantages of conventional vaccination. In this study, a needle-free intradermal (ID) delivery system was evaluated for delivering a live PRRS vaccine as compared with the traditional needle-syringe method. Fifty-two 4-week-old piglets were divided into six groups: piglets in groups A-C were immunized using ID delivery system with 10, 10 and 10 TCID of PRRS candidate vaccine strain rHN-NP49, respectively; piglets in group D were immunized IM with 10 TCID of rHN-NP49; and group E and F were used as challenge and control groups, respectively. At 28 days post vaccination, piglets in group A to E were challenged with a lethal dose of highly-pathogenic PRRSV. Similar results were found in viremia and antibody response among the ID and IM groups during the immunization stage. After challenge, similar results were found in average body weight gain, viral shedding, serum viral load, and clinical score among the immunization groups, with a higher protection ratio in the ID group compared with IM group with the same immunization dose. These results demonstrated that the ID delivery system could provide similar or even better protection compared with IM route, and could be an effective route for PRRS vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2021.08.023DOI Listing
September 2021

Use of proteomics to identify mechanisms of hepatocellular carcinoma with the CYP2D6*10 polymorphism and identification of ANGPTL6 as a new diagnostic and prognostic biomarker.

J Transl Med 2021 08 19;19(1):359. Epub 2021 Aug 19.

Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, 450052, Henan, China.

Background: Although an association between the cytochrome P4502D6 (CYP2D6) *10 (100C>T) polymorphism and hepatocellular carcinoma (HCC) is known, the mechanism remains unclear. Here we aimed to explore mechanisms of CYP2D6*10 (100C>T) polymorphism conferring to HCC, and screen markers for HCC.

Methods: Label-free global proteome profiling with 34 normal livers and peritumor tissue from 61 HCC patients was performed, and angiopoietin-like protein-6 (ANGPTL6) was evaluated in 2 liver samples validation cohorts and 2 blood specimens validation cohorts.

Results: We found a significantly decreased frequency of TT in HCC patients which reduced HCC susceptibility by 69.2% and was accompanied by lowered enzymatic activity for CYP2D6. Proteomic analysis revealed 1342 differentially expressed proteins (DEPs) that were associated with HCC and 88 DEPs were identified as 100 TT-related proteins, likely underlying the susceptibility to HCC. Twenty-two upregulated DEPs and 66 downregulated DEPs were mainly related to lipid metabolism and the extracellular matrix, respectively. High ANGPTL6 was associated with a higher risk to HCC and worse prognosis. ANGPTL6 was both an independent risk factor and an independent prognostic factor for HCC and exhibited strong potential for predicting HCC occurrence, with comparable AUC values and higher sensitivity compared with alpha-fetoprotein.

Conclusions: The TT genotype-associated decreased risk of HCC appears to be related to lowered CYP2D6 activity and altered protein expression in the tumor microenvironment, and ANGPTL6 is a promising new diagnostic and prognostic biomarker for HCC. Our findings reveal new mechanistic insights for polymorphisms related to HCC risk and provide avenues for screening for HCC.
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http://dx.doi.org/10.1186/s12967-021-03038-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375140PMC
August 2021

USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway.

J Inflamm (Lond) 2021 Aug 19;18(1):25. Epub 2021 Aug 19.

Department of Critical Care Medicine, The Second Affiliated Hospital of Zunyi Medical University, Intersection of Xinlong Avenue and Xinpu Avenue, Xinpu New District, Honghuagang District, 563000, Zunyi City, Guizhou Province, China.

Background: Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. HO, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis.

Results: In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury.

Conclusions: This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.
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http://dx.doi.org/10.1186/s12950-021-00291-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375185PMC
August 2021

The diagnostic value of the combination of hemoglobin, CA199, CA125, and HE4 in endometriosis.

J Clin Lab Anal 2021 Sep 18;35(9):e23947. Epub 2021 Aug 18.

The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

Background: We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined diagnostic model.

Methods: We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes.

Results: Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte-to-lymphocyte ratio (MLR) (p = 0.001), platelet-to-lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)-199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)-4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis.

Conclusion: The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non-invasive diagnosis of endometriosis.
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http://dx.doi.org/10.1002/jcla.23947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418510PMC
September 2021

Establishment of a humanized swine model for COVID-19.

Cell Discov 2021 Aug 17;7(1):70. Epub 2021 Aug 17.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

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http://dx.doi.org/10.1038/s41421-021-00313-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371120PMC
August 2021
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