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1.
Dalton Trans ; 49(39): 13797-13804, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33000838

RESUMO

Three novel phosphorescent iridium(iii) complexes with thieno[2,3-d]pyridazine derivatives as cyclometalating chelates were successfully synthesized. These complexes exhibited intense green or yellow phosphorescence emission with short lifetimes of 1.71-1.91 µs and very high quantum yields of over 85% in PMMA films. Even in air-equilibrated CH2Cl2, their quantum yields could be up to 36%. They also showed good thermal stability with Td > 338 °C. The electronic structure information of these complexes was discussed by density functional theory. The tris-cyclometalated complex Ir1 was an excellent yellow phosphorescent dopant for OLED applications, and the maximum CE and PE based on it were 58.5 cd A-1 and 45.9 lm W-1, respectively, with the maximum EQE of 18.2% which was ca. 1.4 times more efficient than that of PO-01. These results indicate that these new complexes have potential applications as efficient phosphors in OLEDs.

2.
Curr Drug Metab ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33038908

RESUMO

BACKGROUND: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world's scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate of the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). METHOD: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. RESULTS: The vast majority of literatures on preclinical PK of TCM use single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM is still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK of TCM.

3.
Pharmacol Ther ; : 107698, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039419

RESUMO

The contribution of natural products (NPs) to cardiovascular medicine has been extensively documented, and many have been used for centuries. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 40 years, approximately 50% of newly developed cardiovascular drugs were based on NPs, suggesting that NPs provide essential skeletal structures for the discovery of novel medicines. After a period of lower productivity since the 1990s, NPs have recently regained scientific and commercial attention, leveraging the wealth of knowledge provided by multi-omics, combinatorial biosynthesis, synthetic biology, integrative pharmacology, analytical and computational technologies. In addition, as a crucial part of complementary and alternative medicine, Traditional Chinese Medicine has increasingly drawn attention as an important source of NPs for cardiovascular drug discovery. Given their structural diversity and biological activity NPs are one of the most valuable sources of drugs and drug leads. In this review, we briefly described the characteristics and classification of NPs in CVDs. Then, we provide an up to date summary on the therapeutic potential and the underlying mechanisms of action of NPs in CVDs, and the current view and future prospect of developing safer and more effective cardiovascular drugs based on NPs.

4.
Biosens Bioelectron ; 171: 112737, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080464

RESUMO

Olfaction is a synthetic sense in which odor mixtures elicit emergent perceptions at the expense of perceiving the individual components. The most common result of mixing two odors is masking one component by another. However, there is lack of analytical techniques for measuring the sense of smell, which is mediated by cross-odorant interactions. Here, we propose a biohybrid nose for objective and quantitative evaluation of malodor masking efficiency of perfumed products. This biohybrid nose is constructed by integrating mammalian olfactory epithelium with microelectrode array chip to read out the olfactory information as electrical signal from multiple tissue sites. The intrinsic odor response of olfactory epithelium is found to be represented by widespread spatiotemporal oscillatory activity. The masking efficiency of fragrance is quantified by calculating the relative difference between the malodor and the binary mixture (malodor + fragrance) response patterns. Results indicate that masking efficiency of fragrance is concentration-dependent, whereas completely masking may occurs when fragrance is employed at a concentration 2-3 orders of magnitude higher than malodor. This study demonstrates for the first time that capitalizing on the biological sense of smell to create biohybrid system provides an effective technique to resolve more complex biosensing-related issues such as odor interactions in mixtures.

5.
Medicine (Baltimore) ; 99(42): e22738, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080734

RESUMO

BACKGROUND & GOALS: We observed that the number of colorectal polyps found intraoperatively was often higher than that encountered preoperatively during elective colonoscopic polypectomy. To evaluate whether more polyps can be detected when they are purposely sought than when they are routinely examined during colonoscopy. MATERIALS AND METHODS: Patients undergoing colonoscopy were randomized into groups A and B. Before colonoscopy was performed, endoscopists were instructed to seek polyps for group A purposely but not for group B. Polypectomy was electively completed. In groups A and B, the cases of elective polypectomy were named groups AR and BR, including groups AR-1 and BR-1, during the first colonoscopy and groups AR-2 and BR-2 during the second colonoscopy for polypectomy, respectively. The following data were calculated: the number of polyps detected (NPD) and the polyp detection rate (PDR) in all cases and the number of polyps missed (NPM) and partial polyp miss rate (PPMR) in the cases of colorectal polyps. RESULTS: A total of 419 cases were included in group A, 421 in group B, 43 in group AR, and 35 in group BR. No significant differences in PDR were found between groups A and B and in PPMR between groups AR-1 and BR-1 (P > .05), although PPMR in group AR-1 was higher than in group AR-2 (P < .05), similar results were found in PPMR between groups BR-1 and BR-2 (P < .05). CONCLUSION: Purposely seeking for colorectal polyps did not result in more polyps detected compared with routine colonoscopy.

6.
Nanomaterials (Basel) ; 10(10)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081163

RESUMO

A sensitive fluorescence resonance energy transfer (FRET) biosensor is proposed to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a typical DNA oxidation damage product excreted in human urine. The FRET biosensor was based on carbon dots (CDs)-modified nanoporous alumina membrane with CDs as fluorescence donors. Gold nanoparticles were encapsulated in zeolitic imidazolate framework-8 to form Au@ZIF-8 nanoparticles as signal quenchers. CDs and Au@ZIF-8 nanoparticles were biofunctionalized by 8-OHdG antibody. The capture of 8-OHdG on the membrane substrates can bring Au@ZIF-8 nanoparticles closely to CDs. With 350 nm excitation, the fluorescence of CDs was quenched by Au@ZIF-8 nanoparticles and FRET effect occurred. The quenching efficiency was analyzed. The limit of detection (LOD) was 0.31 nM. Interference experiments of the FRET biosensor showed good specificity for 8-OHdG detection. The biosensor could detect urinary 8-OHdG sensitively and selectively with simple sample pretreatment processes. It shows applicability for detecting biomarkers of DNA damage in urine or other biological fluids.

7.
Plant Pathol J ; 36(5): 385-397, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33082723

RESUMO

The ascomycete fungus Colletotrichum gloeosporioides infects a wide range of plant hosts and causes enormous economic losses in the world. The transcription factors (TFs) play an important role in development and pathogenicity of many organisms. In this study, we found that the C2H2 TF CgCrzA is localized in both cytoplasm and nucleus under standard condition, and it translocated from cytoplasm to nucleus in a calcineurin-dependent manner. Moreover, the ΔCgCrzA was hypersensitive to cell wall perturbing agents and showed severe cell wall integrity defects. Deletion of the CgCRZA inhibited the development of invasive structures and lost pathogenicity to plant hosts. Our results suggested that calcineurin-responsive TF CgCrzA was not only involved in regulating cell wall integrity, but also in morphogenesis and virulence in C. gloeosporioides.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33082815

RESUMO

Background: Colla Cornus Cervi (CCC) has been used as a traditional Chinese medicine in the treatment of osteoporosis and osteonecrosis of the femoral head. However, the bioavailability of CCC is seriously limited owing to its large molecular weight and complex ingredients. In the present study, antler polypeptide was separated from CCC, and the effects of antler polypeptide on rat bone marrow mesenchymal stem cells (BMSCs) were investigated. Methods: Antler polypeptide was separated from Colla Cornus Cervi by ultrafiltration into different samples according to the molecular weight. The total peptide content of these samples was determined by the biuret method. The content of antler polypeptide in different samples was quantified by high-performance liquid chromatography (HPLC). The effects of antler polypeptide at different concentrations on the proliferation, cell cycle, alkaline phosphatase activity, and BMP7 expression of BMSCs were investigated. Results: Antler polypeptide was separated by ultrafiltration into different samples: A (molecular weight <800 Da), B (molecular weight 800-1500 Da), and C (molecular weight >1500 Da). The total peptide contents of A, B, and C were 0.602 mg/mL, 8.976 mg/mL, and 38.88 mg/mL. Antler polypeptide B eluted at 14.279∼15.351 min showed that the content of antler polypeptide was significantly higher than that of A and C with a peak area of 933.80927. The BMSCs proliferation rate (84.66%) of polypeptide B was the highest at the concentration of 1.578 × 10-2 g/mL. Antler polypeptide B significantly promoted the proliferation of BMSCs with a proliferation index of 38.68%, which was significantly higher than that of the other groups. Antler polypeptide B significantly enhanced the activity of alkaline phosphatase in BMSCs compared to that of the blank group (P < 0.001). Antler polypeptide B increased the BMP7 protein expression in BMSCs. Conclusions: Results suggested that antler polypeptide may promote the proliferation and osteogenic differentiation of BMSCs. Our study lays an experimental foundation for the further development and application of antler polypeptide in medicine.

9.
Exp Ther Med ; 20(6): 134, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33082866

RESUMO

A number of studies have reported the occurrence of long-term metabolic disorders in mammals following intrauterine growth retardation (IUGR). However, the effects of dietary patterns during IUGR have not been fully elucidated. The present study aimed to evaluate the effects of different dietary patterns during critical growth windows on metabolic outcomes in the offspring of rats with IUGR. Male offspring rats from mothers fed either a normal or low-protein diet were randomly assigned to one of the following groups: Normal diet throughout pregnancy, lactation and after weaning (CON); normal diet throughout pregnancy and high-fat diet throughout lactation and after weaning (N + H + H); low-protein diet throughout pregnancy and high-fat diet throughout lactation and after weaning (IUGR + H + H); low-protein diet throughout pregnancy and lactation and high-fat diet after weaning (IUGR + L + H); and low-protein diet throughout pregnancy and normal diet throughout lactation and after weaning. During lactation, the male offspring in the N + H + H group exhibited the fastest growth rate, whereas the slowest rate was in the IUGR + L + H group. Following weaning, all IUGR groups demonstrated significant catch-up growth. Abnormal insulin tolerance were observed in the N + H + H, IUGR + H + H and IUGR + L + H groups and insulin sensitivity was decreased in IUGR + L + H group. The triglycerides/high-density lipoprotein ratio in the IUGR + L + H group was significantly higher compared with in the other groups. The abdominal circumference, Lee's index and adipocyte diameter of IUGR groups were significantly increased compared with the CON group. High levels of leptin and interleukin-6 in adipose tissues, and low adiponectin were observed in the IUGR + L + H group. Different dietary patterns during specific growth windows showed numerous impacts on glycolipid metabolism in IUGR offspring. The present study elucidated the mechanisms and potential options for IUGR treatment and prevention.

10.
iScience ; 23(10): 101567, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33083734

RESUMO

Specific recording, labeling, and spatiotemporal manipulating neurons are essential for neuroscience research. In this study, we developed a tripartite spatiotemporal gene induction system in C. elegans, which is based on the knockout of two transcriptional terminators (stops in short) by two different recombinases FLP and CRE. The recombinase sites (loxP and FRT) flanked stops after a ubiquitous promoter terminate transcription of target genes. FLP and CRE, induced by two promoters of overlapping expression, remove the stops (subsequent FLP/CRE-out). The system provides an "AND" gate strategy for specific gene expression in single types of cell(s). Combined with an inducible promoter or element, the system can control the spatiotemporal expression of genes in defined cell types, especially in cells or tissues lacking a specific promoter. This tripartite FLP/CRE-out gene expression system is a simple, labor- and cost-saving toolbox for cell type-specific and inducible gene expression in C. elegans.

11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3823-3826, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018834

RESUMO

the purpose of targeted muscle reinnervation (TMR) surgery is to provide more electromyography information for prosthetic control by reconstructing the deconstructed structure between the distal nerve and the stump muscle. Functional electrical stimulation (FES) of denervated muscles or proximal nerve stump after peripheral nerve surgery can effectively promote nerve regeneration and muscle function recovery. This pilot divided SD adult male rats into normal control group, denervation group, TMR group, and FES group according to whether they received TMR surgery and whether they received FES after surgery. The results showed that low-frequency electrical stimulation treatment could effectively promote transplanted nerve regeneration and significantly enhances motor function of target muscles.Clinical Relevance-This experiment successfully established TMR rat models, and explored the recovery of injured neuromuscular function by using electrodes implanted intramuscularly and analyzing myoelectric signals, and the use of low-frequency electrical stimulation treatment had a positive effect on the regeneration of the transplanted nerve.

12.
Sci Total Environ ; 755(Pt 2): 142419, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33049525

RESUMO

Vegetation is a crucial component of terrestrial ecosystems, and its changes are driven mainly by a combination of climate change and human activities. This paper aims to reveal the relationship between vegetation and climate change by using the normalized difference vegetation index (NDVI) and standardized precipitation evapotranspiration index (SPEI), and to find the cause of vegetation change by performing residual analysis on the Loess Plateau during the period from 2000 to 2016. The results showed that the NDVI on the Loess Plateau exhibited an increase of 0.086 per decade, and an increasing trend was observed across 94.86% of the total area. The relationship between the NDVI and SPEI was mainly positive, and the correlation increased as the time scale of the SPEI lengthened, indicating that long-term water availability was the major climate factor affecting vegetation growth. Residual analysis indicated that climate change was responsible for 45.78% of NDVI variation, while human activities were responsible for 54.22%. In areas with degraded vegetation, the relative roles of climate change and human activities were 28.11% and 72.89%, respectively. In addition, the relative role of climate change increased with an increase in the time scales, implying that the long-term NDVI trend was more sensitive to climate change then the short-term trend. The results of this study are expected to enhance our understanding of vegetation changes under climate change and human activities and provide a scientific basis for future ecological restoration in arid regions.

13.
Sci Total Environ ; 755(Pt 1): 142476, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33035973

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is a chemical plasticizer that has been commonly used in the manufacture of polyvinyl chloride. DEHP is one of the environmental pollution sources. In this study, a gram-negative strain RX bacterium utilizing DEHP as sole carbon source was isolated from activated sludge through screening test. This strain RX was identified as Achromobacter sp. RX based on its morphology, physiological properties and 16S rRNA gene sequence analysis. The results showed that the optimal conditions for the DEHP degradation were 30.0 °C and pH 7.0. The DEHP degradation induced by strain RX demonstrated nitrogen source dependent, while followed a decreasing degradation rate under the source of: NO3- > NH4+ > NO2-. The biodegradability of Achromobacter sp. RX was enhanced with Masson pine seed powder as a co-metabolic substrate and Tween-80 as a solubilizing agent. Meanwhile, the degrading kinetics analysis was performed in the condition of DEHP as sole carbon source. The DEHP degradation curves fitted well with the first-order kinetic model at 50-300 mg/L of DEHP, with the half-life ranging from 13.0 to 16.4 h. During the biodegradation of DEHP, mono-(2-ehtylhexyl) phthalate (MEHP) was firstly generated through de-esterification, followed by the formation of phthalic acid and benzoic acid after further de-esterification of MEHP. Benzoic acid was finally mineralized to CO2 and H2O. The decontamination of DEHP-contaminated soil by Achromobacter sp. RX was investigated using a rotating-drum bioreactor. Evolution of total organic carbon from the contaminated soil showed that 86.4%-91.7% of DEHP was mineralized at pH 7.0 and 30.0 °C within 96 h. Reusability of Achromobacter sp. RX and its lifetime were observed over six consecutive cycles. Thus, Achromobacter sp. RX possessed high DEHP biodegradability, which provided a good potential in dealing with DEHP-contaminated soil.

14.
Zootaxa ; 4853(1): zootaxa.4853.1.11, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33056392

RESUMO

Holangus shennongjiaensis sp. nov. from Shennongjia Forestry District, Hubei, China is described and illustrated.

15.
Chem Commun (Camb) ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057501

RESUMO

Correction for 'Pd-Catalyzed oxidative isomerization of propargylic acetates: highly efficient access to α-acetoxyenones via alkenyl Csp2-O bond-forming reductive elimination from PdIV' by Jun Li et al., Chem. Commun., 2016, 52, 10644-10647, DOI: 10.1039/C6CC04463H.

16.
ACS Sens ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064465

RESUMO

Photoanode sensing platforms with remarkable photoelectrochemical (PEC) response and satisfying visible-light absorption have become the most promising detection systems. Nevertheless, their inevitable electrophilic character limits their expansion in the bioassay because of reductive substances in serum or other body fluids that can severely interfere with the photocurrent to be read. To solve it, a PEC platform-assembled dual-active electrode is designed to realize the separation of biological monitoring from the photoanode. The ferricyanide ([Fe(CN)6]3-)-mediated redox cycle is first proposed to meet the gain and loss electron requirements of the PEC system. It can avoid the self-reaction in the electrolyte caused by the addition of a traditional electron donor and acceptor, for instance, ascorbic acid and hydrogen peroxide. As a consequence, the traditional counter electrode (Pt wire) is replaced by Fe2O3/AgInS2 heterojunction, which can amplify the PEC response of the cathode to meet the requirement of trace analysis. An aptasensor fabricated by the above strategies exhibits convincing data for 17ß-estradiol (E2) detection from which a wide detection range is obtained in 10 fg/mL to 1 µg/mL with a detection limit of 2.74 fg/mL (S/N = 3). These advanced elements show a rosy prospect for environmental monitoring and point-of-care biomarker diagnosis.

17.
Medicine (Baltimore) ; 99(41): e21913, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031257

RESUMO

INTRODUCTION: The incidence of psoriasis vulgaris is increasing worldwide. Chronic recurrence of the disease, as well as accompanying cardiovascular disease, metabolic syndrome, and depression has affected the physical and mental health of these patients. Psoriasis vulgaris is a difficult and major disease in the dermatology field. Short-term curative effects using conventional therapy for psoriasis vulgaris has made major strides. However, traditional Chinese medicine (TCM) treatment has long-term curative advantages for psoriasis vulgaris but lacks the scientific and clinical evidence for its use. This study intends to demonstrate and provide scientific and clinical evidence for the use of TCM to delay the recurrence of psoriasis vulgaris. METHODS AND ANALYSIS: This will be a prospective, multicenter cohort study. We intend to recruit 1521 psoriasis vulgaris patients from 14 hospitals in Beijing, Tianjin, and Hebei. Treatment will be based on the diagnosis specifications and clinical practice guidelines of TCM and conventional therapy. During inclusion and the subsequent follow-up period, doctors through electronic case reports will collect different therapeutic TCM regimens and conventional therapy that were administered. Information on life condition, skin lesions at each visit, World Health Organization Quality of Life Instruments, Zung Self-rating Anxiety Scale, Zung Self-assessment of Depression, laboratory examinations, incidence of new rash and recurrence during the remission and recurrence stages will be recorded. ETHICS AND DISSEMINATION: The clinical trial protocol for this study was approved by the ethics committee of the Beijing hospital of TCM affiliated to capital medical university (Ethics number: 2019BL02-010-02). We will publish and present our results at national and international conferences and in peer-reviewed journals specialized in dermatology. TRIAL REGISTRATION: This protocol has been registered in clinicaltrials. gov (ChiCTR1900021629).


Assuntos
Medicina Tradicional Chinesa , Psoríase/terapia , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos
18.
Biosens Bioelectron ; 170: 112667, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33035902

RESUMO

Electrochemical immunoassays are often used in the detection of biomarkers, and their sensitivity depends on the nature of the substrate and the catalytic activity of the signal amplification platform. In this work, a novel sandwich-type signal amplification strategy with a "gold-plated" organometallic frame (Au/IRMOF-3) as the substrate and the sea cucumber-like Pd@PtRh trimetallic nanomaterial (Pd@PtRh SNRs) as label was fabricated. For the substrate, gold nanoparticles (Au NPs) are stably connected to the free amino groups on the surface of organometallic frame (IRMOF-3), which not only prevent the agglomeration of Au NPs, but also greatly enhance the conductivity of the nanocomposites. The synergy between the two nanomaterials further shows a stronger affinity for the fixation of capture antibodies (Ab1). For the label, the effective high catalytic activity comes from the Pd@PtRh SNRs with a sea cucumber-like morphology. The nano-scale spherical PtRh crystals epitaxially grown on smooth Pd nanorods (Pd NRs) have more catalytically active sites because of the abundant edge and corner atoms, resulting in high catalytic activity and durability towards H2O2 reduction. Choosing calcitonin (PCT) as the target, differential pulse voltammetry (DPV) and amperometric i-t dual-mode detection was used to demonstrate the feasibility of the immunosensor. The results confirmed that the immunosensor exhibits excellent analytical capabilities and is satisfied in the analysis of human serum samples. Therefore, this strategy has great potential in the clinical application of electrochemical immunosensors.

19.
Front Immunol ; 11: 2140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013905

RESUMO

Sepsis is a severe state of infection with high mortality. Pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) initiate dysregulated systemic inflammation upon binding to pattern recognition receptors. Exosomes are endosome-derived vesicles, which carry proteins, lipids and nucleic acids, and facilitate intercellular communications. Studies have shown altered contents and function of exosomes during sepsis. In sepsis, exosomes carry increased levels of cytokines and DAMPs to induce inflammation. Exosomal DAMPs include, but are not limited to, high mobility group box 1, heat shock proteins, histones, adenosine triphosphate, and extracellular RNA. Exosomes released during sepsis have impact on multiple organs, including the lungs, kidneys, liver, cardiovascular system, and central nervous system. Here, we review the mechanisms of inflammation caused by exosomes, and their contribution to multiple organ dysfunction in sepsis.

20.
J Leukoc Biol ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070370

RESUMO

Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern. Neutrophils present in the mononuclear cell fraction of Ficoll gradient separation are called low-density neutrophils (LDNs). Here we report the novel role of eCIRP on LDNs' heterogeneity in sepsis. Sepsis was induced in male C57BL/6 wild-type (WT) and CIRP-/- mice by cecal ligation and puncture (CLP). At 20 h after CLP, LDNs in the blood were isolated by Ficoll gradient separation, followed by staining the cells with anti-Ly6G and anti-CD11b Abs and detection by flow cytometry. Sepsis or recombinant murine CIRP (rmCIRP) injection in mice resulted in significant increase in the frequency (%) and number of Ly6G+ CD11bhi and Ly6G+ CD11blo LDNs in the blood compared to sham- or vehicle-treated mice. At 20 h of CLP, CIRP-/- mice had significantly lower frequency and number of Ly6G+ CD11bhi and Ly6G+ CD11blo LDNs in the blood compared to WT mice. In sepsis mice or rmCIRP-injected mice, compared to Ly6G+ CD11blo LDNs, the expression of CXCR4, ICAM-1, and iNOS and formation of reactive oxygen species, and neutrophil extracellular traps in Ly6G+ CD11bhi LDNs in the blood were significantly increased. Treatment of WT bone marrow-derived neutrophils (BMDNs) with rmCIRP increased Ly6G+ CD11bhi LDN frequency, whereas treatment of TLR4-/- BMDNs with rmCIRP significantly decreased the frequency of Ly6G+ CD11bhi LDNs. BMDNs' stimulation with rmCIRP increased the expression of transcription factors in LDNs. eCIRP induces the formation of a proinflammatory phenotype Ly6G+ CD11bhi of LDNs through TLR4. Targeting eCIRP may provide beneficial outcomes in sepsis by decreasing proinflammatory Ly6G+ CD11bhi LDNs.

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