Publications by authors named "Chao Ye"

187 Publications

The Critical Role of NLRP6 Inflammasome in Infection In Vitro and In Vivo.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

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

() causes severe pulmonary diseases, leading to high morbidity and mortality. It has been reported that inflammasomes such as NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) play an important role in the host defense against infection. However, the role of NLRP6 in vivo and in vitro against remains unclear. Therefore, we investigated the role of NLRP6 in regulating the -induced inflammatory signaling pathway in vitro and the role of NLRP6 in the host defense against in vivo by using NLRP6 mice. The results showed that the NLRP6 inflammasome regulated the maturation and secretion of IL-1β, but it did not affect the induction of IL-1β transcription in -infected macrophages. Furthermore, the activation of caspase-1, caspase-11, and gasdermin D (GSDMD) as well as the oligomerization of apoptosis-associated speck-like protein (ASC) were also mediated by NLRP6 in -infected macrophages. However, the activation of NLRP6 reduced the expression of NF-κB and ERK signaling pathways in -infected macrophages. In vivo study showed that NLRP6 mice had a higher survival rate, lower number of bacteria, and milder inflammatory response in the lung compared with wild-type (WT) mice during infection, indicating that NLRP6 plays a negative role in the host defense against . Furthermore, increased bacterial clearance in NLRP6 deficient mice was modulated by the recruitment of macrophages and neutrophils. Our study provides a new insight on -induced activation of NLRP6 and suggests that blocking NLRP6 could be considered as a potential therapeutic strategy to treat infection.
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http://dx.doi.org/10.3390/ijms22083876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069100PMC
April 2021

Pseudorabies virus pUL16 assists the nuclear import of VP26 through protein-protein interaction.

Vet Microbiol 2021 Apr 20;257:109080. Epub 2021 Apr 20.

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

Pseudorabies virus (PRV) is related to alphaherpesvirus and varicellovirus. pUL16 is a conserved protein in all herpesviruses, and studies have shown that UL16 can interact with the viral proteins pUL11, pUL49, pUL21, gD, and gE. In this study, we found that pUL16 interacted with the viral capsid protein VP26, which could not translocate into the nucleus itself but did appear in the nucleus. We further determined whether pUL16 assists the translocation of VP26 into the nucleus. We found that pUL16 interacted with VP26 with or without viral proteins, and since VP26 itself did not contain a nuclear location signal, we concluded that pUL16 assisted the translocation of VP26 into the nucleus. Deletion of UL16 and UL35 significantly reduced the 50 % tissue culture infective dose, virulence, attachment, and internalization of PRV in cells. These results show that the interaction between pUL16 and VP26 influences the growth and virulence of pseudorabies virus. Our research is the first study to show that pUL16 interacts with VP26, which may explain the targeting site of UL16 and viral capsids. It is also the first to show that UL16 assists the transport of other viral proteins to organelles. Previous researches on pUL16 usually emphasized its interaction with pUL11, pUL21, and gE, and sometimes commented on pUL49 and gD. Our research focuses on the novel interaction between pUL16 and VP26, thereby enriching the studies on herpesviruses and possibly providing different directions for researchers.
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http://dx.doi.org/10.1016/j.vetmic.2021.109080DOI Listing
April 2021

Predicting the conformations of the silk protein through deep learning.

Analyst 2021 Apr;146(8):2490-2498

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

As with other proteins, the conformation of the silk protein is critical for determining the mechanical, optical and biological performance of materials. However, an efficient, accurate and time-efficient method for evaluating the protein conformation from Fourier transform infrared (FTIR) spectra is still desired. A set of convolutional neural network (CNN)-based deep learning models was developed in this study to identify the silk proteins and evaluate their relative content of each conformation from FTIR spectra. Compared with the conventional deconvolution algorithm, our CNN models are highly accurate and time-efficient, showing promise in processing massive FTIR data sets, such as data from FTIR imaging, and in quick analysis feedback, such as on-line and time-resolved FTIR measurements. We compiled an open-source and user-friendly graphical Python program that allows users to analyze their own FTIR data set, which can be from the silk protein or other proteins, for the encouragement and convenience of interested researchers to use the CNN models.
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http://dx.doi.org/10.1039/d1an00290bDOI Listing
April 2021

Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function.

Aging (Albany NY) 2021 Apr 21;13(8):11678-11695. Epub 2021 Apr 21.

School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.

Piccolo is a presynaptic protein with high conservation among different species, and the expression of Piccolo is extensive in vertebrates. Recently, a small fragment of Piccolo (Piccolino), arising due to the incomplete splicing of intron 5/6, was found to be present in the synapses of retinas and cochleae. However, the comprehensive function of Piccolo in the retina and cochlea remains unclear. In this study, we generated knockout mice using CRISPR-Cas9 technology to explore the function of Piccolo. Unexpectedly, whereas no abnormalities were found in the cochlear hair cells of the mutant mice, significant differences were found in the retinas, in which two layers (the outer nuclear layer and the outer plexiform layer) were absent. Additionally, the amplitudes of electroretinograms were significantly reduced and pigmentation was observed in the fundoscopy of the mutant mouse retinas. The expression levels of Bassoon, a homolog of Piccolo, as well as synapse-associated proteins CtBP1, CtBP2, Kif3A, and Rim1 were down-regulated. The numbers of ribbon synapses in the retinas of the mutant mice were also reduced. Altogether, the phenotype of -/- mice resembled the symptoms of retinitis pigmentosa (RP) in humans, suggesting might be a candidate gene of RP and indicates knockout mice are a good model for elucidating the molecular mechanisms of RP.
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http://dx.doi.org/10.18632/aging.202861DOI Listing
April 2021

Extracellular vesicle-mediated miR135a-5p transfer in hypertensive rat contributes to vascular smooth muscle cell proliferation via targeting FNDC5.

Vascul Pharmacol 2021 Apr 16:106864. Epub 2021 Apr 16.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing 211166, China; Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address:

Background Extracellular vesicles (EVs) from vascular adventitial fibroblasts (AFs) contribute to the proliferation of vascular smooth muscle cells (VSMCs) and vascular remodeling in spontaneously hypertensive rat (SHR). This study shows the crucial roles of EVs-mediated miR135a-5p transfer in VSMC proliferation and the underlying mechanisms in hypertension. Methods AFs and VSMCs were obtained from the aorta of Wistar-Kyoto rat (WKY) and SHR. EVs were isolated from the culture of AFs with ultracentrifugation method. Results MiR135a-5p level in SHR-EVs was significantly increased. MiR135a-5p inhibitor prevented the SHR-EVs-induced VSMC proliferation. Fibronectin type III domain containing 5 (FNDC5) was a target gene of miR135a-5p. FNDC5 level was lower in VSMCs of SHR. MiR135a-5p inhibitor not only increased FNDC5 expression, but reversed the SHR-EVs-induced FNDC5 downregulation in VSMCs of SHR. MiR135a-5p mimic inhibited FNDC5 expression, but failed to promote the SHR-EVs-induced FNDC5 downregulation in VSMCs of SHR. Exogenous FNDC5 prevented the SHR-EVs-induced VSMC proliferation of both WKY and SHR. Knockdown of miR135a-5p in fibroblasts completely prevented the upregulation of miR135a-5p in the EVs. The SHR-EVs from the miR135a-5p knockdown-treated fibroblasts lost their roles in inhibiting FNDC5 expression and promoting proliferation in VSMCs of both WKY and SHR. Conclusions Increased miR135a-5p in the SHR-EVs promoted VSMC proliferation of WKY and SHR via inhibiting FNDC5 expression. MiR135a-5p and FNDC5 are crucial targets for intervention of VSMC proliferation in hypertension.
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http://dx.doi.org/10.1016/j.vph.2021.106864DOI Listing
April 2021

Role of the central renin‑angiotensin system in hypertension (Review).

Int J Mol Med 2021 Jun 13;47(6). Epub 2021 Apr 13.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Present in more than one billion adults, hypertension is the most significant modifiable risk factor for mortality resulting from cardiovascular disease. Although its pathogenesis is not yet fully understood, the disruption of the renin‑angiotensin system (RAS), consisting of the systemic and brain RAS, has been recognized as one of the primary reasons for several types of hypertension. Therefore, acquiring sound knowledge of the basic science of RAS and the underlying mechanisms of the signaling pathways associated with RAS may facilitate the discovery of novel therapeutic targets with which to promote the management of patients with cardiovascular and kidney disease. In total, 4 types of angiotensin II receptors have been identified (AT1R‑AT4R), of which AT1R plays the most important role in vasoconstriction and has been most extensively studied. It has been found in several regions of the brain, and its distribution is highly associated with that of angiotensin‑like immunoreactivity in nerve terminals. The effect of AT1R involves the activation of multiple media and signaling pathways, among which the most important signaling pathways are considered to be AT1R/JAK/STAT and Ras/Raf/MAPK pathways. In addition, the regulation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) and cyclic AMP response element‑binding (CREB) pathways is also closely related to the effect of ATR1. Their mechanisms of action are related to pro‑inflammatory and sympathetic excitatory effects. Central AT1R is involved in almost all types of hypertension, including spontaneous hypertension, salt‑sensitive hypertension, obesity‑induced hypertension, renovascular hypertension, diabetic hypertension, L‑NAME‑induced hypertension, stress‑induced hypertension, angiotensin II‑induced hypertension and aldosterone‑induced hypertension. There are 2 types of central AT1R blockade, acute blockade and chronic blockade. The latter can be achieved by chemical blockade or genetic engineering. The present review article aimed to highlight the prevalence, functions, interactions and modulation means of central AT‑1R in an effort to assist in the treatment of several pathological conditions. The identification of angiotensin‑derived peptides and the development of AT‑2R agonists may provide a wider perspective on RAS, as well as novel therapeutic strategies.
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http://dx.doi.org/10.3892/ijmm.2021.4928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041481PMC
June 2021

Short-Range Ordered Iridium Single Atoms Integrated into Cobalt Oxide Spinel Structure for Highly Efficient Electrocatalytic Water Oxidation.

J Am Chem Soc 2021 Apr 25;143(13):5201-5211. Epub 2021 Mar 25.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, Australia.

Noble metals manifest themselves with unique electronic structures and irreplaceable activity toward a wide range of catalytic applications but are unfortunately restricted by limited choice of geometric structures spanning single atoms, clusters, nanoparticles, and bulk crystals. Herein, we propose how to overcome this limitation by integrating noble metal atoms into the lattice of transition metal oxides to create a new type of hybrid structure. This study shows that iridium single atoms can be accommodated into the cationic sites of cobalt spinel oxide with short-range order and an identical spatial correlation as the host lattice. The resultant IrCoO catalyst exhibits much higher electrocatalytic activity than the parent oxide by 2 orders of magnitude toward the challenging oxygen evolution reaction under acidic conditions. Because of the strong interaction between iridium and cobalt oxide support, the IrCoO catalyst shows significantly improved corrosion resistance under acidic conditions and oxidative potentials. This work eliminates the "close-packing" limitation of noble metals and offers promising opportunity to create analogues with desired topologies for various catalytic applications.
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http://dx.doi.org/10.1021/jacs.1c01525DOI Listing
April 2021

Inhibition of the DNA-Sensing pathway by pseudorabies virus UL24 protein via degradation of interferon regulatory factor 7.

Vet Microbiol 2021 Apr 27;255:109023. Epub 2021 Feb 27.

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

The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays an important role in the innate immune response by the production of type I interferon (IFN) against DNA virus infection. However, viruses have evolved a variety of strategies to antagonize the host antiviral response to facilitate infection and replication. Pseudorabies virus (PRV), a DNA virus that causes great economic losses to the swine industry, encodes approximate 70 proteins, including some that are involved in evasion of host immunity. However, the mechanism employed by PRV to regulate type I IFN remains unclear. The results of the present study showed that the transcription levels of type I IFN were significantly upregulated by a UL24-deleted PRV strain. Furthermore, IFN-β activation induced by poly(dA:dT) or stimulated by cGAS-STING was inhibited by UL24 overexpression in PK15 cells. Co-immunoprecipitation analysis demonstrated that UL24 interacts with and can degrade interferon regulatory factor 7 (IRF7) through the proteasome pathway in a dose-dependent manner. Together, these results showed that PRV UL24 interacted with IRF7 via the proteasome pathway and antagonized cGAS-STING-mediated activation of IFN-β.
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http://dx.doi.org/10.1016/j.vetmic.2021.109023DOI Listing
April 2021

Involvement of clathrin-dependent endocytosis in cellular dsRNA uptake in aphids.

Insect Biochem Mol Biol 2021 May 25;132:103557. Epub 2021 Feb 25.

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

RNAi is an essential technology for studying gene function in eukaryotes, and is also considered to be a potential strategy for pest control. However, the mechanism behind the cellular uptake of dsRNA in aphids, a group of important agricultural sucking pests, remains unknown. Here, using the pea aphid Acyrthosiphon pisum as model for aphids, we identified two core genes of clathrin-dependent endocytosis (CDE), Apchc and Apvha16. We confirmed that expression of Apchc, Apvha16 and RNAi core component genes (ApAgo2, ApDcr2 and ApR2d2) were simultaneously induced at 12 h after feeding dsRNA. By using an RNAi-of-RNAi approach, we demonstrated that suppression of Apchc and Apvha16 transcripts by RNAi significantly impaired RNAi efficiency of selected reporter genes (RGs), including ApGNBP1, Apmts and Aphb, suggesting the involvement of CDE in cellular dsRNA uptake in aphids. Further confirmation was also provided using two inhibitors, chlorpromazine (CPZ) and bafilomycin A1 (BafA1). Administration of CPZ and of BafA1 both led to an impaired silencing efficiency of the RGs in the pea aphid. Finally, these RNAi-of-RNAi results were reconfirmed in the peach aphid Myzus persicae. Taking these findings together, we conclude that CDE is involved in cellular dsRNA uptake in aphids.
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http://dx.doi.org/10.1016/j.ibmb.2021.103557DOI Listing
May 2021

Deficiency for Lcn8 causes epididymal sperm maturation defects in mice.

Biochem Biophys Res Commun 2021 Apr 22;548:7-13. Epub 2021 Feb 22.

School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, PR China. Electronic address:

Lipocalin family members, LCN8 and LCN9, are specifically expressed in the initial segment of mouse caput epididymis. However, the biological functions of the molecules in vivo are yet to be clarified. In this study, CRISPR/Cas9 technology was used to generate Lcn8 and Lcn9 knockout mice, respectively. Lcn8 and Lcn9 male mice showed normal spermatogenesis and fertility. In the cauda epididymis of Lcn8 male mice, morphologically abnormal sperm was increased significantly, the proportion of progressive motility sperm was decreased, the proportion of immobilized sperm was elevated, and the sperm spontaneous acrosome reaction (AR) frequency was increased. Conversely, the knockout of Lcn9 did not have any effect on the ratio of morphologically abnormal sperm, sperm motility, and sperm spontaneous AR frequencies. These results demonstrated the role of LCN8 in maintaining the sperm quality in the epididymis, and suggested that the deficiency of LCN8 leads to epididymal sperm maturation defects.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.052DOI Listing
April 2021

Thermodynamic and Economic Analysis of Oxy-Fuel-Integrated Coal Partial Gasification Combined Cycle.

ACS Omega 2021 Feb 2;6(6):4262-4272. Epub 2021 Feb 2.

State Key Laboratory of Clean Energy Utilization, Zhejiang University, Zhejiang, Hangzhou 310027, China.

A novel partial gasification combined cycle (PGCC) system integrating coal partial gasification, oxy-fuel combustion, combined cycle, and CO separation is proposed. The coal-CO partial gasification technology is introduced in the coal gasification unit, and the oxy-fuel combustion technology is employed in the char combustion unit and gas turbine (GT) unit. The thermodynamic and economic analysis of the proposed system is carried out, showing that both energy and exergy efficiency have an increasing/decreasing tendency when the recycled flue gas (RFG) ratio of char combustion and GT increase. When the RFG ratios of char combustion and GT are 0.43 and 0.34, energy and exergy efficiencies reach maximum values of 48.18 and 45.11%, respectively. The energy efficiency of the PGCC-Oxy system is higher than that of the integrated gasification combined cycle (IGCC)-Oxy system by approximately 3%. It can be concluded from the economic analysis that the total investment on the PGCC-Oxy system is 3272.71 million RMB, and the internal rate of return (IRR) and payback time is 8.07% and 12.38 years, respectively.
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http://dx.doi.org/10.1021/acsomega.0c05277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893634PMC
February 2021

Inhibition of miR-135a-5p attenuates vascular smooth muscle cell proliferation and vascular remodeling in hypertensive rats.

Acta Pharmacol Sin 2021 Feb 15. Epub 2021 Feb 15.

Department of Physiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, 211166, China.

Proliferation of vascular smooth muscle cells (VSMCs) greatly contributes to vascular remodeling in hypertension. This study is to determine the roles and mechanisms of miR-135a-5p intervention in attenuating VSMC proliferation and vascular remodeling in spontaneously hypertensive rats (SHRs). MiR-135a-5p level was raised, while fibronectin type III domain-containing 5 (FNDC5) mRNA and protein expressions were reduced in VSMCs of SHRs compared with those of Wistar-Kyoto rats (WKYs). Enhanced VSMC proliferation in SHRs was inhibited by miR-135a-5p knockdown or miR-135a-5p inhibitor, but exacerbated by miR-135a-5p mimic. VSMCs of SHRs showed reduced myofilaments, increased or even damaged mitochondria, increased and dilated endoplasmic reticulum, which were attenuated by miR-135a-5p inhibitor. Dual-luciferase reporter assay shows that FNDC5 was a target gene of miR-135a-5p. Knockdown or inhibition of miR-135a-5p prevented the FNDC5 downregulation in VSMCs of SHRs, while miR-135a-5p mimic inhibited FNDC5 expressions in VSMCs of both WKYs and SHRs. FNDC5 knockdown had no significant effects on VSMC proliferation of WKYs, but aggravated VSMC proliferation of SHRs. Exogenous FNDC5 or FNDC5 overexpression attenuated VSMC proliferation of SHRs, and prevented miR-135a-5p mimic-induced enhancement of VSMC proliferation of SHR. MiR-135a-5p knockdown in SHRs attenuated hypertension, normalized FNDC5 expressions and inhibited vascular smooth muscle proliferation, and alleviated vascular remodeling. These results indicate that miR-135a-5p promotes while FNDC5 inhibits VSMC proliferation in SHRs. Silencing of miR-135a-5p attenuates VSMC proliferation and vascular remodeling in SHRs via disinhibition of FNDC5 transcription. Either inhibition of miR-135a-5p or upregulation of FNDC5 may be a therapeutically strategy in attenuating vascular remodeling and hypertension.
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http://dx.doi.org/10.1038/s41401-020-00608-xDOI Listing
February 2021

Microbial physiological engineering increases the efficiency of microbial cell factories.

Crit Rev Biotechnol 2021 May 4;41(3):339-354. Epub 2021 Feb 4.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Microbial cell factories provide vital platforms for the production of chemicals. Advanced biotechnological toolboxes have been developed to enhance their efficiency. However, these tools have limitations in improving physiological functions, and therefore boosting the efficiency (e.g. titer, rate, and yield) of microbial cell factories remains a challenge. In this review, we propose a strategy of microbial physiological engineering (MPE) to improve the efficiency of microbial cell factories. This strategy integrates tools from synthetic and systems biology to characterize and regulate physiological functions during chemical synthesis. MPE strategies mainly focus on the efficiency of substrate utilization, growth performance, stress tolerance, and the product export capacity of cell factories. In short, this review provides a new framework for resolving the bottlenecks that currently exist in low-efficiency cell factories.
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http://dx.doi.org/10.1080/07388551.2020.1856770DOI Listing
May 2021

Antimicrobial Resistance and Molecular Characterization of Class 1 Integron in Isolates Recovered from Pig Farms in Chongqing, China.

Foodborne Pathog Dis 2021 Jan 25. Epub 2021 Jan 25.

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

is considered one of the leading causes for foodborne diseases in humans. Pork and its products contaminated with are increasingly recognized as an important source of human salmonellosis. The aim of this study was to investigate the antimicrobial resistance and prevalence of integrons in isolates from pig farms. In total, 92 of 724 (12.7%) samples were -positive, including 64 (15.0%) from fecal samples, 27 (12.6%) from floor samples, 1 (4.5%) from water samples, and 0 from feed and air samples. These isolates showed the highest resistance to tetracycline (85.9%), followed by trimethoprim (67.4%), ampicillin (60.9%), and chloramphenicol (51.1%). In addition, 51 isolates carried the complete class 1 integron, most of which (42/51) harbored antibiotic resistance cassettes. A total of six gene cassettes including , , , , , and were identified, in which the most prevalent one was (29.4%). Furthermore, all 19 class 1 integron-positive isolates harboring genes showed resistance to trimethoprim (SXT), suggesting that the trimethoprim resistance gene () may contribute to the emergence of SXT resistance phenotype. Therefore, considering the significance of integrons and related resistance genes for public health, special measures should be taken to control spp. on the pig farms and to prevent spread of integrons and associated resistance genes.
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http://dx.doi.org/10.1089/fpd.2020.2881DOI Listing
January 2021

The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.

Proc Natl Acad Sci U S A 2021 Jan;118(4)

Department of Digestive Disease, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001 Hefei, China;

RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the tissue- or cell-specific function of RNA helicases owing to the lethality of mice with complete knockout of RNA helicases; further, there is a lack of evidence about the antibacterial role of helicases. Here, we investigated the in vivo role of Dhx15 in intestinal antibacterial responses by generating mice that were intestinal epithelial cell (IEC)-specific deficient for Dhx15 (Dhx15 f/f Villin1-cre, Dhx15). These mice are susceptible to infection with enteric bacteria (), owing to impaired α-defensin production by Paneth cells. Moreover, mice with Paneth cell-specific depletion of Dhx15 (Dhx15 f/f Defensinα6-cre, Dhx15) are more susceptible to DSS (dextran sodium sulfate)-induced colitis, which phenocopy Dhx15 mice, due to the dysbiosis of the intestinal microbiota. In humans, reduced protein levels of Dhx15 are found in ulcerative colitis (UC) patients. Taken together, our findings identify a key regulator of Wnt-induced α-defensins in Paneth cells and offer insights into its role in the antimicrobial response as well as intestinal inflammation.
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http://dx.doi.org/10.1073/pnas.2017432118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848544PMC
January 2021

Toxic Shock Syndrome Toxin 1 Induces Immune Response via the Activation of NLRP3 Inflammasome.

Toxins (Basel) 2021 01 18;13(1). Epub 2021 Jan 18.

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

is a Gram-positive opportunistic pathogen which causes infections in a variety of vertebrates. Virulence factors are the main pathogenesis of as a pathogen, which induce the host's innate and adaptive immune responses. Toxic shock syndrome toxin 1 (TSST-1) is one of the most important virulence factors of . However, the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) in TSST-1-induced innate immune response is still unclear. Here, purified recombinant TSST-1 (rTSST-1) was prepared and used to stimulate mouse peritoneal macrophages. The results showed that under the action of adenosine-triphosphate (ATP), rTSST-1 significantly induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) production in mouse macrophages and the production was dose-dependent. In addition, rTSST-1+ATP-stimulated cytokine production in macrophage depends on the activation of toll like receptor 4 (TLR4), but not TLR2 on the cells. Furthermore, the macrophages of NLRP3 mice stimulated with rTSST-1+ATP showed significantly low levels of IL-1β production compared to that of wild-type mice. These results demonstrated that TSST-1 can induce the expression of inflammatory cytokines in macrophages via the activation of the TLR4 and NLRP3 signaling pathways. Our study provides new information about the mechanism of the TSST-1-inducing host's innate immune responses.
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http://dx.doi.org/10.3390/toxins13010068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829800PMC
January 2021

Boosting Zinc Electrode Reversibility in Aqueous Electrolytes by Using Low-Cost Antisolvents.

Angew Chem Int Ed Engl 2021 03 24;60(13):7366-7375. Epub 2021 Feb 24.

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

Antisolvent addition has been widely studied in crystallization in the pharmaceutical industries by breaking the solvation balance of the original solution. Here we report a similar antisolvent strategy to boost Zn reversibility via regulation of the electrolyte on a molecular level. By adding for example methanol into ZnSO electrolyte, the free water and coordinated water in Zn solvation sheath gradually interact with the antisolvent, which minimizes water activity and weakens Zn solvation. Concomitantly, dendrite-free Zn deposition occurs via change in the deposition orientation, as evidenced by in situ optical microscopy. Zn reversibility is significantly boosted in antisolvent electrolyte of 50 % methanol by volume (Anti-M-50 %) even under harsh environments of -20 °C and 60 °C. Additionally, the suppressed side reactions and dendrite-free Zn plating/stripping in Anti-M-50 % electrolyte significantly enhance performance of Zn/polyaniline coin and pouch cells. We demonstrate this low-cost strategy can be readily generalized to other solvents, indicating its practical universality. Results will be of immediate interest and benefit to a range of researchers in electrochemistry and energy storage.
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http://dx.doi.org/10.1002/anie.202016531DOI Listing
March 2021

Analysis of the Contribution of Conformation and Fibrils on Tensile Toughness and Fracture Resistance of Camel Hairs.

ACS Biomater Sci Eng 2020 Dec 24. Epub 2020 Dec 24.

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

Animal hairs, like other natural fibers, display excellent mechanical properties, especially, the tensile toughness and fracture resistance. Several structure-mechanics models have attributed mechanical superiority of hair to its unique nanocomposite structure which consists of intermediate filaments and matrix. However, the contribution of fibrils and their associated interfaces on the mechanical properties of animal hairs remains unclear. Herein, using the small- and wide-angle X-ray scattering, and an ultrahigh-speed microcamera system, it is confirmed that the conformation and fibrils (which represent both nanofibrils and microfibrils) of the keratin channel endow tensile toughness and fracture resistance to camel hairs. During the stretching process, an α-β transition occurred at the secondary structure level, leading to the formation of a tensile plateau, which improves the toughness compared with the structure without a conformation transition. Meanwhile, fibrils further toughened the camel hairs and resisted their crack propagation through confined fibrillar slippage, splitting, and pulling. These structure-property relations in natural hairs can inspire damage-tolerant polymer fiber design.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00892DOI Listing
December 2020

Employing ATP as a New Adjuvant Promotes the Induction of Robust Antitumor Cellular Immunity by a PLGA Nanoparticle Vaccine.

ACS Appl Mater Interfaces 2020 Dec 20;12(49):54399-54414. Epub 2020 Nov 20.

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.

Tumor vaccines based on synthetic human papillomavirus (HPV) oncoprotein E7 and/or E6 peptides have shown encouraging results in preclinical model studies and human clinical trials. However, the clinical efficacy may be limited by the disadvantages of vulnerability to enzymatic degradation and low immunogenicity of peptides. To further improve the potency of vaccine, we developed a poly(lactide--glycolide)-acid (PLGA) nanoparticle, which encapsulated the antigenic peptide HPV16 E7, and used adenosine triphosphate (ATP), one of the most important intracellular metabolites and an endogenous extracellular danger signal for the immune system, as a new adjuvant component. The results showed that PLGA nanoparticles increased the stability, lymph node accumulation, and dendritic cell (DC) uptake of the E7 peptide; in addition, ATP further increased the migration, nanoparticle uptake, and maturation of DCs. Preventive immunization with ATP-adjuvanted nanoparticles completely abolished the growth of TC-1 tumors in mice and produced long-lasting immunity against tumor rechallenge. When tumors were fully established, therapeutic immunization with ATP-adjuvanted nanoparticles still significantly inhibited tumor progression. Mechanistically, ATP-adjuvanted nanoparticles significantly improved the systemic generation of antitumor effector cells, boosted the local functional status of these cells in tumors, and suppressed the generation and tumor infiltration of immunosuppressive Treg cells and myeloid-derived suppressor cells. These findings indicate that ATP is an effective vaccine adjuvant and that nanoparticles adjuvanted with ATP were able to elicit robust antitumor cellular immunity, which may provide a promising therapeutic vaccine candidate for the treatment of clinical malignancies, such as cervical cancer.
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http://dx.doi.org/10.1021/acsami.0c15522DOI Listing
December 2020

Risk factors for person-to-person transmission of severe fever with thrombocytopenia syndrome.

Authors:
Chao Ye Rui Qi

Infect Control Hosp Epidemiol 2020 Nov 9:1-4. Epub 2020 Nov 9.

School of Public Health, Lanzhou University, Lanzhou, Gansu Province, China.

Objective: To determine the risk factors for person-to-person transmission of severe fever with thrombocytopenia syndrome (SFTS).

Design: Studies reporting the person-to-person transmission or cluster infection of SFTS were identified and included for risk-factor analyses.

Methods: Risk factors were investigated by analyzing characteristics of index patients who caused cluster infection and correlation between exposure history and secondary infection.

Results: Analyses of 23 clusters of SFTS infections indicated that all index patients died and that they all had a symptom of bleeding 24 hours before death. Of 89 secondary cases, 82% had been exposed to the index patients' blood. The blood-contact-specific secondary attack rate was 62.4% (73 of 117). The risk relative value was 25 (95% CI, 15-42); thus, the probability of a person getting infected was 25 times more likely when they had contacted blood than when they had not.

Conclusion: Exposure to blood of SFTS patients is the highest risk factor for person-to-person infection with SFTSV. SFTS patients' families and healthcare workers should be educated to handle SFTS patients properly and safely to prevent the spread of SFTSV.
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http://dx.doi.org/10.1017/ice.2020.1258DOI Listing
November 2020

Author Correction: Light-powered Escherichia coli cell division for chemical production.

Nat Commun 2020 Nov 4;11(1):5684. Epub 2020 Nov 4.

State Key Laboratory of Food Science and Technology, Jiangnan University, 214122, Wuxi, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-19642-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642438PMC
November 2020

Factors influencing early recurrence of hepatocellular carcinoma after curative resection.

J Int Med Res 2020 Aug;48(8):300060520945552

Department of Liver Surgery, The First Affiliated Hospital of USTC, Hefei, Anhui, P.R. China.

Objective: To identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection.

Methods: Clinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression.

Results: Twenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner.

Conclusion: Tumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.
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http://dx.doi.org/10.1177/0300060520945552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780562PMC
August 2020

Study on traces left on a mechanical lock picked by a 3D printed key in toolmarks examination.

Forensic Sci Int 2020 Dec 18;317:110514. Epub 2020 Sep 18.

Department of Trace Examination, Criminal Investigation Police University of China, Shenyang, China.

The three-dimensional (3D) printed key is a key that can be manufactured from its virtual model by means of a 3D printer. This research focuses on the picking feasibilities and traces that can be observed and exploited from a forensic point of view after the picking of such type of keys. In this paper, 40 printed keys were manufactured using three different polymer materials (white resin, white nylon powder and black ABS). All the experiments were carried out under controlled conditions to allow the collections of data and traces produced by the picking. Of the 40 prints, only 38 picked the locks and the total picking ratio was 95 percent, meaning that a 3D printed key using polymer materials can be used to pick a lock. Elements of lock - pins and keyways - appeared to carry polymer materials (flakes or pieces) transferred from the prints during picking process. Additional, characteristic marks of a 3D printed key on the surface of pins was identical to those of an original key, but not similar to those of other picking tools. Indeed, this method could not create more marks on the bits of an original key while striations were left by the picking method using a duplicated key. Besides, FT-IR was a useful method of analyzing the type of polymer material used. When receiving original keys and a lock suspected to be picked in a crime scene, the toolmark examiners can quickly determine whether or not the lock was picked by a 3D printed key based on the examination results of these traces.
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http://dx.doi.org/10.1016/j.forsciint.2020.110514DOI Listing
December 2020

Yiqi Yangyin Huoxue Method in Treating IdiopathicPulmonary Fibrosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med 2020 3;2020:8391854. Epub 2020 Oct 3.

College of Clinical Medical, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: Idiopathic pulmonary fibrosis (IPF) is a common respiratory disease that can lead to respiratory failure in severe condition. Despite notable advances in its treatment, some patients show poor effect when treated with conventional western medicine (CWM). Traditional Chinese medicine with the Yiqi Yangyin Huoxue method (YQYYHXM) has been reported to be positive for IPF. In order to explore the effectiveness and safety of YQYYHXM in the treatment of IPF, we performed this meta-analysis.

Method: We searched six databases including Embase, Cochrane, PubMed, CNKI, Wan Fang, and VIP database from their inception to June 1, 2019, and then selected eight studies. Two reviewers independently conducted methodological evaluation and data analysis by the software RevMan 5.3.3 and Stata 12.0.

Results: The meta-analysis revealed that when YQYYHXM was adopted in combination with CWM, cough, chest pain, and shortness of breath of IPF patients improved significantly. After treatment with YQYYHXM combined with CWM, the SGRQ of IPF patients substantially enhanced. YQYYHXM also has positive effect on 6MWD and TLC, but the improvement on FVC was not obvious. In addition, YQYYHXM has no significance in improving PaO. All the adverse events were reported in the control group.

Conclusion: YQYYHXM is more effective and safe as adjunctive treatment for patients with IPF. However, in the future, long-term, large-scale, and high-quality trials will be required to provide more convincing evidence of YQYYHXM due to some limitations of this review.
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http://dx.doi.org/10.1155/2020/8391854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548958PMC
October 2020

Systematic review and meta-analysis of the efficacy and safety of vancomycin combined with β-lactam antibiotics in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections.

J Glob Antimicrob Resist 2020 12 9;23:303-310. Epub 2020 Oct 9.

Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. Electronic address:

Objective: Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in recent years, but its efficacy and safety have not been systematically evaluated. This is a systematic review and meta-analysis to clarify the efficacy and safety of Combo therapy in patients with MRSA BSIs.

Methods: Relevant articles reporting on the clinical or microbiology outcomes of Combo treatment in adult patients with MRSA bacteraemia throughout November 2019 were searched in PubMed, EMBASE and Cochrane Library databases. Summary odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were evaluated using a fixed- or random-effects model.

Results: Six articles (806 patients) consisting of one RCT and five retrospective cohort studies were included in this study. The pooled data showed that Combo therapy could significantly reduce the risk of microbiological failure (OR = 0.54, 95% CI 0.35-0.83, I 40%, P = 0.005) and persistent bacteraemia (OR=0.48, 95% CI 0.30-0.77, I 13%, P = 0.002), as well as shorten the duration of bacteraemia (MD = -1.06, 95% CI -1.53 to -0.60, I 0%, P < 0.00001). In addition, it did not significantly increase the incidence of nephrotoxicity (OR = 1.17, 95% CI 0.64-2.13, I 0%, P = 0.61). However, no significant difference was detected between the groups regarding 28/30-day mortality, MRSA-related mortality, bacteraemia relapse or length of hospitalization.

Conclusions: These results demonstrate that Combo therapy clears the pathogenic bacteria of MRSA bacteraemia but does not improve the clinical prognosis. As the sample size was small and most of the studies were retrospective cohort studies with substantial heterogeneity, there is a need for further studies encompassing large-scale multicentre RCTs to validate our results.
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http://dx.doi.org/10.1016/j.jgar.2020.09.024DOI Listing
December 2020

Prevalence and Characterisation of Class 1 and 2 Integrons in Multi-drug Resistant Isolates from Pig Farms in Chongqing, China.

J Vet Res 2020 Sep 16;64(3):381-386. Epub 2020 Sep 16.

College of Animal Science and Technology, Southwest University, Beibei District, Chongqing, 400715, China.

Introduction: Integrons are mobile DNA elements that allow for acquisition and dissemination of antibiotic-resistance genes among pig farm-derived bacteria. Limited information is available on integrons of from pig farms. The aim of this study was to characterise and investigate the prevalence of class 1 and 2 integrons in multi-drug resistant (MDR) isolates from pig farms.

Material And Methods: A total of 724 swabs were collected from 12 pig farms in Chongqing, China, and examined by conventional microbial and molecular methods.

Results: In total, 68 isolates were , 57 of which were methicillin resistant (MRSA). All 68 isolates were MDR strains and carried integrons, of which 88.2% (60/68) harboured both class 1 and 2. In addition, 85.3% (58/68) of the class 2 integron-positive isolates carried the β-lactam resistance gene ( ), and 66.7% (40/60) of the class 1 integron-positive isolates carried the , or gene for respective streptomycin and spectinomycin or trimethoprim resistance.

Conclusions: Class 1 and 2 integrons are common among the pig farm-derived isolates. On account of their significance for public health, the prevalence of the integrons and their associated resistance genes in pig farm-derived isolates should be paid special attention.
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http://dx.doi.org/10.2478/jvetres-2020-0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497750PMC
September 2020

Naringin and bone marrow mesenchymal stem cells repair articular cartilage defects in rabbit knees through the transforming growth factor-β superfamily signaling pathway.

Exp Ther Med 2020 Nov 4;20(5):59. Epub 2020 Sep 4.

Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, P.R. China.

The present study aimed to assess the effect of a combination of naringin and rabbit bone marrow mesenchymal stem cells (BMSCs) on the repair of cartilage defects in rabbit knee joints and to assess possible involvement of the transforming growth factor-β (TGF-β) signaling pathway in this process. After establishing an articular cartilage defect model in rabbit knees, 20 New Zealand rabbits were divided into a sham operation group (Sham), a model group (Mod), a naringin treatment group (Nar), a BMSC group (BMSCs) and a naringin + BMSC group (Nar/BMSCs). At 12 weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS)'s macroscopic evaluation of cartilage repair scale, the ICRS's visual histological assessment scale, the Modified O'Driscoll grading system, histological staining (hematoxylin and eosin staining, toluidine blue staining and safranin O staining) and immunohistochemical staining (type-II collagen, TGF-β3 and SOX-9 immunostaining). Using the above grading systems to quantify the extent of repair, histological quantification and macro quantification of joint tissue repair showed that the Nar/BMSCs group displayed repair after treatment in comparison to the untreated Mod group. Among the injury model groups (Mod, Nar, BMSCs and Nar/BMSCs), the Nar/BMSCs group displayed the highest degree of morphological repair. The results of histological and immunohistochemical staining of the repaired region of the joint defect indicated that the BMSCs had a satisfactory effect on the repair of the joint structure but had a poor effect on the repair of cartilage quality. The Nar/BMSCs group displayed satisfactory therapeutic effects on both repair of the joint structure and cartilage quality. The expression level of type-II collagen was high in the Nar/BMSCs group. Additionally, staining of TGF-β3 and SOX-9 in the Nar/BMSCs group was the strongest compared with that of any other group in the present study. Naringin and/BMSCs together demonstrated a more efficient repair effect on articular cartilage defects in rabbit knees than the use of either treatment alone in terms of joint structure and cartilage quality. One potential mechanism of naringin action may be through activation and continuous regulation of the TGF-β superfamily signaling pathway, which can promote BMSCs to differentiate into chondrocytes.
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http://dx.doi.org/10.3892/etm.2020.9187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485297PMC
November 2020

Interleukin-1β in hypothalamic paraventricular nucleus mediates excitatory renal reflex.

Pflugers Arch 2020 11 11;472(11):1577-1586. Epub 2020 Sep 11.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (ATR) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1β (IL-1β) in the PVN mediates the ERR, and whether the IL-1β production in the PVN is dependent on the ATR-superoxide anion signaling. Experiments were performed in adult rats under anesthesia. The ERR was induced by renal infusion of capsaicin, and evaluated by the responses of the contralateral renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). Inhibition of IL-1β production with MCC950 in the PVN dose-dependently inhibited the capsaicin-induced ERR and sympathetic activation. The PVN microinjection of IL-1 receptor antagonist IL-1Ra or specific IL-1β antibody abolished the capsaicin-induced ERR, while IL-1β enhanced the ERR. Renal infusion of capsaicin promoted p65-NFκB phosphorylation and IL-1β production in the PVN, which were prevented by PVN microinjection of NADPH oxidase inhibitor apocynin or the superoxide anion scavenger tempol. The PVN microinjection of NFκB inhibitor BMS-345541 abolished the capsaicin induced-ERR and IL-1β production, but not the NADPH oxidase activation and superoxide anion production. Furthermore, capsaicin-induced p65-NFκB phosphorylation and IL-1β production in the PVN were prevented by ATR antagonist losartan, or angiotensin converting enzyme inhibitor captopril. These results indicate that capsaicin-induced ERR and sympathetic activation are mediated by IL-1β in the PVN. The IL-1β production in the PVN is dependent on the ATR-mediated superoxide anion generation and NFκB activation.
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http://dx.doi.org/10.1007/s00424-020-02461-7DOI Listing
November 2020

Adjuvant β-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-analysis.

Antimicrob Agents Chemother 2020 10 20;64(11). Epub 2020 Oct 20.

Neurosurgery, People's Hospital of Ningxiang City, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Infections due to methicillin-resistant bacteremia (MRSAB) seriously threaten public health due to poor outcomes and high mortality. The objective of this study is to perform a systematic review and meta-analysis of the current evidence on adjuvant β-lactam (BL) therapy combined with vancomycin (VAN) or daptomycin (DAP) for MRSAB. PubMed, Embase, and Cochrane Library were systematically searched for publications reporting clinical outcomes of BLs+VAN or BLs+DAP for adult patients with MRSAB through 5 April 2020. Meta-analysis techniques were applied using random effects modeling. Three randomized controlled trials and 12 retrospective cohort studies were identified, totaling 2,594 patients. Combination treatment significantly reduced the risk of clinical failure (risk ratio [RR] = 0.80; 95% confidence interval [CI], 0.66 to 0.96;  = 0.02; I = 39%), bacteremia recurrence (RR = 0.66; 95% CI, 0.50 to 0.86;  = 0.002; I = 0%), and persistent bacteremia (RR = 0.65; 95% CI, 0.55 to 0.76;  < 0.00001; I = 0%) and shortened the duration of bacteremia (standardized mean difference [SMD] = -0.37; 95% CI, -0.48 to -0.25;  < 0.00001; I = 0%). There was no significant difference in the risk of crude mortality, nephrotoxicity, or thrombocytopenia between groups. Notably, combination treatment might nonsignificantly increase the risk of infection (CDI) (RR = 2.13; 95% CI, 0.98 to 4.63;  = 0.06; I = 0%). Subgroup analysis suggested that DAP+BLs could reduce crude mortality (RR = 0.53; 95% CI, 0.28 to 0.98;  = 0.04; I = 0%). The meta-analysis suggested that although combination therapy with BLs could improve some microbial outcomes, it could not reduce crude mortality but might increase the risk of CDI and should be applied very cautiously. Regarding mortality reduction, the combination of DAP+cephalosporins appears more promising.
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http://dx.doi.org/10.1128/AAC.01377-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577142PMC
October 2020

Selective dysregulation of ROCK2 activity promotes aberrant transcriptional networks in ABC diffuse large B-cell lymphoma.

Sci Rep 2020 08 4;10(1):13094. Epub 2020 Aug 4.

Autoimmunity and Inflammation Program, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive subtype of lymphoma usually associated with inferior outcomes. ABC-DLBCL exhibits plasmablastic features and is characterized by aberrancies in the molecular networks controlled by IRF4. The signaling pathways that are dysregulated in ABC-DLBCL are, however, not fully understood. ROCK2 is a serine-threonine kinase whose role in lymphomagenesis is unknown. Here we show that ROCK2 activity is constitutively dysregulated in ABC-DLBCL but not in GCB-DLBCL and BL. We furthermore show that ROCK2 phosphorylates IRF4 and that the ROCK2-mediated phosphorylation of IRF4 modulates its ability to regulate a subset of target genes. In addition to its effects on IRF4, ROCK2 also controls the expression of MYC in ABC-DLBCL by regulating MYC protein levels. ROCK inhibition furthermore selectively decreases the proliferation and survival of ABC-DLBCL in vitro and inhibits ABC-DLBCL growth in xenograft models. Thus, dysregulated ROCK2 activity contributes to the aberrant molecular program of ABC-DLBCL via its dual ability to modulate both IRF4- and MYC-controlled gene networks and ROCK inhibition could represent an attractive therapeutic target for the treatment of ABC-DLBCL.
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http://dx.doi.org/10.1038/s41598-020-69884-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403583PMC
August 2020