Publications by authors named "Yanhong Zhang"

283 Publications

Impacts of Ethanol Production and Drying Conditions on the Chemical, Physical, and Flowability Properties of Distillers Dried Grains With Solubles.

Front Bioeng Biotechnol 2021 27;9:716634. Epub 2021 Aug 27.

National Corn to Ethanol Research Center, Edwardsville, IL, United States.

The production of corn-based ethanol in the U.S. has dramatically increasied in recent years, and consequently so has the quantity of coproduct feed ingredients generated from this segment of the grain processing industry. These streams are almost exclusively utilized as livestock feed, which partially offsets the need for corn in feed rations, but other value-added applications do exist. Because of its use as an animal feed, considerable research has been conducted into the nutritional properties, but to a lesser extent the physical and flowability properties of commercially-produced distillers dried grains with solubles (DDGS). There can be occasions when the quality of coproducts is not consistent. Thus questions regarding the influence of processing operations on the resulting coproduct characteristics must be examined. The objective of this research was to conduct extensive physical and flowability property analyses on DDGS samples which were produced under varying conditions in a pilot plant-scale ethanol plant, in order to investigate the effects of various manufacturing operations (specifically ethanol production and drying conditions) on the resulting properties of the DDGS. Using various laboratory methods, a variety of properties, including bulk density and angle of repose, were determined. DDGS fat content was highly correlated with aerated and packed bulk densities, which indicates that fat level plays a key role in flowability behavior. Future studies should examine this potential relationship in more depth, especially as the industry has moved to fat reduction via oil separation processes.
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http://dx.doi.org/10.3389/fbioe.2021.716634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429502PMC
August 2021

MiR-129-5p prevents depressive-like behaviors by targeting MAPK1 to suppress inflammation.

Exp Brain Res 2021 Sep 4. Epub 2021 Sep 4.

The Third Department of Psychiatry, Huai'an No. 3 People's Hospital, 272 Huaihai West Road, Huaian, Jiangsu, China.

Depression is a complex etiological disease with limited effective treatments. Previous studies have indicated the involvement of miRNAs in the pathophysiology of mood disorders. In this study, we focused on the role and mechanisms of miR-129-5p in depression by successfully constructing mice models of depressive-like behavior via chronic unpredictable mild stress (CUMS) exposure. Herein, miR-129-5p expression was decreased in the hippocampus of CUMS mice model. Upregulation of miR-129-5p reduced depressive-like behaviors of CUMS mice, as revealed in sucrose preference test, novelty suppressed feeding test, forced swim test, tail suspension test, social interaction test. MiR-129-5p upregulation decreased the concentrations and protein levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α), indicating the inhibitory role of miR-129-5p in inflammation. Furthermore, miR-129-5p was identified to target MAPK1. MAPK1 was negatively regulated by miR-129-5p, and silencing of MAPK1 attenuated depressive-like behaviors in CUMS mice. Moreover, MAPK1 downregulation decreased inflammation in the hippocampus of CUMS mice. Upregulation of MAPK1 reversed the suppressive effects of miR-129-5p upregulation on depressive-like behaviors and inflammation in CUMS mice. In conclusion, the current study identified that miR-129-5p reduces depressive-like behaviors and suppresses inflammation by targeting MAPK1 in CUMS mice, offering a novel molecular interpretation for depression prevention.
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http://dx.doi.org/10.1007/s00221-021-06203-8DOI Listing
September 2021

Seadragon genome analysis provides insights into its phenotype and sex determination locus.

Sci Adv 2021 Aug 18;7(34). Epub 2021 Aug 18.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 510301 Guangzhou, China.

The iconic phenotype of seadragons includes leaf-like appendages, a toothless tubular mouth, and male pregnancy involving incubation of fertilized eggs on an open "brood patch." We de novo-sequenced male and female genomes of the common seadragon () and its closely related species, the alligator pipefish (). Transcription profiles from an evolutionary novelty, the leaf-like appendages, show that a set of genes typically involved in fin development have been co-opted as well as an enrichment of transcripts for potential tissue repair and immune defense genes. The zebrafish mutants for , which is lost in all syngnathids, were found to lack or have deformed pharyngeal teeth, supporting the hypothesis that the loss of has contributed to the loss of teeth in syngnathids. A putative sex-determining locus encoding a male-specific gene shared by common seadragon and alligator pipefish was identified.
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http://dx.doi.org/10.1126/sciadv.abg5196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373133PMC
August 2021

Abnormal regulation of microRNAs and related genes in pediatric β-thalassemia.

J Clin Lab Anal 2021 Sep 16;35(9):e23945. Epub 2021 Aug 16.

Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: MicroRNAs (miRNAs) participate in the reactivation of γ-globin expression in β-thalassemia. However, the miRNA transcriptional profiles of pediatric β-thalassemia remain unclear. Accordingly, in this study, we assessed miRNA expression in pediatric patients with β-thalassemia.

Methods: Differentially expressed miRNAs in pediatric patients with β-thalassemia were determined using microRNA sequencing.

Results: Hsa-miR-483-3p, hsa-let-7f-1-3p, hsa-let-7a-3p, hsa-miR-543, hsa-miR-433-3p, hsa-miR-4435, hsa-miR-329-3p, hsa-miR-92b-5p, hsa-miR-6747-3p and hsa-miR-495-3p were significantly upregulated, whereas hsa-miR-4508, hsa-miR-20a-5p, hsa-let-7b-5p, hsa-miR-93-5p, hsa-let-7i-5p, hsa-miR-6501-5p, hsa-miR-221-3p, hsa-let-7g-5p, hsa-miR-106a-5p, and hsa-miR-17-5p were significantly downregulated in pediatric patients with β-thalassemia. After integrating our data with a previously published dataset, we found that hsa-let-7b-5p and hsa-let-7i-5p expression levels were also lower in adolescent or adult patients with β-thalassemia. The predicted target genes of hsa-let-7b-5p and hsa-let-7i-5p were associated with the transforming growth factor β receptor, phosphatidylinositol 3-kinase/AKT, FoxO, Hippo, and mitogen-activated protein kinase signaling pathways. We also identified 12 target genes of hsa-let-7a-3p and hsa-let-7f-1-3p and 21 target genes of hsa-let-7a-3p and hsa-let-7f-1-3p, which were differentially expressed in patients with β-thalassemia. Finally, we found that hsa-miR-190-5p and hsa-miR-1278-5p may regulate hemoglobin switching by modulation of the B-cell lymphoma/leukemia 11A gene.

Conclusion: The results of the study show that several microRNAs are dysregulated in pediatric β-thalassemia. Further, the results also indicate toward a critical role of let7 miRNAs in the pathogenesis of pediatric β-thalassemia, which needs to be investigated further.
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http://dx.doi.org/10.1002/jcla.23945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418487PMC
September 2021

Tissue distribution and developmental changes of PTEN in the immune organs of chicken and effect of IBDV infection on it.

Poult Sci 2021 Sep 27;100(9):101356. Epub 2021 Jun 27.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, Henan, China. Electronic address:

Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, functions in antiviral innate immunity and regulates the development and function of T cells and B cells. However, limited information about PTEN is available in poultry. In the present study, quantitative real-time polymerase chain reaction and immunohistochemistry staining were used to study the tissue distribution and developmental changes of PTEN in the main immune organs of chicken. The effects of infectious bursal disease virus (IBDV) infection on PTEN mRNA expression in the bursa of Fabricius (BF) of chickens were also investigated. The results are as follows. 1) The order of PTEN mRNA expression levels at the 18th d of hatching (E18) was: muscle and immune organs (spleen and thymus) > visceral organs (heart, lung, kidney, and liver) > hypothalamus and digestive tracts (duodenum, jejunum, ileum, cecum, proventriculus, BF [originates from cloaca], and cecum tonsil [locates at the lamina propria of cecum]). However, at the 15th d of raising (D15), the PTEN mRNA expression in the heart was the highest among all the tissues, followed by those in the liver, proventriculus, and kidney. The PTEN mRNA expression levels in the rest tissues were very low and were only 1.20 to 19.47% as much as that in the heart (P < 0.05). 2) The changes in the expression of PTEN mRNA in the BF, spleen, and thymus from E15 to D15 had no obvious regularity. PTEN-immunopositive (PTEN-ip) cells in the BF were distributed in epithelium mucosa, bursal follicles and interfollicles before hatching, but only in bursal follicles after hatching. PTEN-ip cells in the spleen were expressed in the periarterial lymphatic sheath from E18 to D15. Most of PTEN-ip cells distributed in the thymic medulla and only a few distributed in the thymic cortex during the whole experiment. 3) Chicken with IBDV infection had a remarkable decrease in PTEN mRNA expression from 1 d postinfection (dpi) to 7 dpi. Although PTEN mRNA level was reversed at 7 dpi, it was still significantly lower than that at 0 dpi (P < 0.05). These findings suggest that the PTEN of chicken might play important roles in the development of embryos and T/B lymphocytes, and the downregulation of PTEN in chickens infected with IBDV might be a mechanism of IBDV evasion from host immunity. Strategies designed to restore PTEN expression may be a therapy for preventing chickens from IBDV infection.
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http://dx.doi.org/10.1016/j.psj.2021.101356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350381PMC
September 2021

The Role of TRPC6 in Renal Ischemia/Reperfusion and Cellular Hypoxia/Reoxygenation Injuries.

Front Mol Biosci 2021 8;8:698975. Epub 2021 Jul 8.

Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and tubular apoptosis, and calcium (Ca) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca overload, the underlying protective mechanism of TRPC6 may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.
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http://dx.doi.org/10.3389/fmolb.2021.698975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295989PMC
July 2021

escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5.

J Med Microbiol 2021 Jul;70(7)

Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, PR China.

is an intracellular bacterial pathogen that utilizes a type III secretion apparatus to inject effector proteins into host cells. The T3SS effector IpaH4.5 is important for the virulence of . This study aimed to elucidate the molecular mechanism and host target of the IpaH4.5 as well as its roles in infection. The GAP assay was used to identify substrate Rab GTPases of IpaH4.5. A coimmunoprecipitation assay was applied to identify the interaction of Rab GTPases with IpaH4.5. A confocal microscopy analysis was used to assess the effects of IpaH4.5 on mannose 6-phosphate receptor (MPR) trafficking. To identify the effects of IpaH4.5 GAP activity on the activity of lysosomal cathepsin B, the Magic Red-RR assay was used. Finally, the intracellular persistence assay was used to identify IpaH4.5 GAP activity in intracellular growth. We found that the effector IpaH4.5 disrupts MPR trafficking and lysosomal function, thereby counteracting host lysosomal degradation. IpaH4.5 harbours TBC-like dual-finger motifs and exhibits potent RabGAP activities towards Rab31. IpaH4.5 disrupts the transport of the cation-dependent mannose 6-phosphate receptor (CD-MPR) from the Golgi to the endosome by targeting Rab31, thereby attenuating lysosomal function. As a result, the intracellular persistence of requires IpaH4.5 TBC-like GAP activity to mediate bacterial escape from host lysosome-mediated elimination. We identified an unknown function of IpaH4.5 and its potential role in infection.
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http://dx.doi.org/10.1099/jmm.0.001382DOI Listing
July 2021

The N- and C-terminal carbohydrate recognition domains of galectin-9 from Carassius auratus contribute differently to its immunity functions to Aeromonas hydrophila and Staphylococcus aureus.

J Fish Dis 2021 Jul 20. Epub 2021 Jul 20.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.

Galectin-9, an important pathogen recognition receptor (PRR), could recognize and bind pathogen-associated molecular patterns (PAMPs) on the surface of invading microorganisms, initiating the innate immune responses. A galectin-9 was identified from Qihe crucian carp Carassius auratus and designated as CaGal-9. The predicted CaGal-9 protein contained two non-identical carbohydrate recognition domains (CRDs), namely, N-CRD and C-CRD. The recombinant proteins (rCaGal-9, rN-CRD and rC-CRD) were purified from Escherichia coli BL21 (DE3) and exhibited strong agglutinating activity with erythrocytes of rabbit. The haemagglutination was inhibited by D-galactose, α-lactose and N-acetyl-D-galactose. Results of microbial agglutination assay showed that three recombinant proteins agglutinated Gram-negative bacterium Aeromonas hydrophila and Gram-positive bacterium Staphylococcus aureus. With regard to the binding activity, each recombinant protein could bind to LPS, PGN and the examined microorganisms (A. hydrophila and S. aureus) with different binding affinities. The integrated analyses suggested that CaGal-9 with two CRD domains could play an important role in immune defence against pathogenic microorganisms for C. auratus.
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http://dx.doi.org/10.1111/jfd.13497DOI Listing
July 2021

Indoleamine 2, 3-dioxygenase 1 aggravates acetaminophen-induced acute liver failure by triggering excess nitroxidative stress and iron accumulation.

Free Radic Biol Med 2021 08 6;172:578-589. Epub 2021 Jul 6.

Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510000, Guangdong, China. Electronic address:

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.07.008DOI Listing
August 2021

Wound Management of Multi-Site Pressure Ulcer at Different Stages in Elderly Patients.

Clin Cosmet Investig Dermatol 2021 29;14:747-751. Epub 2021 Jun 29.

Department of Wound Repair, Hongmei Hospital of Dongguan, Dongguang, Guangdong, 523160, People's Republic of China.

Objective: The present study aims to explore the individualized treatment options for multisite pressure ulcer (PU) at various stages in elderly patients with multiple medical conditions.

Methods: Stages 1 and 2 PU at 146 sites were treated with closed negative pressure suction combined with continuous micro-oxygen perfusion and the local application of foam dressings, silver ion dressings, and moist burn cream. Stages 3 and 4 PU in the sacrococcygeal region were treated with skin or myocutaneous flap transplantation.

Results: Stages 1 and 2 PU healed after treatment with closed negative pressure suction combined with continuous micro-oxygen perfusion and dressing changes. One case died during hospitalization due to an illness. Skin or myocutaneous flap repair was conducted in 34 cases of stage 3 or 4 PU in the sacrococcygeal area. Of these cases, 28 achieved primary healing, and 6 required two or three surgeries, 5 of which received micro-skin implantation. In addition, 10 small deep PU at other sites were repaired by direct excision and suturing or local flap repair. Seven cases were transferred to other departments or hospitals due to concomitant diseases or were discharged automatically without surgical treatment.

Conclusion: Home care for geriatric patients is difficult. PU often occur at multiple sites because of the duration of various pressures, and different sites may demonstrate different stages because of varying degrees of pressure. When actively treating stages 3 and 4 PU, the trauma management of stages 1 and 2 PU should not be neglected.
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http://dx.doi.org/10.2147/CCID.S316694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254520PMC
June 2021

Kakonein restores diabetes-induced endothelial junction dysfunction via promoting autophagy-mediated NLRP3 inflammasome degradation.

J Cell Mol Med 2021 Aug 27;25(15):7169-7180. Epub 2021 Jun 27.

School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China.

In diabetes-induced complications, inflammatory-mediated endothelial dysfunction is the core of disease progression. Evidence shows that kakonein, an isoflavone common in Pueraria, can effectively treat diabetes and its complications. Therefore, we explored whether kakonein protects cardiovascular endothelial function by inhibiting inflammatory responses. In this study, C57BL/6J mice were injected with streptozocin to establish a diabetes model and treated with kakonein or metformin for 7 days. The protective effect of kakonein on cardiovascular endothelial junctions and NLRP3 inflammasome activation was verified through immunofluorescence and ELISA assay. In addition, the regulation of autophagy on the NLRP3 inflammasome was investigated through Western blot, immunofluorescence and RT-qPCR. Results showed that kakonein restored the function of endothelial junctions and inhibited the assembly and activation of the NLRP3 inflammasome. Interestingly, kakonein decreased the expression of NLRP3 inflammasome protein by not reducing the transcriptional levels of NLRP3 and caspase-1. Kakonein activated autophagy in an AMPK-dependent manner, which reduced the activation of the NLRP3 inflammasome. In addition, kakonein inhibited both hyperglycaemia-induced cardiovascular endothelial junction dysfunction and NLRP3 inflammasome activation, similar to autophagy agonist. Our findings indicated that kakonein exerts a protective effect on hyperglycaemia-induced chronic vascular disease by regulating the NLRP3 inflammasome through autophagy.
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http://dx.doi.org/10.1111/jcmm.16747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335672PMC
August 2021

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats.

Biomed Res Int 2021 27;2021:6649085. Epub 2021 May 27.

Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin 130021, China.

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC-MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3-hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.
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http://dx.doi.org/10.1155/2021/6649085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175156PMC
May 2021

Synergistic bactericidal activities of tobramycin with ciprofloxacin and azithromycin against Klebsiella pneumoniae.

J Antibiot (Tokyo) 2021 Aug 28;74(8):528-537. Epub 2021 May 28.

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, 300071, China.

Trans-translation is a unique bacterial ribosome rescue system that plays important roles in the tolerance to environmental stresses. It is composed of an ssrA-encoded tmRNA and a protein SmpB. In this study, we examined the role of trans-translation in antibiotic tolerance in Klebsiella pneumoniae and explored whether the inhibition of this mechanism could enhance the bactericidal activities of antibiotics. We found that deletion of the ssrA gene reduced the survival of K. pneumoniae after treatment with kanamycin, tobramycin, azithromycin, and ciprofloxacin, indicating an important role of the trans-translation in bacterial antibiotic tolerance. By using a modified ssrA gene with a 6×His tag we demonstrated that tobramycin suppressed the azithromycin and ciprofloxacin-elicited activation of trans-translation. The results were further confirmed with a trans-translation reporter system that is composed of a normal mCherry gene and a gfp gene without the stop codon. Compared to each individual antibiotic, combination of tobramycin with azithromycin or ciprofloxacin synergistically enhanced the killing activities against planktonic K. pneumoniae cells and improved bacterial clearance in a murine cutaneous abscess infection model. In addition, the combination of tobramycin and ciprofloxacin increased the bactericidal activities against biofilm-associated cells. Overall, our results suggest that the combination of tobramycin with azithromycin or ciprofloxacin is a promising strategy in combating K. pneumoniae infections.
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http://dx.doi.org/10.1038/s41429-021-00427-0DOI Listing
August 2021

Factors influencing depression in primary caregivers of patients with dementia in China: A cross-sectional study.

Geriatr Nurs 2021 May-Jun;42(3):734-739. Epub 2021 Apr 12.

Nursing Department, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Gulou District, 210029, Nanjing, China; School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, 211166, Nanjing, China. Electronic address:

This study aims to estimate the prevalence and factors of depression in primary caregivers of people with dementia in China, based on a biopsychosocial medical model. A sample of 285 caregiver-patient dyads was recruited from a tertiary psychiatric hospital in Nanjing, between December 2018 and November 2019. The prevalence of depression among primary caregivers of people with dementia was 42.8%. Binary logistic regression analyses revealed that caregivers' gender (OR=4.692), social support (OR=0.131), health condition (OR=12.994), extraversion (OR=0.102) and neuroticism (OR=2.978) were predictive of depression in those caregivers. Of the above, health condition was the major factor associated with caregiver's depression. The Box-Tidwell method was used to show a linear relationship between continuous independent variables and dependent variable logit conversion values (p = 0.0045). Suggestions are provided to develop support service programs and interventions tailored to caregivers, to help meet their basic substance and mental health needs. (147 words).
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http://dx.doi.org/10.1016/j.gerinurse.2021.03.017DOI Listing
April 2021

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

PLoS Negl Trop Dis 2021 03 24;15(3):e0009233. Epub 2021 Mar 24.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen City, Fujian Province, People's Republic of China.

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model.

Methods: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time.

Results: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions.

Conclusions: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.
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http://dx.doi.org/10.1371/journal.pntd.0009233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021164PMC
March 2021

Stable CuO with variable valence states cooperated with active Co as catalyst/co-catalyst for oxygen reduction/methanol oxidation reactions.

J Colloid Interface Sci 2021 Jul 9;593:345-358. Epub 2021 Mar 9.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of the People's Republic of China, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China. Electronic address:

Catalysts/co-catalysts for cathodic oxygen reduction and anodic methanol oxidation reactions (ORR/MOR) play the major roles in promoting the commercialization of direct methanol fuel cells. Herein, bimetallic zeolite-imidazolate-frameworks (CoZn-ZIFs) is used as precursor to synthesize [email protected]/CuO composites as catalysts for ORR and Pt supports/co-catalysts for MOR. The ORR activity (E = 0.83 V) and long-term stability (activity retention of 85.5% after 30,000 s) of [email protected]/CuO-400 (400 °C) dodecahedron are better than those of commercial Pt/C (10 wt%) in alkaline electrolytes. The surface CuO with variable valence states (Cu and Cu) can be used as both the active component for ORR and the protective layer for CoO to enhance catalytic stability. Partial removal of CoO from carbon framework promotes the exposure of highly active sites (Co) on the CoO. For MOR, the mass activity of [email protected]/CuO-400 (5 wt%) (1947 mA mg) is much higher than that of Pt/C (751 mA mg), mainly attributing to that the Pt active sites are uniformly dispersed on [email protected]/CuO support. The strong interaction between Pt and CuO can reduce the bond strength of Pt-CO to enhance CO resistance. CoO can activate HO molecules to provide sufficient OH species to promote MOR. This study provides a new idea for preparation of active ORR catalysts and MOR co-catalyst from bimetallic ZIFs.
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http://dx.doi.org/10.1016/j.jcis.2021.02.125DOI Listing
July 2021

Fine-tuning p53 activity by modulating the interaction between eukaryotic translation initiation factor eIF4E and RNA-binding protein RBM38.

Genes Dev 2021 04 4;35(7-8):542-555. Epub 2021 Mar 4.

Comparative Oncology Laboratory, School of Veterinary Medicine, School of Medicine, University of California at Davis, Davis, California 95616, USA.

p53 is critical for tumor suppression but also elicits detrimental effects when aberrantly overexpressed. Thus, multiple regulators, including RNA-binding protein RBM38, are found to tightly control p53 expression. Interestingly, RBM38 is unique in that it can either suppress or enhance p53 mRNA translation via altered interaction with eIF4E potentially mediated by serine-195 (S195) in RBM38. Thus, multiple RBM38/eIF4E knock-in (KI) cell lines were generated to investigate the significance of eIF4E-RBM38 interaction in controlling p53 activity. We showed that KI of RBM38-S195D or -Y192C enhances, whereas KI of RBM38-S195K/R/L weakens, the binding of eIF4E to p53 mRNA and subsequently p53 expression. We also showed that KI of eIF4E-D202K weakens the interaction of eIF4E with RBM38 and thereby enhances p53 expression, suggesting that D202 in eIF4E interacts with S195 in RBM38. Moreover, we generated an Rbm38 S193D KI mouse model in which human-equivalent serine-193 is substituted with aspartic acid. We showed that S193D KI enhances p53-dependent cellular senescence and that S193D KI mice have a shortened life span and are prone to spontaneous tumors, chronic inflammation, and liver steatosis. Together, we provide in vivo evidence that the RBM38-eIF4E loop can be explored to fine-tune p53 expression for therapeutic development.
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http://dx.doi.org/10.1101/gad.346148.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015715PMC
April 2021

Genome sequences reveal global dispersal routes and suggest convergent genetic adaptations in seahorse evolution.

Nat Commun 2021 02 17;12(1):1094. Epub 2021 Feb 17.

CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou, China.

Seahorses have a circum-global distribution in tropical to temperate coastal waters. Yet, seahorses show many adaptations for a sedentary, cryptic lifestyle: they require specific habitats, such as seagrass, kelp or coral reefs, lack pelvic and caudal fins, and give birth to directly developed offspring without pronounced pelagic larval stage, rendering long-range dispersal by conventional means inefficient. Here we investigate seahorses' worldwide dispersal and biogeographic patterns based on a de novo genome assembly of Hippocampus erectus as well as 358 re-sequenced genomes from 21 species. Seahorses evolved in the late Oligocene and subsequent circum-global colonization routes are identified and linked to changing dynamics in ocean currents and paleo-temporal seaway openings. Furthermore, the genetic basis of the recurring "bony spines" adaptive phenotype is linked to independent substitutions in a key developmental gene. Analyses thus suggest that rafting via ocean currents compensates for poor dispersal and rapid adaptation facilitates colonizing new habitats.
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http://dx.doi.org/10.1038/s41467-021-21379-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889852PMC
February 2021

Mechanical Thrombectomy in Nonagenarians: a Systematic Review and Meta-analysis.

Transl Stroke Res 2021 06 2;12(3):394-405. Epub 2021 Feb 2.

China International Neuroscience Institute (China-INI), Beijing, China.

This systematic review and meta-analysis aimed to summarize the current literature on mechanical thrombectomy (MT) in nonagenarians and to provide updated clinical evidence of its feasibility, effectiveness, and safety in nonagenarians. PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for relevant randomized controlled trials and observational studies that reported the clinical outcomes of nonagenarians with acute ischemic stroke after undergoing mechanical thrombectomy. Risk of bias was assessed using different scales. I statistic was used to evaluate the heterogeneity of the results, while meta-regression and sensitivity analyses were performed to investigate the source of heterogeneity. Thirteen studies and 657 patients were included. The estimated rate of successful revascularization was 80.82% (95% confidence interval [CI]: 77.48-83.97%), and the rate of favorable outcome (modified Rankin score [mRS] 0-2) was 21.60% (95% CI: 13.81-30.41%). The rate of good outcome (mRS score 0-3) was 23.08% (95% CI: 18.88-27.55%). The estimated risk of death during hospitalization was 20.55% (95% CI: 15.93-25.55%), while the mortality rate at 3 months was 44.38% (95% CI: 33.66-55.36%). The rate of intracranial hemorrhage (ICH) occurrence was 12.84% (95% CI: 5.27-22.68%), while the rate of symptomatic intracranial hemorrhage (sICH) was 3.52% (95% CI: 1.67-5.85%). The rate of hospital-related complications was 26.93% (95% CI: 10.53-47.03%). MT in nonagenarians demonstrated a high rate of successful revascularization. Conversely, the rate of futile revascularization is high with a low functional independence proportion. Therefore, MT should not be indiscriminately advocated in nonagenarians. Satisfactory results require careful selection of patients. Further high-quality studies are needed to clarify the selection algorithm.
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http://dx.doi.org/10.1007/s12975-021-00894-5DOI Listing
June 2021

Repression of the stress granule protein G3BP2 inhibits immune checkpoint molecule PD-L1.

Mol Oncol 2021 Feb 1. Epub 2021 Feb 1.

Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.

Mounting evidence suggests that cancer stemness and immunosuppression are related, but the underlying mechanisms behind these are not clear. We previously reported that the stress granule-associated protein G3BP2 is involved in the regulation of tumor-initiating (stem) cells. In this study we show that this protein also upregulates the immune checkpoint molecule PD-L1 under conditions of stress in breast and glioblastoma cancer cells, revealing a previously-unknown connection between stemness programs, stress responses and immune checkpoint control. We also identified a significant correlation between G3BP2 and PD-L1 co-expression in tumor tissues from cancer patients. To assess the targetability of G3BP2, we employed a small molecule (C108) that binds G3BP2 and interferes with the stress response. Tumors treated with C108 had increased CD8 T cell proliferation and infiltration. Moreover, treatment of breast tumor-bearing mice with C108 resulted in a significant survival benefit and long-term cures. Cancer cells treated with C108 or cancer cells with genetically repressed G3BP2 had decreased PD-L1 expression due to enhanced mRNA degradation. Our study provides a compelling mechanism linking stress granule formation and immune checkpoint program of cancer, suggesting this link may provide new opportunities for improving anti-cancer immunotherapy.
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http://dx.doi.org/10.1002/1878-0261.12915DOI Listing
February 2021

Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial-Mesenchymal Transition.

Front Cell Dev Biol 2020 15;8:602703. Epub 2021 Jan 15.

Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Kidney fibrosis is generally confirmed to have a significant role in chronic kidney disease, resulting in end-stage kidney failure. Epithelial-mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6 and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6 mice compared to WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6 mice, while the loss of Na/K-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.
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http://dx.doi.org/10.3389/fcell.2020.602703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843578PMC
January 2021

Corrigendum to Ethanol induces apoptosis in hepatocytes by a pathway involving novel protein kinase C isoforms Cellular Signaling, 2007, 2339-2350, 07.013.

Cell Signal 2021 Apr 23;80:109925. Epub 2021 Jan 23.

The Transplant Research Institute, University of California, Davis Medical Center, Sacramento, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cellsig.2021.109925DOI Listing
April 2021

Protocol for evaluation of perioperative risk in patients aged over 75 years: Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT study).

BMC Geriatr 2021 01 6;21(1):14. Epub 2021 Jan 6.

China National Clinical Research Center for Geriatric Disorders, Beijing, 100053, China.

Background: With the extended life expectancy of the Chinese population and improvements in surgery and anesthesia techniques, the number of aged patients undergoing surgery has been increasing annually. However, safety, effectiveness, and quality of life of aged patients undergoing surgery are facing major challenges. In order to standardize the perioperative assessment and procedures, we have developed a perioperative evaluation and auxiliary decision-making system named "Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT)".

Methods: We will conduct a perioperative risk evaluation and targeted intervention, with follow-ups at 1, 3, and 6 months after surgery. The primary objective of the study is to evaluate the effectiveness of the "Aged Patient Perioperative Longitudinal Evaluation-Multiple Disciplinary Trial Path" (hereinafter referred to as the APPLE-MDT path) in surgical decision-making for aged patients (≥75 years) undergoing elective surgery under non-local anesthesia in the operating room. The secondary objectives of the study are to evaluate the postoperative outcome and health economics of the APPLE-MDT path applied to the surgical decision-making of aged patients (≥75 years) undergoing elective surgery under non-local anesthesia and to optimize intervention strategies for aged patients undergoing surgery to reduce the occurrence of postoperative complications and improve the quality of life after surgery.

Discussion: It is necessary to formulate a reliable, effective, and concise evaluation tool, which can effectively predict the perioperative complications and mortality of aged patients, support targeted intervention strategies, and allow for a more comprehensive risk and benefit analysis, thereby forming an effective senile perioperative surgery management path. It is expected that the implementation of this protocol can reduce the occurrence of postoperative complications, improve the postoperative quality of life, shorten hospital stay, reduce hospitalization expenses, reduce social burden, and allow the elderly to have a good quality of life after surgery.

Trial Registration: ChiCTR, ChiCTR1800020363 , Registered 15 December 2018.
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http://dx.doi.org/10.1186/s12877-020-01956-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788705PMC
January 2021

The effect of ghrelin on the fibrosis of chicken bursa of fabricius infected with infectious bursal disease virus.

Gen Comp Endocrinol 2021 03 24;303:113705. Epub 2020 Dec 24.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China. Electronic address:

The present study aimed to investigate the effect of ghrelin on the degree of bursa of Fabricius (BF) fibrosis in infectious bursal disease virus-infected chickens. Specific pathogen free (SPF) chicks were divided into four groups. One group was used as the control ("C"). The other three groups were inoculated with IBDV on the 19th day, of which two were injected intraperitoneally with 0.5 nmol ("LG") or 1.0 nmol ("HG") ghrelin/100 g weight from the 18th day to the 22nd day, and one was injected intraperitoneally with PBS ("I"). Hematoxylin-eosin staining, Masson's staining, and quantitative real-time PCR were used to determine the effects of ghrelin on the degree of inflammatory cell infiltration, the bursal fibrosis degree, and the expression of TGF-β and MMP-9 mRNA in IBDV-infected SPF chicks. The results showed that ghrelin administration reduced the number of infiltrated inflammatory cells in BF from 5 dpi and significantly attenuated the degree of fibrosis induced by IBDV from 2 dpi to 7 dpi (P < 0.05). Moreover, the TGF-β expression in the LG and HG groups were significantly or highly significantly lower (P < 0.05 or P < 0.01) than those of I group from 2 dpi to 5 dpi. In addition, ghrelin administration downregulated MMP-9 expression evoked by IBDV from 2 dpi to 7 dpi (P < 0.05 or P < 0.01). These results suggested that ghrelin attenuated the bursal fibrosis degree of IBDV-infected SPF chicks by reducing the number of inflammatory cells and by decreasing the expression of TGF-β and MMP-9, which shortened the process of bursa recovery.
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http://dx.doi.org/10.1016/j.ygcen.2020.113705DOI Listing
March 2021

HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.

Nat Metab 2020 12 26;2(12):1391-1400. Epub 2020 Nov 26.

Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.
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http://dx.doi.org/10.1038/s42255-020-00324-0DOI Listing
December 2020

Ghrelin attenuates infectious bursal disease virus-induced early inflammatory response and bursal injury in chicken.

Poult Sci 2020 Nov 26;99(11):5399-5406. Epub 2020 Aug 26.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China. Electronic address:

Studies demonstrated that chicken ghrelin mRNA was expressed in immune organs of chicken. However, it was not known for its functions in chicken immune system. This study aimed to investigate the effects of ghrelin on infectious bursal disease virus (IBDV)-induced acute inflammatory and bursal injury. Chickens were divided into 4 groups. One group was used as control ("C"). The other three groups incubated with IBDV on the 19th d, of which 2 were injected intraperitoneally with 0.5 nmol ("LG") or 1.0 nmol ("HG") ghrelin/100g body weight from 18th to 22nd d, respectively, and one was injected intraperitoneally with PBS ("I"). Results showed that cytokines including interleukin (IL)-6, IL-1β, and IL-8 mRNA expression in I group were upregulated significantly after chickens infected with IBDV from 1 d post-infection (dpi) to 3 dpi (P < 0.05). However, the expression level of IL-6, IL-1β, and IL-8 mRNA in LG and HG groups was 7.3, ∼43.3% as much as that of the I group at 2 dpi and 3 dpi (P < 0.05). Moreover, ghrelin administration attenuated significantly the bursal injury from 1 dpi to 7 dpi and prevents the reduction of bird weight gain at 5 dpi and 7 dpi, which were induced by IBDV (P < 0.05). The results indicated that ghrelin could play an important role in the immune system of chicken.
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http://dx.doi.org/10.1016/j.psj.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647848PMC
November 2020

Tissue distribution and developmental changes of interferon regulatory factors in chickens and effects of infectious bursal disease virus infection.

Microb Pathog 2021 Mar 1;152:104601. Epub 2020 Nov 1.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, 453003, Henan, China. Electronic address:

Interferon regulatory factors (IRFs) are a family of transcription factors that play a role in a variety of biological processes including immune regulation of interferon and expression of inflammatory cytokines. However, the data on IRFs are rather limited in chickens. In the present study, qRT-PCR was used to study the tissue distribution of IRFs in chickens at D15 (the 15th day of raising) and developmental changes of all chIRFs (Chicken interferon regulatory factors) in BF from E15 (the 15th day of incubation) to D15. The effects of IBDV infection with chickens on the transcriptional level of chIRFs were also investigated. The results showed: (1) chIRF1 mRNA was expressed much more abundantly in intestinal tract, chIRF2, chIRF6, chIRF7, chIRF8 and chIRF10 distributed mainly in liver or/and kidney. The expression of chIRF5 was mainly in spleen and chIRF4 distributed uniquely abundantly in BF. (2) The mRNA expression levels of chIRF5, chIRF7, chIRF8 and chIRF10 was low before hatching of chicken and at D1 and increased significantly from D5 till to the experiment end and the fold change of chIRF5 at D10 and chIRF7 at D5 reached 41.0-fold and 15.7-fold compared to that of E15, respectively (P < 0.05). ChIRF4 mRNA level was always high during the whole experiment except for E15 and it was 11.9-fold at the highest time point than that of E15 (the lowest time point). (3) When chicken was infected with IBDV, the expression levels of chIRF2, chIRF7 and chIRF10 mRNA had the tendency of increasing first and then decreasing but they peaked at 1dpi, 2 dpi, and 3dpi, respectively. The expression of chIRF5 mRNA was suppressed obviously during the whole experiment stage in IBDV-infected chicken. And chIRF4 expression was up-regulated transitorily at 1dpi and then was suppressed on a very low level till to the experiment end. Conclusion: The chIRFs were constitutively expressed in different tissues examined and has tissue-specific expression. Of them, chIRF2, chIRF4, chIRF5, chIRF7, chIRF8 and chIRF10 were related closely with the development or immune response of BF, and when chicken was infected with IBDV, some of them were activated, earlier or later on, some of them were suppressed. These findings would help to sieve out a few antiviral chIRF candidate gene to improve the host's innate immune and provide a foundation of the further exploiting a new vaccine adjuvant.
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http://dx.doi.org/10.1016/j.micpath.2020.104601DOI Listing
March 2021

The Type III Secretion Effector IpaH4.5 Targets NLRP3 to Activate Inflammasome Signaling.

Front Cell Infect Microbiol 2020 30;10:511798. Epub 2020 Sep 30.

Department of Genetic Engineering, Beijing Institute of Biotechnology, Beijing, China.

Activation of the NLRP3 inflammasome requires the expression of NLRP3, which is strictly regulated by its capacity to directly recognize microbial-derived substances. Even though the involvement of caspase-1 activation in macrophages NLRP3 and NLRC4 has been discovered, the accurate mechanisms by which infection triggers NLRP3 activation remain inadequately understood. Here, we demonstrate that IpaH4.5, a T3SS effector, triggers inflammasome activation by regulating NLRP3 expression through the E3 ubiquitin ligase activity of IpaH4.5. First, we found that IpaH4.5 interacted with NLRP3. As a result, IpaH4.5 modulated NLRP3 protein stability and inflammasome activation. Bacteria lacking IpaH4.5 had dramatically reduced ability to induce pyroptosis. Our results identify a previously unrecognized target of IpaH4.5 in the regulation of inflammasome signaling and clarify the molecular basis for the cytosolic response to the T3SS effector.
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http://dx.doi.org/10.3389/fcimb.2020.511798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561375PMC
May 2021

Enhanced cellular functions of hepatocytes in the hyaluronate-alginate-chitosan microcapsules.

Int J Artif Organs 2021 May 24;44(5):340-349. Epub 2020 Sep 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The study aimed to develop a biocompatible microcapsule for hepatocytes and create a bio-mimic microenvironment for maintaining hepatic-specific functions of hepatocytes in vitro. The work is proposed for the bioartificial liver system in the treatment of liver failure. In this study, microcapsules were prepared with hyaluronate (HA)/sodium alginate (SA) as an inner core and an outer chitosan (CS) shell via one-step spraying method. C3A cells were encapsulated in microcapsules to examine the biocompatibility of HA-SA-CS microcapsules. MTT and fluorescence microscopy indicated that C3A cells had high viability in the HA-SA-CS microcapsules. The liver-specific functions, such as urea and albumin synthesis, and CYP1A2 and CYP3A4 activities from encapsulated cells were increased in the HA-SA-CS microcapsules compared to the SA-CS microcapsules. The gene expressions of CYP450 related genes were also increased by HA on day 3. The study suggests that HA-SA-CS microcapsules have good biocompatibility and can maintain a favorable environment for hepatocytes. This approach has improved the preservation of liver cells' metabolic functions and could be a candidate for the bioartificial liver system.
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http://dx.doi.org/10.1177/0391398820959345DOI Listing
May 2021

Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells.

Nat Commun 2020 09 14;11(1):4591. Epub 2020 Sep 14.

Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA.

Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy.
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http://dx.doi.org/10.1038/s41467-020-18245-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490264PMC
September 2020
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