Publications by authors named "Li Yu"

4,683 Publications

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Comparative Profiling of Button Mushroom, Agaricus bisporus (Agaricomycetes), Possessing Textural, Antibacterial, Elemental, and Antioxidant Properties in Diverse Collections from China.

Int J Med Mushrooms 2021 ;23(5):79-90

Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, People's Republic of China.

Button mushroom (Agaricus bisporus) is cultured commercially and consumed worldwide for its unique flavor, texture, and culinary qualities. The objective of this study was to assess the textural profile together with the phenolic content and antioxidant, antibacterial, and elemental composition of wild and commercially cultivated A. bisporus from China. Of the six mushroom strains studied, both cultivated strains CCMJ1013 (fresh: 85.8 N/m2; stored: 57.9 N/m2) and CCMJ1343 (fresh: 94.7 N/m2; stored: 52.9 N/m2) recorded elevated hardness. Our results revealed that wild A. bisporus strain CCMJ1363 contained the highest phenolic content (7.840 mg gallic acid equivalents [GAE]/g), followed by CCMJ1361 (7.125 mg GAE/g) and CCMJ1351 (6.709 mg GAE/g). Antioxidant activity was elevated in CCMJ1351 (inhibition concentration at 50% inhibition [IC50] = 1.04 mg/mL) followed by CCMJ1361 (IC50 = 1.67 mg/mL) in the 1,1-diphenyl-2-picrylhydrazyl assay, whereas CCMJ1351 showed the maximum antioxidant activity (353.54 mg Trolox equivalents/g) in the ferric reducing antioxidant power assay. The maximum 2,2'-azobis(2-amidinopropane) di-hydrochloride-induced erythrocyte hemolysis inhibition was found in wild A. bisporus CCMJ1363 (86.09% inhibition) followed by CCMJ1351 (84.45% inhibition). In terms of antibacterial activity, only a wild A. bisporus strain (CCMJ1361) showed antibacterial activity against pathogenic bacteria (Bacillus coli and Staphylococcus aureus). Wild strain CCMJ1110 contained the highest level of zinc and magnesium; CCMJ1361 showed higher levels of calcium and iron, and CCMJ1363 contained a comparatively higher composition of nitrogen, sodium, and aluminum. Therefore, the current study lays a foundation for creating high-performance, culinary-quality, and stress-resistant germplasms in breeding for A. bisporus strains.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2021038270DOI Listing
January 2021

Chemical screening identifies ROCK1 as a regulator of migrasome formation.

Cell Discov 2020 Aug 4;6(1):51. Epub 2020 Aug 4.

Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University, 100191, Beijing, China.

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http://dx.doi.org/10.1038/s41421-020-0179-6DOI Listing
August 2020

Machine learning takes a village: Assessing neighbourhood-level vulnerability for an overdose and infectious disease outbreak.

Int J Drug Policy 2021 Jul 31:103395. Epub 2021 Jul 31.

Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. Electronic address:

Background: Multiple areas in the United States of America (USA) are experiencing high rates of overdose and outbreaks of bloodborne infections, including HIV and hepatitis C virus (HCV), due to non-sterile injection drug use. We aimed to identify neighbourhoods at increased vulnerability for overdose and infectious disease outbreaks in Rhode Island, USA. The primary aim was to pilot machine learning methods to identify which neighbourhood-level factors were important for creating "vulnerability assessment scores" across the state. The secondary aim was to engage stakeholders to pilot an interactive mapping tool and visualize the results.

Methods: From September 2018 to November 2019, we conducted a neighbourhood-level vulnerability assessment and stakeholder engagement process named The VILLAGE Project (Vulnerability Investigation of underlying Local risk And Geographic Events). We developed a predictive analytics model using machine learning methods (LASSO, Elastic Net, and RIDGE) to identify areas with increased vulnerability to an outbreak of overdose, HIV and HCV, using census tract-level counts of overdose deaths as a proxy for injection drug use patterns and related health outcomes. Stakeholders reviewed mapping tools for face validity and community distribution.

Results: Machine learning prediction models were suitable for estimating relative neighbourhood-level vulnerability to an outbreak. Variables of importance in the model included housing cost burden, prior overdose deaths, housing density, and education level. Eighty-nine census tracts (37%) with no prior overdose fatalities were identified as being vulnerable to such an outbreak, and nine of those were identified as having a vulnerability assessment score in the top 25%. Results were disseminated as a vulnerability stratification map and an online interactive mapping tool.

Conclusion: Machine learning methods are well suited to predict neighborhoods at higher vulnerability to an outbreak. These methods show promise as a tool to assess structural vulnerabilities and work to prevent outbreaks at the local level.
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http://dx.doi.org/10.1016/j.drugpo.2021.103395DOI Listing
July 2021

Degranulation enhances presynaptic membrane packing, which protects NK cells from perforin-mediated autolysis.

PLoS Biol 2021 Aug 3;19(8):e3001328. Epub 2021 Aug 3.

Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, United States of America.

Natural killer (NK) cells kill a target cell by secreting perforin into the lytic immunological synapse, a specialized interface formed between the NK cell and its target. Perforin creates pores in target cell membranes allowing delivery of proapoptotic enzymes. Despite the fact that secreted perforin is in close range to both the NK and target cell membranes, the NK cell typically survives while the target cell does not. How NK cells preferentially avoid death during the secretion of perforin via the degranulation of their perforin-containing organelles (lytic granules) is perplexing. Here, we demonstrate that NK cells are protected from perforin-mediated autolysis by densely packed and highly ordered presynaptic lipid membranes, which increase packing upon synapse formation. When treated with 7-ketocholesterol, lipid packing is reduced in NK cells making them susceptible to perforin-mediated lysis after degranulation. Using high-resolution imaging and lipidomics, we identified lytic granules themselves as having endogenously densely packed lipid membranes. During degranulation, lytic granule-cell membrane fusion thereby further augments presynaptic membrane packing, enhancing membrane protection at the specific sites where NK cells would face maximum concentrations of secreted perforin. Additionally, we found that an aggressive breast cancer cell line is perforin resistant and evades NK cell-mediated killing owing to a densely packed postsynaptic membrane. By disrupting membrane packing, these cells were switched to an NK-susceptible state, which could suggest strategies for improving cytotoxic cell-based cancer therapies. Thus, lipid membranes serve an unexpected role in NK cell functionality protecting them from autolysis, while degranulation allows for the inherent lytic granule membrane properties to create local ordered lipid "shields" against self-destruction.
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http://dx.doi.org/10.1371/journal.pbio.3001328DOI Listing
August 2021

Examining Changes to Food and Beverage Availability and Marketing in a Low-Income Community after the Opening of a High-End Supermarket.

Public Health Nutr 2021 Aug 3:1-28. Epub 2021 Aug 3.

Division of Health Policy and Administration, School of Public Health, University of Illinois at Chicago, 1603 W. Taylor St., Chicago, IL, USA 60612.

Objective: In 2016, a Whole Foods Market© opened in the Englewood community of Chicago, IL - a predominately low-income African American community. This study aimed to examine changes to food and beverage availability and marketing in Englewood's existing food stores after the opening of this supermarket.

Design: Quasi-experimental study.

Setting: Two low-income African American communities in Chicago, IL.

Participants: Fieldworkers audited all small grocery and limited-service stores (e.g., convenience stores, liquor stores, dollar/discount stores) located within one-square mile of the new supermarket and a one-square mile area of a demographically comparable community that also lacked a supermarket. Stores were audited before (2016) and after (2017 and 2018) the supermarket opened.

Results: Of the 78 stores audited at baseline, 71.8% were limited-service stores and 85.9% accepted Supplemental Nutrition Assistance Program (SNAP) benefits. Overall, the availability of healthy food and beverage options in nearby small stores was low at baseline and both follow-up periods. Difference-in-Difference regression models revealed a significant increase in 1) the percentage of stores in the intervention community (i.e., Englewood) offering regular cheese and promoting salty snacks at check-out from 2016 - 2017 and 2) the percentage of stores in the comparison community with interior store promotions for other sweetened beverages from 2016 - 2018.

Conclusions: Minimal changes in food and beverage availability and marketing occurred one and two years after the opening of a new supermarket. However, the wide range of staple food items offered by the supermarket expanded healthy food retail in Chicago's Englewood community.
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http://dx.doi.org/10.1017/S1368980021003165DOI Listing
August 2021

TLR7/8 signalling affects X-sperm motility via the GSK3 α/β-hexokinase pathway for the efficient production of sexed dairy goat embryos.

J Anim Sci Biotechnol 2021 Aug 3;12(1):89. Epub 2021 Aug 3.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi, 712100, People's Republic of China.

Background: Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion. To derive greater economic benefit, farmers require more female offspring (does); however, the buck-to-doe offspring sex ratio is approximately 50%. At present, artificial insemination after the separation of X/Y sperm using flow cytometry is the primary means of controlling the sex of livestock offspring. However, flow cytometry has not been successfully utilised for the separation of X/Y sperm aimed at sexing control in dairy goats.

Results: In this study, a novel, simple goat sperm sexing technology that activates the toll-like receptor 7/8 (TLR7/8), thereby inhibiting X-sperm motility, was investigated. Our results showed that the TLR7/8 coding goat X-chromosome was expressed in approximately 50% of round spermatids in the testis and sperm, as measured from cross-sections of the epididymis and ejaculate, respectively. Importantly, TLR7/8 was located at the tail of the X-sperm. Upon TLR7/8 activation, phosphorylated forms of glycogen synthase kinase α/β (GSK3 α/β) and nuclear factor kappa-B (NF-κB) were detected in the X-sperm, causing reduced mitochondrial activity, ATP levels, and sperm motility. High-motility Y-sperm segregated to the upper layer and the low-motility X-sperm, to the lower layer. Following in vitro fertilisation using the TLR7/8-activated sperm from the lower layer, 80.52 ± 6.75% of the embryos were XX females. The TLR7/8-activated sperm were subsequently used for in vivo embryo production via the superovulatory response; nine embryos were collected from the uterus of two does that conceived. Eight of these were XX embryos, and one was an XY embryo.

Conclusions: Our study reveals a novel TLR7/8 signalling mechanism that affects X-sperm motility via the GSK3 α/β-hexokinase pathway; this technique could be used to facilitate the efficient production of sexed dairy goat embryos.
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http://dx.doi.org/10.1186/s40104-021-00613-yDOI Listing
August 2021

Scale- and Slice-aware Net (S aNet) for 3D segmentation of organs and musculoskeletal structures in pelvic MRI.

Magn Reson Med 2021 Aug 2. Epub 2021 Aug 2.

Institute for AI in Medicine, School of Automation, Nanjing University of Information Science and Technology, Nanjing, China.

Purpose: MRI of organs and musculoskeletal structures in the female pelvis presents a unique display of pelvic anatomy. Automated segmentation of pelvic structures plays an important role in personalized diagnosis and treatment on pelvic structures disease. Pelvic organ systems are very complicated, and it is a challenging task for 3D segmentation of massive pelvic structures on MRI.

Methods: A new Scale- and Slice-aware Net ( aNet) is presented for 3D dense segmentation of 54 organs and musculoskeletal structures in female pelvic MR images. A Scale-aware module is designed to capture the spatial and semantic information of different-scale structures. A Slice-aware module is introduced to model similar spatial relationships of consecutive slices in 3D data. Moreover, aNet leverages a weight-adaptive loss optimization strategy to reinforce the supervision with more discriminative capability on hard samples and categories.

Results: Experiments have been performed on a pelvic MRI cohort of 27 MR images from 27 patient cases. Across the cohort and 54 categories of organs and musculoskeletal structures manually delineated, aNet was shown to outperform the UNet framework and other state-of-the-art fully convolutional networks in terms of sensitivity, Dice similarity coefficient and relative volume difference.

Conclusion: The experimental results on the pelvic 3D MR dataset show that the proposed aNet achieves excellent segmentation results compared to other state-of-the-art models. To our knowledge, aNet is the first model to achieve 3D dense segmentation for 54 musculoskeletal structures on pelvic MRI, which will be leveraged to the clinical application under the support of more cases in the future.
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http://dx.doi.org/10.1002/mrm.28939DOI Listing
August 2021

Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma.

Allergol Int 2021 Jul 28. Epub 2021 Jul 28.

Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), The First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China. Electronic address:

Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma.

Methods: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control.

Results: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment.

Conclusions: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.
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http://dx.doi.org/10.1016/j.alit.2021.07.004DOI Listing
July 2021

Elucidating the Mechanism of Fast Na Storage Kinetics in Ether Electrolytes for Hard Carbon Anodes.

Adv Mater 2021 Jul 30:e2008810. Epub 2021 Jul 30.

Beijing Key Laboratory of Environmental Science and Engineering, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.

The sodium storage performance of a hard carbon (HC) anode in ether electrolytes exhibits a higher initial Coulombic efficiency (ICE) and better rate performance compared to conventional ester electrolytes. However, the mechanism behind faster Na storage kinetics for HC in ether electrolytes remains unclear. Herein, a unique solvated Na and Na co-intercalation mechanism in ether electrolytes is reported using designed monodispersed HC nanospheres. In addition, a thin solid electrolyte interphase film with a high inorganic proportion formed in an ether electrolyte is visualized by cryo transmission electron microscopy and depth-profiling X-ray photoelectron spectroscopy, which facilitates Na transportation, and results in a high ICE. Furthermore, the fast solvated Na diffusion kinetics in ether electrolytes are also revealed via molecular dynamics simulation. Owing to the contribution of the ether electrolytes, an excellent rate performance (214 mAh g at 10 A g with an ultrahigh plateau capacity of 120 mAh g ) and a high ICE (84.93% at 1 A g ) are observed in a half cell; in a full cell, an attractive specific capacity of 110.3 mAh g is achieved after 1000 cycles at 1 A g .
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http://dx.doi.org/10.1002/adma.202008810DOI Listing
July 2021

Favorable outcomes after heart transplantation in Barth syndrome.

J Heart Lung Transplant 2021 Jul 10. Epub 2021 Jul 10.

Departments of Pediatrics and Clinical and Translational Science, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address:

Background: Barth Syndrome (BTHS) is a rare, X-linked disease characterized by cardioskeletal myopathy and neutropenia. Comparative outcomes after heart transplantation have not been reported.

Methods: We identified BTHS recipients across 3 registries (Pediatric Heart Transplant Study Registry [PHTS], Barth Syndrome Research Registry and Repository, and Scientific Registry of Transplant Recipient-Pediatric Health Information System) and matched them 1:4 to non-BTHS, male heart transplant (HT) recipients listed with dilated cardiomyopathy in PHTS. Demographics and survival data were analyzed for all recipients, whereas post-HT infection, malignancy, allograft vasculopathy, and acute rejection were only available for analysis for individuals with PHTS data.

Results: Forty-seven BTHS individuals with 51 listings and 43 HTs (including 2 re-transplants) were identified. Age at primary HT was 1.7 years (IQR: 0.6-4.5). Mechanical circulatory support at HT was common (ventricular assist device 29%, extracorporeal membrane oxygenation 5%). Over a median follow-up of 4.5 years (IQR 2.7-9.1), survival for BTHS HT recipients was no different than non-BTHS HT recipients (HR 0.91, 95% CI 0.40-2.12, p = 0.85). Among those with PHTS data (n = 28), BTHS HT recipients showed no difference in freedom from infection (HR 0.64, 0.34-1.22; p = 0.18), malignancy (HR 0.22, 0.02-2.01, p = 0.18), and allograft vasculopathy (HR 0.58, 0.16-2.1, p = 0.41). Freedom from acute rejection (HR 0.39, 0.17-0.86, p = 0.02) was greater for BTHS HT recipients despite similar use of induction (61 vs 73%, p = 0.20), steroids at 30-days (75 vs 62%, p = 0.27), and dual/triple drug immunosuppression at 1-year (80 vs 84%, p = 0.55).

Conclusions: In this largest cohort yet reported, individuals with BTHS have equivalent survival with less acute rejection and no difference in infection or malignancy after HT. When indicated, HT for individuals with BTHS is appropriate.
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http://dx.doi.org/10.1016/j.healun.2021.06.017DOI Listing
July 2021

Perpendicular and turbulent flow in acute aortic paravalvular leak: case report.

Ann Palliat Med 2021 Jul 14. Epub 2021 Jul 14.

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

Paravalvular leaks (PVL) are well-recognized complications after artificial valve replacement and symptomatic periprosthetic leaks are closely associated with increased mobility and mortality. Owing to the difference in types of prosthetic valve and options of suture technique, echocardiography of PVL can be diverse and challenge to diagnose. Herein, we report a patient with continuous low cardiac output syndrome on the second day after surgery after aortic replacement, which was misdiagnosed as coronary-left ventricular fistula by transthoracic echocardiogram (TTE). However, transesophageal echocardiogram (TEE) detected a perpendicular and turbulent jet flow from the outer side of the sewing ring, which was eventually diagnosed as an acute aortic PVL combined with cardiac angiography. The significant PVLs were treated by reoperation previously, while they are recommended for transcatheter closure recently. This patient was received successful percutaneous closure by the Cardi-O-Fix Plug. The cardiac symptom was relieved without additional complications. This report highlights the important role of multi-modality imaging, including the combination of TTE, TEE and cardiac angiography, in the diagnosis and treatment of PVL. Percutaneous closure is an appropriate option for the repair of PVL with long-term symptom relief and reduced mortality compared to reoperation. Therefore, this article describes the diagnosis and treatment of this patient with acute aortic PVL.
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http://dx.doi.org/10.21037/apm-21-698DOI Listing
July 2021

Association of Clinical Severity With Family Affluence-Based Socioeconomic Status Among Hospitalized Pediatric Hand, Foot, and Mouth Disease Patients in Henan, China: A Single Hospital-Based Case Series Study.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab150. Epub 2021 Mar 26.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Background: The association between the clinical severity of hand, foot, and mouth disease (HFMD) inpatients and socioeconomic status (SES) is important for quantifying SES inequality in HFMD disease burden and informing decision-makers regarding medical subsidy and reimbursement policies. Here, this association was investigated using a quantitative SES measurement.

Methods: Laboratory-confirmed HFMD cases hospitalized at Henan Children's Hospital from February 15, 2017, to February 15, 2018, were invited. We utilized the revised Family Affluence Scale for family affluence-based SES measurement. Clinical severity was diagnosed based on central nervous system (CNS) complications, treatments, and length of stay. We applied logistic regression for association analyses and multiple imputation for missing data.

Results: A total of 1229 laboratory-confirmed HFMD inpatients responded. Adjusted by age, sex, rural residence, EV-A71 infection, and health-seeking behavior, CNS complications (odds ratio [OR], 2.72; 95% CI, 1.41-5.31), intensive care unit (ICU) admission (OR, 7.30; 95% CI, 2.21-25.97), and prolonged hospitalization (OR, 4.28; 95% CI, 2.44-7.58) were significantly associated with lower family affluence-based SES. These associations increased as the SES category descended. For EV-A71-infected inpatients, severe HFMD was significantly associated with low and intermediate SES. For non-EV-A71-infected inpatients, only the association of prolonged hospitalization with low SES increased significantly. Also, severe HFMD inpatients, especially those admitted to the ICU, incurred high hospitalization costs.

Conclusions: The clinical severity of HMFD inpatients was significantly associated with family affluence-based SES. Severe HFMD inpatients were more likely to have lower SES than nonsevere inpatients and suffered a heavy economic burden. Therefore, medical subsidy and reimbursement policies should offer sufficient monetary support to severe HFMD inpatients to alleviate economic burden in low-SES populations and reduce potential SES inequality.
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http://dx.doi.org/10.1093/ofid/ofab150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314950PMC
July 2021

Sequencing and Comparative Transcriptome Analyses Provide First Insights Into Polysaccharide Biosynthesis During Fruiting Body Development of .

Front Microbiol 2021 13;12:627099. Epub 2021 Jul 13.

College of Resources, Sichuan Agricultural University, Chengdu, China.

Polysaccharides separated from are well known for their medicinal properties. However, the precise molecular mechanisms of polysaccharide biosynthesis in remain unclear. In this study, the fruiting bodies of in four developmental stages with significant differences in polysaccharide yield were collected, and the characteristics of polysaccharides were studied. sequencing and comparative transcriptomic analysis were performed by using high-throughput Illumina RNA-sequencing. KS1P30, KS2P30, KS3P30, and KS4P30 were obtained from the four developmental stages, respectively, by hot water extraction and 30% ethanol precipitation. These four polysaccharides had good immune activity ; all of them were β-glucopyranose with a high molecular weight. Glucose was the main monosaccharide component of these polysaccharides. High-quality clean reads (57.88, 53.17, 53.28, and 47.56 million for different growth stages) and mapping ratios ranging from 84.75 to 90.11% were obtained. In total, 11,493 (96.56%) unigenes and 18,924 (97.46%) transcripts were successfully annotated in five public databases. The biosynthetic pathway and related genes of LEFP30 were mined. The molecular mechanism of LEFP30 yield change in the different developmental stages was predicted. The results provide some insights into the possible mechanisms involved in the biosynthetic pathway of this kind of polysaccharide in fruiting bodies. They also indicate that candidate genes can be used as important resources for biotechnology and molecular breeding to regulate fruiting body polysaccharide biosynthesis.
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http://dx.doi.org/10.3389/fmicb.2021.627099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313990PMC
July 2021

High-Temperature and Large-Polarization Ferroelectric with Second Harmonic Generation Response in a Novel Crown Ether Clathrate.

Chemistry 2021 Jul 28. Epub 2021 Jul 28.

JiangXi University of Science and Technology, Faculty of Materials Metallurgy and Chemistry, CHINA.

Molecular ferroelectrics of high-temperature reversible phase-transition are very rare and have attracted increasing attention in recent years. In this paper, we have successfully synthesized a novel high-temperature host-guest inclusion ferroelectric: [ (C 6 H 5 NF 3 ) (18-crown-6)][BF 4 ] (1) , which shows a pair of reversible peaks at 348 K (heating) and 331 K (cooling) with a heat hysteresis about 17 K by differential scanning calorimetry (DSC) measurements, indicating that 1 undergoes a reversible structural phase transition. The variable-temperature PXRD and temperature-dependent dielectric measurements further prove the phase-transition behavior of 1 . The second harmonic response demonstrates that 1 belongs to a non-centrosymmetric space group at room temperature and is a good nonlinear optical material. Meanwhile, 1 shows a wide optical band gap of about 4.43 eV in semiconducting property and is chiefly contributed by C, H and O atoms of the crystals. In particular, the ferroelectric measurements of 1 exhibit a typical polarization-electric hysteresis loop with large spontaneous polarization ( P s ) of about 4.06 μC/ cm 2 . This finding offers an alternative pathway for designing new ferroelectric-dielectric and nonlinear optical materials and related physical properties in organic- inorganic and other hybrid crystals.
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http://dx.doi.org/10.1002/chem.202101707DOI Listing
July 2021

Discovery and Bioactivity of the Novel Lasso Peptide Microcin Y.

J Agric Food Chem 2021 Jul 27. Epub 2021 Jul 27.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, People's Republic of China.

Lasso peptides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) secreted by bacteria, have antimicrobial activity. Here, a novel lasso peptide, microcin Y (MccY), was discovered and characterized. The gene cluster for MccY synthesis was cloned for expression in . This peptide was purified by HPLC and characterized by Q-TOF. MIC assays showed that some , , , , and strains were sensitive to MccY. Interestingly, and were efficiently inhibited by MccY, while they were not affected by MccJ25, a lasso peptide that has antibacterial effects on many strains. Furthermore, MccY-resistant strains of were screened, and mutations were found in FhuA and SbmA, indicating the importance of these transporters for MccY absorption. This novel peptide can greatly broaden the antimicrobial spectrum of MccJ25 in and is expected to be used in food preservation and animal feed additive areas.
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http://dx.doi.org/10.1021/acs.jafc.1c02659DOI Listing
July 2021

sp. nov., sp. nov., sp. nov., sp. nov., sp. nov., sp. nov., sp. nov. and sp. nov., isolated from traditional Chinese pickle and the gut of honeybee ().

Int J Syst Evol Microbiol 2021 Jul;71(7)

College of Life Sciences, Northeast Agricultural University, Harbin 150030 PR China.

Thirteen Gram-stain-positive bacterial strains were isolated from Chinese traditional pickle and the gut of honeybee (). These strains were characterized using a polyphasic taxonomic approach. The data demonstrated that 12 of the 13 strains represented eight novel species belonging to the genera , , and ; strains HN36-1, 887-11, F79-211-2, 866-3, 6-5(1), 13B17, 117-1 and ZW152 were designated as the type strains. Based upon the data of polyphasic characterization obtained in the present study, eight novel species, sp. nov., sp. nov., sp. nov., sp. nov., sp. nov., sp. nov., sp. nov. and sp. nov., are proposed and the type strains are HN36-1 (=JCM 33867=CCTCC AB 2019385), 887-11 (=NCIMB 15201=CCM 8950=JCM 33864=CCTCC AB 2018396), F79-211-2 (=NCIMB 15254=JCM 33866=CCTCC AB 2019384), 866-3 (=JCM 33863=CCTCC AB 2019383), 6-5(1) (=NCIMB 15229=CCM 8977=JCM 33564=CCTCC AB 2019168), 13B17 (=NCIMB 15230=CCM 8979=JCM 33565=CCTCC AB 2019167), 117-1 (=NCIMB 15232=CCM 8980=JCM 33567) and ZW152 (=JCM 34363=CCTCC AB 2020299=LMG 32143=CCM 9110), respectively.
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http://dx.doi.org/10.1099/ijsem.0.004898DOI Listing
July 2021

Anti-neoplastic characteristics and potential targets of calycosin against bisphenol A-related osteosarcoma: bioinformatics analysis.

Bioengineered 2021 Dec;12(1):4278-4288

Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Guilin, PR China.

Environmentally, bisphenol A (BPA) is a well-known pollutant caused human health risk, including osteosarcoma (OS). OS, a deadly bone neoplasia, may occur in children and adults. However, the anti-OS pharmacotherapy prescribes limitedly in clinical practice. Interestingly, previous experimental evidences indicate calycosin-exerting potential anti-OS actions. Thus, in this report, we aimed to further characterize and detail the therapeutic targets and molecular mechanisms of calycosin-anti-BPA-related OS by using network pharmacology and molecular docking analyses. In results, the bioinformatics data disclosed all mapped, core targets, biological functions, molecular pathways of calycosin to treat BPA-related OS. The computational analysis using molecular docking indicated that potential binding ability of core targets in calycosin to treat BPA-related OS was identified. Moreover, detailed biological functions and optimal pathways of calycosin-anti-BPA-related OS were revealed, as shown in integrated network maps. Taken together, these network pharmacology and structural biology findings illustrate the core biotargets, pharmacological functions and pathways of calycosin-anti-BPA-related OS. Potentially, these core targets identified by molecular docking may attribute to the potential clinical application of calycosin against BPA-related OS.[Formula: see text].
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http://dx.doi.org/10.1080/21655979.2021.1956401DOI Listing
December 2021

Reliability and validity of the Chinese version of the Head and Neck Information Needs Questionnaire for patients with head and neck cancer and their caregivers.

Int J Nurs Sci 2021 Jul 6;8(3):354-360. Epub 2021 Jun 6.

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

Objectives: This study aimed to assess the reliability and validity of the Chinese version of the Head and Neck Information Needs Questionnaire (HaNiQ).

Methods: The HaNiQ was translated into a Chinese version using internationally recognized forward- and back-translation procedures. The reliability and validity of the HaNiQ were measured using Cronbach's α coefficient, split-half reliability, exploratory factor analysis, and Pearson correlation analysis.

Results: A total of 207 patients in different head and neck cancer (HNC) stages and 174 caregivers completed the Chinese version of the HaNiQ. Internal consistencies varied between good and very well (Cronbach's α coefficient 0.74-0.90); the split-half coefficient and the content validity index (CVI) of the questionnaire were 83.5% and 83.33%, respectively. The cumulative contribution rates of the 5 subscales in patients with HNCand their caregivers were 62.41% and 61.19%, respectively. However, there are some differences between the Chinese questionnaire for caregiver and the original questionnaire regarding the attribution of items. Items 22, 23, and 27 in the Psychosocial subscale of the English version were assigned to the Survivorship subscale in the Chinese version for caregivers.

Conclusions: The results demonstrated that the Chinese version of the HaNiQ is a reliable and valid instrument for measuring the information needs of patients with HNC and that of their caregivers. Though the structure of the Chinese version was different from the English version for caregivers of HNC patients, the Chinese version of the HaNiQ appears to be reliable and would benefit from further testing.
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http://dx.doi.org/10.1016/j.ijnss.2021.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283703PMC
July 2021

Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways.

Bioengineered 2021 Dec;12(1):4475-4488

Pulmonary and Critical Care Medicine of The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-β1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-β1-induced IMR-90 cells. Moreover, the combination of PLB with/without TβRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-β1 induction. For studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-β1/Smad and Akt/mTOR pathways were detected for both and models. PLB effectively inhibited the proliferation and differentiation of TGF-β1-induced IMR-90 cells, and suppressed TGF-β1/Smad and Akt/mTOR signaling pathways both and . Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-β1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS.
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http://dx.doi.org/10.1080/21655979.2021.1954580DOI Listing
December 2021

An efficient cell culture system for the studies of heterogeneous astrocytes: Time gradient digestion.

J Neurosci Methods 2021 Jul 22;362:109292. Epub 2021 Jul 22.

Laboratory of Medical Systems Biology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623 Guangzhou, China; Third Affiliated Hospital of Zhengzhou University, 450052 Zhengzhou, China; School of Medicine, South China University of Technology, 510006 Guangzhou, China. Electronic address:

Background: Astrocytes are the most abundant glial cell type in mammal brain, but there exists a lot of unknown in cell development and cell function. We aim to establish an astrocytes culture system for obtaining highly enriched primary astrocytes from the neonatal mouse brain and separating Aldh1l1Gfap and Aldh1l1Gfap cells.

New Method: C57BL/J6 mouse pups at postnatal 1-4 days were used for cell preparation. Brain cortex was collected and digested with 0.25% trypsin followed by 0.5 mg/ml DNase. Cells were plated on PDL-coated flasks. After 8-10 days culture, cells were shaken at 260 rpm for 4 h at 37 ℃ to remove oligodendrocytes and microglia cells. Time gradient digestion was performed to obtain astrocyte subtypes. The digestion time was 0-2 min and 2-4 min, and 4-6 min. Flow cytometry, Immunostaining, CCK-8 assay and EdU staining was carried out to investigate the purity of the astrocytes, the ability of cell proliferation and to identify different subtypes.

Results: After shaking, percentage of oligodendrocytes significantly decreased from 22.6 ± 3.6% to 7.4 ± 1.4% (CNPase cells) and from 4.36 ± 0.6% to 0.75 ± 0.2% (Pdgfrα cells) while percentage of microglia cells reduced from 4.4 ± 0.2% to 0.6 ± 0.2%. Aldh1l1Gfap astrocytes were the dominant cell types in 0-2 min group while Aldh1l1Gfap astrocytes were the dominant cell types in 2-4 min group. Moreover, compared with Aldh1l1Gfap astrocytes, Aldh1l1Gfap astrocytes had a higher proliferative ability.

Comparison With Existing Methods: Aldh1l1Gfap and Aldh1l1Gfap cells were separated. The percentage of residual Tmem119 and Gfap cells showed no significant difference. However, the percentage of Pdgfrα cells were significant decreased, and the time consuming of the new system was lower. The astrocytes acquired possess higher viability.

Conclusions: A new astrocytes culture system with time gradient digestion was established. Highly enriched primary astrocytes from the neonatal mouse brain were obtained with short shaking time. Aldh1l1Gfap and Aldh1l1Gfap cells were separated by different digestion condition. This system has advantages of high efficiency and low cost, which deserves promising application in management of astrocytes research in central nerve system.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109292DOI Listing
July 2021

Evaluation of GeneXpert PA assay compared to genomic and (semi-)quantitative culture methods for direct detection of Pseudomonas aeruginosa in endotracheal aspirates.

Antimicrob Resist Infect Control 2021 Jul 23;10(1):110. Epub 2021 Jul 23.

Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute , University of Antwerp, Wilrijk, Belgium.

Introduction: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Rapid and accurate detection of lower respiratory tract colonization and/or infection with P. aeruginosa may advise targeted preventive (antibody-based) strategies and antibiotic therapy. To investigate this, we compared semi-quantitative culture results from 80 endotracheal aspirates (ETA) collected from mechanically-ventilated patients, to two culture and two non-culture-based methods for detection of P. aeruginosa.

Methods: P. aeruginosa-positive (n = 40) and -negative (n = 40) ETAs from mechanically ventilated patients analyzed initally by (i) routine semi-quantitative culture, were further analyzed with (ii) quantitative culture on chromogenic ChromID P. aeruginosa and blood agar; (iii) enrichment in brain heart infusion broth followed by plating on blood agar and ChromID P. aeruginosa; (iv) O-antigen acetylase gene-based TaqMan qPCR; and (v) GeneXpert PA PCR assay.

Results: Of the 80 ETA samples included, one sample that was negative for P. aeruginosa by semi-quantitative culture was found to be positive by the other four methods, and was included in an "extended" gold standard panel. Based on this extended gold standard, both semi-quantitative culture and the GeneXpert PA assay showed 97.6% sensitivity and 100% specificity. The quantitative culture, enrichment culture and O-antigen acetylase gene-based TaqMan qPCR had a sensitivity of 97.6%, 89.5%, 92.7%, and a specificity of 97.4%, 100%, and 71.1%, respectively.

Conclusion: This first evaluation of the GeneXpert PA assay with ETA samples found it to be as sensitive and specific as the routine, hospital-based semi-quantitative culture method. Additionally, the GeneXpert PA assay is easy to perform (hands-on time ≈ 5 min) and rapid (≈ 55 min assay time). The combination of the high sensitivity and high specificity together with the rapid acquisition of results makes the GeneXpert PA assay a highly recommended screening technique. Where this equipment is not available, semi-quantitative culture remains the most sensitive of the culture methods evaluated here for P. aeruginosa detection in ETA samples.
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http://dx.doi.org/10.1186/s13756-021-00978-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300976PMC
July 2021

Characterization, Pathogenicity, Phylogeny, and Comparative Genomic Analysis of Pseudomonas tolaasii Strains Isolated from Various Mushrooms in China.

Phytopathology 2021 Jul 22. Epub 2021 Jul 22.

Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, Jilin, China.

Since 2016, devastating bacterial blotch affecting the fruiting bodies of Agaricus bisporus, Cordyceps militaris, Flammulina filiformis, and Pleurotus ostreatus in China has caused severe economic losses. We isolated 102 bacterial strains and characterized them polyphasically. We identified the causal agent as Pseudomonas tolaasii and confirmed the pathogenicity of the strains. A host range test further confirmed the pathogen's ability to infect multiple hosts. This is the first report in China of bacterial blotch in C. militaris caused by P. tolaasii. Whole-genome sequences were generated for three strains: Pt11 (6.48 Mb), Pt51 (6.63 Mb), and Pt53 (6.80 Mb), and pangenome analysis was performed with 13 other publicly accessible P. tolaasii genomes to determine their genetic diversity, virulence, antibiotic resistance, and mobile genetic elements. The pangenome of P. tolaasii is open, and many more gene families are likely to emerge with further genome sequencing. Multilocus sequence analysis using the sequences of four common housekeeping genes (glns, gyrB, rpoB, and rpoD) showed high genetic variability among the P. tolaasii strains, with 115 strains clustered into a monophyletic group. The P. tolaasii strains possess various genes for secretion systems, virulence factors, carbohydrate-active enzymes, toxins, secondary metabolites, and antimicrobial resistance genes that are associated with pathogenesis and adapted to different environments. The myriad of insertion sequences, integrons, prophages, and genome islands encoded in the strains may contribute to genome plasticity, virulence, and antibiotic resistance. These findings advance understanding of the determinants of virulence, which can be targeted for the effective control of bacterial blotch disease.
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http://dx.doi.org/10.1094/PHYTO-12-20-0550-RDOI Listing
July 2021

Surface soil metal elements variability affected by environmental and soil properties.

PLoS One 2021 22;16(7):e0254928. Epub 2021 Jul 22.

College of Resources and Environment, Southwest University, Chongqing, China.

Identifying the factors controlling the spatial variability of soil metal elements could be a challenge task due to the interaction of environmental attributes and human activities. This study aimed to investigate the critical explanatory variables controlling total Ca, Cd, Cr, Cu, Zn, Fe, Mn, Mg, Pb, and Zn variations in the arable topsoil using classical statistics, principal component analysis, and random forest techniques. The work was conducted in the core region of the Three Gorges Reservoir of China. The explanatory variables included soil, topography, climate, vegetation, land use type, and distance-related parameters. Average concentrations of the metal elements were in order of Fe > Mg > Ca > Mn > Zn > Cr > Ni > Pb > Cu > Cd. Soil Cr, Fe, and Pb showed low variability while others presented medium variability. Average concentrations of Cr, Fe, Cd, and Mg exceeded their corresponding background values. There were highly positive correlations between all metal elements except Pb, Cd and Cr. The principal component analysis further demonstrated that the sources of Pb, Cd, and Cr differed with other elements. The results of random forest suggested that soil properties followed by topography were critical parameters affecting the variations of Ca, Mg, Mn, Fe, Ni, Zn, and Cu. Agricultural activities and soil properties were major factors controlling the variations of Pb, Cr, and Cd. Further study should be conducted to understand the relations between the metal elements and soil properties.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254928PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297850PMC
July 2021

An Activity-Based Sensing Fluorogenic Probe for Monitoring Ethylene in Living Cells and Plants.

Angew Chem Int Ed Engl 2021 Jul 21. Epub 2021 Jul 21.

Nanjing Agricultural University College of Plant Protection, Department of Pesticide Science, Weigang 1, 210000, Nanjing, CHINA.

Ethylene (ET) is an important gaseous plant hormone. It is highly desirable to develop fluorescent probes for monitoring ethylene in living cells. Herein we report an efficient Rh(III)-catalysed coupling of  N -phenoxyacetamides to ethylene in the presence of  an alcohol. The newly discovered coupling reaction exhibited a wide scope of  N -phenoxyacetamides and excellent regioselectivity. More importantly, we successfully develop  three fluorophore-tagged Rh(III)-based fluorogenic probes (coumarin-ethylene probes,  CEPs ) using this strategy for the selective and quantitative detection of ethylene. Among the probes,  CEP-1  exhibited the  highest sensitivity with a limit of detection of ethylene at 52 ppb in air. Furthermore,  CEP-1  was  successfully applied for imaging in living CHO-K1 cells and for monitoring endogenous-induced changes in ethylene biosynthesis in tobacco and  Arabidopsis  thaliana  plants. These results indicated that  CEP-1  has great potential to illuminate the spatiotemporal regulation of ethylene biosynthesis and ethylene signal transduction in living biological systems.
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http://dx.doi.org/10.1002/anie.202108335DOI Listing
July 2021

Distribution of COPD Comorbidities and Creation of Acute Exacerbation Risk Score: Results from SCICP.

J Inflamm Res 2021 15;14:3335-3348. Epub 2021 Jul 15.

Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities.

Methods: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations.

Results: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, =0.001), angina (OR=10.155, =0.025) and hypertension (OR=3.142, =0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample.

Conclusion: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index - BODEx - and comorbidity parameters can identify patients at high risk of acute exacerbation.
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http://dx.doi.org/10.2147/JIR.S315600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289369PMC
July 2021

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study.

Mol Psychiatry 2021 Jul 20. Epub 2021 Jul 20.

CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.

Previous coronavirus pandemics were associated elevated post-traumatic stress symptoms (PTSS), but the self-report and neurological basis of PTSS in patients who survived coronavirus disease 2019 (COVID-19) are largely unknown. We conducted a two-session study to record PTSS in the COVID-19 survivors discharged from hospitals for a short (i.e., about 3 months, Session 1) to a medium period (i.e., about 6 months, Session 2), as well as brain imaging data in Session 2. The control groups were non-COVID-19 locals. Session 1 was completed for 126 COVID-19 survivors and 126 controls. Session 2 was completed for 47 COVID-19 survivors and 43 controls. The total score of post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) score was significantly higher in COVID-19 survivors compared with controls in both sessions. The PCL-5 score in COVID-19 survivors was positively correlated with the duration after discharge (r = 0.27, p = 0.003 for Session 1), and increased by 20% from Session 1 to Session 2 for the survivors who participated both sessions. The increase was positively correlated with individual's test-retest duration (r = 0.46, p = 0.03). Brain structural volume and functional activity in bilateral hippocampus and amygdala were significantly larger in COVID-19 survivors compared with controls. However, the volumes of the left hippocampus and amygdala were negatively correlated with the PCL-5 score for the COVID-19 survivors. Our study suggests that COVID-19 survivors might face possible PTSS deteriorations, and highlights the importance of monitoring mental wellness of COVID-19 survivors.
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http://dx.doi.org/10.1038/s41380-021-01223-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290134PMC
July 2021

A novel epigenetic drug conjugating flavonoid and HDAC inhibitor confers to suppression of acute myeloid leukemogenesis.

Clin Sci (Lond) 2021 Jul 20. Epub 2021 Jul 20.

Shenzhen University General Hospital, Shenzhen, China.

Epigenetic dysregulation has long been identified as a key driver of leukemogenesis in acute myeloid leukemia (AML). However, epigenetic drugs such as histone deacetylase inhibitors (HDACi) targeting epigenetic alterations in AML have obtained only limited clinical efficiency without clear mechanism. Fortunately, we screened out a novel epigenetic agent named Apigenin-Vorinostat-Conjugate (AVC), which provides us a possibility to handle the heterogenous malignancy. Its inhibition on HDACs was presented by HDACs expression, enzyme activity, and histone acetylation level. Its efficacy against AML was detected by cell viability assay and tumor progression of AML mouse model. Apoptosis is the major way causing cell death. We found AVC efficiently suppresses leukemogenesis whereas sparing the normal human cells. Kasumi-1 cells are at least twenty-fold higher sensitive to AVC (IC50=0.024μM) than vorinostat (IC50=0.513μM) and Ara-C (IC50=0.4366μM). Furthermore, it can efficiently regress the tumorigenesis in AML mouse model while keeping the pivotal organs safe, demonstrating a feasibility and favorable safety profile in treatment of AML. Collectively, these pre-clinical data suggest a promising potential utilizing flavonoid-HDACi-conjugate as a next-generation epigenetic drug for clinical therapy against AML.
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http://dx.doi.org/10.1042/CS20210571DOI Listing
July 2021

NEU4 inhibits motility of HCC cells by cleaving sialic acids on CD44.

Oncogene 2021 Jul 19. Epub 2021 Jul 19.

School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang Provence, China, 150008.

Hepatocellular carcinoma (HCC) is an extremely metastatic tumor. Sialic acids (SAs) are associated with cancer development and metastasis. NEU4 is a sialidase that removes SAs from glycoconjugates, while the function of the NEU4 in HCC has not been clearly explored. In our research, we found the NEU4 expression was significantly down-regulated in HCC tissues, which was correlated with high grades and poor outcomes of HCC. The NEU4 expression could be regulated by histone acetylation. In the functional analysis of NEU4, the cell motility was inhibited when NEU4 was overexpressed, and restored when NEU4 expression was down-regulated. Similarly, NEU4 over-expressed HCC cells showed less metastasis in athymic nude mice. Further study revealed that NEU4 could inhibit cell migration by enzymatic decomposition of SAs. Our results verified a NEU4 active site (NEU4) and overexpressing inactivates NEU4 that weakens the inhibition ability to cell migration. Further, 70 kinds of specific interacting proteins of NEU4 including CD44 were identified through mass spectrum. Moreover, the α2,3-linked SAs on CD44 were decreased and the hyaluronic acid (HA) binding ability was increased when NEU4 over-expressed or activated. Additionally, the mutation of CD44 with six N-glycosylation sites showed less sensibility to NEU4 on cell migration compared with wild-type CD44. In summary, our results revealed the mechanism of low expression of NEU4 in HCC and its inhibitory effect on cell migration by removal of SAs on CD44, which may provide new treatment strategies to control the motility and metastasis of HCC.
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http://dx.doi.org/10.1038/s41388-021-01955-7DOI Listing
July 2021

Genomic Analysis of Reveals the Basis of Its Medicinal Properties and Evolutionary Relationships.

Front Microbiol 2021 1;12:652324. Epub 2021 Jul 1.

Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China.

Yuanmo [ (Y.C. Dai, Niemelä & G.F. Qin) T. Saito, Tonouchi & T. Harada] is an important edible and medicinal mushroom endemic to Northeastern China. Here we report the sequencing and assembly of the genome using single-molecule real-time sequencing technology. The whole genome was approximately 35.65 Mb, with a G + C content of 48.31%. Genome assembly generated 41 contigs with an N50 length of 1,772,559 bp. The genome comprised 9,364 annotated protein-coding genes, many of which encoded enzymes involved in the modification, biosynthesis, and degradation of glycoconjugates and carbohydrates or enzymes predicted to be involved in the biosynthesis of secondary metabolites such as terpene, type I polyketide, siderophore, and fatty acids, which are responsible for the pharmacodynamic activities of . We also identified genes encoding 1,3-β-glucan synthase and endo-1,3(4)-β-glucanase, which are involved in polysaccharide and uridine diphosphate glucose biosynthesis. Phylogenetic and comparative analyses of Basidiomycota fungi based on a single-copy orthologous protein indicated that the genus is an independent group that evolved from the Pleurotaceae family. The annotated whole-genome sequence of can serve as a reference for investigations of bioactive compounds with medicinal value and the development and commercial production of superior varieties.
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http://dx.doi.org/10.3389/fmicb.2021.652324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281127PMC
July 2021

Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study.

Front Pharmacol 2021 2;12:581833. Epub 2021 Jul 2.

Department of Nephropathy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care. In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide 16.7% for grp 1 patients (2/12) ( = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 ( 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 ( 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14-28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.
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http://dx.doi.org/10.3389/fphar.2021.581833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284962PMC
July 2021
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