Publications by authors named "Zhiping Zhang"

334 Publications

Targeting the p300/NONO axis sensitizes melanoma cells to BRAF inhibitors.

Oncogene 2021 May 20. Epub 2021 May 20.

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Central Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang, PR China.

BRAF inhibitors (BRAFi) that target BRAF V600E kinase, a driver mutation found in 50% of melanomas, show a significant antitumor response, but the common emergence of acquired resistance remains a challenge. Abnormal expression of RAF isoforms CRAF and ARAF reactivates pERK1/2, which plays crucial roles in the acquisition of resistance of melanoma cells. However, the mechanisms of dysregulation of RAF isoforms in resistant melanoma cells remain unknown. Here, we identified NONO interacted with and stabilized both CRAF and ARAF in melanoma cells, and that NONO was acetylated at 198K by p300 acetyltransferase, which stabilized NONO via antagonizing its ubiquitination/degradation mediated by RNF8. The upregulation of both p300 and NONO promoted the rebound of pERK1/2 and the subsequent resistance of melanoma cells to BRAFi, and the activation of ERK1/2 in turn induced p300 to form a positive feedback loop in resistant melanoma cells. There was a positive correlation between p300 and NONO in resistant melanoma cells and clinical samples, and p300 inhibitor C646 overcame the resistance of resistant melanoma cells to BRAF inhibitors in vitro and in vivo. Our findings reveal that targeting the positive feedback loop of p300-NONO-CRAF/ARAF-pERK1/2 may be excellent strategies to overcome the resistance of BRAF inhibitors for melanoma patients.
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http://dx.doi.org/10.1038/s41388-021-01834-1DOI Listing
May 2021

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design.

Acta Pharm Sin B 2021 May 7. Epub 2021 May 7.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.
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http://dx.doi.org/10.1016/j.apsb.2021.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102084PMC
May 2021

Ten-eleven translocation protein 1 modulates medulloblastoma progression.

Genome Biol 2021 Apr 29;22(1):125. Epub 2021 Apr 29.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes.

Results: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes.

Conclusions: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
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http://dx.doi.org/10.1186/s13059-021-02352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082834PMC
April 2021

Role of surfactant in affecting photo-fermentative bio-hydrogen production performance from corncob.

Bioresour Technol 2021 Aug 15;333:125173. Epub 2021 Apr 15.

Henan Agricultural University, Henan International Joint Laboratory of Biomass Energy and Nanomaterials, Zhengzhou 450002, PR China. Electronic address:

Surfactant addition can cause a significant change in the interface state of the solution system, which is helpful to avoid agglomeration and sedimentation of solid state, and improve the mass transfer capacity. Hence, the performance of high-solid photo-fermentative bio-hydrogen production system with bio-surfactant addition was evaluated in this work. Corncob was selected as raw material, and cumulative hydrogen yield (CHY) was taken as reference. The effect of Rhamnolipids (RLs) and Tea Saponin (TSn) addition on hydrogen yield capacity was investigated. The results showed that CHY was effectively increased by the addition of RLs and TSn, the highest CHY of 356.42 ± 16.5 mL and 265.38 ± 7.5 mL appeared when the concentrations of surfactant addition were 0.08 g/L RLs and 1.5 g/L TSn, which were 67.85% and 24.97% higher than control group, respectively. The maximum energy conversion efficiency reached 5.47% and 4.08% with an increase of 67.8% and 25.2%.
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http://dx.doi.org/10.1016/j.biortech.2021.125173DOI Listing
August 2021

HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU.

Biosci Rep 2021 Apr;41(4)

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, Center Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang 330008, China.

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms.

Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo.

Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo.

Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.
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http://dx.doi.org/10.1042/BSR20203905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150159PMC
April 2021

endothelialization and neointimal hyperplasia assessment after rabbit carotid endarterectomy with bovine pericardium.

Ann Transl Med 2021 Mar;9(6):471

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Previous studies have reported that the use of a patch in carotid endarterectomy (CEA) surgery can reduce the rate of restenosis and perioperative complications. The goal of this study was to compare the short- and medium-term outcomes of endothelialization and neointimal hyperplasia of patch closure (PC) angioplasty in CEA with direct closure (DC) in a rabbit model. A bovine pericardial patch (BPP) was used in the PC procedures.

Methods: Two carotid arteries were dried by air flow to simulate endarterectomy and selected for PC and DC in each rabbit. Different animals were sacrificed at 1, 2, 3, 4, and 8 weeks after the procedure. The endarterectomized segments were extracted and examined microscopically with histopathological and immunohistochemical analysis, and electron-microscopy measurements.

Results: In all, 19 rabbits were included in this study; 3 rabbits were placed in a 2-week postoperative group and 4 rabbits were placed in the 1-, 3-, 4-, and 8-week postoperative group respectively. Hematoxylin-eosin (HE) staining showed neointima on the PC side at an early stage (1-week postoperatively), and intimal hyperplasia could be seen on both sides. Immunohistochemical analysis showed that Ki-67 was higher on the PC side than on the DC side at an early stage (1,661.5±1,122.9 cells/mm, P=0.060). In the 2-week postoperative group, von Willebrand factor (vWF) was higher on the DC side (-377.0±155.6 cells/mm, P=0.052). Alpha-smooth muscle actin (α-SMA) values were comparable on both sides (P>0.05). Electron microscopy measurements showed that functional endothelial cells exhibited a cobblestone-like morphology and were nicely elongated in the direction of blood flow.

Conclusions: The use of BPP in PC angioplasty during CEA can maintain stability and also provide rapid endothelialization. PC with BPP has comparable ability of efficient endothelialization with DC, but is more likely to have early endothelialization.
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http://dx.doi.org/10.21037/atm-20-8103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039648PMC
March 2021

Role of LncRNAs in regulating cancer amino acid metabolism.

Cancer Cell Int 2021 Apr 13;21(1):209. Epub 2021 Apr 13.

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Northern 128 Xiangshan Road, Nanchang, 330008, Jiangxi, People's Republic of China.

The metabolic change of tumor cells is an extremely complicated process that involves the intersection and integration of various signal pathways. Compared with normal tissues, cancer cells show distinguished metabolic characteristics called metabolic reprogramming, which has been considered as a sign of cancer occurrence. With the deepening of tumor research in recent years, people gradually found that amino acid metabolism played crucial roles in cancer progression. Long non-coding RNAs (lncRNAs), which are implicated in many important biological processes, were firstly discovered dysregulating in cancer tissues and participating in extensive regulation of tumorigenesis. This review focuses on the reprogramming of amino acid metabolism in cancers and how lncRNAs participate in the regulatory network by interacting with other macromolecular substances. Understanding the functions of lncRNA in amino acid reprogramming in tumors might provide a new vision on the mechanisms of tumorigenesis and the development of new approaches for cancer therapy.
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http://dx.doi.org/10.1186/s12935-021-01926-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045299PMC
April 2021

Recycling of shrub landscaping waste: Exploration of bio-hydrogen production potential and optimization of photo-fermentation bio-hydrogen production process.

Bioresour Technol 2021 Jul 24;331:125048. Epub 2021 Mar 24.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy (MOA of China), Henan Agricultural University, Zhengzhou 450002, China; Institute of Agricultural Engineering, Huanghe S & T University, Zhengzhou 450006, China. Electronic address:

Shrub landscaping waste, derived from afforestation of city, has increased annually, making it a promising feedstock for energy production. In this work, the photo-fermentation bio-hydrogen production potential from shrub landscaping waste was evaluated. Eight kinds of shrub landscaping wastes (Photinia fraseri, Buxus megistophylla, Buxus sinica, Pittosporum tobira, Sabina Chinensis, Berberis thunbergii, Ligustrum vicaryi and Ligustrum quihoui) were selected as substrate and the photo-fermentation bio-hydrogen production process of which was optimized. Buxus megistophylla was found to be the most suitable substrate for photo-fermentation bio-hydrogen production. Moreover, the initial pH value, temperature and substrate concentration had significant influence on photo-fermentation bio-hydrogen production. The maximum cumulated hydrogen yield of Buxus megistophylla was 73.82 ± 0.06 mL/g TS under the optimal conditions of light intensity of 3000 Lux, substrate mass concentration of 21.49 g/L, temperature of 29.78 °C, inoculant amount of 25% and initial pH value of 6.78.
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http://dx.doi.org/10.1016/j.biortech.2021.125048DOI Listing
July 2021

Numerical simulation of wind field and sand flux in crescentic sand dunes.

Sci Rep 2021 Mar 2;11(1):4973. Epub 2021 Mar 2.

State Key Laboratory Breeding Base of Desertification and Aeolian Sand Disaster Combating, Gansu Desert Control Research Institute, Lanzhou, 730070, China.

Sand flux is the key factor to determine the migration of sand dunes and the erosion to the surrounding environment. There are crescent-shaped sand dunes of various scales in the desert, and there are significant differences in spatial wind field and sand flux among them. However, due to the difficulty of monitoring, it is difficult to continuously observe the spatial wind field and sand flux around the larger crescentic dunes. On the basis of the Reynolds-Average Navier-Stokes (RA-NS) equation and the stress and sand flux model, the distribution of wind field and sand flux of a circular dune with a height of 4.2 m and a length of about 100 m during the four evolutionary periods of the evolution into a crescentic dune was simulated in this study. By comparing with the measured results, we verified that the closer to the leeward side, the more the simulated values of the velocity in wind field and sand flux were in line with the measured results. In order to further analyze the influence of the height of dune and other relevant parameters on sand flux, we simulated the influence on wind field and sand flux by changing the air viscosity and wind velocity of upper boundary. We found that the air viscosity mainly affected the amount of deposited sand on the leeward side of sand dune, while the increase of wind velocity would undoubtedly increase the sand flux of the whole sand dune. In addition, the simulation results also showed that the influence of changes in height of dune on the turbulent intensity of leeward side was very significant, and the turbulent intensity increased with the height of dune. The height changes of tall dunes gradually affected the transport of sand caused by wind flow behind the leeward side because that the rotation of the wind flow would form new vortexes at the large pores behind the leeward side, which would increase the turbulent energy in space and thus would increase the distance of migration of the lifting sand. While the low sand dunes could not form extra small vortexes at the bottom of the leeward side, so the wind velocity was small and the eddy currents behind the leeward side were more stable. The simulation results indicated that wind velocity was not the only reason for increasing the amount of sand flux, and the fluctuation of wind flow caused by turbulence could also stimulate the movement of sand particles on the ground.
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http://dx.doi.org/10.1038/s41598-021-84509-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925693PMC
March 2021

A strategy for successive feedstock reuse to maximize photo-fermentative hydrogen production of Arundo donax L.

Bioresour Technol 2021 Jun 23;329:124878. Epub 2021 Feb 23.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy of Ministry of Agriculture and Rural Affairs, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

This study proposed a strategy to maximize the hydrogen yield by reusing feedstock of Arundo donax L. For this purpose, a successive 4-batch photo-fermentative hydrogen production (PFHP) was carried out to test the strategy. About 50% of total hydrogen yield was additionally obtained by reusing the Arundo donax L for successive 4 times in comparison to single 1st batch (161.4 mL/U. cell dry weight). In addition to the highest hydrogen yield, the maximum hydrogen production rate (6.0 mL/U. cell dry weight /h), and the highest volatile fatty acids (VFAs) concentration (32 mM) were also obtained from the 1st batch, while the 2nd batch gave the maximum substrate conversion efficiency (96.5%). Moreover, a positive relationship between the sum of acetic and butyric acids with hydrogen yields was observed. This strategy would help in enhancing hydrogen yield that coupled with cost reduction for biohydrogen production.
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http://dx.doi.org/10.1016/j.biortech.2021.124878DOI Listing
June 2021

HIV-1 uses dynamic podosomes for entry into macrophages.

J Virol 2021 Feb 24. Epub 2021 Feb 24.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, P.R.China

Macrophages are one of the major targets of (HIV-1) and play crucial roles in viral dissemination and persistence during AIDS progression. Here, we reveal the dynamic podosome-mediated entry of HIV-1 into macrophages. Inhibition of podosomes prevented HIV-1 entry into macrophages, while stimulation of podosome formation promoted viral entry. Single-virus tracking revealed the temporal and spatial mechanism of the dynamic podosome-mediated viral entry process. The core and ring structures of podosomes played complex roles in viral entry. The HIV coreceptor, CCR5, was recruited to form specific clusters at the podosome ring, where it participated in viral entry. The podosome facilitated HIV-1 entry with a rotation mode triggered by dynamic actin. Our discovery of this novel HIV-1 entry route into macrophages, mediated by podosomes critical for cell migration and tissue infiltration, provides a new view of HIV infection and pathogenesis, which may assist in the development of new antiviral strategies.Macrophages are motile leukocytes and play critical roles in HIV-1 infection and AIDS progression. Podosomes, as small dynamic adhesion microdomains driven by the dynamic actin cytoskeleton, are mainly involved in cell migration of macrophages. Herein, we found that HIV-1 uses dynamic podosomes to facilitate its entry into macrophages. Single-virus imaging coupled with drug assays revealed the mechanism underlying the podosome-mediated route of HIV-1 entry into macrophages, including the dynamic relationship between the viral particles and the podosome core and ring structures, the CCR5 coreceptor. The dynamic podosome-mediated entry of HIV-1 into macrophages will be very significant for HIV-1 pathogenesis, especially for viral dissemination via macrophage migration and tissue infiltration. Thus, we report a novel HIV-1 entry route into macrophages mediated by podosomes, which extends our understanding of HIV infection and pathogenesis.
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http://dx.doi.org/10.1128/JVI.02480-20DOI Listing
February 2021

No Association Between Gene Polymorphisms and Central Nervous System Tumor Susceptibility in Chinese Children.

Pharmgenomics Pers Med 2021 19;14:109-115. Epub 2021 Jan 19.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Changsha, People's Republic of China.

Background: Central nervous system (CNS) tumor is a malignancy commonly seen occurring in childhood, worldwide. Fat mass and obesity-associated (FTO) enzyme, initially identified as an obesity-related protein, also functions as a susceptibility gene for cancers. However, predisposing effect of gene single nucleotide polymorphisms (SNPs) on CNS tumor risk remains unknown.

Methods: Herein, we genotyped 314 CNS tumor patients and 380 healthy controls samples from three hospitals to explore whether gene SNPs impact CNS tumor risk. TaqMan SNP genotyping assay was applied for the genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from multinomial logistic regression, were applied to determine the associations of SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G) in gene with risk of CNS tumor.

Results: We failed to detect significant associations between gene SNPs and CNS tumor risk, either in single-locus or combined analysis. A significantly increased ependymoma risk was found for carriers with 3-4 risk genotypes in comparison to 0-2 risk genotypes (adjusted OR=1.94, 95% CI=1.11-3.37, =0.020).

Conclusion: Our data indicated that gene SNPs are unlikely to have large effects on CNS tumor risk but may have weaker effects.
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http://dx.doi.org/10.2147/PGPM.S289345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826062PMC
January 2021

The Pathogenesis Based on the Glymphatic System, Diagnosis, and Treatment of Idiopathic Normal Pressure Hydrocephalus.

Clin Interv Aging 2021 15;16:139-153. Epub 2021 Jan 15.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China.

Idiopathic normal pressure hydrocephalus (iNPH) is a rare neurological disorder with no clear prevalence factors and is a significant danger to the elderly. The intracranial glymphatic system is the internal environment that maintains brain survival and metabolism, and thus fluid exchange changes in the glymphatic system under various pathological conditions can provide important insights into the pathogenesis and differential diagnosis of many neurodegenerative diseases such as iNPH. iNPH can be diagnosed using a combination of clinical symptoms, imaging findings and history, and cerebrospinal fluid biomarkers due to the glymphatic system disorder. However, only few researchers have linked the two. Shunt surgery can improve the glymphatic system disorders in iNPH patients, and the surgical approach is determined using a combination of clinical diagnosis and trials. Therefore, we have composed this review to provide a future opportunity for elucidating the pathogenesis of iNPH based on the glymphatic system, and link the glymphatic system to the diagnosis and treatment of iNPH. The review will provide new insights into the medical research of iNPH.
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http://dx.doi.org/10.2147/CIA.S290709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815082PMC
May 2021

Immunogenic Hybrid Nanovesicles of Liposomes and Tumor-Derived Nanovesicles for Cancer Immunochemotherapy.

ACS Nano 2021 02 20;15(2):3123-3138. Epub 2021 Jan 20.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.

Exploring a rational delivery system of integrating chemotherapy with immunotherapy to broaden benefits of cancer immunochemotherapy is still under challenge. Herein, we developed doxorubicin (DOX)-loaded biomimetic hybrid nanovesicles ([email protected]) fusing artificial liposomes (LIPs) with tumor-derived nanovesicles (TNVs) for combinational immunochemotherapy. [email protected] with a homologous targeting ability could deliver DOX to tumor tissue and elicit an effective immunogenic cell death response to improve the immunogenicity of a tumor. Meanwhile, the preserved tumor antigens and endogenous danger signals in [email protected] activated dendritic cells and induced a subsequent antigen-specific T cell immune response. [email protected] displayed a specific antitumor effect on murine melanoma, Lewis lung cancer, and 4T1 breast cancer based on the infiltration of effector immune cells and improvement of the immunosuppressive tumor microenvironment. Furthermore, the combination of [email protected] with immune checkpoint inhibitor amplified antitumor efficacy with 33.3% of the mice being tumor-free. Therefore, the hybrid LINV is a promising drug delivery platform with a boosted antitumor immune response for effective immunochemotherapy.
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http://dx.doi.org/10.1021/acsnano.0c09681DOI Listing
February 2021

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent.

Drug Deliv 2021 Dec;28(1):134-143

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, PR China.

This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both and . Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM·s. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, =.041). The analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice ( < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.
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http://dx.doi.org/10.1080/10717544.2020.1862363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782420PMC
December 2021

Decreased MiR-30a promotes TGF-β1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus.

Transl Neurosci 2020 26;11(1):60-74. Epub 2020 May 26.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. China.

Background: Fibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-β1 (TGF-β1) may be involved in thrombin-induced arachnoid fibrosis.

Methods: A rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed.

Results: Decreased expression of miR-30a and increased expression of TRAF3IP2, TGF-β1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3'UTR and inhibits the expression of TRAF3IP2, TGF-β1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2.

Conclusions: This study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.
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http://dx.doi.org/10.1515/tnsci-2020-0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711221PMC
May 2020

Insights into correlation between hydrogen yield improvement and glycerol addition in photo-fermentation of Arundo donax L.

Bioresour Technol 2021 Feb 1;321:124467. Epub 2020 Dec 1.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy of Ministry of Agriculture and Rural Affaires, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

This study aimed to explore the correlation between hydrogen yield improvement of photo-fermentation of Arundo donax L. and glycerol addition. Different glycerol concentrations (g/L) (0, 10, 15, 20, and 30) were replenished to establish co-substrate system. And statistical analysis was introduced to evaluate the correlation. The maximum hydrogen yield improvement (294%) was obtained from glycerol addition of 15 g/L in comparison with mono-substrate system of Arundo donax L. Under the optimal glycerol addition (15 g/L), the glycerol/Arundo donax L. ratio, C/N ratio, initial medium redox potential (E), and solid/liquid ratio were 1:1, 25.1, 57 mV, and 1/68, respectively. In addition, canonical correlation analysis (CCA) indicated that initial and final medium redox potential (E) had the strongest relationship with yield improvement of photo-fermentation. Moreover, Pearson's correlation analysis claimed that Arundo donax L./glycerol ratio played a key role during the photo-fermentative hydrogen production (PFHP) process.
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http://dx.doi.org/10.1016/j.biortech.2020.124467DOI Listing
February 2021

Injectable Liquid Crystal Formation System for Reshaping Tumor Immunosuppressive Microenvironment to Boost Antitumor Immunity: Postoperative Chemoimmunotherapy.

Small 2020 12 18;16(50):e2004905. Epub 2020 Nov 18.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.

Exploring optimal strategies to improve patient outcome postoperatively is still under challenge. Cancer immunotherapy has great potential to prevent the postoperative tumor recurrence and metastasis, which could be further strengthened by re-education of tumor microenvironment (TME). Herein, a local and sustained drug delivery system of liquid crystal formation system (LCFS) co-loaded with doxorubicin (DOX) and resiquimod (R848) (D/[email protected]) is reported to confer effective chemoimmunotherapy with reduced systematic toxicity. After local administration, D/[email protected] turns tumor into in situ vaccine via DOX-triggered immunogenic cell death effect accompanied with immunostimulatory effect of R848. Meanwhile, combination treatment of D/[email protected] facilitates the recruitment of effector CD8 T cells and the polarization of myeloid-derived suppressor cells and immunosuppressive type 2-polarized macrophages to tumoricidal antigen-presenting cells, favoring antigen-specific T cell immune response and inducing more immunogenic phenotypes in tumors. The generated in situ vaccine as well as reshaped TME by D/[email protected] elicited systematic immune response and long term immune-memory effect in combination with immune checkpoint blockade to significantly prevent postoperative B16F10 or 4T1 tumor recurrence and metastasis. Therefore, this combination strategy of spatiotemporal TME modulation is expected to provide a clinical available option for effective postoperative chemoimmunotherapy.
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http://dx.doi.org/10.1002/smll.202004905DOI Listing
December 2020

Reliability of Preoperative Prediction of the Location of the Facial Nerve Using Diffusion Tensor Imaging-Fiber Tracking in Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

World Neurosurg 2021 02 28;146:351-361.e3. Epub 2020 Oct 28.

Department of Neurosurgery, XuanWu Hospital, Capital Medical University, Beijing, China; International Neuroscience Institute (China-INI), Beijing, China. Electronic address:

The popularization and application of microscopy, the in-depth study of the microanatomy of the cerebellopontine angle, and the application of intraoperative electrophysiological monitoring technology to preserve facial nerve function have laid a solid foundation for the modern era of neurosurgery. The preoperative prediction of the location of the facial nerve is a long-desired goal of neurosurgeons. The advances in neuroimaging seem to be making this goal a reality. Many studies investigating the reliability of the preoperative prediction of the location of the facial nerve using diffusion tensor imaging-fiber tracking in vestibular schwannoma have been reported in the last 20 years. The PubMed, Embase, and Cochrane databases were searched for articles published before March 30, 2020. A comprehensive review of published studies was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Authors performed a systematic review and meta-analysis of the reported data to assess the reliability of the preoperative prediction of the location of the facial nerve using diffusion tensor imaging-fiber tracking in vestibular schwannoma. The data were analyzed using a fixed-effects model. The estimated overall intraoperative verification concordance rate was 89.05% (95% confidence interval 85.06%-92.58%). Preoperatively predicting the location of the facial nerve using diffusion tensor imaging-fiber tracking in vestibular schwannoma is reliable, but the extent to which it contributes to long-term facial nerve function is still unclear. To further verify these results, studies with larger sample sizes are needed in the future, especially prospective randomized controlled trials focusing on the long-term functional preservation of the facial nerve.
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http://dx.doi.org/10.1016/j.wneu.2020.10.136DOI Listing
February 2021

Corrigendum: Characterization of Gene as a Pathogenicity Factor of .

Front Microbiol 2020 18;11:595238. Epub 2020 Sep 18.

College of Plant Protection/Beijing Key Laboratory of Seed Disease Testing and Control (BKL-SDTC), China Agricultural University, Beijing, China.

[This corrects the article DOI: 10.3389/fmicb.2020.01824.].
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http://dx.doi.org/10.3389/fmicb.2020.595238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530560PMC
September 2020

Enhancement of the biohydrogen production performance from mixed substrate by photo-fermentation: Effects of initial pH and inoculation volume ratio.

Bioresour Technol 2021 Jan 25;319:124153. Epub 2020 Sep 25.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy, MOA of China, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

Co-digestion of substrates can improve hydrogen yield (HY) by adjusting carbon nitrogen ratio (C/N) of fermentation substrates. This study evaluated the enhancement of hydrogen production from co-digestion of duckweed and corn straw via photo-fermentation. The maximum HY of 78.0 mL/g Total solid (TS) was obtained from the mixed ratio of 5:1 (C/N of 13.2), which was 25.4% and 29.6% higher than those of single substrate of duckweed and corn straw, respectively. The effects of initial pH and inoculation volume ratio (IVR) on co-digestion photo-fermentative hydrogen production (CD-PFHP) from duckweed and corn straw were further studied. A maximum HY of 85.6 mL/g TS was achieved under the optimal condition (initial pH 8, IVR 20%, mix ratio of duckweed and corn straw of 5:1). Additionally, both mix ratio and initial pH showed statistical difference (p < 0.05). Acetic acid and butyric acid were found to be the main metabolic by-products during CD-PFHP.
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http://dx.doi.org/10.1016/j.biortech.2020.124153DOI Listing
January 2021

Downregulation of MicroRNA-34c-5p facilitated neuroinflammation in drug-resistant epilepsy.

Brain Res 2020 12 17;1749:147130. Epub 2020 Sep 17.

Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China. Electronic address:

Drug-resistant epilepsy patients has aberrant inflammatory mediator levels. However, the mechanism of which is remains unillustrated. Here the molecular mechanism underlying the neuroinflammatory process in patients with drug-resistant epilepsy were investigated. Bioinformatics analysis revealed that miR-34c-5p was significantly downregulated in patients with drug-resistant epilepsy, compared to control population. Then, luciferase reporter assays indicated that HMGB1, inflammation-related mediators, was the target gene of miR-34c-5p. The kainic acid-induced epileptic rats were established and divided into drug-sensitive epilepsy and drug-resistant epilepsy according to their seizure behavior and EEG after antiepileptic drug administration. Downregulation of miR-34c-5p, elevated expression of HMGB1 and IL-1β had been found in rats with drug-resistant epilepsy, compared to drug-sensitive epilepsy rats. Aggravated hippocampal neuron loss was demonstrated in rats with drug-resistant epilepsy. The results from epileptic rats were subsequently validated from children with drug-resistant epilepsy. Analysis manifested that miR-34c-5p was obviously decreased, while HMGB1 was increased on serum of children with drug-resistant epilepsy. Our study highlights that decreased miR-34c-5p in drug-resistant epilepsy exacerbates neuroinflammation, which aggravates hippocampal neuron loss in epileptogenesis. Thus, miR-34c-5p could be considered as a potential noninvasive biomarker and shed novel light on the development of an effective therapeutic strategy for children with drug-resistant epilepsy in the future.
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http://dx.doi.org/10.1016/j.brainres.2020.147130DOI Listing
December 2020

Effects of long-distance transportation on blood constituents and composition of the nasal microbiota in healthy donkeys.

BMC Vet Res 2020 Sep 15;16(1):338. Epub 2020 Sep 15.

College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, P.R. China.

Background: This study aims to determine the effects of transportation on the nasal microbiota of healthy donkeys using 16S rRNA sequencing.

Results: Deep nasal swabs and blood were sampled from 14 donkeys before and after 21 hours' long-distance transportation. The values of the plasma hormone (cortisol (Cor), adrenocorticotrophic hormone (ACTH)), biochemical indicators (total protein (TP), albumin (ALB), creatinine (CREA), lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), blood urea (UREA), plasma glucose (GLU)) and blood routine indices (white blood cell (WBC), lymphocyte (LYM), neutrophil (NEU), red blood cell (RBC), hemoglobin (HGB)) were measured. 16S rRNA sequencing was used to assess the nasal microbiota, including alpha diversity, beta diversity, and phylogenetic structures. Results showed that levels of Cor, ACTH, and heat-shock protein 90 (HSP90) were significantly increased (p < 0.05) after long-distance transportation. Several biochemical indicators (AST, CK) and blood routine indices (Neu, RBC, and HGB) increased markedly (p < 0.05), but the LYM decreased significantly (p < 0.05). Nine families and eight genera had a mean relative abundance over 1%. The predominant phyla in nasal microbiota after and before transportation were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Transportation stress induced significant changes in terms of nasal microbiota structure compared with those before transportation based on principal coordinate analysis (PCoA) coupled with analysis of similarities (ANOSIM) (p < 0.05). Among these changes, a notably gain in Proteobacteria and loss in Firmicutes at the phylum level was observed.

Conclusions: These results suggest transportation can cause stress to donkeys and change the richness and diversity of nasal microbiota. Further studies are required to understand the potential effect of these microbiota changes on the development of donkey respiratory diseases.
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http://dx.doi.org/10.1186/s12917-020-02563-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493398PMC
September 2020

LncRNA GSEC promotes the proliferation, migration and invasion by sponging miR-588/ EIF5A2 axis in osteosarcoma.

Biochem Biophys Res Commun 2020 11 29;532(2):300-307. Epub 2020 Aug 29.

Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, China; Department of Orthopedics, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, China; Nanchang Key Laboratory of Orthopaedics, The Third Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address:

Background: Long noncoding RNAs (LncRNAs) show dysregulation in a variety of cancers. However, the function and specific mechanism of LncRNA GSEC in the progression of osteosarcoma remain mostly unknown. In this study, we sought to elucidate the role and mechanism of LncRNA GSEC in the occurrence and progression of osteosarcoma.

Methods: we examined the expression of LncRNA GSEC in osteosarcoma cell lines by quantitative real time PCR. In vitro experiments, including transwell assays, cck8 assays, and flow cytometry analysis have biologically demonstrated the effect of LncRNA GSEC on the proliferation and migration of osteosarcoma cell lines. Furthermore, the regulation of miR-588 by LncRNA GSEC was determined by luciferase reporter assay and quantitative real time PCR. What's more, subcutaneous tumor formation was performed in nude mice to monitor the growth of the tumor in vivo.

Results: We found that the expression of LncRNA GSEC was up-regulated in osteosarcoma cell lines. Overexpression of LncRNA GSEC promoted the proliferating and migratory capacity, and inhibited the apoptosis of osteosarcoma cells. Conversely, knockdown of LncRNA GSEC resulted in the opposite effect. Mechanistically, we identified LncRNA GSEC functioned as the sponge of miR-588, thus inhibiting the miR-588/EIF5A2 signal pathway. In addition, the expression of miR-588 was negatively correlated with LncRNA GSEC, and the effect by silencing or overexpressing LncRNA GSEC could be rescued by the introduction of miR-588 mimics or inhibitors, respectively.

Conclusions: In summary, this study shows that LncRNA GSEC promotes the proliferation and invasion of OS through the regulation of miR-588/EIF5A2 pathway, which might provide a new strategy for the treatment of osteosarcoma in the future.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.056DOI Listing
November 2020

Characterization of Gene as a Pathogenicity Factor of .

Front Microbiol 2020 31;11:1824. Epub 2020 Jul 31.

College of Plant Protection/Beijing Key Laboratory of Seed Disease Testing and Control (BKL-SDTC), China Agricultural University, Beijing, China.

causes mango wilt with significant economic losses. In the infection court, cerato-platanin (CP) family proteins (CPPs) are believed to involve in pathogenesis but has not been determined in . To confirm this function, a CP protein (CmCP) of was characterized in this study. A protoplast of was prepared by treating its mycelia with driselase and lysing enzymes. The gene was edited using CRISPR/Cas-U6-1 expression vectors in 60% PEG and 50 μg/mL hygromycin B in the medium, resulting in mutants with deletion (Δ). A complemented mutant (Δ-C) was obtained by transforming to Δ. Both Δ and Δ-C were characterized by comparing them with a wild-type strain on morphology, mycelial growth, conidial production and pathogenicity. Additionally, was transformed and expressed in , and the derived recombinant protein CmCP caused a severe necrosis on leaves. CmCP-treated plant leaves showed symptoms of hypersensitive response including electrolyte leakage, reactive oxygen species generation and overexpression of defense-related genes , , , , and . All those results suggested that gene was required for the growth development of and functioned as a major pathogenicity factor in mango infection.
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http://dx.doi.org/10.3389/fmicb.2020.01824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411389PMC
July 2020

Enhanced buffer capacity of fermentation broth and biohydrogen production from corn stalk with NaHPO/NaHPO.

Bioresour Technol 2020 Oct 6;313:123783. Epub 2020 Jul 6.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy (Ministry of Agriculture and Rural Affairs of China), Henan Agricultural University, Zhengzhou 450002, China; Institute of Agricultural Engineering, Huanghe S & T University, Zhengzhou 450006, China. Electronic address:

The remarkable buffer capacity of buffer solution can significantly improve the biohydrogen production yield and energy conversion efficiency. In the present study, the effect of buffer solution NaHPO/NaHPO on buffer capacity of fermentation broth and photo-fermentation biohydrogen production (PFHP) was studied. Gas characteristics, fermentation broth properties, and kinetic parameters in PFHP were investigated. With the increase in pH values (5-7) of buffer solution NaHPO/NaHPO, firstly hydrogen yield increased and then decreased. Maximum energy conversion efficiency 9.84%, hydrogen yield 132.69 mL/g corn stalk, and hydrogen content 53.88% were achieved at pH value of 6. The results of one-way ANOVA showed that pH values of fermentation broth and cumulative hydrogen production were strongly affected by pH values of buffer solution. Buffer solution NaHPO/NaHPO retarded the decrease of pH value of photo-fermentation broth, and significantly improved the PFHP.
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http://dx.doi.org/10.1016/j.biortech.2020.123783DOI Listing
October 2020

Allyl Isothiocyanate (AITC) Triggered Toxicity and (a STRPC Family Member) Responded Sense in .

Front Microbiol 2020 12;11:870. Epub 2020 May 12.

Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing Key Laboratory of Seed Disease Testing and Control, Beijing, China.

Allyl isothiocyanate (AITC) is a natural product used as a food additive. Due to its strong volatility and broad biological activity, AITC is considered as a bio-fumigant to control soil-borne fungal diseases in agriculture, creating an urgent need for evaluation of the antifungal activity of AITC. Here we study the effect of AITC on growth and explore the molecular mechanisms. The results indicated that AITC causes rapid inhibition of . after 5 min, hyphal deformity, and electrolyte leakage. A yeast-like vacuolar transient receptor potential channel regulator (, a STRPC family member) was identified in . that seems to play a role in this fungi AITC sensitivity. Genetic evidence suggests the gene is involved in . growth, development, and pathogenicity. Loss of resulted in hypersensitivity of . to AITC and induced reactive oxygen species (ROS) accumulation ∼ 1.3 to 1.45- folds that of the wild type (WT), and no difference responses to CaCl, NaCl, KCl, SDS, and Congo red when compared with WT. In addition, Δ showed significantly reduced (∼ 1-fold) glutathione-S-transferase (GST) expression compared with the WT without AITC induction. Upon exposure to 4.8 μg/mL AITC for 3 h, the relative expression levels were ∼ 12-30 fold higher in both the WT and Δ. Nevertheless, no difference in GST expression level was observed between the WT and Δ. The current study provides novel insights into the toxicity mechanisms of AITC. Considering our results that show the key role of , we propose that it could act as a new molecular target for future fungicide development.
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http://dx.doi.org/10.3389/fmicb.2020.00870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235336PMC
May 2020

Investigation of the interaction between lighting and mixing applied during the photo-fermentation biohydrogen production process from agricultural waste.

Bioresour Technol 2020 Sep 23;312:123570. Epub 2020 May 23.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy of Ministry of Agriculture and Rural Affairs, College of Mechanical & Electrical Engineering, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

To better clarify the effect of lighting and mixing on the hydrogen production from agricultural waste, experiments under diverse constant and dynamic light intensities and mixing speeds were conducted. Cumulative hydrogen yield, hydrogen production rate, OD, pH, reducing sugar concentration were monitored. Results showed that mixing had positive effects on high substrate concentration. The interaction between lighting and mixing was drawn. Higher light intensity (7000 Lux) was suitable for hydrogen production under mixing. Higher light intensity with higher mixing speed (150 RPM) showed the highest cumulative hydrogen yield of 78.1 mL/g TS. Different periods of hydrogen production process required distinct lighting and mixing. Combined with Gompertz model, dynamic lighting and mixing strategies were discussed. Dynamic light intensity (4000-7000-4000 Lux) accompanied with dynamic mixing speed (50-150-50 RPM) was the optimal condition for PFHP. Highest hydrogen yield of 84.7 mL/g TS and highest light conversion efficiency of 36.32% were obtained.
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http://dx.doi.org/10.1016/j.biortech.2020.123570DOI Listing
September 2020

Photo-fermentation biohydrogen production and electrons distribution from dark fermentation effluents under batch, semi-continuous and continuous modes.

Bioresour Technol 2020 Sep 19;311:123549. Epub 2020 May 19.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy MOA of China, Henan Agricultural University, Zhengzhou 450002, China.

In this work, the influence of batch, semi-continuous and continuous mode on biohydrogen production from dark fermentation effluents (DFEs) as substrate and electron distribution was investigated. Results indicated a better H production performance was obtained in semi-continuous mode. 50% decanting volume ratio (DVR) and 24 h feeding interval time (FIT) were found to be the best condition. Maximum average H production rate (HPR) and H yield were obtained of 8.44 mL/h and 1386.22 ± 44.23 mL H/g TOC, respectively. 37.71% substrate electrons partitioning to hydrogen were detected. For continuous mode, more substrate electrons were diverted toward SMPs with the increasing of HRT due to the fact that longer cell retention, more chances were provided for cell lysis. The bad performance in batch mode ascribed to 56.39% substrate electrons were transferred to cell growth and soluble microbial products (SMPs).
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http://dx.doi.org/10.1016/j.biortech.2020.123549DOI Listing
September 2020