Publications by authors named "Guoliang Zhang"

300 Publications

Application of the "Hand as Foot" analogy teaching method in great saphenous vein anatomy.

Asian J Surg 2021 Jul 24. Epub 2021 Jul 24.

Inner Mongolia Medical University, Department of Orthopedics, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010050, China.

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http://dx.doi.org/10.1016/j.asjsur.2021.07.024DOI Listing
July 2021

The advantages of carbon nanoparticles in level VII lymph node dissection in patients with papillary thyroid cancer.

Gland Surg 2021 Jun;10(6):2028-2036

First Department of Thyroid Surgery, the Affiliated Hospital of Putian University, Putian, China.

Background: The characteristics of level VII lymph nodes were explored and the advantages of using carbon nanoparticles (CNs) in papillary thyroid cancer (PTC) surgeries were examined. This was a retrospective study investigating the clinical data of patients with PTC who underwent surgical treatment.

Methods: From September 2019 to December 2020, a total of 191 consecutive patients with PTC were retrospectively analyzed. The patients were randomly divided into the CNs group and the control group. CNs were used in the CNs group during the operation. There were 103 cases in the CNs group, including 25 males and 78 females, and 88 cases in the control group, including 21 males and 67 females. Parameters, including the characteristics of dissected lymph nodes in level VII, metastatic rate, postoperative complications, and other inpatient-related indicators, were compared between the two groups.

Results: The number of lymph nodes dissected in level VII in the CNs group was significantly greater than that in the control group, and the metastatic rate of black-stained lymph nodes was significantly higher than that of non-black-stained lymph nodes (P<0.05). The postoperative hypoparathyroidism rate in the CNs group was significantly lower than that in the control group (P<0.05). There were no differences in the operation duration, intraoperative blood loss, postoperative drainage duration, or hospitalization days between the two groups (P>0.05).

Conclusions: The application of CNs for patients with PTC significantly increased the number of lymph nodes dissected in level VII and helped to protect the parathyroid glands (PGs). Moreover, the use of CNs did not increase the rate of postoperative complications. Thus, CNs may be a simple and safe approach when performing surgery in PTC patients.
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http://dx.doi.org/10.21037/gs-21-281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258881PMC
June 2021

Pentoxifylline Enhances Antioxidative Capability and Promotes Mitochondrial Biogenesis in D-Galactose-Induced Aging Mice by Increasing Nrf2 and PGC-1 through the cAMP-CREB Pathway.

Oxid Med Cell Longev 2021 22;2021:6695613. Epub 2021 Jun 22.

Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1-) dependent mitochondrial biogenesis genes. The results demonstrated that PTX improved cognitive deficits, reduced oxidative damage, ameliorated abnormal mitochondrial ultrastructure, increased mitochondrial content and Nrf2 activation, and upregulated antioxidant and mitochondrial biogenesis gene expression in the hippocampus of wild-type aging mice. However, the above antiaging effects of PTX were obviously decreased in the brains of Nrf2-deficient D-gal-induced aging mice. Moreover, in hydrogen peroxide-treated SH-SY5Y cells, we found that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and Nrf2/PGC-1 act in a linear way by CREB siRNA transfection. Thus, PTX administration improved the aging-related decline in brain function by enhancing antioxidative capability and promoting mitochondrial biogenesis, which might depend on increasing Nrf2 and PGC-1 by activating the cAMP-CREB pathway.
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http://dx.doi.org/10.1155/2021/6695613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245236PMC
June 2021

Antiviral drugs arbidol and interferon alpha-1b contribute to reducing the severity of COVID-19 patients: a retrospective cohort study.

Virol J 2021 07 8;18(1):142. Epub 2021 Jul 8.

National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, 518112, China.

Objectives: The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia.

Methods: This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People's Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir-ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness.

Results: Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084-0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15-0.58, p =  0.0005). The use of lopinavir-itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of - 5.2 days (IQR - 3.0 to - 7.5, p = 4e-06) compared with the control group.

Conclusion: Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients' recovery time.
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http://dx.doi.org/10.1186/s12985-021-01617-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264997PMC
July 2021

Novel Thin Film Nanocomposite Forward Osmosis Membranes Prepared by Organic Phase Controlled Interfacial Polymerization with Functional Multi-Walled Carbon Nanotubes.

Membranes (Basel) 2021 Jun 28;11(7). Epub 2021 Jun 28.

College of Chemical and Biological Engineering, State Key Laboratory of Chemical Engineering, Zhejiang University, Hangzhou 310027, China.

Novel high-quality thin film nanocomposite (TFN) membranes for enhanced forward osmosis (FO) were first synthesized through organic phase controlled interfacial polymerization by utilizing functional multi-walled carbon nanotubes (MWCNTs). As 3-aminopropyltriethoxysilane (APTES) grafted MWCNTs via an amidation reaction significantly promoted the dispersion in organic solution, MWCNTs-APTES with better compatibility effectively restricted the penetration of trimesoyl chloride (TMC), thus adjusting the morphology and characters of TFN membranes. Various techniques such as Fourier transform infrared spectra (FTIR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), sessile droplet analysis and FO experiments and reverse osmosis (RO) operation were taken to characterize and evaluate the performance of nanocomposites and membranes. The prepared TFN FO membranes exhibited good hydrophilicity and separation efficiency, in which water flux was about twice those of thin film composite (TFC) membranes without MWCNTs-APTES in both AL-DS and AL-FS modes. Compared with the original TFC membrane, the membrane structural parameter of the novel TFN FO membrane sharply was cut down to 60.7%. Based on the large number of low mass-transfer resistance channels provided by functional nanocomposites, the progresses may provide a facile approach to fabricate novel TFN FO membranes with advanced selectivity and permeability.
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http://dx.doi.org/10.3390/membranes11070476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304348PMC
June 2021

Confined assembly of ultrathin nanoporous nitrogen-doped graphene nanofilms with dual metal coordination chemistry.

iScience 2021 Jun 21;24(6):102576. Epub 2021 May 21.

Center for Membrane and Water Science, Institute of Oceanic and Environmental Chemical Engineering, State Key Lab Breeding Base of Green Chemical Synthesis Technology, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Graphene oxide (GO) nanosheets with unique structure have received much attention in providing opportunity for high-performance membranes in separation. However, the rational design of ultrathin graphene membranes with controlled structures remains a big challenge. Here, we report a methodology to synthesize dual metal-coordinated ultrathin nanoporous graphene nanofilms by tailoring well-aligned nanocrystals as building blocks on heteroatom-doped GO nanosheets with tunable architectures. Manipulation of metal nitrate as bifunctional dopants realizes N-doping of graphene oxide and preferential growth of α-MnO nanocrystals. Generation of Mn-O-C bond during cross-linking greatly strengthens the stability of membranes for long-term steady operation. Meanwhile, because of spatial confinement effects and high binding energy, N-doped reduced GO nanosheets are desirable supports to construct numerous Mn-N-C bonds, thus generating artificial nanopores to significantly increase nanochannels for ultrafast mass transport. Moreover, the size-selective permeability of ultrathin nanoporous GO-based nanofilms can be optimized by managing the types of metal source for target coordination.
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http://dx.doi.org/10.1016/j.isci.2021.102576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188556PMC
June 2021

Testosterone ameliorates age-related brain mitochondrial dysfunction.

Aging (Albany NY) 2021 06 17;13(12):16229-16247. Epub 2021 Jun 17.

Department of Neurobiology, Hebei Medical University, Shijiazhuang, China.

Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men. Although evidence suggests that the two phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain. Here, we show that testosterone supplementation significantly alleviates exploratory behavioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats. These effects were consistent with improved mitochondrial function, reflected by testosterone-induced increases in mitochondrial membrane potential (MMP), antioxidant enzyme (GSH-PX, catalase, and Mn-SOD) expression/activity, and mitochondrial respiratory complex activities in both brain regions. Furthermore, elevated PGC-1α, NRF-1, and TFAM expression (suggestive of enhanced mitochondrial biogenesis), increased citrate synthase activity, mtDNA copy number, and ND1, COX1, and ATP6 expression (indicative of increased mitochondrial content), as well as increased PINK1/Parkin and decreased P62 expression (suggesting mitophagy activation), were detected in the substantial nigra and hippocampus of aged male rats after testosterone supplementation. These findings suggest that testosterone supplementation may be a viable approach to ameliorating brain mitochondrial dysfunction and thus prevent or treat cognitive-behavioral deficits and neurodegenerative conditions associated with aging.
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http://dx.doi.org/10.18632/aging.203153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266321PMC
June 2021

Nitrogen-carbon materials base on pyrolytic graphene hydrogel for oxygen reduction.

J Colloid Interface Sci 2021 Jun 8;602:274-281. Epub 2021 Jun 8.

Lab of Advanced Nano-structures & Transfer Processes, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China; Chemistry and Chemical Engineering Guangdong Laboratory, Shantou 515031 China. Electronic address:

Hypothesis: Oxygen reduction reaction (ORR) has played a significant role in the utilization of energy nowadays. Nitrogen-doped carbon materials are seen as promising catalysts for ORR, so it is of great significance in studying the functions of different nitrogen moieties.

Experiments: The graphene hydrogel-based nitrogen-arbon materials (GH N-C) were fabricated by first obtaining a gel through hydrothermal treatment using graphene oxide (GO) as precursor, and then calcined in an ammonia atmosphere at different temperatures to form N-doped graphitized materials with divers nitrogen configuration.

Findings: GH N-C materials with tunable nitrogen configuration were synthesized by a two-step method base on graphene hydrogel. Benefiting from the 3D hydrogel structure, rich defects and optimized chemical properties, GH N-C-900 prepared by NH pyrolysis at 900 °C exhibits an excellent electrocatalytic performance toward ORR, with the onset potential of 0.947 ± 0.013 V versus RHE, half-wave potential of 0.830 ± 0.010 V versus RHE, electron transfer number of 3.61-3.99, along as methanol tolerance and superior long-term stability. Comprehensive studies have shown that there is a positive correlation between the total amount of pyrrolic-N and quaternary-N and the catalytic performance of ORR.
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http://dx.doi.org/10.1016/j.jcis.2021.06.036DOI Listing
June 2021

Reduced hyaluronan cross-linking induces breast cancer malignancy in a CAF-dependent manner.

Cell Death Dis 2021 Jun 7;12(6):586. Epub 2021 Jun 7.

Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, 200233, Shanghai, China.

Hyaluronan (HA) cross-linking is a conformational state of HA, a covalent complex between HA and heavy chains (HCs) from inter-α-trypsin inhibitor (I-α-I) mediated by tumor necrosis factor-induced protein 6 (TSG6). Cross-linked HA has been identified as a protective factor in physiological and inflammatory conditions. However, the state of HA cross-linking in tumor microenvironment has not been fully elucidated. As a major constituent of the extracellular matrix (ECM), HA is mainly synthesized by cancer-associated fibroblasts (CAFs). Our study aimed to clarify the role of HA cross-linking in breast cancer malignancy. Compared to normal mammary gland tissues, cross-linked HA levels were significantly decreased in breast cancer and associated with tumor malignancy. When NFbs were activated into CAFs, the levels of cross-linked HA and TSG6 were both suppressed. Through upregulating TSG6, CAFs restored the high level of cross-linked HA and significantly inhibited breast cancer malignancy, whereas NFbs promoted the malignancy when the cross-linked HA level was reduced. Furthermore, the inhibitory role of HA cross-linking in tumor malignancy was directly verified using the synthesized HA-HC complex. Collectively, our study found that the deficiency of cross-linked HA induced breast cancer malignancy in a CAF-dependent manner, suggesting that recovering HA cross-linking may be a potential therapeutic strategy.
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http://dx.doi.org/10.1038/s41419-021-03875-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184848PMC
June 2021

Parecoxib alleviates the motor behavioral decline of aged rats by ameliorating mitochondrial dysfunction in the substantia nigra via COX-2/PGE2 pathway inhibition.

Neuropharmacology 2021 08 3;194:108627. Epub 2021 Jun 3.

Department of Neurobiology, Hebei Medical University, Shijiazhuang, 050017, China; Neuroscience Research Center, Hebei Medical University, Shijiazhuang, 050017, China; Hebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, 050017, China. Electronic address:

Mitochondrial dysfunction manifests as an early event in the substantia nigra (SN) in aging and Parkinson disease. Cyclooxygenase 2 (COX-2), the rate-limiting enzyme in the prostaglandin E2 (PGE2) synthesis pathway, is implicated in aging and age-related neurodegenerative diseases; moreover, inhibition of COX-2 expression has been shown to be neuroprotective for nigrostriatal dopaminergic neurons. However, it is not known whether the neuroprotective effect of COX-2 inhibition is related to improved mitochondrial function during the aging process. To this end, we explored the effects of the selective COX-2 inhibitor parecoxib on mitochondrial function in the SN of aged rats. We found that parecoxib administration to aged rats for 10 weeks decreased COX-2/PGE2 expression, increased tyrosine hydroxylase and dopamine transporter expression in nigrostriatal dopaminergic neurons, and alleviated motor behavioral decline. Decreased malondialdehyde levels and an increased GSH/GSSG ratio as well as enhanced enzymatic activities of catalase and manganese superoxide dismutase in parecoxib-treated aged rats indicate that parecoxib administration elevated antioxidative ability in the SN during the aging process. Parecoxib treatment to aged rats promoted mitochondrial biogenesis by upregulating PGC-1α/NRF-1/TFAM, enhancing mitochondrial fusion by decreasing Drp1 levels and increasing Mfn1 and OPA1 levels, and activated mitophagy by increasing PINK1/Parkin levels while reducing p62/SQSTM1 levels, thereby coordinating mitochondrial homeostasis via inhibiting the COX-2/PGE2 pathway. Thus, our results strongly support the conclusion that parecoxib treatment is conducive to improving mitochondrial dysfunction in the SN upon aging in rats.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108627DOI Listing
August 2021

Bimetallic ZIF-Derived Co/N-Codoped Porous Carbon Supported Ruthenium Catalysts for Highly Efficient Hydrogen Evolution Reaction.

Nanomaterials (Basel) 2021 May 6;11(5). Epub 2021 May 6.

Lab of Advanced Nano-Structure and Transfer Process, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China.

Exploring the economical, powerful, and durable electrocatalysts for hydrogen evolution reaction (HER) is highly required for practical application. Herein, nanoclusters-decorated ruthenium, cobalt nanoparticles, and nitrogen codoped porous carbon ([email protected]) are prepared with bimetallic zeolite imidazole frameworks (ZnCo-ZIF) as the precursor. Thus, the prepared [email protected] catalyst with a low Ru loading of 3.13 wt% exhibits impressive HER catalytic behavior in 1 M KOH, with an overpotential of only 30 mV at the current density of 10 mA cm, Tafel slope as low as 32.1 mV dec, and superior stability for long-time running with a commercial 20 wt% Pt/C. The excellent electrocatalytic properties are primarily by virtue of the highly specific surface area and porosity of carbon support, uniformly dispersed Ru active species, and rapid reaction kinetics of the interaction between Ru and O.
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http://dx.doi.org/10.3390/nano11051228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148513PMC
May 2021

TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4 T Cell Response.

J Immunol 2021 May 28. Epub 2021 May 28.

Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia;

The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions, and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4 T cells with different peptide:MHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition or the functional output of individual effectors following mycobacterial infection in mice. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation, and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR binding affinity in Th1 differentiation and suggest that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.
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http://dx.doi.org/10.4049/jimmunol.2001271DOI Listing
May 2021

Minimally invasive surgery rib fracture fixation based on location and anatomical landmarks.

Eur J Trauma Emerg Surg 2021 May 13. Epub 2021 May 13.

Department of Cardiothoracic Surgery, Shijiazhuang Third Hospital, No. 15 Tiyu South Street, Shijiazhuang, 050011, Hebei, China.

Background: Rib fracture is closely related to thoracic injury with high morbidity and mortality. This study aimed to investigate the clinical effect of Zhang ZhiFei (ZZF) zoning method on the selection of incision and approach in minimally invasive surgery for rib fracture.

Methods: A total of 110 patients with rib fractures from July 2017 to July 2019 were enrolled in the study. Preoperative computed tomography and three-dimensional reconstruction of ribs was performed. Then, the rib fractures to be surgically fixed were divided into costal cartilage zone, chest zone, lateral costal zone, high posterior costal zone, low posterior costal subscapular zone, and low posterior costal paraspinal zone, which was called ZZF zoning method. Rib fractures in each zone had unique minimally invasive incision approach, and the open reduction and internal fixation of rib fracture was performed under minimally invasive surgery of corresponding small incision.

Results: The average incision length and number of incisions of the 110 patients were 6.2 cm and 1.3, respectively. The average number of internal fixation was 5.3 and the average operation time was 82 min. The postoperative fracture end was well aligned. After 3 months of follow-up, no internal fixation was displaced or detached.

Conclusion: Based on the anatomical characteristics of different zones of the chest wall, ZZF zoning method provides a new idea and reference for the selection of incision and approach in minimally invasive internal fixation for rib fracture.
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http://dx.doi.org/10.1007/s00068-021-01676-2DOI Listing
May 2021

Hyaluronan synthase 2 (HAS2) regulates cell phenotype and invadopodia formation in luminal-like breast cancer cells.

Mol Cell Biochem 2021 May 5. Epub 2021 May 5.

Department of Molecular Biology Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Although luminal breast cancer cells are typically highly cohesive epithelial cells and have low invasive ability, many eventually develop metastasis. Until now, the underlying mechanisms remain obscure. In this work, we showed that the level of hyaluronic acid synthase 2 (HAS2) was positively correlated with the malignant phenotype of breast cancer cells. Notably, the increased expression of HAS2 promoted the invasive and migratory abilities of luminal breast cancer cells in vitro, followed by a reduced expression of E-cadherin, β-catenin, and ZO-1, and an elevated expression of N-cadherin and vimentin. Furthermore, overexpression of HAS2 promoted while knockdown of HAS2 impeded invadopodia formation, which subsequently increased or decreased the activation of cortactin, Tks5, and metalloproteinases (MMPs). Activation of these invadopodia-related proteins was prevented by inhibition of HAS2 or disruption of HA, which in turn attenuated the increased motility and invasiveness. Further, in vivo study showed that, HAS2 increased tumor growth and the rate of lung metastasis via driving transition to an invasive cell phenotype in SCID mice that were orthotopically transplanted with luminal breast cancer cells. Collectively, our results showed that HAS2 promoted cell invasion by inducing transition to an invasive phenotype and by enhancing invadopodia formation in luminal breast cancer cells, which may provide new mechanistic insights into its role in tumor metastasis.
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http://dx.doi.org/10.1007/s11010-021-04165-7DOI Listing
May 2021

Facile synthesis of iron oxide supported on porous nitrogen doped carbon for catalytic oxidation.

Sci Total Environ 2021 Sep 24;785:147296. Epub 2021 Apr 24.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300050, China. Electronic address:

Iron oxide (FeO) supported on porous nitrogen doped carbon is synthesized by a facile pyrolysis method. SiO and NaNO are used as the template and activation agent respectively for porous structure generation and large specific surface area (SSA) creation. The obtained materials show superior catalytic oxidation ability and can activate peroxymonosulfate (PMS) in a wide pH range (3-9) to degrade organic pollutants. The degradation process is a two-stage reaction, including a rapid initial decay and a following slow reaction stage. According to the free radical quenching experiments, electron paramagnetic resonance (EPR) spectroscopy analysis, and electrochemical tests, the superoxide radical (O) and singlet oxygen (O) are proved to play crucial roles in organics degradation. The high SSA (773 m g), abundant of structural defects, and synergistic effect between FeO and the nitrogen doped carbon are the key factors for the enhanced activity. The catalysts in this study can be synthesized easily and contain no toxic metals, thus should have great potential in the wastewater remediation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147296DOI Listing
September 2021

PPE31 Contributes to Host Cell Death.

Front Cell Infect Microbiol 2021 13;11:629836. Epub 2021 Apr 13.

Center for Infection and Immunity, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Zhuhai, China.

Genome scale mutagenesis identifies many genes required for mycobacterial infectivity and survival, but their contributions and mechanisms of action within the host are poorly understood. Using CRISPR interference, we created a knockdown of gene in (), which reduced the resistance to acid medium. To further explore the function of PPE31, the mutant strain was generated in and (), respectively. Macrophages infected with the mutant strain caused a reduced inflammatory mediator expressions. In addition, macrophages infected with Δ had decreased host cell death dependent on JNK signaling. Consistent with these results, deletion of from increased the sensitivity to acid medium and reduced cell death in macrophages. Furthermore, we demonstrate that both mutants from and resulted in reduced survival in macrophages, and the survivability of was deceased in zebrafish due to loss of . Our findings confirm that PPE31 as a virulence associated factor that modulates innate immune responses to mycobacterial infection.
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http://dx.doi.org/10.3389/fcimb.2021.629836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078103PMC
July 2021

A non-invasive model for predicting liver fibrosis in HBeAg-positive patients with normal or slightly elevated alanine aminotransferase.

Medicine (Baltimore) 2021 Apr;100(17):e25581

Department of Hepatology, Beijing University of Chinese Medicine Affiliated Shenzhen Hospital.

Abstract: Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population.A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group.The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age -2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] -0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 ×  aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of -2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis.In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.
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http://dx.doi.org/10.1097/MD.0000000000025581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084058PMC
April 2021

Berbamine inhibits SARS-CoV-2 infection by compromising TRPMLs-mediated endolysosomal trafficking of ACE2.

Signal Transduct Target Ther 2021 04 24;6(1):168. Epub 2021 Apr 24.

City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.

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http://dx.doi.org/10.1038/s41392-021-00584-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065329PMC
April 2021

OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Infection.

Front Immunol 2021 11;12:626017. Epub 2021 Mar 11.

Department of Gastroenterology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou, China.

Mucosal associated invariant T (MAIT) cells play a critical role in ()-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in -positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in -induced gastritis, which may provide potential targeting strategies for gastritis treatment.
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http://dx.doi.org/10.3389/fimmu.2021.626017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990886PMC
March 2021

A Radiomic Nomogram for the Ultrasound-Based Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma.

Front Oncol 2021 4;11:625646. Epub 2021 Mar 4.

Department of Ultrasound, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.

Purpose: To construct a sequence diagram based on radiological and clinical factors for the evaluation of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC).

Materials And Methods: Between January 2016 and January 2020, 161 patients with PTC who underwent preoperative ultrasound examination in the Affiliated People's Hospital of Jiangsu University were enrolled in this retrospective study. According to the pathology results, the enrolled patients were divided into a non-ETE group and an ETE group. All patients were randomly divided into a training cohort (n = 97) and a validation cohort (n = 64). A total of 479 image features of lesion areas in ultrasonic images were extracted. The radiomic signature was developed using least absolute shrinkage and selection operator algorithms after feature selection using the minimum redundancy maximum relevance method. The radiomic nomogram model was established by multivariable logistic regression analysis based on the radiomic signature and clinical risk factors. The discrimination, calibration, and clinical usefulness of the nomogram model were evaluated in the training and validation cohorts.

Results: The radiomic signature consisted of six radiomic features determined in ultrasound images. The radiomic nomogram included the parameters tumor location, radiological ETE diagnosis, and the radiomic signature. Area under the curve (AUC) values confirmed good discrimination of this nomogram in the training cohort [AUC, 0.837; 95% confidence interval (CI), 0.756-0.919] and the validation cohort (AUC, 0.824; 95% CI, 0.723-0.925). The decision curve analysis showed that the radiomic nomogram has good clinical application value.

Conclusion: The newly developed radiomic nomogram model is a noninvasive and reliable tool with high accuracy to predict ETE in patients with PTC.
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http://dx.doi.org/10.3389/fonc.2021.625646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970696PMC
March 2021

CD44 activation state regulated by the CD44v10 isoform determines breast cancer proliferation.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Department of Clinical Laboratory and Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.

The cell surface glycoprotein CD44 displays different active statuses; however, it remains unknown whether the activation process of CD44 is critical for tumor development and progression. The aim of the present study was to investigate whether breast cancer (BCa) cells with different activation states of CD44 show similar or distinct functional characteristics and to further examine the mechanisms regulating CD44 activities. A feature for the 'activated' state of CD44 is that it can bind to its principal ligand hyaluronan (HA). The binding of CD44 with HA is usually influenced by CD44 alternative splicing, resulting in multiple CD44 isoforms that determine CD44 activities. Flow cytometry was used to sort BCa cell subsets based on CD44‑HA binding abilities (HA vs. HA). Subsequently, cell proliferation and colony formation assays were performed , and CD44 expression patterns were analyzed via western blotting. The results demonstrated that the CD44 variant isoform 10 (CD44v10) was highly expressed in a HA binding subset of BCa cells, which exhibited a significantly higher proliferation capacity compared with the HA binding subpopulation. Knockdown of CD44v10 isoform in HA binding subpopulation induced an increase in HA binding ability and markedly inhibited proliferation. Furthermore, the mechanistic analysis identified that CD44v10 facilitated cell proliferation via activation of ERK/p38 MAPK and AKT/mTOR signaling. Moreover, the knockdown of CD44v10 expression downregulated the phosphorylation of ERK, AKT and mTOR, while no alteration was observed in p38 phosphorylation. Collectively, the present study identified a subset of fast‑growing BCa cells characterized by CD44v10 expression, which may serve as a specific therapeutic target for BCa.
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http://dx.doi.org/10.3892/or.2021.7958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876991PMC
April 2021

H∞ Exponential Synchronization of Complex Networks: Aperiodic Sampled-Data-Based Event-Triggered Control.

IEEE Trans Cybern 2021 Feb 18;PP. Epub 2021 Feb 18.

This article studies the H∞ exponential synchronization problem for complex networks with quantized control input. An aperiodic sampled-data-based event-triggered scheme is introduced to reduce the network workload. Based on the discrete-time Lyapunov theorem, a new method is adopted to solve the sampled-data problem. In view of the aforementioned method, several sufficient conditions to ensure the H∞ exponential synchronization are acquired. Numerical simulations show that the proposed control schemes can significantly reduce the amount of transmitted signals while preserving the desired system performance.
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http://dx.doi.org/10.1109/TCYB.2021.3052098DOI Listing
February 2021

Dose calculation in proton therapy using a discovery cross-domain generative adversarial network (DiscoGAN).

Med Phys 2021 May 16;48(5):2646-2660. Epub 2021 Mar 16.

Department of Medical Physics, Wuhan University, Wuhan, 430072, China.

Purpose: Accurate dose calculation is a critical step in proton therapy. A novel machine learning-based approach was proposed to achieve comparable accuracy to that of Monte Carlo simulation while reducing the computational time.

Methods: Computed tomography-based patient phantoms were used and three treatment sites were selected (thorax, head, and abdomen), comprising different beam pathways and beam energies. The training data were generated using Monte Carlo simulations. A discovery cross-domain generative adversarial network (DiscoGAN) was developed to perform the mapping between two domains: stopping power and dose, with HU values from CT images incorporated as auxiliary features. The accuracy of dose calculation was quantitatively evaluated in terms of mean relative error (MRE) and mean absolute error (MAE). The relationship between the DiscoGAN performance and other factors such as absolute dose, beam energy and location within the beam cross-section (center and off-center lines) was examined.

Results: The DiscoGAN model is found to be effective in dose calculation. For the abdominal case, the MRE is found to 1.47% (mean), 3.30% (maximum) and 0.67% (minimum). For the thoracic case, the MRE is found to ~2.43% (mean), 4.80% (maximum) and 0.71% (minimum). For the head case, the MRE is found to ~2.83% (mean), 4.84% (maximum) and 1.01% (minimum). Comparable accuracy is found in the independent validation dataset (different CT images), achieving a mean MRE of ~1.65% (thorax), 4.02% (head) and 1.64% (abdomen). For the energy span between 80 and 130 MeV, no strong dependency of accuracy on beam energy is found. The results imply that no systematic deviation, either over-dose or under-dose, occurs between the predicted dose and raw dose.

Conclusion: The DiscoGAN framework demonstrates great potential as a tool for dose calculation in proton therapy, achieving comparable accuracy yet being more efficient relative to Monte Carlo simulation. Its comparison with the pencil beam algorithm (PBA) will be the next step of our research. If successful, our proposed approach is expected to find its use in more advanced applications such as inverse planning and adaptive proton therapy.
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http://dx.doi.org/10.1002/mp.14781DOI Listing
May 2021

Emerging biosensing technologies for improved diagnostics of COVID-19 and future pandemics.

Talanta 2021 Apr 13;225:121986. Epub 2020 Dec 13.

Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, 518060, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, 518060, China. Electronic address:

Diagnostic tools play significant roles in the fight against COVID-19 and other pandemics. Existing tests, such as RT-qPCR, have limitations including long assay time, low throughput, inadequate sensitivity, and suboptimal portability. Emerging biosensing technologies hold the promise to develop tests that are rapid, highly sensitive, and suitable for point-of-care testing, which could significantly facilitate the testing of COVID-19. Despite that, practical applications of such biosensors in pandemics have yet to be achieved. In this review, we consolidate the newly developed diagnostic tools for COVID-19 using emerging biosensing technologies and discuss their application promise. In particular, we present nucleic acid tests and antibody tests of COVID-19 based on both conventional and emerging biosensing methods. We then provide perspectives on the existing challenges and potential solutions.
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http://dx.doi.org/10.1016/j.talanta.2020.121986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733602PMC
April 2021

Application of 3D printing and framework internal fixation technology for high complex rib fractures.

J Cardiothorac Surg 2021 Feb 15;16(1). Epub 2021 Feb 15.

Department of Thoracic Surgery, the Second Hospital of Hebei Medical University, No. 215, Heping west road, Shijiazhuang, 050000, China.

Objective: To explore the clinical effect of 3D printing combined with framework internal fixation technology on the minimally invasive internal fixation of high complex rib fractures.

Methods: Total 16 patients with high complex rib fractures were included in the study. Before the procedure, the 3D rib model was reconstructed based on the thin-layer chest CT scan. According to the 3D model, the rib locking plate was pre-shaped, and the preoperative planning were made including the direction of the locking plate, the location of each nail hole and the length of the screw. During the operation, the locking plate was inserted from the sternum to the outermost fracture lines of ribs with screws at both ends. In addition, the locking plate was used as the frame to sequentially reduce the middle fracture segment and fix with screws or steel wires. Chest x-rays or chest CT scans after surgery were used to assess the ribs recovery. All patients were routinely given non-steroidal anti-inflammatory drugs (NSAIDS) for analgesia, and the pain level was evaluated using numerical rating scale (NRS).

Results: The preoperative planning according to the 3D printed rib model was accurate. The reduction and fixation of each fracture segment were successfully completed through the framework internal fixation technology. No cases of surgical death, and postoperative chest pain was significantly alleviated. Five to 10 months follow up demonstrated neither loosening of screws, nor displacement of fixtures among patients. The lungs of each patients were clear and in good shape.

Conclusion: The application of 3D printing combined with framework internal fixation technology to the high complex rib fractures is beneficial for restoring the inherent shape of the thoracic cage, which can realize the accurate and individualized treatment as well as reduces the operation difficulty.
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http://dx.doi.org/10.1186/s13019-020-01377-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883420PMC
February 2021

MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-γ.

Front Microbiol 2020 21;11:512581. Epub 2021 Jan 21.

Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministryof Education, Sun Yat-sen University, Guangzhou, China.

Tuberculosis (TB), which is a frequent and important infectious disease caused by , has resulted in an extremely high burden of morbidity and mortality. The importance of intestinal dysbacteriosis in regulating host immunity has been implicated in TB, and accumulating evidence suggests that microRNAs (miRNAs) might act as a key mediator in maintaining intestinal homeostasis through signaling networks. However, the involvement of miRNA in gut microbiota, TB and the host immune system remains unknown. Here we showed that intestinal dysbacteriosis increases the susceptibility to TB and remotely increased the expression of miR-21 in lung. Systemic antagonism of miR-21 enhanced IFN-γ production and further conferred immune protection against TB. Molecular experiments further indicated that miR-21a-3p could specifically target IFN-γ mRNA. These findings revealed regulatory pathways implicating intestinal dysbacteriosis induced-susceptibility to TB: intestinal dysbiosis→lung miRNA→targeting IFN-γ→impaired anti-TB immunity. This study also suggested that deregulated miRNAs by commensal bacteria could become promising targets as TB therapeutics.
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http://dx.doi.org/10.3389/fmicb.2020.512581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859650PMC
January 2021

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery.

Nat Commun 2021 01 20;12(1):488. Epub 2021 Jan 20.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC of 2.1 μM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLpro in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.
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http://dx.doi.org/10.1038/s41467-020-20718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817691PMC
January 2021

Preparation of Amino-Functional UiO-66/PIMs Mixed Matrix Membranes with [bmim][TfN] as Regulator for Enhanced Gas Separation.

Membranes (Basel) 2021 Jan 4;11(1). Epub 2021 Jan 4.

Department of Chemical and Biological Engineering, State Key Laboratory of Chemical Engineering, Zhejiang University, Hangzhou 310027, China.

Development of mixed matrix membranes (MMMs) with excellent permeance and selectivity applied for gas separation has been the focus of world attention. However, preparation of high-quality MMMs still remains a big challenge due to the lack of enough interfacial interaction. Herein, ionic liquid (IL)-modified UiO-66-NH filler was first incorporated into microporous organic polymer material (PIM-1) to prepare dense and defect-free mixed matrix membranes via a coating modification and priming technique. IL [bmim][TfN] not only improves the hydrophobicity of UiO-66-NH and facilitates better dispersion of UiO-66-NH nanoparticles into PIM-1 matrix, but also promotes the affinity between MOFs and polymer, sharply reducing interface non-selective defects of MMMs. By using this strategy, we can not only facilely synthesize high-quality MMMs ignoring non-selective interfacial voids, but also structurally regulate MOF nanoparticles in the polymer substrate and greatly improve interface compatibility and stability of MMMs. The method also gives suitable level of generality for fabrication of versatile defect-free MMMs based on different combination of MOFs and PIMs. The prepared [email protected]/PIM-1 membrane exhibited outstanding gas separation behavior with large CO permeation of 8283.4 Barrer and high CO/N selectivity of 22.5.
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http://dx.doi.org/10.3390/membranes11010035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824137PMC
January 2021

Easily Regenerated CuO/γ-AlO for Persulfate-Based Catalytic Oxidation: Insights into the Deactivation and Regeneration Mechanism.

ACS Appl Mater Interfaces 2021 Jan 5;13(2):2630-2641. Epub 2021 Jan 5.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China.

In this work, γ-AlO-supported CuO (-CuO/AlO) materials are successfully synthesized using a novel impregnation-precipitation-decomposition method. The obtained -CuO/AlO catalyst shows excellent catalytic activities for bisphenol A (BPA) degradation with sodium persulfate (PDS) as an oxidant. Radical quenching tests and electron paramagnetic resonance (EPR) studies indicate that PDS activation is a combined mechanism involving both free radical and nonfree radical pathways. In a continuous large-scale degradation process, about 1.78 L of 20 ppm BPA can be completely removed within 480 min. Although -CuO/AlO can be deactivated after several reaction cycles, the catalytic activity can be regenerated after simple aerobic calcination. X-ray photoelectron spectroscopy (XPS) and Raman analysis confirm that the deactivation of -CuO/AlO should be attributed to the conversion of Cu(II) to Cu(I). The aerobic calcination could oxidize Cu(I) back to Cu(II), thus recovering the catalytic activity. In addition, the density functional technology (DFT) and temperature-programmed oxidation (TPD) results reveal that γ-AlO can not only serve as a carrier to anchor the CuO particles but also can adsorb and activate PDS by introducing more basic sites on the surface. -CuO/AlO has high activity and can be regenerated easily, thus having great potential applications for wastewater treatment.
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http://dx.doi.org/10.1021/acsami.0c19013DOI Listing
January 2021

Bamboo-like nitrogen-doped carbon nanotubes on iron mesh for electrochemically-assisted catalytic oxidation.

J Hazard Mater 2021 Apr 29;408:124899. Epub 2020 Dec 29.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China. Electronic address:

In this study, bamboo-like nitrogen-doped carbon nanotubes (BN-CNTs) are successfully deposited on etched iron mesh (d-Fe) using chemical vapor deposition (CVD) method with acetonitrile as precursor. The acidic etching process is necessary for the special BN-CNTs structure formation by exposing more Fe sites. The BN-CNTs/d-Fe is then evaluated for the electrochemically-assisted PMS activation to degrade phenol. Under cyclic voltammetry (CV, 0-1 V vs. RHE) assistant, 20 ppm phenol can be degraded in 30 min with a rate constant of 0.2837 min, ~78 times more than that without CV. Some Fe species in the catalyst will be reduced at the initial stage, a two-step pseudo-first-order kinetic is thus used for the degradation curves fitting. Both the structure defects and doped nitrogen atoms are responsible for the high catalytic activity of BN-CNTs. According to the quenching tests, both radical and non-radical processes are present for PMS activation, thus obtaining enhanced organics removal efficiency. The electrochemically assistant could enhance the PMS adsorption on the electrode as well as electrons transfer between Fe and PMS, thus increasing the PMS activation efficiency. The utilization of earth-abundant Fe mesh for the fabricating free-standing electrodes provide a potential low-cost and effective strategy of waste water remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124899DOI Listing
April 2021
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