Publications by authors named "Zhen Wang"

3,670 Publications

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Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis.

JAMA 2021 Jun;325(23):2357-2369

Mayo Clinic Evidence-based Practice Center, Rochester, Minnesota.

Importance: Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.

Objective: To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.

Data Sources: Multiple databases from database inception to February 24, 2021.

Study Selection: Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.

Data Extraction And Synthesis: Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.

Main Outcomes And Measures: The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.

Findings: Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.

Conclusions And Relevance: There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.
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http://dx.doi.org/10.1001/jama.2021.7939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207243PMC
June 2021

Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3.

Int J Biol Macromol 2021 Jun 11. Epub 2021 Jun 11.

International Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China; Collaborative Innovation Center for prevention and control of high incidence zoonotic infectious diseases in Western China, College of Animal Science and Technology, Shihezi University, 832003 Shihezi, Xinjiang, China. Electronic address:

Anaplasma phagocytophilum is an obligate intracellular bacterium and a common tick-borne infectious pathogen that can cause human granulocytic anaplasmosis (HGA). Effector proteins play an important role in the pathogenic mechanism of A. phagocytophilum, but the specifics of the disease mechanism are unclear. We studied the effector protein AptA (A. phagocytophilum toxin A) using yeast two hybrid assays to screen its interacting protein proteasome assembly chaperone 3 (PSMG3, PAC3), and identified new mechanisms for the pathogenicity of A. phagocytophilum in HEK293T cells. After AptA enters the host cell, it interacts with PSMG3 to enhance the activity of the proteasome, causing ubiquitination and autophagy in the host cell and thereby increasing cross-talk between the ubiquitination-proteasome system (UPS) and autophagy. AptA also reduces the apoptotic efficiency of the host cells. These results offer new clues as to the pathogenic mechanism of A. phagocytophilum and support the hypothesis that AptA interacts with host PSMG3.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.039DOI Listing
June 2021

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Front Med (Lausanne) 2021 26;8:585851. Epub 2021 May 26.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.
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http://dx.doi.org/10.3389/fmed.2021.585851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187559PMC
May 2021

Corrigendum to "Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health".

Neural Plast 2021 25;2021:9762592. Epub 2021 May 25.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

[This corrects the article DOI: 10.1155/2020/8815195.].
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http://dx.doi.org/10.1155/2021/9762592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172309PMC
May 2021

Assessment of the risks from dietary lead exposure in China.

J Hazard Mater 2021 May 24;418:126134. Epub 2021 May 24.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Science, Beijing 10012, China.

The dietary lead (Pb) risk across China was assessed based on the margin of exposure (MOE) approach by comparing the level (1.5 μg/kg/d) based on the Pb concentrations in foodstuffs from1386 published articles. The Pb averages of the 18 foods were lower than their corresponding limits enacted by the Chinese government, ranging from 0.09 to 0.30 mg/kg. Food from plants had a much higher contribution to dietary Pb intake than that from animals (86% vs. 14%), and cereals and vegetables contributed 79% of the Pb intake from plant-based food. Although each category of food contained a relatively low Pb concentration, the accumulated Pb from the total diet posed a high risk to human health. The MOE risk from dietary Pb averaged 1.57 and ranged from 0.13 to 6.18, with high risks in southern, southwestern, eastern, central, and northern China. The MOE risk from Pb could be decreased by adjusting the dietary structure, and the ratio of people categorized as high risk (MOE < 1) would decrease from 56% to 37%, 41%, or 24% if the category of cereal or vegetable or both cereals and vegetables with the lowest Pb concentration in their local areas were selected, respectively.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126134DOI Listing
May 2021

The effects of 2-aminoethoxydiphenyl borate and dantrolene on rat bones treated with NaAsO2.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar 1. Epub 2021 Mar 1.

Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832008, China.

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http://dx.doi.org/10.1093/abbs/gmab075DOI Listing
March 2021

Molecular genetic analysis of Mi -positive hybrid glycophorins revealed two novel alleles of GP.Vw and multiple variant transcripts of GYPB existing in both the homozygous GP.Mur and wild-type GPB individuals.

Transfusion 2021 Jun 12. Epub 2021 Jun 12.

Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, People's Republic of China.

Background: The hybrid glycophorins of MNS blood group system express a series of low incidence antigens including Mi , which are commonly found in Southeast Asian populations. In this study, the molecular basis of Mi -positive hybrid glycophorins was firstly clarified in the Chinese Southern Han population. RNA transcripts of GYPB gene in the homozygous GP.Mur individuals were also analyzed.

Study Design And Methods: DNAs were extracted from the whole blood samples of 111 Mi -positive donors. Then, high-resolution melting (HRM) analysis for GYP(B-A-B) was used to analyze the genotypes. Sequencing of GYPB pseudoexon 3 was conducted in the samples with variant melting curves. TA-cloning and subsequent sequencing of GYPA exons 2-4 were performed in the Mi -positive samples with normal GYPB/GYPB genotype by HRM. The transcript analysis of GYPB was conducted in homozygous GP.Mur and wild-type glycophorin B (GPB) individuals using RNA extracted from the cultured erythroblast.

Results: The heterozygous GYP*Mur/GYPB (n = 101), homozygous GYP*Mur/GYP*Mur (n = 7) including one novel GYP*Mur allele with an extra GYPA/GYPE specific nucleotide substitution (c.229+110A>T), heterozygous GYP*Bun/GYPB (n = 1) and GYP*Vw/GYPA (n = 2) with two novel GYP*Vw alleles were identified. RNA transcript analysis revealed multiple transcripts of GYPB existing in both homozygous GP.Mur and normal GPB individuals.

Conclusion: The results showed the genetic diversity of hybrid glycophorins in the Chinese population. Besides, the successful analysis of GYPB transcripts indicates that the cultured erythroblast is a good source for RNA transcript analysis for the protein only expressed on the red blood cells.
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http://dx.doi.org/10.1111/trf.16450DOI Listing
June 2021

Downhill Running Decreases the Acetylation of Tubulins and Impairs Autophagosome Degradation in Rat Skeletal Muscle.

Med Sci Sports Exerc 2021 Jun 11. Epub 2021 Jun 11.

School of Sports Science, Beijing Sport University, Beijing, CHINA College of Rehabilitation, Gannan Medical University, Ganzhou, CHINA.

Purpose: This study was designed to probe the effect of downhill running on microtubule acetylation and autophagic flux in rat skeletal muscle.

Methods: Sprague-Dawley rats were subjected to an exercise protocol of a 90-min downhill run with a slope of -16° and a speed of 16 m/min, and then the soleus was sampled at 0 h, 12 h, 24 h, 48 h, and 72 h after exercise. Protein expression levels of microtubule-associated protein 1 light chain 3 (LC3), p62/sequestosome 1 (p62), α-tubulin and acetylated α-tubulin (AcK40 α-tubulin) were detected by Western blotting. Alpha-tubulin was costained with acetylated α-tubulin (AcK40 α-tubulin) or cytoplasmic dynein intermediate chain in a single muscle fiber, and LC3 was costained with lysosomal associated membrane protein 1 (LAMP1) in cryosections. To assess autophagic flux in vivo, colchicine or vehicle was injected intraperitoneally 3 days before the exercise experiment, and the protein levels of LC3 and p62 were measured by Western blotting.

Results: Downhill running induced a significant increase in the protein levels of LC3-II and p62, while the level and proportion of AcK40 α-tubulin were markedly decreased. Furthermore, the amount of dynein on α-tubulin was decreased after downhill running, and autophagosomes accumulated in the middle of myofibrils. Importantly, LC3-II flux was decreased following downhill running compared with that in the control group.

Conclusions: A bout of downhill running decreases microtubule acetylation, which may impair dynein recruitment and autophagosome transportation, causing blocked autophagic flux.
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http://dx.doi.org/10.1249/MSS.0000000000002728DOI Listing
June 2021

Whole-Genome Sequencing of Micrococcus luteus MT1691313, Isolated from the Mariana Trench.

Microbiol Resour Announc 2021 Jun 10;10(23):e0036921. Epub 2021 Jun 10.

School of Ocean, Yantai University, Yantai, China.

Micrococcus luteus MT1691313 is a Gram-positive bacterium isolated from the deep-sea sediment located at a 4,448-m depth in the Mariana Trench. Here, we report the complete genome sequence of this strain, which has a genome size of 2.32 Mb with a GC content of 72.04%.
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http://dx.doi.org/10.1128/MRA.00369-21DOI Listing
June 2021

Asymmetric alkoxy- and hydroxy-carbonylations of functionalized alkenes assisted by β-carbonyl group.

Angew Chem Int Ed Engl 2021 Jun 9. Epub 2021 Jun 9.

East China Normal University, School of Chemistry and Molecular Engineering, 500 Dongchuan Rd, 200241, Shanghai, CHINA.

As a fundamental type of carbonylation reactions, alkoxy- and hydroxy-carbonylations of unsaturated hydrocarbons constitutes one of the most important industrial applications of homogeneous catalysis. Since the birth of asymmetric catalysis, the enantioselective variant of such transformation has been recognized as a direct and efficient approach for the synthesis of chiral carbonyl compounds. However, owing to the difficulties in controlling multi-selectivities for asymmetric hydrocarbonylation of alkenes, to date this reaction is typically limited to vinylarenes and analogues. In this work, a highly efficient asymmetric alkoxy- and hydroxy-carbonylations of β-carbonyl functionalized alkenes was developed, providing a practical and ready access to various densely functionalized chiral molecules with high optical purity from broadly available alkenes, CO, and nucleophiles (>90 examples, 84-99% ee). This protocol features mild reaction conditions and broad substrate scope, and the products can be readily transformed into a diverse array of chiral heterocycles. Control experiments revealed the key role of the β-carbonyl group in determining the enantioselectivity and promoting the activity, which facilitates chiral induction by coordination to the transition-metal as rationalized by DFT calculations. The strategy of utilizing an innate functional group as the directing group on the alkene substrate might find further applications in catalytic asymmetric hydrocarbonylation reactions.
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http://dx.doi.org/10.1002/anie.202105977DOI Listing
June 2021

Methylation gene is associated with overall survival in patients with seminoma.

Oncol Rep 2021 05 9;45(5). Epub 2021 Jun 9.

Affiliated Hospital of Putian University, Putian, Fujian 351100, P.R. China.

The aim of the present study was to explore and verify the potential mechanism of seminoma progression. Data on 132 RNA‑seq and 156 methylation sites from stage II/III and I seminoma specimens were downloaded from The Cancer Genome Atlas database. An initial filter of |fold‑change| >2 and false discovery rate <0.05 were used to identify differentially expressed genes (DEGs) which were associated with differential methylation site genes; these genes were considered potential candidates for further investigation by survival analysis. Potassium voltage‑gated channel subfamily C member 1 () expression was verified in seminoma human tissues and three seminoma cell lines. The invasive, proliferative and apoptotic abilities of the human testicular tumor Ntera‑2 and normal human testis Hs1.Tes cell lines were assessed following aberrant expression. was identified as a DEG, in which hypermethylation inhibited its expression and it was associated with poor overall survival in patients with seminoma. The present results demonstrated that is negatively correlated with methylation. Due to the abnormal expression of in seminoma cells, it was suggested that could be used as a diagnostic indicator and therapeutic target for the progression of seminoma.
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http://dx.doi.org/10.3892/or.2021.8024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020201PMC
May 2021

Isolation, characterization, and interaction of lignin-degrading bacteria from rumen of buffalo (Bubalus bubalis).

J Basic Microbiol 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education; Department of Hubei Province Engineering Research Center in Buffalo Breeding and Products, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, PR China.

The purpose of this study was to isolate lignin-degrading bacteria from buffalo rumen and to explore their interactions further. Using lignin as the carbon source, three bacteria, B-04 (Ochrobactrum pseudintermedium), B-11 (Klebsiella pneumoniae), and B-45 (Bacillus sonorensis), which have shown lignin degradation potential, were successfully isolated and identified from the rumen fluid of buffalo by colony morphology, 16S ribosomal RNA gene sequencing, and biochemical and physiological analyses. The degradation rates of lignin were determined, and the maximum values were 4.86%, 11.1%, and 7.68% for B-04, B-11, and B-45, respectively. The maximum laccase activities were 0.65, 0.93, and 1.15 U/ml, while the maximum lignin peroxidase activities were 5.72, 8.29, and 18.69 U/ml, respectively. Pairwise interaction studies showed inhibitory interaction between B-04 and B-45, inhibitory interaction between B-04 and B-11, and symbiotic interaction between B-11 and B-45. This is the first report on the lignin degradation ability of bacteria isolated from the buffalo's rumen, which provides a new understanding for revealing the mechanism of roughage tolerance of buffalo.
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http://dx.doi.org/10.1002/jobm.202100068DOI Listing
June 2021

pH-Controlled Protein Orthogonal Ligation Using Asparaginyl Peptide Ligases.

J Am Chem Soc 2021 Jun 7;143(23):8704-8712. Epub 2021 Jun 7.

School of Biological Sciences, Nanyang Technological University, Singapore 637551.

Peptide asparaginyl ligases (PALs) catalyze transpeptidation at the Asn residue of a short Asn-Xaa-Xaa tripeptide motif. Due to their high catalytic activity toward the P1-Asn substrates at around neutral pH, PALs have been used extensively for peptide ligation at asparaginyl junctions. PALs also bind to aspartyl substrates, but only when the COOH of P1-Asp remains in its neutral, protonated form, which usually requires an acidic pH. However, this limits the availability of the amine nucleophile and, consequently, the ligation efficiency at aspartyl junctions. Because of this perceived inefficiency, the use of PALs for Asp-specific ligation remains largely unexplored. We found that PAL enzymes, such as VyPAL2, display appreciable catalytic activities toward P1-Asp substrates at pH 4-5, which are at least 2 orders of magnitude higher than that of sortase A, making them practically useful for both intra- and intermolecular ligations. This also allows sequential ligations, first at Asp and then at Asn junctions, because the newly formed aspartyl peptide bond is resistant to the ligase at the pH used for asparaginyl ligation in the second step. Using this pH-controlled orthogonal ligation method, we dually labeled truncated sfGFP with a cancer-targeting peptide and a doxorubicin derivative at the respective N- and C-terminal ends in the N-to-C direction. In addition, a fluorescein tag and doxorubicin derivative were tagged to an EGFR-targeting affibody in the C-to-N direction. This study shows that the pH-dependent catalytic activity of PAL enzymes can be exploited to prepare multifunction protein biologics for pharmacological applications.
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http://dx.doi.org/10.1021/jacs.1c02638DOI Listing
June 2021

The role of iron homeostasis and iron-mediated ROS in cancer.

Am J Cancer Res 2021 15;11(5):1895-1912. Epub 2021 May 15.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College Hangzhou 310014, Zhejiang Province, P. R. China.

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167679PMC
May 2021

Delineating the Role of Mitophagy Inducers for Alzheimer Disease Patients.

Aging Dis 2021 Jun 1;12(3):852-867. Epub 2021 Jun 1.

2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Alzheimer's disease (AD) is the most common cause of dementia in elderly that serves to be a formidable socio-economic and healthcare challenge in the 21 century. Mitochondrial dysfunction and impairment of mitochondrial-specific autophagy, namely mitophagy, have emerged as important components of the cellular processes contributing to the development of AD pathologies, namely amyloid-β plaques (Aβ) and neurofibrillary tangles (NFT). Here, we highlight the recent advances in the association between impaired mitophagy and AD, as well as delineate the potential underlying mechanisms. Furthermore, we conduct a systematic review the current status of mitophagy modulators and analyzed their relevant mechanisms, evaluating on their advantages, limitations and current applications in clinical trials for AD patients. Finally, we describe how deep learning may be a promising method to rapid and efficient discovery of mitophagy inducers as well as general guidance for the workflow of the process.
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http://dx.doi.org/10.14336/AD.2020.0913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139196PMC
June 2021

Effect of Different Nuclear Localization Signals on the Subcellular Localization and Anti-HIV-1 Function of the MxB Protein.

Front Microbiol 2021 20;12:675201. Epub 2021 May 20.

Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.

Interferon exerts its antiviral activity by stimulating the expression of antiviral proteins. These interferon stimulate genes (ISGs) often target a group of viruses with unique molecular mechanisms. One such ISG is myxovirus resistance B (MxB) that has been reported to inhibit human immunodeficiency virus type 1 (HIV-1) by targeting viral capsid and impairing nuclear import of viral DNA. The antiviral specificity of MxB is determined by its N-terminal 25 amino acids sequence which has the nuclear localization activity, therefore functions as a nuclear localization signal (NLS). In this study, we report that the bipartite NLS, but not the classic NLS, the PY-NLS, nor the arginine-rich NLS, when used to replace the N-terminal sequence of MxB, drastically suppress HIV-1 gene expression and virus production, thus creates a new anti-HIV-1 mechanism. MxB preserves its anti-HIV-1 activity when its N-terminal sequence is replaced by the arginine-rich NLS. Interestingly, the arginine-rich NLS allows MxB to inhibit HIV-1 CA mutants that are otherwise resistant to wild type MxB, which suggests sequence specific targeting of viral capsid. Together, these data implicate that it is not the nuclear import function itself, but rather the sequence and the mechanism of action of the NLS which define the antiviral property of MxB.
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http://dx.doi.org/10.3389/fmicb.2021.675201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173038PMC
May 2021

Alteration of Autonomic Nervous System Is Associated With Severity and Outcomes in Patients With COVID-19.

Front Physiol 2021 19;12:630038. Epub 2021 May 19.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Previous studies suggest that coronavirus disease 2019 (COVID-19) is a systemic infection involving multiple systems, and may cause autonomic dysfunction.

Objective: To assess autonomic function and relate the findings to the severity and outcomes in COVID-19 patients.

Methods: We included consecutive patients with COVID-19 admitted to the 21st COVID-19 Department of the east campus of Renmin Hospital of Wuhan University from February 6 to March 7, 2020. Clinical data were collected. Heart rate variability (HRV), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and lymphocytes and subsets counts were analysed at two time points: nucleic-acid test positive and negative. Psychological symptoms were assessed after discharge.

Results: All patients were divided into a mild group (13) and a severe group (21). The latter was further divided into two categories according to the trend of HRV. Severe patients had a significantly lower standard deviation of the RR intervals (SDNN) ( < 0.001), standard deviation of the averages of NN intervals (SDANN) ( < 0.001), and a higher ratio of low- to high-frequency power (LF/HF) ( = 0.016). Linear correlations were shown among SDNN, SDANN, LF/HF, and laboratory indices ( < 0.05). Immune function, D-dimer, and NT-proBNP showed a consistent trend with HRV in severe patients ( < 0.05), and severe patients without improved HRV parameters needed a longer time to clear the virus and recover ( < 0.05).

Conclusion: HRV was associated with the severity of COVID-19. The changing trend of HRV was related to the prognosis, indicating that HRV measurements can be used as a non-invasive predictor for clinical outcome.
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http://dx.doi.org/10.3389/fphys.2021.630038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170133PMC
May 2021

Lignin degradation by water buffalo.

Trop Anim Health Prod 2021 Jun 5;53(3):344. Epub 2021 Jun 5.

College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

So far, few animals with the ability of lignin degradation have been reported except termite and longicorn. In this study, it was found that the crude fiber and acid detergent lignin (ADL) of rice straw can be degraded dramatically higher by buffalo than those by cattle. In order to further study this ability of buffalo, the digestion of roughages in buffalo rumen was studied using rumen nylon bag experiment, scanning electron microscopy (SEM), and Van Soest fiber analysis. The SEM results showed that the degradation degree of rice straw was dramatically higher in buffalo than that in cattle. The digestibility of crude fiber was significantly higher in buffalo than that in cattle (P < 0.01). The digestibility of ADL, cellulose, hemicellulose, acid detergent, fiber, and neutral detergent fiber of rice straw in buffalo rumen was significantly higher than that in cattle (P < 0.05). The ADL degradation rate of rice straw in buffalo rumen was significantly higher than that in cattle rumen, indicating that buffalo was capable of utilizing lignin and had superior utilizing capability than cattle. It was observed that various roughages can be dramatically digested by buffalo rumen with the ranking of ADL degradation rate: peanut vine (15.04%) > rice silage > maize silage > rice straw > corn stover > wheat stalk > bract leaf > potato vine (7.22%), verifying that buffalo rumen possessed the ability to digest universal roughages. In conclusion, this study revealed that buffalo was more efficient in ADL degradation compared with cattle.
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http://dx.doi.org/10.1007/s11250-021-02787-zDOI Listing
June 2021

Design, synthesis and biological evaluation of N-anthraniloyl tryptamine derivatives as pleiotropic molecules for the therapy of malignant glioma.

Eur J Med Chem 2021 May 29;222:113564. Epub 2021 May 29.

School of Pharmaceutical Science, University of South China, Hengyang, 421001, China; School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address:

COX-2 and STAT3 are two key culprits in the glioma microenvironment. Herein, to inhibit COX-2 and block STAT3 signaling, we disclosed 27 N-anthraniloyl tryptamine compounds based on the combination of melatonin derivatives and N-substituted anthranilic acid derivatives. Among them, NP16 showed the best antiproliferative activity and moderate COX-2 inhibition. Of note, NP16 decreased the level of p-JAK2 and p-STAT3, and blocked the nuclear translocation of STAT3 in GBM cell lines. Moreover, NP16 downregulated the MMP-9 expression of BV2 cells in a co-culture system of BV2 and C6 glioma cells, abrogated the proliferative/invasive/migratory abilities of GBM cells, induced apoptosis by ROS and the Bcl-2-regulated apoptotic pathway, and induced obvious G/M arrest in glioma cells in vitro. Furthermore, NP16 displayed favorable pharmacokinetic profiles covering long half-life (11.43 ± 0.43 h) and high blood-brain barrier permeability. Finally, NP16 effectively inhibited tumor growth, promoted the survival rate, increased the expression of E-cadherin and reduced overproduction of PGE, MMP-9, VEGF-A and the level of p-STAT3 in tumor tissue, and improved the anxiety-like behavior in C6 glioma model. All these evidences demonstrated N-anthraniloyl tryptamine derivatives as multifunctional anti-glioma agents with high potency could drain the swamp to beat glioma.
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http://dx.doi.org/10.1016/j.ejmech.2021.113564DOI Listing
May 2021

Magnetism and NIR dual-response polypyrrole-coated FeO nanoparticles for bacteria removal and inactivation.

Mater Sci Eng C Mater Biol Appl 2021 Jul 29;126:112143. Epub 2021 Apr 29.

College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Hexing Road 26, Harbin, 150040, PR China. Electronic address:

Microbial contamination of water represents a great threat to the public health that has attracted worldwide attention. In this work, polypyrrole magnetic nanoparticles ([email protected] NPs) with sterilization properties were fabricated. More specifically, the [email protected] NPs obtained via aqueous dispersion polymerization and an in situ chemical oxidative polymerization exhibited a cationic surface and high photothermal conversion efficiency. More than 50% of bacteria adsorption can be achieved at a dosage of 100 μg/mL [email protected] NPs under magnetic field, and high photothermal sterilization efficacy (~100%) can be obtained upon NIR exposure at the same dosage for 10 min. Noteworthy, the [email protected] NPs can be recycled by magnetism and reused without affecting their photothermal sterilization capability. This study clearly provides experimental evidence of the great potential of [email protected] NPs as stable and reusable nanocomposite materials for bacteria adsorption and photothermal sterilization performance. The application of [email protected] NPs can realize enviromental-friendly bacterial contaminated water treatment as well as provide stratgies for synergistical antibacterial materials design.
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http://dx.doi.org/10.1016/j.msec.2021.112143DOI Listing
July 2021

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study.

Reprod Sci 2021 Jun 3. Epub 2021 Jun 3.

Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.
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http://dx.doi.org/10.1007/s43032-021-00637-9DOI Listing
June 2021

Fabrication of Magnetic Catalyst FeO-SiO-V and Its Application on Lignin Extraction from Corncob in Deep Eutectic Solvent.

Polymers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

State Key Laboratory of Biobased Material and Green Papermaking, School of Environmental Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

FeO-SiO-V was prepared by deposited HPMoVO on FeO-SiO and employed as a catalyst to extract lignin from corncob in deep eutectic solvent (choline chloride/lactic acid = 1/10). Batch experiments were conducted in an autoclave under the conditions of 500 kPa, 90-130 °C and 15 h, while the dosage of the catalyst was set as a variable. Results indicated that the catalyst could effectively improve the qualities of the lignin, while the characteristics of the lignin showed prominent changes with the participation of the catalyst: the extraction rate increased from 71.65% to 98.13%, the purity was improved from 85.62% to 97.09%, and both the number average molecular weight and the weight average molecular weight also decreased significantly. Besides, the molecular distribution of the lignin achieved from the CC-LA-Fe-Si-V reaction system was found to be more highly concentrated (Polydispersity index = 1.746). Results from 2D NMR HSQC analysis indicated that lignin fractions achieved from the CC-LA-Fe-Si-V system showed distinct destruction involving C-H in guaiacyl units (G), C-H in guaiacyl units (G), and the C-H in γ-hydroxylated β-O-4' substructures, but little changes in the C-H in phenylcoumaran substructures.
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http://dx.doi.org/10.3390/polym13101545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151408PMC
May 2021

Correction: Assembly of fluorinated chromanones enantioselective tandem reaction.

Chem Commun (Camb) 2021 Jun;57(47):5842-5843

School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China.

Correction for 'Assembly of fluorinated chromanones via enantioselective tandem reaction' by Mengxue Lu et al., Chem. Commun., 2021, 57, 4722-4725, DOI: 10.1039/D1CC01187A.
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http://dx.doi.org/10.1039/d1cc90194jDOI Listing
June 2021

A practice of using five-colour chart to guide the control of COVID-19 and resumption of work in Zhejiang Province, China.

Sci Rep 2021 05 31;11(1):11317. Epub 2021 May 31.

Zhejiang Provincial Center for Disease Control and Prevention, Zhejiang, China.

Since the outbreak of COVID-19 in December 2019 in Wuhan, Zhejiang has become the province with the largest number of cases. The aim of this article is to present Zhejiang province's experience of establishing an accurate and smart control mechanism for epidemic prevention and control and resumption of work and production using a 'five-colour epidemic chart'. The number of confirmed cases, proportion of local cases, and occurrence of clustered outbreaks were used as evaluation indicators to calculate the county-level epidemic risk and were assigned different weight coefficients; the absence of cases for 3 and 7 consecutive days was used as the adjustment index. When the first chart was published on February 9, there were 1 very-high-risk, 12 high-risk, and 12 low-risk counties. Under the five-colour chart, Zhejiang began to adopt precise measures to prevent and control the epidemic and resume work and production. By February 24, the low-risk counties had expanded to 82, with no high-risk and very-high-risk counties. The epidemic situation in Zhejiang province has been effectively controlled. The experience of epidemic prevention and control in Zhejiang is worthy to be emulated and learned by other countries and regions.
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http://dx.doi.org/10.1038/s41598-021-90808-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167099PMC
May 2021

Comprehensive Analysis of PD-L1 Expression, Immune Infiltrates, and m6A RNA Methylation Regulators in Esophageal Squamous Cell Carcinoma.

Front Immunol 2021 12;12:669750. Epub 2021 May 12.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME).

Methods: The transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail.

Results: Six m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells.

Conclusion: Our study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.
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http://dx.doi.org/10.3389/fimmu.2021.669750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149800PMC
May 2021

Involvement of circRNAs in Proinflammatory Cytokines-Mediated -Cell Dysfunction.

Mediators Inflamm 2021 4;2021:5566453. Epub 2021 May 4.

Center for Medical Research, The Second Xiangya Hospital, Central South University, Changsha, 410011 Hunan, China.

Aim: During the initial stage of type 1 diabetes, prolonged exposure of pancreatic -cell to proinflammatory cytokines such as IL-1, TNF-, and IFN- results in a decreased capacity to produce and release insulin, as well as cell loss by apoptosis. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs (ncRNAs) with closed loop with no free ends. circRNAs have been reported to be participated in the development of many diseases. As little is known about their role in insulin-secreting cells, this study is aimed at evaluating their contribution in the process of inflammation-induced -cell damage.

Methods: circRNA expression profile of MIN6 cells stimulated with a mix of cytokines, including IL-1, IFN-, and TNF-, was detected by circRNA microarrays. Four dysregulated circRNAs were validated by qRT-PCR. The involvement of the selected circRNAs in -cell dysfunction was tested after their inhibition in MIN6 cells. MicroRNA target prediction software and multiple bioinformatic approaches were used to predict the targeting genes of circRNAs and analyze possible functions of the circRNAs.

Results: 1020 upregulated and 902 downregulated circRNAs were identified in cytokines-treated -cells. Inhibition of circRNAs 000286 and 017277 in -cells could promote -cell apoptosis and affect insulin biosynthesis and secretion. GO analysis enriched terms such as regulation of transcription and regulation of gene expression and KEGG analysis enriched top pathways included TGF- and MAPK signaling pathways.

Conclusions: The data shows that circRNAs may be involved in proinflammatory cytokines-mediated -cell dysfunction and suggests the involvement of circRNAs in the development of type 1 diabetes.
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http://dx.doi.org/10.1155/2021/5566453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112919PMC
May 2021

Fluorinated Oligomer Wrapped Perovskite Crystals for Inverted MAPbI Solar Cells with 21% Efficiency and Enhanced Stability.

ACS Appl Mater Interfaces 2021 Jun 30;13(22):26093-26101. Epub 2021 May 30.

School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu 611731, China.

Defects at the grain boundary provide sites for nonradiative recombination in halide perovskite solar cells (PSCs). Here, by polymerization and fluorination of a Lewis acid of 4,4-bis(4-hydroxyphenyl)pentanoic acid, a fluorinated oligomer (FO-19) is synthesized and applied to passivate these defects in methlyammonium lead iodide (MAPbI). It is demonstrated that the carboxyl bond of FO-19 was coordinated with Pb ions in the perovskite films to achieve a wrapping effect on the perovskite crystals. The defects of perovskite film are effectively passivated, and the undesirable nonradiative recombination is greatly inhibited. As a result, FO-19 gives a power conversion efficiency of 21.23% for the inverted MAPbI-based PSCs, which is among the highest reported values in the literature. Meanwhile, the corresponding device with FO-19 exhibits significantly improved humidity and thermal stability. Therefore, this work offers insights into the realization of high-efficiency and stable PSCs through fluorinated additive engineering.
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http://dx.doi.org/10.1021/acsami.1c06216DOI Listing
June 2021

Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-κB signaling pathway.

Bioorg Chem 2021 May 27;113:104978. Epub 2021 May 27.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. Electronic address:

Osteoarthritis (OA) is a chronic disease featured by joint hyperplasia, deterioration of articular cartilage, and progressive degeneration. Abnormal expression of microRNAs (miRNAs) has been found to be implicated in the pathological process of OA. In this study, the role of miR-361-5p transferred by exosomes derived from human bone mesenchymal stem cells (hBMSCs) in OA was investigated. The expression of Asp-Glu-Ala-Asp-box polypeptide 20 (DDX20) and miR-361-5p in interleukin-1β (IL-1β)-treated chondrocytes was determined by reverse transcription quantitative polymerase chain reaction. DDX20 was knocked down by transfection of short hairpin RNA targeting DDX20, and the effects of DDX20 downregulation on IL-1β-induced damage of chondrocytes were detected. The interaction between DDX20 and miR-361-5p was tested by luciferase report assay. hBMSCs-derived exosomes loaded with miR-361-5p were co-incubated with chondrocytes followed by detection of cell viability, proliferation and inflammatory response. An OA rat model was established to further explore the role of miR-361-5p in vivo. Western blot, luciferase reporter and immunofluorescence staining assays were used to evaluate the activation of the nuclear factor kappa-B (NF-κB) signaling pathway. We found that DDX20 was upregulated, while miR-361-5p was underexpressed in IL-1β-treated chondrocytes. Downregulation of DDX20 inhibits levels of matrix metalloproteinases (MMPs) and suppresses inflammation induced by IL-1β. Mechanistically, miR-361-5p was verified to directly target DDX20. In addition, hBMSC-derived exosomes-transferred miR-361-5p alleviates chondrocyte damage and inhibits the NF-κB signaling pathway via targeting DDX20. Inhibition of NF-κB signaling reverses the effect of overexpressed DDX20 on IL-1β-induced chondrocyte damage. Moreover, exosomal miR-361-5p alleviates OA damage in vivo. Overall, hBMSC-derived exosomal miR-361-5p alleviates OA damage by targeting DDX20 and inactivating the NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.104978DOI Listing
May 2021

Hyperbranched concave octahedron of PtIrCu nanocrystals with high-index facets for efficiently electrochemical ammonia oxidation reaction.

J Colloid Interface Sci 2021 Apr 17;601:1-11. Epub 2021 Apr 17.

Collaborative Innovation Center of Sustainable Energy Materials, School of Physical Science and Technology; Guangxi Key Laboratory of Electrochemical Energy Materials; Key Laboratory of New Processing Technology for Non-ferrous Metal and Materials, Ministry of Education, Guangxi University, Nanning, 530004, China.

Ammonia oxidation reaction (AOR) via electrocatalysis is one of the most efficient ways of utilizing ammonia (a zero-carbon fuel with high hydrogen content) for renewable energy systems. However, AOR seriously suffers from the slow kinetics, and low durability due to its multi-electron transfer process and the poison of the reaction intermediates (N and NO) to precious metal catalysts. Herein, hyperbranched concave octahedral nanodendrites of PtIrCu (HCOND) with high-index facets of {553}, {331} and {221} were developed for the first time using a solvothermal method. The HCOND possesses PtIr-rich edges and exhibit highly efficient AOR activity and stability in alkaline media, wherein their onset potential is 0.35 V vs.RHE, which is 60 mV and 160 mV lower than that of the PtIrCu nanoparticles (NPs) (0.41 V) and commercial Pt/C (0.51 V), respectively, and its high mass activity of 40.6 A g at the 0.5 V vs.RHE is 10.3 times, 2.34 times higher than that of commercial Pt/C (3.9 A g) and PtIrCu NPs (17.3 A g), respectively. In addition, its peak current density (122.9 A g) is only reduced by 17.7% after 2000-cycles accelerated durability test. Meanwhile, the performance of PtIrCu HCOND is also better than that of other previously reported morphologies of Pt based catalysts (eg. nanoparticles, nanocubes, nanofilm, nanoflowers). The improvement is critically ascribed to unique advantages of the specific HCOND structure including PtIr rich surface, high-index faceted nanodendrites, strong lattice strain and electronic effects. These characteristics endow the HCOND with great promise to reduce Pt and Ir loading dramatically in the practical application of direct ammonia fuel cells.
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http://dx.doi.org/10.1016/j.jcis.2021.04.068DOI Listing
April 2021

Regulation and control methods for the unattached fraction of Rn progeny in a Rn progeny chamber.

J Environ Radioact 2021 Sep 26;235-236:106653. Epub 2021 May 26.

School of Nuclear Science and Technology, University of South China, Hengyang, Hunan, 421001, China.

The unattached fraction of Rn progeny is one of the key parameters in lung dose evaluation models. To study the behavior of unattached Rn progeny and to prepare for calibration of the unattached Rn progeny monitors, a Rn progeny chamber that could stably regulate different unattached fractions of Rn progeny was established. A recirculation loop to eliminate the effects of the sampling and a loop connected to the dilution chamber to supplement the carrier aerosol were set up. Also, a theoretical model regarding the regulation of the unattached fraction of Rn progeny was established. Continuous measurements of the unattached fraction were conducted using the combination of a single-layer wire screen and a filter membrane. The experimental results showed that, under different aerosol levels, the relative standard deviation (RSD) of Pb concentration during the continuous samplings was within 10.7% and the RSD of the unattached fraction of Pb was within 9.9%. The relative deviation between the theoretical and the experimental values of Pb concentration was within 16.7% and the model calculation values of the unattached fraction of Pb were consistent with measured results.
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http://dx.doi.org/10.1016/j.jenvrad.2021.106653DOI Listing
September 2021