Publications by authors named "Chao Ye"

230 Publications

NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Infection.

Front Microbiol 2022 25;13:898559. Epub 2022 May 25.

Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, China.

is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against , but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6 mice in the lung had lower bacterial burdens after infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6) mice during infection. Also, NLRP6 mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6 neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection.
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http://dx.doi.org/10.3389/fmicb.2022.898559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174927PMC
May 2022

Naringin in the repair of knee cartilage injury via the TGF-β/ALK5/Smad2/3 signal transduction pathway combined with an acellular dermal matrix.

J Orthop Translat 2022 Jan 6;32:1-11. Epub 2021 Aug 6.

Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation.

Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining).

Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best ( < 0.05). ② Quantitative scoring of joint defect tissue showed that the Nar/ADM group had the best repair efficacy in the quantitative scores of the above two scales compared with the other groups ( < 0.05). ③ Micro-CT scan showed that the ADM group had obvious repair of the defect structure, while the ADM/Nar group had blurred repair boundaries, and the layers of cartilage and subchondral bone were clear. ④ Histological staining (H & E staining, Alcian blue stain, Safranin-O staining) showed that the ADM group had a better effect on the repair of joint structure at the joint defect, the Nar group had a better effect on the repair of cartilage quality at the joint defect, and the ADM/Nar group had satisfactory results in both of the above aspects. ⑤ Immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining) revealed that the Nar group showed more abundant expression of the above proteins in articular cartilage defects than the Mod and ADM groups and that the Nar/ADM groups showed extensive TGF-β2, TGF-β3 and Sox-9 protein expression, with uniform expression and smooth distribution.

Conclusions: Oral administration of naringin, the active ingredient of Rhizoma Drynariae, combined with acellular dermal matrix can achieve better repair effects in both joint structure repair and cartilage quality repair at the defect site when repairing cartilage defects in rabbit knees, and the generation of this effect may be caused by the activation of the TGF-β/ALK5/Smad2/3 signal transduction pathway by naringin, resulting in the increased expression of TGF-β2, TGF-β3, and Sox-9 in cartilage defects.

The Translational Potential Of This Article: Naringin combined with acellular dermal matrix can facilitate the repair of osteochondral defects and has potential for application in osteochondral tissue engineering.
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http://dx.doi.org/10.1016/j.jot.2021.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072805PMC
January 2022

Metal-metal interactions in correlated single-atom catalysts.

Sci Adv 2022 Apr 29;8(17):eabo0762. Epub 2022 Apr 29.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, Australia.

Single-atom catalysts (SACs) include a promising family of electrocatalysts with unique geometric structures. Beyond conventional ones with fully isolated metal sites, an emerging class of catalysts with the adjacent metal single atoms exhibiting intersite metal-metal interactions appear in recent years and can be denoted as correlated SACs (C-SACs). This type of catalysts provides more opportunities to achieve substantial structural modification and performance enhancement toward a wider range of electrocatalytic applications. On the basis of a clear identification of metal-metal interactions, this review critically examines the recent research progress in C-SACs. It shows that the control of metal-metal interactions enables regulation of atomic structure, local coordination, and electronic properties of metal single atoms, which facilitate the modulation of electrocatalytic behavior of C-SACs. Last, we outline directions for future work in the design and development of C-SACs, which is indispensable for creating high-performing new SAC architectures.
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http://dx.doi.org/10.1126/sciadv.abo0762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054016PMC
April 2022

Effects of Erchen Decoction on Oxidative Stress-Related Cytochrome P450 Metabolites of Arachidonic Acid in Dyslipidemic Mice with Phlegm-Dampness Retention Syndrome: A Randomized, Controlled Trial on the Correspondence between Prescription and Syndrome.

Evid Based Complement Alternat Med 2022 29;2022:1079803. Epub 2022 Mar 29.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Phlegm-dampness retention (PDR) syndrome is one of the main syndromes of dyslipidemia. This study investigated the effects of Erchen decoction (ECD) on concentrations of two oxidative stress-related cytochrome P450 (CYP450) metabolites of arachidonic acid-14,15-dihydroxyeicosatrienoic acid (14,15-DHET) and 20-hydroxyeicosatetraenoic acid (20-HETE)-in mice with dyslipidemia and phlegm-dampness retention (PDR) syndrome ( = 5 C57BL/6J mice and  = 30 apolipoprotein E knockout mice). Murine models of the disease and syndrome were established using multifactor stimulation. Then, all mice were assigned to normal, model, low- (L-), medium- (M-), or high- (H-) dose ECD groups or to a control or an unmatched prescription-syndrome (unmatched P-S) group; five mice were included in each group. Dose formulations were administered by oral gavage for 30 days to animals in the corresponding groups. We detected and analyzed hematoxylin and eosin (HE) staining characteristics of the mouse aorta and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), peroxynitrite (ONOO), 14,15-DHET, and 20-HETE concentrations in each group. TC and LDL-C concentrations significantly decreased in the M-ECD versus control group ( < 0.05); however, the TC and LDL-C concentrations were not significantly different in the unmatched P-S versus model group ( > 0.05). After treatment in the P-S correspondence groups (L-ECD, M-ECD, and H-ECD groups), the concentration of ONOO decreased to different degrees in each group. Among these groups, the concentration of ONOO significantly decreased in the L-ECD, M-ECD, and H-ECD groups versus the model group ( < 0.05). However, the concentration of ONOO was not significantly different in the unmatched P-S versus the model group ( > 0.05). From the perspective of aortic HE staining, the P-S group experienced an improved endothelium structure after treatment. 14,15-DHET concentrations significantly increased in the normal, M-ECD, and H-ECD groups versus the model group; in the H-ECD versus the L-ECD group; and in the H-ECD versus the control group (all < 0.05) to various extents after different doses of the prescription. 20-HETE concentrations pronouncedly decreased in the M-ECD versus normal group; in the M- and H-ECD groups versus the model group; in the M-ECD versus the L-ECD group; in the M-ECD versus the control group; and in the M-ECD versus the unmatched P-S ( < 0.05). However, the concentrations of 14,15-DHET and 20-HETE in the model group were not significantly different from those of the unmatched P-S ( > 0.05). In this study, ECD reversed blood lipid indexes and ameliorated oxidative stress-related metabolites, elevating serum 14,15-DHET and lowering serum 20-HETE in mice with dyslipidemia and PDR syndrome via CYP450 pathways of arachidonic acid metabolism. The efficacy of ECD relies on correspondence between the prescription and the syndrome. These findings scientifically validate the treatment according to traditional Chinese medicine syndrome differentiation. ECD can strengthen the protective effect on the vascular endothelium by driving out pathogenic factors and strengthening healthy resistance. Its efficacy may be related to the adjustment of the polarization state of macrophages.
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http://dx.doi.org/10.1155/2022/1079803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983189PMC
March 2022

Glucocorticoid Treatment Strategies in Liver Failure.

Front Immunol 2022 16;13:846091. Epub 2022 Mar 16.

Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Liver failure is characterized by serious liver decompensation and high mortality. The activation of systemic immune responses and systemic inflammation are widely accepted as the core pathogenesis of liver failure. Glucocorticoids (GCs) are most regularly utilized to suppress excessive inflammatory reactions and immunological responses. GCs have been used in the clinical treatment of liver failure for nearly 60 years. While there has been no unanimity on the feasibility and application of GC treatment in liver failure until recently. The most recent trials have produced conflicting results when it comes to the dose and time for GC therapy of different etiology of liver failure. Our review outlines the issues and options in managing GC treatment in liver failure based on an investigation of the molecular mechanism that GC may give in the treatment.
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http://dx.doi.org/10.3389/fimmu.2022.846091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965693PMC
March 2022

The Critical Role of Potassium Efflux and Nek7 in -Induced NLRP3 Inflammasome Activation.

Front Microbiol 2022 8;13:849482. Epub 2022 Mar 8.

Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, China.

is a zoonotic pathogen causing respiratory infection in different animal species such as cattle, sheep, pigs, chickens and humans. Inflammasome is a complex assembled by multiple proteins in the cytoplasm and plays an important role in the host defense against microbial infection. Bovine type A (PmCQ2) infection induces NLRP3 inflammasome activation and IL-1β secretion, but the mechanism of PmCQ2-induced activation of NLRP3 inflammasome is still unknown. Therefore, the underlying mechanism was investigated in this study. The results showed that potassium efflux mediated PmCQ2-induced IL-1β secretion and blocking potassium efflux attenuated PmCQ2-induced caspase-1 activation and ASC oligomerization. Furthermore, NIMA-related kinase 7 (Nek7) was also involved in PmCQ2-induced caspase-1 activation and IL-1β secretion. In addition, PmCQ2 infection promoted Nek7-NLRP3 interaction, which is dependent on potassium efflux. In conclusion, our results indicate the critical role of potassium efflux and Nek7 in -induced NLRP3 inflammasome activation, which provides useful information about induced host immune response.
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http://dx.doi.org/10.3389/fmicb.2022.849482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957907PMC
March 2022

Chronic infusion of ELABELA alleviates vascular remodeling in spontaneously hypertensive rats via anti-inflammatory, anti-oxidative and anti-proliferative effects.

Acta Pharmacol Sin 2022 Mar 8. Epub 2022 Mar 8.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.

Inflammatory activation and oxidative stress promote the proliferation of vascular smooth muscle cells (VSMCs), which accounts for pathological vascular remodeling in hypertension. ELABELA (ELA) is the second endogenous ligand for angiotensin receptor-like 1 (APJ) receptor that has been discovered thus far. In this study, we investigated whether ELA regulated VSMC proliferation and vascular remodeling in spontaneously hypertensive rats (SHRs). We showed that compared to that in Wistar-Kyoto rats (WKYs), ELA expression was markedly decreased in the VSMCs of SHRs. Exogenous ELA-21 significantly inhibited inflammatory cytokines and NADPH oxidase 1 expression, reactive oxygen species production and VSMC proliferation and increased the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) in VSMCs. Osmotic minipump infusion of exogenous ELA-21 in SHRs for 4 weeks significantly decreased diastolic blood pressure, alleviated vascular remodeling and ameliorated vascular inflammation and oxidative stress in SHRs. In VSMCs of WKY, angiotensin II (Ang II)-induced inflammatory activation, oxidative stress and VSMC proliferation were attenuated by pretreatment with exogenous ELA-21 but were exacerbated by ELA knockdown. Moreover, ELA-21 inhibited the expression of matrix metalloproteinase 2 and 9 in both SHR-VSMCs and Ang II-treated WKY-VSMCs. We further revealed that exogenous ELA-21-induced inhibition of proliferation and PI3K/Akt signaling were amplified by the PI3K/Akt inhibitor LY294002, while the APJ receptor antagonist F13A abolished ELA-21-induced PI3K/Akt inhibition and Nrf2 activation in VSMCs. In conclusion, we demonstrate that ELA-21 alleviates vascular remodeling through anti-inflammatory, anti-oxidative and anti-proliferative effects in SHRs, indicating that ELA-21 may be a therapeutic agent for treating hypertension.
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http://dx.doi.org/10.1038/s41401-022-00875-wDOI Listing
March 2022

Efficacy of Yiqi Wenyang Huoxue method in treating adult bronchial asthma: A protocol for systematic review and meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2022 Mar;101(9):e28958

Affiliated Hospital, Jiangxi University of Chinese Medicine, Nanchang, China.

Background: Bronchial asthma (BA) is a chronic inflammatory disease of the airway, which has the characteristics of recurrent attacks and difficult to cure. Glucocorticoid and bronchodilator are the primary treatment drugs for asthma. Although the treatment has made some progress, the control status is still not ideal. According to clinical reports, the Yi-qi Wen-yang Huo-xue method (YQWYHXM) of Traditional Chinese Medicine (TCM) is safe and effective in the treatment of BA, but there is not enough evidence to prove it. Based on it, we conducted this systematic evaluation.

Methods: Eight databases and Clinical trial registries (Embase, Cochrane, PubMed, CNKI, CBM, Wanfang, VIP, China Clinical Trial Registry and Clinical Trails) were searched from the establishment of those until January 22, 2021 with the following terms for retrieval: BS, TCM, Chinese medicinal herb, Chinese herbal medicine and randomized controlled trial. Data analysis was performed by 2 researchers using RevMan 5.3 and SATA 16.0 separately from the Cochrane Collaboration.

Results: This study will be able to provide definitive evidence to clarify all the suspicions we seek, confirming the effectiveness of YQWYHXM in the treatment of adults with BA.

Conclusion: This study will prove that YQWYHXM is a safe and effective TCM adjuvant therapy for BA.

Registration: Efficacy of Yiqi Wenyang Huoxue method in Treating Adult Bronchial Asthma.

Asthma: A protocol for Systematic Review and Meta-Analysis of Randomized Controlled Trials. PROSPERO 2021 CRD42021256791. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256791.
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http://dx.doi.org/10.1097/MD.0000000000028958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896478PMC
March 2022

Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss.

Proc Natl Acad Sci U S A 2022 03 1;119(10):e2107357119. Epub 2022 Mar 1.

Shandong Provincial Hospital, Shandong First Medical University, Jinan 250021, China.

Significance The mechanistic target of rapamycin (mTOR) plays a central role in growth, metabolism, and aging. It is assembled into two multiprotein complexes, namely, mTORC1 and mTORC2. We previously demonstrated the efficacy of sirolimus in ARHL in mice by decreasing mTORC1. However, the aspect of mTORC2 regulation in the cochlea is poorly characterized. Herein, based on pharmacological and genetic interventions, we found that a high dose of sirolimus resulted in severe hearing loss by reducing the mTORC2/AKT signaling pathway in the cochlea. Furthermore, selective activation of mTORC2 could protect against hearing loss induced by acoustic trauma and cisplatin-induced ototoxicity. Hence, the therapeutic activation of mTORC2 in conjunction with decreasing mTORC1 might represent a promising and effective strategy in preventing hearing loss.
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http://dx.doi.org/10.1073/pnas.2107357119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917383PMC
March 2022

Electroassisted Core-Spun Triboelectric Nanogenerator Fabrics for IntelliSense and Artificial Intelligence Perception.

ACS Nano 2022 03 3;16(3):4415-4425. Epub 2022 Mar 3.

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China.

IntelliSense fabrics that can sense transient mechanical stimuli are widely anticipated in flexible and wearable electronics. However, most IntelliSense fabrics developed so far are only sensitive to quasi-static forces, such as stretching, bending, or twisting. In this work, a sheath-core triboelectric nanogenerator (SC-TENG) yarn was developed via a rational design, electroassisted core spinning technique, that consisted of a rough nanoscale dielectric surface and mechanically strong and electrically conductive core yarns. The resulting system was used to sense and distinguish the instantaneous mechanical stimuli generated by different materials. To further improve the sensing accuracy, a machine learning model, based on a classification coding and recurrent neural network, was built to predict the type of contact materials from the peak profiles of output voltages. With these experimental and algorithmic optimizations, we finally used SC-TENG yarn to identify the type of materials in real-time. Moreover, by applying Internet of Things techniques, we investigated that SC-TENG yarn could be integrated into an IntelliSense system to recognize and control various electronic and electrical systems, demonstrating promising applications in wearable energy supply, IntelliSense fabrics, and human-machine interactions.
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http://dx.doi.org/10.1021/acsnano.1c10680DOI Listing
March 2022

Chicken cathelicidin-2 promotes IL-1β secretion via the NLRP3 inflammasome pathway and serine proteases activity in LPS-primed murine neutrophils.

Dev Comp Immunol 2022 06 18;131:104377. Epub 2022 Feb 18.

Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China; Immunology Research Center, Institute of Medical Research, Southwest University, Chongqing, 402460, China. Electronic address:

Cathelicidins have antimicrobial and immunomodulatory activities. Previous studies have shown that chicken cathelicidin-2 (CATH-2) exerts strong anti-inflammatory activity through LPS neutralization. However, it is still unclear whether other intracellular signaling pathways are involved in CATH-2 immunomodulation. Therefore, the CATH-2-meadiated immune response was investigated in LPS-primed neutrophils. Firstly, inflammatory cytokines release was determined in LPS-primed neutrophils. The results showed that CATH-2 significantly promoted secretion of IL-1β and IL-1α while IL-6 and TNF-α were not affected. IL-1β is the key indicator of inflammasome activation. Next, NLRP3 inflammasome signaling pathway was explored using neutrophils of Nlrp3, Asc and Casp1 mice and the results showed that the CATH-2-enhanced IL-1β release was completely abrogated, indicating it is NLRP3-dependent. Moreover, CATH-2 significantly induced activation of caspase-1 and gasdermin D (GSDMD) but did not affect LPS-induced mRNA expression of IL-1β and NLRP3, demonstrating that CATH-2 serves as the second signal activating the NLRP3 inflammasome. Furthermore, CATH-2-mediated IL-1β secretion and caspase-1 activation is dependent on potassium efflux but independent of P2X7R. In addition, other signaling pathways including JNK, ERK and SyK were investigated using different inhibitors and the results showed that these signaling pathway inhibitors partially attenuated CATH-2-enhanced IL-1β secretion, especially the JNK inhibitor. Finally, the role of serine protease in CATH-2-mediated NLRP3 inflammasome activation was investigated in neutrophils and the results showed that serine protease activity is involved in CATH-2-enhanced IL-1β secretion and caspase-1 activation. In conclusion, after LPS priming in neutrophils, CATH-2 can be an agonist of the NLRP3 inflammasome. Our study increases the understanding on immunomodulatory effects of chicken cathelicidins and provides new insight on chicken cathelicidins-mediated immune response.
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http://dx.doi.org/10.1016/j.dci.2022.104377DOI Listing
June 2022

Functional characterization of four Hsp70 genes involved in high-temperature tolerance in Aphis aurantii (Hemiptera: Aphididae).

Int J Biol Macromol 2022 Mar 15;202:141-149. Epub 2022 Jan 15.

Chongqing Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China; International Joint Laboratory of China-Belgium on Sustainable Crop Pest Control, Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. Electronic address:

The tea aphid, Aphis aurantii (Boyer de Fonscolombe), is a serious pest that can infest many economically important plants. Tea aphids damage plants by directly sucking phloem sap, transmitting viruses, and secreting honeydew to cause sooty mold. At present, tea aphids has become one of the most important pests in tropical and subtropical tea plants. The heat shock protein 70 (Hsp70) is a key protein involved in heat stress tolerance. In this study, we cloned four Hsp70 genes that are highly expressed in tea aphids after heat shock. Bioinformatic analysis of the deduced amino acid sequences showed that these four AaHsp70s had a close genetic relationship to Hsp70 in Hemiptera insects and shared a conserved ATPase domain. After incubation at low (14 °C) or high (36 °C) temperature, the expression of four AaHsp70s was significantly up-regulated compared to the control (25 °C); however, the up-regulation of the AaHsp70s in the low-temperature treatment was far less than that of the high-temperature treatment. The ATPase activity of the four purified recombinant AaHsp70 proteins after high-temperature treatment was significantly increased compared to the control. In addition, these proteins effectively improved the heat tolerance of Escherichia coli in vivo. Our data indicate that AaHsp701, AaHsp702, AaHsp703, AaHsp704 play important roles in response to the high-temperature tolerance in tea aphids.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.01.078DOI Listing
March 2022

Extracellular vesicles in vascular remodeling.

Acta Pharmacol Sin 2022 Jan 12. Epub 2022 Jan 12.

Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Vascular remodeling contributes to the development of a variety of vascular diseases including hypertension and atherosclerosis. Phenotypic transformation of vascular cells, oxidative stress, inflammation and vascular calcification are closely associated with vascular remodeling. Extracellular vesicles (EVs) are naturally released from almost all types of cells and can be detected in nearly all body fluids including blood and urine. EVs affect vascular oxidative stress, inflammation, calcification, and lipid plaque formation; and thereby impact vascular remodeling in a variety of cardiovascular diseases. EVs may be used as biomarkers for diagnosis and prognosis, and therapeutic strategies for vascular remodeling and cardiovascular diseases. This review includes a comprehensive analysis of the roles of EVs in the vascular remodeling in vascular diseases, and the prospects of EVs in the diagnosis and treatment of vascular diseases.
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http://dx.doi.org/10.1038/s41401-021-00846-7DOI Listing
January 2022

Development of an Efficient Gene Editing Tool in sp. and Improving Its Lipid and Terpenoid Biosynthesis.

Front Nutr 2021 14;8:795651. Epub 2021 Dec 14.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, China.

sp. HX-308 is a marine microalga with fast growth and high lipid content, which has potential as microbial cell factories for lipid compound biosynthesis. It is significant to develop efficient genetic editing tool and discover molecular target in sp. HX-308 for lipid compound biosynthesis. In this study, we developed an efficient gene editing tool in HX-308 which was mediated by AGL-1. Results showed that the random integration efficiency reached 100%, and the homologous recombination efficiency reached about 30%. Furthermore, the metabolic pathway of lipid and terpenoid biosynthesis were engineered. Firstly, the acetyl-CoA -acetyltransferase was overexpressed in HX-308 with a strong constitutive promoter. With the overexpression of acetyl-CoA c-acetyltransferase, more acetyl-CoA was used to synthesize terpenoids, and the production of squalene, β-carotene and astaxanthin was increased 5.4, 1.8, and 2.4 times, respectively. Interestingly, the production of saturated fatty acids and polyunsaturated fatty acids also changed. Moreover, three Acyl-CoA oxidase genes which catalyze the first step of β-oxidation were knocked out using homologous recombination. Results showed that the production of lipids increased in the three knock-out strains. Our results demonstrated that the -mediated transformation method will be of great use for the study of function genes, as well as developing sp. as a strong cell factory for producing high value products.
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http://dx.doi.org/10.3389/fnut.2021.795651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712325PMC
December 2021

Identification of a new amino acid mutation in the HN protein of NDV involved in pathogenicity.

Vet Res 2021 Dec 20;52(1):147. Epub 2021 Dec 20.

College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.

The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.
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http://dx.doi.org/10.1186/s13567-021-01019-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686287PMC
December 2021

CRISPR-Based Construction of a BL21 (DE3)-Derived Variant Strain Library to Rapidly Improve Recombinant Protein Production.

ACS Synth Biol 2022 01 17;11(1):343-352. Epub 2021 Dec 17.

School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2 Xuelin Road, Qixia District, Nanjing 210023, People's Republic of China.

BL21 (DE3) is the most widely used host for recombinant protein expression. However, not every protein can be highly expressed in BL21 (DE3), so individual optimization strategies are often required for different proteins, which is time-consuming and difficult to apply rapidly for industrial production. Constructing more hosts is a good choice to enrich protein expression selection. The expression level of T7 RNAP is the core control node of the pET expression system, so regulating its expression level is an effective way of improving the production of difficult-to-express proteins. Various BL21 (DE3)-derived variant hosts with different translation levels of T7 RNAP could be obtained by changing the ribosomal binding site (RBS) sequences of T7 RNAP in a genome. Here, a BL21 (DE3)-derived variant strain library with different RBS sequences of T7 RNAP was constructed using a base editor and CRISPR-Cas9. Notably, the CRISPR-Cas9 system combined with degenerate primers enabled the construction of an RBS library with 87.5% of the theoretical coverage in single editing, which is more convenient and efficient than the use of a base editor. The expression level of a target gene in the variant strain library ranged from 28 to 220% of the parental strain. Furthermore, a high-throughput host-screening platform for recombinant protein production was constructed, which enabled us to obtain the best expression host for certain target proteins in only 3 days. As a proof of concept, the production of all eight difficult-to-express proteins was greatly improved, including autolytic protein, membrane proteins, antimicrobial peptides, and hardly soluble proteins. Among them, the expression of glucose dehydrogenase in the best host exhibited a 298-fold increase compared to the parental strain. This strategy is simple and effective, requires no advanced equipment, and can be carried out in any laboratory.
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http://dx.doi.org/10.1021/acssynbio.1c00463DOI Listing
January 2022

Synchrotron X-ray Spectroscopic Investigations of In-Situ-Formed Alloy Anodes for Magnesium Batteries.

Adv Mater 2022 Feb 20;34(8):e2108688. Epub 2022 Jan 20.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia.

Magnesium batteries present high volumetric energy density and dendrite-free deposition of Mg, drawing wide attention in energy-storage devices. However, their further development remains stagnated due to relevant interfacial issues between the Mg anode and the electrolyte and sluggish solid-state diffusion kinetics of Mg ions. Herein, an in situ conversion chemistry to construct a nanostructured Bi anode from bismuth selenide driven by Li is proposed. Through the combination of operando synchrotron X-ray diffraction, ex situ synchrotron X-ray absorption spectroscopy, and comprehensive electrochemical tests, it is demonstrated that the nanosize of the in-situ-formed Bi crystals contributes to the fast Mg diffusion kinetics and highly efficient Mg-Bi alloingy/de-alloying. The resultant Bi anodes exhibit superior long-term cycling stability with over 600 cycles under a high current density of 1.0 A g . This work provides a new approach to construct alloy anode and paves the way for exploring novel electrode materials for magnesium batteries.
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http://dx.doi.org/10.1002/adma.202108688DOI Listing
February 2022

A MoN electrocatalyst for efficient NaS electrodeposition in room-temperature sodium-sulfur batteries.

Nat Commun 2021 Dec 10;12(1):7195. Epub 2021 Dec 10.

School of Chemical Engineering & Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia.

Metal sulfides electrodeposition in sulfur cathodes mitigates the shuttle effect of polysulfides to achieve high Coulombic efficiency in secondary metal-sulfur batteries. However, fundamental understanding of metal sulfides electrodeposition and kinetics mechanism remains limited. Here using room-temperature sodium-sulfur cells as a model system, we report a MoN cathode material that enables efficient NaS electrodeposition to achieve an initial discharge capacity of 512 mAh g at a specific current of 1 675 mA g, and a final discharge capacity of 186 mAh g after 10,000 cycles. Combined analyses from synchrotron-based spectroscopic characterizations, electrochemical kinetics measurements and density functional theory computations confirm that the high d-band position results in a low NaS dissociation free energy for MoN. This promotes NaS electrodeposition, and thereby favours long-term cell cycling performance.
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http://dx.doi.org/10.1038/s41467-021-27551-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664834PMC
December 2021

Discovery of a widespread presence bunyavirus that may have symbiont-like relationships with different species of aphids.

Insect Sci 2021 Dec 7. Epub 2021 Dec 7.

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.

Aphids are important agricultural pests, vectors of many plant viruses and have sophisticated relationships with symbiotic microorganisms. Abundant asymptomatic RNA viruses have been reported in aphids due to the application of RNA-seq, but aphid-virus interactions remain unclear. Bunyavirales is the most abundant RNA virus order, which can infect mammals, arthropods, and plants. However, many bunyaviruses have specific hosts, such as insects. Here, we discovered 18 viruses from 10 aphid species by RNA-seq. Importantly, a widespread presence bunyavirus, Aphid bunyavirus 1 (ABV-1), was determined to have a wide host range, infecting and replicating in all 10 tested aphid species. ABV-1 may be transmitted horizontally during feeding on plant leaves and vertically through reproduction. In a comparison of the physiological parameters of ABV-1 and ABV-1 strains of pea aphid, higher ABV-1 titers reduced the total nymphal duration and induced the reproduction. Moreover, viral titer significantly affected the lipid and protein contents in pea aphids. In summary, we proposed that ABV-1 may have stable symbiont-like relationships with aphids, and these observations may provide a new direction for studying bunyaviruses in aphids and establishing a model for virus-aphid interactions.
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http://dx.doi.org/10.1111/1744-7917.12989DOI Listing
December 2021

Fabrication of Iron Pyrite Thin Films and Photovoltaic Devices by Sulfurization in Electrodeposition Method.

Nanomaterials (Basel) 2021 Oct 26;11(11). Epub 2021 Oct 26.

Materials Genome Institute, Shanghai University, Shanghai 200444, China.

Iron pyrite is a cheap, stable, non-toxic, and earth-abundant material that has great potential in the field of photovoltaics. Electrochemical deposition is a low-cost method, which is also suitable for large-scale preparation of iron pyrite solar cells. In this work, we prepared iron pyrite films by electrochemical deposition with thiourea and explored the effect of sulfurization on the synthesis of high-quality iron pyrite films. Upon sulfurization, the amorphous precursor film becomes crystallized iron pyrite film. Optical and electrical characterization show that its band gap is 0.89 eV, and it is an n type semiconductor with a carrier concentration of 3.01 × 10 cm. The corresponding photovoltaic device shows light response. This work suggests that sulfurization is essential in the electrochemical preparation for fabricating pure iron pyrite films, and therefore for low-cost and large-scale production of iron pyrite solar cells.
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http://dx.doi.org/10.3390/nano11112844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625642PMC
October 2021

Erianin: A Direct NLRP3 Inhibitor With Remarkable Anti-Inflammatory Activity.

Front Immunol 2021 20;12:739953. Epub 2021 Oct 20.

The Key Laboratory of Targeted Intervention of Clinical Disease, Collaborative Innovation Center of Translational Medicine for Clinical Disease, Nanjing Medical University, Nanjing, China.

Erianin (Eri) is the extract of Lindl. The NLRP3 inflammasome is a multiprotein complex that plays key roles in a wide variety of chronic inflammation-driven human diseases. Nevertheless, little is known about the protection of Eri against NLRP3 inflammasome-related diseases. In this study, we demonstrated that Eri inhibited NLRP3 inflammasome activation and . Mechanistically, Eri directly interacted with NLRP3, leading to inhibition of NLRP3 inflammasome assembly. Eri associated with the Walker A motif in the NACHT domain and suppressed NLRP3 ATPase activity. In mouse models, Eri had therapeutic effects on peritonitis, gouty arthritis and type 2 diabetes, NLRP3. More importantly, Eri was active for synovial fluid cells and monocytes from patients with IAV infection and gout. Eri may serve as a potential novel therapeutic compound against NLRP3-driven diseases.
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http://dx.doi.org/10.3389/fimmu.2021.739953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564113PMC
December 2021

Catalytic Oxidation of KS via Atomic Co and Pyridinic N Synergy in Potassium-Sulfur Batteries.

J Am Chem Soc 2021 Oct 8;143(41):16902-16907. Epub 2021 Oct 8.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, Australia.

Potassium-sulfur batteries hold practical promise for next-generation batteries because of their high theoretical gravimetric energy density and low cost. However, significant impediments are the sluggish KS oxidation kinetics and a lack of atomic-level understanding of KS oxidation. Here, for the first time, we report the catalytic oxidation of KS on a sulfur host with Co single atoms immobilized on nitrogen-doped carbon. On the basis of combined spectroscopic characterizations, electrochemical evaluation, and theoretical computations, we show a synergistic effect of dynamic Co-S and N-K interactions to catalyze KS oxidation. The resultant potassium-sulfur battery exhibited high capacities of 773 and 535 mAh g under high current densities of 1 and 2 C, respectively. These findings provide atomic-scale insights for the rational design of highly efficient sulfur hosts.
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http://dx.doi.org/10.1021/jacs.1c06255DOI Listing
October 2021

The Effect of Combination Therapy on Mortality and Adverse Events in Patients with Staphylococcus aureus Bacteraemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Infect Dis Ther 2021 Dec 1;10(4):2643-2660. Epub 2021 Oct 1.

Department of Pharmacy, People's Hospital of Ningxiang City Affiliated to Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.

Introduction: The findings of randomized controlled trials (RCTs), observational studies, and meta-analyses vary regarding the effectiveness and safety of combination therapy for patients with Staphylococcus aureus bacteraemia (SAB). We aimed to identify the effectiveness and safety of combination therapy in patients with SAB compared with those of monotherapy.

Methods: We performed a systematic review and meta-analysis to compare combination therapy versus monotherapy in patients with SAB. Two authors independently searched PubMed, Embase, and the Cochrane Library of clinical trials until 17 February 2021. Any RCT comparing mortality or adverse events (AEs) of combination therapy versus monotherapy for patients with SAB was eligible. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were evaluated using a random-effects model. The primary outcome was all-cause mortality at any time point. This meta-analysis is registered with the PROSPERO database (CRD42020188176) and reported according to PRISMA guidelines.

Results: In total, 1906 articles were identified and screened, and 14 studies (2367 patients) were included in the meta-analysis. There was no significant difference in the risk of all-cause mortality between the two groups (RR = 1.00; 95% CI 0.83-1.20; P = 0.99; I = 0%). Similar results were obtained by subgroup analysis of mortality recording time, endocarditis, pathogen resistance, article publication time, number of patients, and adjuvant antibiotics. Notably, combination treatment might significantly increase the risk of drug-related AEs (RR = 1.68; 95% CI 1.06-2.66; P = 0.03; I = 67%) and nephrotoxicity (RR = 2.30; 95% CI 1.68-3.16; P < 0.00001; I = 0%), although the occurrences of AEs leading to treatment discontinuation and serious AEs were not significantly different between the two groups.

Conclusions: The meta-analysis suggested that combination therapy could not reduce mortality but might increase the risk of drug-related AEs and nephrotoxicity and should be applied very cautiously. Future studies on combined drug therapy for SAB need careful and rigorous design for specific antibiotic combinations.
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http://dx.doi.org/10.1007/s40121-021-00539-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572899PMC
December 2021

Reversible electrochemical oxidation of sulfur in ionic liquid for high-voltage Al-S batteries.

Nat Commun 2021 Sep 29;12(1):5714. Epub 2021 Sep 29.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia.

Sulfur is an important electrode material in metal-sulfur batteries. It is usually coupled with metal anodes and undergoes electrochemical reduction to form metal sulfides. Herein, we demonstrate, for the first time, the reversible sulfur oxidation process in AlCl/carbamide ionic liquid, where sulfur is electrochemically oxidized by AlCl to form AlSCl. The sulfur oxidation is: 1) highly reversible with an efficiency of ~94%; and 2) workable within a wide range of high potentials. As a result, the Al-S battery based on sulfur oxidation can be cycled steadily around ~1.8 V, which is the highest operation voltage in Al-S batteries. The study of sulfur oxidation process benefits the understanding of sulfur chemistry and provides a valuable inspiration for the design of other high-voltage metal-sulfur batteries, not limited to Al-S configurations.
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http://dx.doi.org/10.1038/s41467-021-26056-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481422PMC
September 2021

Analysis of Phenol Biodegradation in Antibiotic and Heavy Metal Resistant NL1.

Front Microbiol 2021 10;12:725755. Epub 2021 Sep 10.

College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China.

Phenol is a common environmental contaminant. The purpose of this study was to isolate phenol-degrading microorganisms from wastewater in the sections of the Chinese Medicine Manufactory. The phenol-degrading NL1 was identified based on a combination of biochemical characteristics and 16S rRNA genes. To analyze the molecular mechanism, the whole genome of . NL1 was sequenced, yielding 3499 genes on one circular chromosome and three plasmids. Enzyme activity analysis showed that . NL1 degraded phenol the -cleavage rather than the -cleavage pathway. Key genes encoding phenol hydroxylase and catechol 1,2-dioxygenase were located on a megaplasmid (pNL1) and were found to be separated by mobile genetic elements; their function was validated by heterologous expression in and quantitative real-time PCR. . NL1 could degrade 0.5 g/L phenol within 12 h and tolerate a maximum of 1.1 g/L phenol, and showed resistance against multiple antibiotics and heavy metal ions. Overall, this study shows that . NL1 can be potentially used for efficient phenol degradation in heavy metal wastewater treatment.
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http://dx.doi.org/10.3389/fmicb.2021.725755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461059PMC
September 2021

Studying the Conversion Mechanism to Broaden Cathode Options in Aqueous Zinc-Ion Batteries.

Angew Chem Int Ed Engl 2021 Nov 21;60(47):25114-25121. Epub 2021 Oct 21.

School of Chemical Engineering & Advanced Materials, The University of Adelaide, Adelaide, SA, 5005, Australia.

Aqueous Zn-ion batteries (ZIBs) are regarded as alternatives to Li-ion batteries benefiting from both improved safety and environmental impact. The widespread application of ZIBs, however, is compromised by the lack of high-performance cathodes. Currently, only the intercalation mechanism is widely reported in aqueous ZIBs, which significantly limits cathode options. Beyond Zn-ion intercalation, we comprehensively study the conversion mechanism for Zn storage and its diffusion pathway in a CuI cathode, indicating that CuI occurs a direct conversion reaction without Zn intercalation due to the high energy barrier for Zn intercalation and migration. Importantly, this direct conversion reaction mechanism can be readily generalized to other high-capacity cathodes, such as Cu S (336.7 mA h g ) and Cu O (374.5 mA h g ), indicating its practical universality. Our work enriches the Zn-ion storage mechanism and significantly broadens the cathode horizons towards next-generation ZIBs.
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http://dx.doi.org/10.1002/anie.202111398DOI Listing
November 2021

Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection.

Cell Rep 2021 09;36(12):109750

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address:

The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotics.
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http://dx.doi.org/10.1016/j.celrep.2021.109750DOI Listing
September 2021

Study on the Effect of Macrophages on Vascular Endothelium in Mice With Different TCM Syndromes of Dyslipidemia and its Biological Basis Based on RNA-Seq Technology.

Front Pharmacol 2021 26;12:665635. Epub 2021 Aug 26.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

"Treating the same disease with different methods" is a Traditional Chinese medicine (TCM) therapeutic concept suggesting that, while patients may be diagnosed with the same disease, they may also have different syndromes that require distinct drug administrations. This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia in relation to phlegm-dampness retention (PDR) syndrome and spleen and kidney Yang deficiency (SKYD) syndrome using transcriptomic analysis. Ten ApoE mice were used for the establishment of dyslipidemic disease-syndrome models via multifactor-hybrid modeling, with five in the PDR group and five in the SKYD group. Additionally, five C57BL/6J mice were employed as a normal control group. Test model-quality aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq. A quality assessment of the disease-syndrome model showed that levels of lipids significantly increased in the PDR and SKYD groups, compared to the normal control group, < 0.05. Applying, in addition, hematoxylin and eosin staining of aorta, the disease model was also successfully established. A quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of PDR syndrome, and mice in the SKYD group had related manifestations of SKYD syndrome, indicating that the syndrome models were successfully constructed as well. After comparing the differentially expressed gene expressions in macrophages of the dyslipidemic mice with different syndromes, 4,142 genes were identified with statistical significance, < 0.05. Gene ontology analysis for the differentially expressed genes showed that the biological process of difference between the PDR group and the SKYD group included both adverse and protective processes. The differentially expressed genes between PDR syndrome and SKYD syndrome indicate different biological mechanisms between the onsets of the two syndromes. They have distinctive biological processes, including adverse and protective processes that correspond to the invasion of pathogenic factors into the body and the fight of healthy Qi against pathogenic factors, respectively, according to TCM theory. Our results provide biological evidence for the TCM principle of "treating the same disease with different treatments."
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http://dx.doi.org/10.3389/fphar.2021.665635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427158PMC
August 2021

A Novel Immunomodulator Delivery Platform Based on Bacterial Biomimetic Vesicles for Enhanced Antitumor Immunity.

Adv Mater 2021 Oct 12;33(43):e2103923. Epub 2021 Sep 12.

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, 650118, China.

T cell activation-induced cell death (AICD) during tumor pathogenesis is a tumor immune escape process dependent on dendritic cells (DCs). Proper immune-modulatory therapies effectively inhibit tumor-specific CD8 T cell exhaustion and enhance antitumor immune responses. Here, high-pressure homogenization is utilized to drive immunomodulator IL10-modified bacteria to extrude through the gap and self-assemble into bacterial biomimetic vesicles exposing IL10 (IL10-BBVs) on the surface with high efficiency. IL10-BBVs efficiently target DCs in tumor-draining lymph nodes and thus increase the interaction between IL10 on BBVs and IL10R on DCs to suppress AICD and mitigate CD8 T cell exhaustion specific to tumor antigens. Two subcutaneous peripheral injections of IL10-BBVs 1 week apart in tumor-bearing mice effectively increase systemic and intratumoral proportions of CD8 T cells to suppress tumor growth and metastasis. Tumor-specific antigen E7 is enclosed into the periplasm of IL10-BBVs (IL10-E7-BBVs) to realize concurrent actions of the immunomodulator IL10 and the tumor antigen human papillomavirus (HPV) 16E7 in lymph nodes, further enhancing the antitumor effects mediated by CD8 T cells. The development of this modified BBV delivery platform will expand the application of bacterial membranes and provide novel immunotherapeutic strategies for tumor treatment.
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http://dx.doi.org/10.1002/adma.202103923DOI Listing
October 2021

The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases.

Int J Mol Sci 2021 Sep 6;22(17). Epub 2021 Sep 6.

Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.

c-Jun N-terminal kinases (JNKs) are among the most crucial mitogen-activated protein kinases (MAPKs) and regulate various cellular processes, including cell proliferation, apoptosis, autophagy, and inflammation. Microbes heavily rely on cellular signaling pathways for their effective replication; hence, JNKs may play important roles in infectious diseases. In this review, we describe the basic signaling properties of MAPKs and JNKs in apoptosis, autophagy, and inflammasome activation. Furthermore, we discuss the roles of JNKs in various infectious diseases induced by viruses, bacteria, fungi, and parasites, as well as their potential to serve as targets for the development of therapeutic agents for infectious diseases. We expect this review to expand our understanding of the JNK signaling pathway's role in infectious diseases and provide important clues for the prevention and treatment of infectious diseases.
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http://dx.doi.org/10.3390/ijms22179640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431791PMC
September 2021
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