Publications by authors named "Chaoqun Wang"

94 Publications

PINK1-mediated mitophagy maintains pluripotency through optineurin.

Cell Prolif 2021 May;54(5):e13034

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

Objectives: Dysfunction of autophagy results in accumulation of depolarized mitochondria and breakdown of self-renewal and pluripotency in ESCs. However, the regulators that control how mitochondria are degraded by autophagy for pluripotency regulation remains largely unknown. This study aims to dissect the molecular mechanisms that regulate mitochondrial homeostasis for pluripotency regulation in mouse ESCs.

Materials And Methods: Parkin and parkin ESCs were established from E3.5 blastocysts of parkin x parkin mating mice. The pink1 , optn and ndp52 ESCs were generated by CRISPR-Cas9. shRNAs were used for function loss assay of target genes. Mito-Keima, ROS and ATP detection were used to investigate the mitophagy and mitochondrial function. Western blot, Q-PCR, AP staining and teratoma formation assay were performed to evaluate the PSC stemness.

Results: PINK1 or OPTN depletion impairs the degradation of dysfunctional mitochondria during reprogramming, and reduces the reprogramming efficiency and quality. In ESCs, PINK1 or OPTN deficiency leads to accumulation of dysfunctional mitochondria and compromised pluripotency. The defective mitochondrial homeostasis and pluripotency in pink1 ESCs can be compensated by gain expression of phosphomimetic Ubiquitin (Ub-S65D) together with WT or a constitutively active phosphomimetic OPTN mutant (S187D, S476D, S517D), rather than constitutively inactive OPTN (S187A, S476A, S517A) or a Ub-binding dead OPTN mutant (D477N).

Conclusions: The mitophagy receptor OPTN guards ESC mitochondrial homeostasis and pluripotency by scavenging damaged mitochondria through TBK1-activated OPTN binding of PINK1-phosphorylated Ubiquitin.
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http://dx.doi.org/10.1111/cpr.13034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088463PMC
May 2021

A mitophagy inhibitor targeting p62 attenuates the leukemia-initiation potential of acute myeloid leukemia cells.

Cancer Lett 2021 Apr 13;510:24-36. Epub 2021 Apr 13.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, PUMC Department of Stem Cell and Regenerative Medicine, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. Electronic address:

There has been an increasing focus on the tumorigenic potential of leukemia initiating cells (LICs) in acute myeloid leukemia (AML). Despite the important role of selective autophagy in the life-long maintenance of hematopoietic stem cells (HSCs), cancer progression, and chemoresistance, the relationship between LICs and selective autophagy remains to be fully elucidated. Sequestosome 1 (SQSTM1), also known as p62, is a selective autophagy receptor for the degradation of ubiquitinated substrates, and its loss impairs leukemia progression in AML mouse models. In this study, we evaluated the underlying mechanisms of mitophagy in the survival of LICs with XRK3F2, a p62-ZZ inhibitor. We demonstrated that XRK3F2 selectively impaired LICs but spared normal HSCs in both mouse and patient-derived tumor xenograft (PDX) AML models. Mechanistically, we observed that XRK3F2 blocked mitophagy by inhibiting the binding of p62 with defective mitochondria. Our study not only evaluated the effectiveness and safety of XRK3F2 in LICs, but also demonstrated that mitophagy plays an indispensable role in the survival of LICs during AML development and progression, which can be impaired by blocking p62.
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http://dx.doi.org/10.1016/j.canlet.2021.04.003DOI Listing
April 2021

Therapeutic targeting of FOS in mutant cancers through removing TERT suppression of apoptosis via regulating and .

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes, and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287

The telomerase reverse transcriptase (TERT) has long been pursued as a direct therapeutic target in human cancer, which is currently hindered by the lack of effective specific inhibitors of TERT. The FOS/GABPB/(mutant) cascade plays a critical role in the regulation of mutant , in which FOS acts as a transcriptional factor for to up-regulate the expression of GABPB, which in turn activates mutant but not wild-type promoter, driving TERT-promoted oncogenesis. In the present study, we demonstrated that inhibiting this cascade by targeting FOS using FOS inhibitor T-5224 suppressed mutant cancer cells and tumors by inducing robust cell apoptosis; these did not occur in wild-type cells and tumors. Mechanistically, among 35 apoptotic cascade-related proteins tested, the apoptosis induced in this process specifically involved the transcriptional activation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 () and inactivation of two key players in the apoptotic cascade, which normally initiate and suppress the apoptotic cascade, respectively. These findings with suppression of FOS were reproduced by direct knockdown of TERT and prevented by prior knockdown of TRAIL-R2. Further experiments demonstrated that TERT acted as a direct transcriptional factor of up-regulating its expression. Thus, this study identifies a therapeutic strategy for promoter mutation-driven cancers by targeting FOS in the FOS/GABPB/(mutant) cascade, circumventing the current challenge in pharmacologically directly targeting TERT itself. This study also uncovers a mechanism through which TERT controls cell apoptosis by transcriptionally regulating two key players in the apoptotic cascade.
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http://dx.doi.org/10.1073/pnas.2022779118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980366PMC
March 2021

The F-box protein MIO1/SLB1 regulates organ size and leaf movement in Medicago truncatula.

J Exp Bot 2021 Apr;72(8):2995-3011

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, CAS Center for Excellence for Molecular Plant Sciences, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, Yunnan, China.

The size of leaf and seed organs, determined by the interplay of cell proliferation and expansion, is closely related to the final yield and quality of forage and crops. Yet the cellular and molecular mechanisms underlying organ size modulation remain poorly understood, especially in legumes. Here, MINI ORGAN1 (MIO1), which encodes an F-box protein SMALL LEAF AND BUSHY1 (SLB1) recently reported to control lateral branching in Medicago truncatula, was identified as a key regulator of organ size. We show that loss-of-function of MIO1/SLB1 severely reduced organ size. Conversely, plants overexpressing MIO1/SLB1 had enlarged organs. Cellular analysis revealed that MIO1/SLB1 controlled organ size mainly by modulating primary cell proliferation during the early stages of leaf development. Biochemical analysis revealed that MIO1/SLB1 could form part of SKP1/Cullin/F-box (SCF) E3 ubiquitin ligase complex, to target BIG SEEDS1 (BS1), a repressor of primary cell division, for degradation. Interestingly, we found that MIO1/SLB1 also played a key role in pulvinus development and leaf movement by modulating cell proliferation of the pulvinus as leaves developed. Our study not only demonstrates a conserved role of MIO1/SLB1 in the control of organ size in legumes, but also sheds light on the novel function of MIO1/SLB1 in leaf movement.
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http://dx.doi.org/10.1093/jxb/erab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023213PMC
April 2021

The geometry of the compound leaf plays a significant role in the leaf movement of Medicago truncatula modulated by mtdwarf4a.

New Phytol 2021 04 16;230(2):475-484. Epub 2021 Feb 16.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, CAS Center for Excellence in Molecular Plant Sciences, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, 88 Xuefu Road, Kunming, Yunnan, 650223, China.

In most legumes, two typical features found in leaves are diverse compound forms and the pulvinus-driven nyctinastic movement. Many genes have been identified for leaf-shape determination, but the underlying nature of leaf movement as well as its association with the compound form remains largely unknown. Using forward-genetic screening and whole-genome resequencing, we found that two allelic mutants of Medicago truncatula with unclosed leaflets at night were impaired in MtDWARF4A (MtDWF4A), a gene encoding a cytochrome P450 protein orthologous to Arabidopsis DWARF4. The mtdwf4a mutant also had a mild brassinosteroid (BR)-deficient phenotype bearing pulvini without significant deficiency in organ identity. Both mtdwf4a and dwf4 could be fully rescued by MtDWF4A, and mtdwf4a could close their leaflets at night after the application of exogenous 24-epi-BL. Surgical experiments and genetic analysis of double mutants revealed that the failure to exhibit leaf movement in mtdwf4a is a consequence of the physical obstruction of the overlapping leaflet laminae, suggesting a proper geometry of leaflets is important for their movement in M. truncatula. These observations provide a novel insight into the nyctinastic movement of compound leaves, shedding light on the importance of open space for organ movements in plants.
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http://dx.doi.org/10.1111/nph.17198DOI Listing
April 2021

The Medium-Term Impact of COVID-19 Lockdown on Referrals to Secondary Care Mental Health Services: A Controlled Interrupted Time Series Study.

Front Psychiatry 2020 26;11:585915. Epub 2020 Nov 26.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

To date, there is a paucity of information regarding the effect of COVID-19 or lockdown on mental disorders. We aimed to quantify the medium-term impact of lockdown on referrals to secondary care mental health clinical services. We conducted a controlled interrupted time series study using data from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment population ~0.86 million). The UK lockdown resulted in an instantaneous drop in mental health referrals but then a longer-term acceleration in the referral rate (by 1.21 referrals per day per day, 95% confidence interval [CI] 0.41-2.02). This acceleration was primarily for urgent or emergency referrals (acceleration 0.96, CI 0.39-1.54), including referrals to liaison psychiatry (0.68, CI 0.35-1.02) and mental health crisis teams (0.61, CI 0.20-1.02). The acceleration was significant for females (0.56, CI 0.04-1.08), males (0.64, CI 0.05-1.22), working-age adults (0.93, CI 0.42-1.43), people of White ethnicity (0.98, CI 0.32-1.65), those living alone (1.26, CI 0.52-2.00), and those who had pre-existing depression (0.78, CI 0.19-1.38), severe mental illness (0.67, CI 0.19-1.15), hypertension/cardiovascular/cerebrovascular disease (0.56, CI 0.24-0.89), personality disorders (0.32, CI 0.12-0.51), asthma/chronic obstructive pulmonary disease (0.28, CI 0.08-0.49), dyslipidemia (0.26, CI 0.04-0.47), anxiety (0.21, CI 0.08-0.34), substance misuse (0.21, CI 0.08-0.34), or reactions to severe stress (0.17, CI 0.01-0.32). No significant post-lockdown acceleration was observed for children/adolescents, older adults, people of ethnic minorities, married/cohabiting people, and those who had previous/pre-existing dementia, diabetes, cancer, eating disorder, a history of self-harm, or intellectual disability. This evidence may help service planning and policy-making, including preparation for any future lockdown in response to outbreaks.
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http://dx.doi.org/10.3389/fpsyt.2020.585915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726266PMC
November 2020

β-Conglycinin induces the formation of neutrophil extracellular traps dependent on NADPH oxidase-derived ROS, PAD4, ERK1/2 and p38 signaling pathways in mice.

Food Funct 2021 Jan 8;12(1):154-161. Epub 2020 Dec 8.

College of Life Sciences and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China.

β-Conglycinin is one of the key thermostable anti-nutritional factors in soybean, which has strong immunogenicity that usually leads to weaning in some young animals such as piglets and calves and allergic reaction in rats. Neutrophils are involved in the pathogenesis of an allergy. However, the contribution of functional neutrophils to allergy needs to be clarified. The formation of neutrophil extracellular traps is a novel effector mechanism of neutrophils and has been extensively investigated in recent years. To the best of our knowledge, there is no information available on β-conglycinin-induced NETs. In this study, β-conglycinin-induced NET formation in mice was examined via immunofluorescence analysis and fluorescence microplate reader. The mechanism of β-conglycinin-induced NETs was investigated using inhibitors and fluorescent microplate methods. The results showed that β-conglycinin induced the classical characteristics of NETs, which mainly consist of DNA as the backbone and decorated with histones, myeloperoxidase (MPO) and neutrophil elastase (NE). Moreover, β-conglycinin significantly induced the formation of NETs in a dose-dependent way. NET degrading enzyme DNase I markedly reduced β-conglycinin-induced NETs, which suggests that β-conglycinin indeed triggered the release of NETs. Further investigation showed that the quantitation of NETs was markedly decreased by the inhibitors of reactive oxygen species (ROS)-derived-NADPH oxidase, ERK1/2, p38, Rac and PAD4 signaling pathways, indicating the crucial role of these signaling pathways in β-conglycinin-induced NETs. Furthermore, our findings revealed that β-conglycinin induced the formation of NETs, which is dependent on NADPH oxidase-derived ROS, ERK1/2, p38, Rac and PAD4 signaling pathways. This study is the first to demonstrate the underlying mechanisms of β-conglycinin-induced NET formation, and it could be helpful to understand diarrhea caused by β-conglycinin overexposure in young animals and provides the corresponding theoretical basis for clinical applications.
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http://dx.doi.org/10.1039/d0fo02337jDOI Listing
January 2021

The WOX family transcriptional regulator SlLAM1 controls compound leaf and floral organ development in Solanum lycopersicum.

J Exp Bot 2021 Feb;72(5):1822-1835

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, CAS Center for Excellence for Molecular Plant Sciences, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, Yunnan, China.

Plant-specific WOX family transcription factors play important roles ranging from embryogenesis to lateral organ development. The WOX1 transcription factors, which belong to the modern clade of the WOX family, are known to regulate outgrowth of the leaf blade specifically in the mediolateral axis; however, the role of WOX1 in compound leaf development remains unknown. Phylogenetic analysis of the whole WOX family in tomato (Solanum lycopersicum) indicates that there are 10 members that represent the modern, intermediate, and ancient clades. Using phylogenetic analysis and a reverse genetic approach, in this study we identified SlLAM1 in the modern clade and examined its function and tissue-specific expression pattern. We found that knocking out SlLAM1 via CRISPR/Cas9-mediated genome editing led to narrow leaves and a reduced number of secondary leaflets. Overexpression of tomato SlLAM1 could rescue the defects of the tobacco lam1 mutant. Anatomical and transcriptomic analyses demonstrated that floral organ development, fruit size, secondary leaflet initiation, and leaf complexity were altered due to loss-of-function of SlLAM1. These findings demonstrate that tomato SlLAM1 plays an important role in the regulation of secondary leaflet initiation, in addition to its conserved function in blade expansion.
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http://dx.doi.org/10.1093/jxb/eraa574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921304PMC
February 2021

The PGC1α/NRF1-MPC1 axis suppresses tumor progression and enhances the sensitivity to sorafenib/doxorubicin treatment in hepatocellular carcinoma.

Free Radic Biol Med 2021 Feb 1;163:141-152. Epub 2020 Dec 1.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:

Targeting energy metabolism holds the potential to effectively treat a variety of malignant diseases, and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) is a key regulator of energy metabolism. However, PGC1α's role in cancer, especially in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we reported that PGC1α was significantly downregulated in HCC cell lines and specimens. Moreover, reduced expression of PGC1α in tumor cells was correlated with poor prognosis. PGC1α overexpression substantially inhibited cell proliferation and induced apoptosis in vitro and in vivo. On the contrary, the knockdown of PGC1α produced the opposite effect. The mechanism was at least partially due to the upregulation of mitochondrial pyruvate carrier 1 (MPC1) caused by PGC1α, which promoted mitochondrial biogenesis by binding to nuclear respiratory factor 1 (NRF1). Consequently, the production of cellular reactive oxygen species (ROS) caused by mitochondrial oxidation was elevated above a critical threshold for survival. Furthermore, we found that PGC1α could enhance the antitumor activity of sorafenib and doxorubicin in HCC through ROS accumulation-mediated cell death. These results indicate that PGC1α/NRF1-MPC1 axis is involved in HCC progression and could be a promising target for HCC treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.035DOI Listing
February 2021

Soil organic carbon fractions, C-cycling hydrolytic enzymes, and microbial carbon metabolism in Chinese fir plantations.

Sci Total Environ 2021 Mar 24;758:143695. Epub 2020 Nov 24.

Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China; State Key Laboratory of Tree Genetics and Breeding, Chinese Academy of Forestry, Beijing 100091, China; Key Laboratory of Tree Breeding and Cultivation of State Forestry Administration, Chinese Academy of Forestry, Beijing 100091, China. Electronic address:

The mechanisms by which planting density affects soil organic carbon (SOC) fractions, C-cycling associated hydrolytic enzyme activities, and microbial carbon metabolism remain unclear. We evaluated the influences of five planting densities (D1: 1667 stems·ha, D2: 3333 stems·ha, D3: 4444 stems·ha, D4: 5000 stems·ha, and D5: 6667 stems·ha) on the concentrations of SOC, microbial biomass carbon (MBC), easily oxidizable carbon (EOC), and dissolved organic carbon (DOC), the activities of invertase, cellulase, and β-glucosidase, and microbial carbon metabolism activities in 5- and 35-year-old Chinese fir plantations. Generally, no significant differences in the SOC and DOC concentrations among five planting densities in 5-year-old plantations were found, but the SOC and DOC were significantly higher in high-density plantations (D3, D4, and D5) than in low-density plantations (D1 and D2) in 35-year-old plantations. The EOC concentration in low-density plantations was lower than that in high-density plantations in both 5- and 35-year-old plantations. The high planting density was associated with higher MBC, activities of invertase and β-glucosidase, and microbial carbon metabolism activity in 5-year-old plantations, but the opposite was found in 35-year-old plantations. The high-density plantations exhibited a significant decrease in cellulase activity in 35-year-old plantations. These results highlight that although increased planting density would enrich SOC storage after a long-term rotation of plantations, it also reduces microbial and enzymatic activities. This has important implications in the formulation of planting density management strategies to increase SOC stocks while maintaining soil fertility.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143695DOI Listing
March 2021

Efficient Suppression of Chain Transfer and Branching via C -Type Shielding in a Neutral Nickel(II) Catalyst.

Angew Chem Int Ed Engl 2021 Feb 23;60(8):4018-4022. Epub 2020 Dec 23.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun, 130022, China.

An effective shielding of both apical positions of a neutral Ni active site is achieved by dibenzosuberyl groups, both attached via the same donors' N-aryl group in a C -type arrangement. The key aniline building block is accessible in a single step from commercially available dibenzosuberol. This shielding approach suppresses chain transfer and branch formation to such an extent that ultrahigh molecular weight polyethylenes (5×10  g mol ) are accessible, with a strictly linear microstructure (<0.1 branches/1000C). Key features of this highly active (4.3×10  turnovers h ) catalyst are an exceptionally facile preparation, thermal robustness (up to 90 °C polymerization temperature), ability for living polymerization and compatibility with THF as a polar reaction medium.
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http://dx.doi.org/10.1002/anie.202013069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898505PMC
February 2021

SLC7A11/xCT in cancer: biological functions and therapeutic implications.

Am J Cancer Res 2020 1;10(10):3106-3126. Epub 2020 Oct 1.

Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou 310016, Zhejiang, China.

Amino acid transporters mediate substrates across cellular membranes and their fine-tuned regulations are critical to cellular metabolism, growth, and death. As the functional component of system Xc-, which imports extracellular cystine with intracellular glutamate release at a ratio of 1:1, SLC7A11 has diverse functional roles in regulating many pathophysiological processes such as cellular redox homeostasis, ferroptosis, and drug resistance in cancer. Notably, accumulated evidence demonstrated that SLC7A11 is overexpressed in many types of cancers and is associated with patients' poor prognosis. As a result, SLC7A11 becomes a new potential target for cancer therapy. In this review, we first briefly introduce the structure and function of SLC7A11, then discuss its pathological role in cancer. We next summarize current available data of how SLC7A11 is subjected to fine regulations at multiple levels. We further describe the potential inhibitors of the SLC7A11 and their roles in human cancer cells. Finally, we propose novel insights for future perspectives on the modulation of SLC7A11, as well as possible targeted strategies for SLC7A11-based anti-cancer therapies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642655PMC
October 2020

Microstructure of the hyoid bone based on micro-computed tomography findings.

Medicine (Baltimore) 2020 Oct;99(44):e22246

Human Anatomy Teaching and Research Section (Digital Medical Center), Inner Mongolia Medical University Basic Medical College.

In this study, micro-CT was used to observe the microscopic anatomy of the hyoid bone, examine the variation of the trabecular bone inside the hyoid bone, and investigate the internal structure of the hyoid bone.A total of 22 hyoid bones were scanned using micro-CT. The changes in the internal bone trabeculae were assessed with 3D reconstructions, and the fine anatomical structure of the hyoid bone was further analyzed.Micro-CT images showed the microstructure of various parts of the hyoid bone. There were significant differences in total volume, bone volume, bone area, bone density, and volume fraction between the body and greater horns of the hyoid bone (P < .05), but no significant differences in the ratio of bone area/volume and bone surface density were found between the body and greater horns of the hyoid bone (P > .05). In addition, significant differences in the trabecular bone measurements, bone trabecular connectivity, and Euler number were found between the body and greater horns of the hyoid bone (P < .05). Other parameters, including bone trabecular thickness, number of trabecular bones, bone trabecular structure model index, and anisotropy of bone trabeculae, did not differ between the body and greater horns of the hyoid bone (P > .05). There was noticeably ossified healing at the joint between the body and greater horns of the hyoid bone.Micro-CT can adequately display the internal structure of the hyoid bone. The identified bone structure may help clarify the physiological function of the hyoid bone. The present findings provide a theoretical basis for further studies aimed at pathological changes due to hyoid injury in clinical and forensic medicine.
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http://dx.doi.org/10.1097/MD.0000000000022246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598853PMC
October 2020

Triggers Neutrophil Extracellular Traps Release in Dogs.

Front Cell Infect Microbiol 2020 25;10:429. Epub 2020 Sep 25.

College of Life Sciences and Engineering, Foshan University, Foshan, China.

() can cause zoonotic toxoplasmosis worldwide. Neutrophil extracellular traps (NETs) have been known as a novel effector mechanism against infection in the innate system of humans, cats, and sheep. Dogs are the intermediate host of , in which the use of NETs against infection remains unclear. Thus, this study aims to examine the effects of on NETs release in dogs, and to further investigate the mechanism involved in the process. -triggered NETs were analyzed by scanning electron microscopy (SEM) and fluorescence confocal microscopy, and the mechanism of -triggered NETs release was determined by using inhibitors and a fluorometric reader. The results showed that tachyzoites significantly triggered NETs-like structures, which consisted of DNA decorated with neutrophil elastase (NE) and myeloperoxidase (MPO). Further investigations revealed that reactive oxygen species (ROS)-, NADPH oxidase-, Rac 1- or p38 mitogen-activated protein kinase (MAPK)-signaling pathways were relevant to tachyzoites-triggered NETs release. Moreover, zymosan-triggered NETs release was strikingly degraded by tachyzoites treatment, indicating that may escape from the NETs-based capture strategy. Taken together, promoting NETs release is suggested to limit motility and evade infection of in dogs.
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http://dx.doi.org/10.3389/fcimb.2020.00429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546211PMC
September 2020

Gli1 mesenchymal stromal cells form a pathological niche to promote airway progenitor metaplasia in the fibrotic lung.

Nat Cell Biol 2020 11 12;22(11):1295-1306. Epub 2020 Oct 12.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cardiovascular Research Institute, San Francisco, CA, USA.

Aberrant epithelial reprogramming can induce metaplastic differentiation at sites of tissue injury that culminates in transformed barriers composed of scar and metaplastic epithelium. While the plasticity of epithelial stem cells is well characterized, the identity and role of the niche has not been delineated in metaplasia. Here, we show that Gli1 mesenchymal stromal cells (MSCs), previously shown to contribute to myofibroblasts during scarring, promote metaplastic differentiation of airway progenitors into KRT5 basal cells. During fibrotic repair, Gli1 MSCs integrate hedgehog activation signalling to upregulate BMP antagonism in the progenitor niche that promotes metaplasia. Restoring the balance towards BMP activation attenuated metaplastic KRT5 differentiation while promoting adaptive alveolar differentiation into SFTPC epithelium. Finally, fibrotic human lungs demonstrate altered BMP activation in the metaplastic epithelium. These findings show that Gli1 MSCs integrate hedgehog signalling as a rheostat to control BMP activation in the progenitor niche to determine regenerative outcome in fibrosis.
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http://dx.doi.org/10.1038/s41556-020-00591-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642162PMC
November 2020

Cl-amidine attenuates lipopolysaccharide-induced mouse mastitis by inhibiting NF-κB, MAPK, NLRP3 signaling pathway and neutrophils extracellular traps release.

Microb Pathog 2020 Dec 24;149:104530. Epub 2020 Sep 24.

College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China. Electronic address:

Cl-amidine, a peptidylarginine deiminase inhibitor, has been shown to ameliorate the disease course and clinical manifestation in variety of disease models. Due to the beneficial effects of Cl-amidine, it has been becoming the hottest compound for the study in inflammatory diseases. However, the anti-inflammatory activity of Cl-amidine in lipopolysaccharide (LPS)-induced mouse mastitis remains unclear. In this study, we investigated the effects of Cl-amidine on LPS-induced mastitis mouse model. The mouse mastitis model was established by injection of LPS through the canals of the mammary gland. Cl-amidine was administered intraperitoneally 1 h before LPS treatment. The results showed that Cl-amidine significantly attenuated the damage of the mammary gland, which suppressed the activity of myeloperoxidase (MPO). The real-time PCR results indicated that Cl-amidine inhibited the production of TNF-α, IL-1β and IL-6 in LPS-induced mouse mastitis. Moreover, the western blot results indicated that Cl-amidine decreased the phosphorylation of IκB, p65, p38, ERK and the expression of NLRP3 in LPS-induced mouse mastitis. Furthermore, the neutrophils extracellular traps (NETs) were determined by Quant-iT picogreen dsDNA assay kit®, which suggested that Cl-amidine significantly inhibited the NETs in mouse serum. This study demonstrated that Cl-amidine decreased the pathological injury in LPS-induced mouse mastitis by inhibiting NF-κB, MAPK, NLRP3 signaling pathway and NETs release, which provides a potential candidate for the treatment of mastitis.
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http://dx.doi.org/10.1016/j.micpath.2020.104530DOI Listing
December 2020

Mitogenome of Tolypocladium guangdongense.

Appl Microbiol Biotechnol 2020 Nov 12;104(21):9295-9308. Epub 2020 Sep 12.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China.

Tolypocladium guangdongense is a high-value edible fungus with various medicinal and food safety properties. However, its evolutionary and genetic information is still limited. Mitochondrial genomes are potential models for molecular evolution and phylogenetic studies. In this study, we sequenced the complete mitogenome of T. guangdongense, demonstrating circular sequence of 46,102 bp, containing 14 standard protein-coding genes (PCGs), 2 ribosomal RNA subunit genes, and 28 tRNA genes. Phylogenetic analysis based on mitochondrial genes indicated that T. guangdongense was clustered into the Tolypocladium genus with high support value, based on the core PCG dataset. In addition, rps3 is also a suitable marker in the phylogenetic analysis in Hypocreales. Gene rearrangement analysis indicated that the gene order of PCGs was highly consistent in Hypocreales, and tRNA rearrangement events occurred in most species of Hypocreales; however, the rearrangement rates were not taxonomically correlated. Divergence time estimation based on the old fossil record and previous reports revealed that T. guangdongense originated approximately in the middle Cenozoic (42 Mya, 95% highest posterior density interval: 43-116) with the Tolypocladium genus differentiation. Our results provided more mitogenomic information of T. guangdongense and shed new insights into evolution of the Tolypocladium genus. KEY POINTS: • The general and unique features of T. guangdongense mitogenome are firstly reported. • Phylogenetic analysis further verified the taxonomic status of T. guangdongense. • Divergence time estimation provides more evolutionary information of T. guangdongense.
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http://dx.doi.org/10.1007/s00253-020-10889-1DOI Listing
November 2020

β-catenin represses miR455-3p to stimulate m6A modification of HSF1 mRNA and promote its translation in colorectal cancer.

Mol Cancer 2020 08 24;19(1):129. Epub 2020 Aug 24.

Labortary of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Heat shock transcription factor1 (HSF1) was overexpressed to promote glutaminolysis and activate mTOR in colorectal cancer (CRC). Here, we investigated the mechanism for cancer-specific overexpression of HSF1.

Methods: HSF1 expression was analyzed by chromatin immunoprecipitation, qRT-PCR, immunohistochemistry staining and immunoblotting. HSF1 translation was explored by polysome profiling and nascent protein analysis. Biotin pulldown and m6A RNA immunoprecipitation were applied to investigate RNA/RNA interaction and m6A modification. The relevance of HSF1 to CRC was analyzed in APC and APC HSF1mice.

Results: HSF1 expression and activity were reduced after the inhibition of WNT/β-catenin signaling by pyrvinium or β-catenin knockdown, but elevated upon its activation by lithium chloride (LiCl) or β-catenin overexpression. There are much less upregulated genes in HSF1-KO MEF treated with LiCl when compared with LiCl-treated WT MEF. HSF1 protein expression was positively correlated with β-catenin expression in cell lines and primary tissues. After β-catenin depletion, HSF1 mRNA translation was impaired, accompanied by the reduction of its m6A modification and the upregulation of miR455-3p, which can interact with 3'-UTR of HSF1 mRNA to repress its translation. Interestingly, inhibition of miR455-3p rescued β-catenin depletion-induced reduction of HSF1 m6A modification and METTL3 interaction. Both the size and number of tumors were significantly reduced in APC mice when HSF1 was genetically knocked-out or chemically inhibited.

Conclusions: β-catenin suppresses miR455-3p generation to stimulate m6A modification and subsequent translation of HSF1 mRNA. HSF1 is important for β-catenin to promote CRC development. Targeting HSF1 could be a potential strategy for the intervention of β-catenin-driven cancers.
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http://dx.doi.org/10.1186/s12943-020-01244-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446108PMC
August 2020

A study of male fertility control in Medicago truncatula uncovers an evolutionarily conserved recruitment of two tapetal bHLH subfamilies in plant sexual reproduction.

New Phytol 2020 11 25;228(3):1115-1133. Epub 2020 Jul 25.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.

Male sterility is an important tool for plant breeding and hybrid seed production. Male-sterile mutants are largely due to an abnormal development of either the sporophytic or gametophytic anther tissues. Tapetum, a key sporophytic tissue, provides nutrients for pollen development, and its delayed degeneration induces pollen abortion. Numerous bHLH proteins have been documented to participate in the degeneration of the tapetum in angiosperms, but relatively little attention has been given to the evolution of the involved developmental pathways across the phylogeny of land plants. A combination of cellular, molecular, biochemical and evolutionary analyses was used to investigate the male fertility control in Medicago truncatula. We characterized the male-sterile mutant empty anther1 (ean1) and identified EAN1 as a tapetum-specific bHLH transcription factor necessary for tapetum degeneration. Our study uncovered an evolutionarily conserved recruitment of bHLH subfamily II and III(a + c)1 in the regulation of tapetum degeneration. EAN1 belongs to the subfamily II and specifically forms heterodimers with the subfamily III(a + c)1 members, which suggests a heterodimerization mechanism conserved in angiosperms. Our work suggested that the pathway of two tapetal-bHLH subfamilies is conserved in all land plants, and likely was established before the divergence of the spore-producing land plants.
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http://dx.doi.org/10.1111/nph.16770DOI Listing
November 2020

Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats.

Clinics (Sao Paulo) 2020 3;75:e1656. Epub 2020 Jun 3.

Department of Endocrinology, Changhai Hospital, the First Affiliated Hospital of the Naval Medical University, Shanghai 200433, China.

Objectives: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism.

Methods: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR).

Results: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated.

Conclusion: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.
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http://dx.doi.org/10.6061/clinics/2020/e1656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247751PMC
July 2020

Ultrahigh Branching of Main-Chain-Functionalized Polyethylenes by Inverted Insertion Selectivity.

Angew Chem Int Ed Engl 2020 Aug 6;59(34):14296-14302. Epub 2020 Jul 6.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun, 130022, China.

Branched polyolefin microstructures resulting from so-called "chain walking" are a fascinating feature of late transition metal catalysts; however, to date it has not been demonstrated how desirable branched polyolefin microstructures can be generated thereby. We demonstrate how highly branched polyethylenes with methyl branches (220 Me/1000 C) exclusively and very high molecular weights (ca. 10  g mol ), reaching the branch density and microstructure of commercial ethylene-propylene elastomers, can be generated from ethylene alone. At the same time, polar groups on the main chain can be generated by in-chain incorporation of methyl acrylate. Key to this strategy is a novel rigid environment in an α-diimine Pd catalyst with a steric constraint that allows for excessive chain walking and branching, but restricts branch formation to methyl branches, hinders chain transfer to afford a living polymerization, and inverts the regioselectivity of acrylate insertion to a 1,2-mode.
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http://dx.doi.org/10.1002/anie.202004763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496749PMC
August 2020

Swine sperm induces neutrophil extracellular traps that entangle sperm and embryos.

Reproduction 2020 08;160(2):217-225

College of Life Sciences and Engineering, Foshan University, Foshan, Guangdong Province, People's Republic of China.

Sperm motility, fertilization and embryo implantation are several important factors in reproduction. Except healthy state of sperm and embryo themselves, successful pregnancy is closely related to the status of female reproductive tract immune system. Increased immune cells in reproductive tract often leads to low sperm motility and low chance of embryo implantation, but the mechanisms remain not well clarified. The aim of this study is to investigate the direct effects of swine polymorphonuclear neutrophils (PMNs) on sperm or embryo in vitro and then try to clarify the molecular mechanisms undergoing the phenomenon. Swine sperm-triggered neutrophil extracellular traps (NETs) were observed by scanning electron microscopy (SEM). PMNs phagocytosis of sperms was examined by transmission electron microscopy (TEM). Sperm-triggered NETs were quantitated by Pico Green®. Vital staining of the interaction between PMNs and embryo were observed by using confocal microscope. It was showed that PMNs were directly activated by sperm in the form of phagocytosis or casting NETs and that sperm-triggered-NETs formation was made up with DNA co-located with citrullinated histone 3 (citH3) and myeloperoxidase (MPO). In addition, the potential mechanism of NETs release was relevant to NADPH oxidase, ERK1/2 or p38 MAPK signaling pathways. Of great interest was that swine embryo was first found entangled in NETs in vitro, but the function and mechanism of this action in vivo fertilization still needed further investigation. In conclusion, this is the first report about swine sperm-induced NETs that entangle sperm and embryo, which might provide an entirely understanding of swine reproductive physiology and immunology.
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http://dx.doi.org/10.1530/REP-19-0327DOI Listing
August 2020

Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer.

Signal Transduct Target Ther 2020 05 13;5(1):53. Epub 2020 May 13.

Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200040, China.

Enolase 2 (ENO2) is a key glycolytic enzyme in the metabolic process of glycolysis, but its potential function in pancreatic ductal adenocarcinoma (PDAC) is unclear. In this study, we observed a significant overexpression of ENO2 in PDAC tissues, and its expression was correlated with metastasis and poor prognosis in PDAC patients. K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity, cell metabolism and PDAC progression. Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC. Re-expression of wild-type (WT) ENO2, but not the K394 acetylation mimetic mutant, could reverse the decreased tumor malignancy. We further characterized histone deacetylase 3 (HDAC3) and P300/CBP-associated factor (PCAF) as the potential deacetylase and acetyltransferase for ENO2, respectively. HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis. Importantly, insulin-like growth factor-1 (IGF-1) was found to decrease K394 acetylation and stimulate ENO2 activity in a dose- and time-dependent manner. The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424, which promoted K394 deacetylation and activation of ENO2. Linsitinib, an oral small-molecule inhibitor of IGF-1R, could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway. Furthermore, linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2. Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis. Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC.
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http://dx.doi.org/10.1038/s41392-020-0146-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217878PMC
May 2020

Psychiatric referral is required in children with vaginal foreign body injury: A case-control study from China.

J Pediatr Nurs 2020 Jul - Aug;53:e195-e198. Epub 2020 Apr 27.

Department of Pediatrics and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Purpose: The rate of vaginal foreign body (VFB) injury has been increasing in recent years. VFB will cause vaginal inflammation, injury and negative psychological impacts in girls. Our study aimed to elucidate the need of psychological referral in children with VFB.

Design And Methods: A case-control study was performed. A total of 67 girls who visited the clinic due to vaginal foreign bodies were recruited. A questionnaire and Family environment scale-Chinese version (FES-CV) and social anxiety scale for children-Chinese version (SASC-CV) were completed by parents and children. Demographic information, parenting pattern, girls' social anxiety status, and their daily life trajectory and outdoor activities were collected.

Results: The mean age of the 67 girls with VFB was 6.6 ± 2.1 years with a range of 2 years10 months-13 years. The 72 girls of the control group were age-matched with the patients. Scorings in two subscales of FES-CV including family cohesion, emotion expression were significantly lower in the VFB group than those in the control group (7.2 ± 2.4 vs. 7.9 ± 1.7, p < 0.05; 5.2 ± 1.6 vs. 6.5 ± 1.3, p < 0.001). Social anxiety level was higher in the VFB group comparing with the control group. Shorter time of outdoor activities (t = 3.205, p = 0.002) and significantly longer screen time were in the VFB group (t = 5.74, p < 0.001).

Conclusions And Implications: The occurrence of VFB was associated with parenting patterns and social anxiety level. Psychiatric referral is required in children with VFB.
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http://dx.doi.org/10.1016/j.pedn.2020.04.002DOI Listing
April 2021

Systematic studies on dibenzhydryl and pentiptycenyl substituted pyridine-imine nickel(ii) mediated ethylene polymerization.

Dalton Trans 2020 Apr;49(15):4824-4833

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130022, China. and University of Science and Technology of China, Hefei 230026, China.

As the analogues of classical α-diimine nickel catalysts, pyridine-imine nickel catalysts are of great interest for olefin polymerization to produce low molecular weight and branched polyethylenes. In this contribution, pyridine-imine nickel complexes Ni1-Ni4 bearing dibenzhydryl- and pentiptycenyl-N-aryl substituents and H- and Me-imine backbones were synthesized and systematically studied for ethylene polymerization. X-ray diffraction studies revealed that Ni1, Ni2 and Ni4 adopted a monoligated/binuclear structure, while Ni3 was found to adopt a monoligated/mononuclear structure, which differed from the bisligated/mononuclear mode reported previously. Upon activation with aluminum reagents such as Et2AlCl, MAO or MMAO, all these nickel complexes displayed very high activities (up to 14 530 kg mol-1 h-1) for ethylene polymerization. Branched (12-69/1000C) polyethylenes with low molecular weights (Mw: 0.7-22.1 kDa) were obtained with internal double bonds as the predominant unsaturated groups. The influences of the catalyst structure, type and amount of cocatalyst, time, temperature, pressure, and polar additive on the catalytic performances were thoroughly investigated.
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http://dx.doi.org/10.1039/d0dt00505cDOI Listing
April 2020

Heterogeneous Iris One-to-One Certification with Universal Sensors based On Quality Fuzzy Inference and Multi-Feature Fusion Lightweight Neural Network.

Sensors (Basel) 2020 Mar 23;20(6). Epub 2020 Mar 23.

Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun 130012, China.

Due to the unsteady morphology of heterogeneous irises generated by a variety of different devices and environments, the traditional processing methods of statistical learning or cognitive learning for a single iris source are not effective. Traditional iris recognition divides the whole process into several statistically guided steps, which cannot solve the problem of correlation between various links. The existing iris data set size and situational classification constraints make it difficult to meet the requirements of learning methods under a single deep learning framework. Therefore, aiming at a one-to-one iris certification scenario, this paper proposes a heterogeneous iris one-to-one certification method with universal sensors based on quality fuzzy inference and a multi-feature entropy fusion lightweight neural network. The method is divided into an evaluation module and a certification module. The evaluation module can be used by different devices to design a quality fuzzy concept inference system and an iris quality knowledge concept construction mechanism, transform human logical cognition concepts into digital concepts, and select appropriate concepts to determine iris quality according to different iris quality requirements and get a recognizable iris. The certification module is a lightweight neural network based on statistical learning ideas and a multi-source feature fusion mechanism. The information entropy of the iris feature label was used to set the iris entropy feature category label and design certification module functions according to the category label to obtain the certification module result. As the requirements for the number and quality of irises changes, the category labels in the certification module function were dynamically adjusted using a feedback learning mechanism. This paper uses iris data collected from three different sensors in the JLU(Jilin University) iris library. The experimental results prove that for the lightweight multi-state irises, the abovementioned problems are ameliorated to a certain extent by this method.
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http://dx.doi.org/10.3390/s20061785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146378PMC
March 2020

Outcome analysis for prediction of intraaortic balloon pump support failure and long-term survival in high-risk patients undergoing mitral valve surgery.

Artif Organs 2020 Aug 25;44(8):827-836. Epub 2020 Mar 25.

Department of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The outcome predictors of intra-aortic balloon pump (IABP) in patients who undergo mitral valve surgery remain unknown. This study aimed to retrospectively review valvular surgery in patients who received an IABP to identify the predictors of failure of IABP support and anticipate the necessary therapy. This retrospective observational study recruited a total of 157 consecutive patients who underwent open-heart mitral valve surgery with IABP implantation intraoperatively or postoperatively. Univariate and multivariate logistic regression analyses were performed to identify the risk factors attributed to 30-day mortality. Follow-up data of survivors were collected to investigate the effect of IABP support to evaluate long-term outcomes. The overall 30-day mortality was 35.7% (56 patients). The following factors that contributed to 30-day mortality included sepsis (P < .001, OR: 5.627, 95%CI: 2.422-11.683); IABP implantation postoperatively rather than intraoperatively (P = .001, OR: 6.395, 95%CI: 2.085-19.511); right heart failure (P = .042, OR: 3.419, 95%CI: 1.225-12.257); and lack of subvalvular apparatus preservation (P = .033, OR: 3.710, 95%CI: 1.094-13.167). Furthermore, follow-up data of these patients showed an estimation of 5-year and 10-year survival rates of 58.9% and 35.7%, respectively. Patients with intraoperative IABP demonstrated better long-term survival outcomes when compared to those with postoperative IABP (χ  = 4.291, P = .038). In summary, this study distinguished the preoperative predictors of 30-day mortality of IABP-support in mitral valve surgery patients. These results indicated that early intervention with IABP should be taken into consideration in case of hemodynamic instability in critically ill patients undergoing mitral valve surgery.
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http://dx.doi.org/10.1111/aor.13669DOI Listing
August 2020

Magnolol Prevents Acute Alcoholic Liver Damage by Activating PI3K/Nrf2/PPARγ and Inhibiting NLRP3 Signaling Pathway.

Front Pharmacol 2019 5;10:1459. Epub 2019 Dec 5.

College of Life Sciences and Engineering, Foshan University, Foshan, China.

Alcoholic liver damage (ALD) is a toxic liver damage caused by excessive drinking. Oxidative stress is one of the most crucial pathogenic factors leading to ALD. Magnolol is one of the main active constituents of traditional Chinese medicine , which has been reported to possess many pharmacological effects including anti-inflammatory, anti-oxidant, and anti-tumor. However, the effects of magnolol on ALD remain unclear. In this study, we firstly evaluated the protective effects of magnolol on ALD, and then tried to clarify the mechanism underlying the pharmacological activities. AST, ALT, GSH-Px, and SOD were detected by respective kits. Histopathological changes of liver tissue were analyzed by H&E staining. The activities of PI3K, Nrf2, and NLRP3 signaling pathways activation were detected by western blotting analysis. It was showed that alcohol-induced ALT and AST levels were significantly reduced by magnolol, but the antioxidant enzymes of GSH-Px and SOD levels were significantly increased. Magnolol attenuated alcohol-induced pathologic damage such as decreasing hepatic cord swelling, hepatocyte necrosis, and inflammatory cell infiltration. Furthermore, it was found that magnolol inhibited oxidative stress through up-regulating the activities of HO-1, Nrf2, and PPARγ and the phosphorylation of PI3K and AKT. And magnolol also decreased inflammatory response by inhibiting the activation of NLRP3inflammasome, caspase-1, and caspase-3 signaling pathway. Above results showed that magnolol could prevent alcoholic liver damage, and the underlying mechanism was through activating PI3K/Nrf2/PPARγ signaling pathways as well as inhibiting NLRP3 inflammasome, which also suggested magnolol might be used as a potential drug for ALD.
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http://dx.doi.org/10.3389/fphar.2019.01459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915046PMC
December 2019

Self-Validated Homogeneous Immunoassay by Single Nanoparticle in-Depth Scrutinization.

Anal Chem 2020 02 17;92(3):2876-2881. Epub 2020 Jan 17.

Analytical & Testing Center , Sichuan University , Chengdu 610064 , China.

The most convenient method for the clinical routine analysis of disease biomarkers is homogeneous immunoassay, which minimizes the requirements for automation and time-/lab-consumption. Despite great success, because sample constituents are not removed by a separation or washing step, a major challenge in conducting homogeneous immunoassays for the practical application is the matrix effect-related inaccuracy. Herein, to guarantee an accurate quantification, a self-validated homogeneous immunoassay was proposed, by simultaneously scrutinizing both frequency and intensity of single gold nanoparticles. The two analytical modes of single particle inductively coupled plasma mass spectrometry (ICPMS) correlated well with each other, resulting in a self-validation mechanism for the accurate immunoassay. Both two modes of the proposed method provided linear ranges of 2 orders of magnitude and LODs of pM level. Thanks to the self-validated strategy and the high tolerance of the matrix effect of ICPMS, the proposed homogeneous immunoassay was successfully demonstrated in a series of human serum samples, with results in good accordance with clinical routine methods.
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http://dx.doi.org/10.1021/acs.analchem.9b05596DOI Listing
February 2020

Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma.

J Cancer 2020 1;11(1):83-91. Epub 2020 Jan 1.

Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Glutathione S-transferase (GST) family members play an important role in detoxification, metabolism and carcinogenesis. The aim of this study is to investigate the effect of Glutathione S-transferase A1 (GSTA1) on the prognosis of HCC and to understand its role in tumor progression and the possible mechanism. GSTA1 in HCC was assessed using immunohistochemical staining, and it was found that HCC patients with better pathological differentiation had higher GSTA1 abundance. Further, high GSTA1 expression was correlated with low AFP, absent PVTT, and early stage TNM for HCC patients. Higher GSTA1 indicated longer overall survival and disease-free survival, while lower GSTA1 indicated poorer prognosis. Subsequently, lentiviral vector carrying GSTA1 gene was successfully constructed and maintained high expression in 97H and SNU449 liver cancer cells. We found that high GSTA1 restrained liver cancer cell proliferation, migration and invasion . Western blot showed that LKB1 and p-AMPK were upregulated while p-mTOR, p-p70 S6 Kinase and MMP-9 were downregulated in high GSTA1 groups. Taken together, high GSTA1 correlated with satisfactory prognosis of HCC. Additionally, GSTA1 may act as a protective factor through suppression of tumorigenesis by targeting AMPK/mTOR in HCC.
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http://dx.doi.org/10.7150/jca.36495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930411PMC
January 2020