Publications by authors named "Wenzhe Li"

125 Publications

PEGylated DOX-coated nano graphene oxide as pH-responsive multifunctional nanocarrier for targeted drug delivery.

J Drug Target 2021 Feb 18:1-8. Epub 2021 Feb 18.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Nano graphene oxide (NGO) has high drug-loading capacity due to its huge surface area. However, the limited stability and the poor biocompatibility of NGO hampered its application as drug delivery carrier under physiological conditions. Thereby, a new strategy of using chemical conjugation on NGO with hydrophilic polymers was adopted but currently was too complicated, low yield and costly. In this study, doxorubicin-hyd-PEG-folic acid (DOX-hyd-PEG-FA) polymers were coated on the surface of NGO π-π stocking and the hydrophobic effect between DOX and NGO. With the PEG shell protection, the biocompatibility of NGO was significantly improved. The drug-loading capacity of nanoparticles was more than 100%. FA ligands on the nanoparticle could guide the nanoparticles actively targeting to tumour cells. The hydrazone bond between DOX and PEG was decomposed spontaneously in the weakly acidic environment, which made PEG layer dissociated from NGO. Furthermore, DOX was easily protonized at low pH conditions, which weakened the interaction between DOX and NGO. Thus, DOX could be released rapidly from the nanoparticles in tumour cells. In summary, NGO@DOX-hyd-PEG-FA is an easy-prepared nanoparticle with excellent biocompatibility, high pH-sensitivity and active tumour targeting. Therefore, it is a promising multifunctional nanocarrier effective for targeted drug delivery.
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http://dx.doi.org/10.1080/1061186X.2021.1887200DOI Listing
February 2021

Rapid glycosylation analysis of mouse serum glycoproteins separated by supported molecular matrix electrophoresis.

J Proteomics 2021 Mar 6;234:104098. Epub 2021 Jan 6.

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning, China. Electronic address:

Previously, we developed a novel separation technique, namely, supported molecular matrix electrophoresis (SMME), which separates mucins on a PVDF membrane that impregnated with a hydrophilic polymer (such as polyvinyl alcohol), so it has the characteristics that are compatible with glycan analysis of the separated bands. Here, we describe the first instance of the application of SMME to mouse sera fractionation and demonstrate their differences from the pooled human sera fractionation by SMME. Furthermore, we have developed a fixation method for the lectin blotting of SMME-separated glycoproteins by immersing the SMME membranes into acetone solvent followed by heating. It showed that the amount of protein samples required for SMME were reduced more than 4-fold than that of the process of SDS-PAGE. We applied these techniques for the detection of glycosylation patterns of serum proteins from Fut8 and Fut8 mice, further analyzed N-linked and O-linked glycans from the separated γ-bands by mass spectrometry, and demonstrated that there are α2,8-sialylated O-glycans contained in mouse sera glycoproteins. SMME can provide simple, rapid sera fractionation, glycan profiling differences between the bands of two samples and a new insight into the underlying mechanism that responsible for related diseases. SIGNIFICANCE: We describe that the first application of SMME can separate mouse serum proteins into six bands and identify the major protein components of each fraction in mouse serum separated by SMME. Furthermore, we successfully developed a fixation method for lectin blotting of SMME-separated glycoproteins and applied to the detection of glycosylation patterns of serum glycoproteins from Fut8 and Fut8 mice, also, the method is promising for detecting glycan profiling differences between two samples in both research and clinical settings.
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http://dx.doi.org/10.1016/j.jprot.2020.104098DOI Listing
March 2021

Dual-shot dynamics and ultimate frequency of all-optical magnetic recording on GdFeCo.

Light Sci Appl 2021 Jan 6;10(1). Epub 2021 Jan 6.

Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communications, Institute of Photonics Technology, Jinan University, Guangzhou, 510632, China.

Although photonics presents the fastest and most energy-efficient method of data transfer, magnetism still offers the cheapest and most natural way to store data. The ultrafast and energy-efficient optical control of magnetism is presently a missing technological link that prevents us from reaching the next evolution in information processing. The discovery of all-optical magnetization reversal in GdFeCo with the help of 100 fs laser pulses has further aroused intense interest in this compelling problem. Although the applicability of this approach to high-speed data processing depends vitally on the maximum repetition rate of the switching, the latter remains virtually unknown. Here we experimentally unveil the ultimate frequency of repetitive all-optical magnetization reversal through time-resolved studies of the dual-shot magnetization dynamics in GdFeCo. Varying the intensities of the shots and the shot-to-shot separation, we reveal the conditions for ultrafast writing and the fastest possible restoration of magnetic bits. It is shown that although magnetic writing launched by the first shot is completed after 100 ps, a reliable rewriting of the bit by the second shot requires separating the shots by at least 300 ps. Using two shots partially overlapping in space and minimally separated by 300 ps, we demonstrate an approach for GHz magnetic writing that can be scaled down to sizes below the diffraction limit.
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http://dx.doi.org/10.1038/s41377-020-00451-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788082PMC
January 2021

[Differential diagnosis of high altitude pulmonary edema and COVID-19 with computed tomography feature].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2020 Dec;37(6):1031-1036

Department of Diagnostic Radiology, Xinjiang General Hospital of PLA, Urumqi 830000, P.R.China.

To investigate the computed tomography (CT) characteristics and differential diagnosis of high altitude pulmonary edema (HAPE) and COVID-19, CT findings of 52 cases of HAPE confirmed in Medical Station of Sanshili Barracks, PLA 950 Hospital from May 1, 2020 to May 30, 2020 were collected retrospectively. The size, number, location, distribution, density and morphology of the pulmonary lesions of these CT data were analyzed and compared with some already existed COVID-19 CT images which come from two files, "Radiological diagnosis of COVID-19: expert recommendation from the Chinese Society of Radiology (First edition)" and "A rapid advice guideline for the diagnosis and treatment of 2019 novel corona-virus (2019-nCoV) infected pneumonia (standard version)". The simple or multiple ground-glass opacity (GGO) lesions are located both in the HAPE and COVID-19 at the early stage, but only the thickening of interlobular septa, called "crazy paving pattern" belongs to COVID-19. At the next period, some increased cloudy shadows are located in HAPE, while lesions of COVID-19 are more likely to develop parallel to the direction of the pleura, and some of the lesions show the bronchial inflation. At the most serious stage, both the shadows in HAPE and COVID-19 become white, but the lesions of HAPE in the right lung are more serious than that of left lung. In summary, some cloudy shadows are the feature of HAPE CT image, and "crazy paving pattern" and "pleural parallel sign" belong to the COVID-19 CT, which can be used for differential diagnosis.
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http://dx.doi.org/10.7507/1001-5515.202007043DOI Listing
December 2020

Rapid determination of lignocellulose in corn stover based on near-infrared reflectance spectroscopy and chemometrics methods.

Bioresour Technol 2021 Feb 28;321:124449. Epub 2020 Nov 28.

College of Engineering, Northeast Agricultural University, Harbin 150030, PR China.

In this study, a rapid detection method based on near-infrared reflectance spectroscopy was proposed for measuring the contents of cellulose, hemicellulose and lignin in corn stover. In the basis of strategies of variable selection, feature extraction and nonlinear modeling, BiPLS-PCA-SVM was constructed using backward interval partial least squares combined with principal component analysis and support vector machine, which was used to improve the performance of spectral regression calibration model. For BiPLS-PCA-SVM model, the determination coefficients, root mean squared error and residual predictive deviation for the validation set were 0.906, 0.900% and 3.213 for cellulose; 0.987, 0.797% and 9.071 for hemicellulose; and 0.936, 0.264% and 4.024 for lignin, correspondingly. The results indicate that near-infrared reflectance spectroscopy combined with BiPLS-PCA-SVM can provide a reliable alternative strategy to detect contents of lignocellulosic components for pretreated corn stover in the anaerobic digestion process.
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http://dx.doi.org/10.1016/j.biortech.2020.124449DOI Listing
February 2021

Engineered Electronic Structure and Carrier Dynamics in Emerging CsAgNaFeCl Perovskite Single Crystals.

J Phys Chem Lett 2020 Nov 28;11(22):9535-9542. Epub 2020 Oct 28.

Institute of New Energy Technology, Department of Electronic Science and Engineering, College of Information Science and Technology, Jinan University, Guangzhou 510632, China.

Lead-free double perovskites have attracted noteworthy attention due to their compositional flexibility and electronic diversity. In this study, we hydrothermally grow a new class of CsAgNaFeCl (0 ≤ ≤ 1) perovskite single crystals with high thermal stability. The substitution of B-site cation allows to regulate the crystallographic and band structure, which gives rise to enlarged band absorbance close to the near-infrared region (∼800 nm) via composition engineering. Ultrafast transient absorption spectroscopy (TAS) certifies that the decay time of excited-state absorption is 5.02 and 2450 ps in the case of CsNaFeCl and CsAgFeCl, respectively. The corresponding charge carrier diffusion length accordingly enhances from 3.7 to 311 nm by means of increasing Ag dopant concentration. Structurally, the primitive cell shrinks due to the partial replacement of [NaCl] octahedra by [AgCl] octahedra. It is proved theoretically as well as experimentally that the introduction of Ag species can effectively enhance the electron mobility (from 1.06 to 15.3 cm V s) by ∼15 times through realizing stronger orbital coupling of the conductive ions, which enables such a novel double perovskite to be a potential candidate for the optoelectronic and photovoltaic applications.
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http://dx.doi.org/10.1021/acs.jpclett.0c02963DOI Listing
November 2020

Evidence for anaphase pulling forces during C. elegans meiosis.

J Cell Biol 2020 Dec;219(12)

Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA.

Anaphase chromosome movement is thought to be mediated by pulling forces generated by end-on attachment of microtubules to the outer face of kinetochores. However, it has been suggested that during C. elegans female meiosis, anaphase is mediated by a kinetochore-independent pushing mechanism with microtubules only attached to the inner face of segregating chromosomes. We found that the kinetochore proteins KNL-1 and KNL-3 are required for preanaphase chromosome stretching, suggesting a role in pulling forces. In the absence of KNL-1,3, pairs of homologous chromosomes did not separate and did not move toward a spindle pole. Instead, each homolog pair moved together with the same spindle pole during anaphase B spindle elongation. Two masses of chromatin thus ended up at opposite spindle poles, giving the appearance of successful anaphase.
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http://dx.doi.org/10.1083/jcb.202005179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577052PMC
December 2020

Association of sex with clinical outcomes in COVID-19 patients: A retrospective analysis of 1190 cases.

Respir Med 2020 11 28;173:106159. Epub 2020 Sep 28.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background: The outbreak of COVID-19 caused by SARS-CoV-2 has been a pandemic. The objective of our study was to explore the association between sex and clinical outcomes in patients with COVID-19.

Methods: Detailed clinical data including clinical characteristics, laboratory tests, imaging features and treatments of 1190 cases of adult patients with confirmed COVID-19 were retrospectively analyzed. Associations between sex and clinical outcomes were identified by multivariable Cox regression analysis.

Results: There were 635 (53.4%) male and 555 (46.6%) female patients in this study. Higher rates of acute kidney injury (5.5% vs. 2.9%, p = 0.026), acute cardiac injury (9.1% vs. 4.3%, p = 0.001), and disseminated intravascular coagulation (2.5% vs. 0.7%, P = 0.024) were observed in males. Compared with female patients, male patients with COVID-19 had a higher inhospital mortality rate (15.7% vs. 10.3%, p = 0.005). However, Cox regression analysis showed that sex did not influence inhospital mortality of COVID-19 patients.

Conclusions: Male sex was associated with a worse prognosis of COVID-19, but it seems not to be an independent prognostic factor.
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http://dx.doi.org/10.1016/j.rmed.2020.106159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521447PMC
November 2020

CRL5-dependent regulation of the small GTPases ARL4C and ARF6 controls hippocampal morphogenesis.

Proc Natl Acad Sci U S A 2020 09 1;117(37):23073-23084. Epub 2020 Sep 1.

Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616;

The small GTPase ARL4C participates in the regulation of cell migration, cytoskeletal rearrangements, and vesicular trafficking in epithelial cells. The ARL4C signaling cascade starts by the recruitment of the ARF-GEF cytohesins to the plasma membrane, which, in turn, bind and activate the small GTPase ARF6. However, the role of ARL4C-cytohesin-ARF6 signaling during hippocampal development remains elusive. Here, we report that the E3 ubiquitin ligase Cullin 5/RBX2 (CRL5) controls the stability of ARL4C and its signaling effectors to regulate hippocampal morphogenesis. Both RBX2 knockout and Cullin 5 knockdown cause hippocampal pyramidal neuron mislocalization and development of multiple apical dendrites. We used quantitative mass spectrometry to show that ARL4C, Cytohesin-1/3, and ARF6 accumulate in the RBX2 mutant telencephalon. Furthermore, we show that depletion of ARL4C rescues the phenotypes caused by Cullin 5 knockdown, whereas depletion of CYTH1 or ARF6 exacerbates overmigration. Finally, we show that ARL4C, CYTH1, and ARF6 are necessary for the dendritic outgrowth of pyramidal neurons to the superficial strata of the hippocampus. Overall, we identified CRL5 as a key regulator of hippocampal development and uncovered ARL4C, CYTH1, and ARF6 as CRL5-regulated signaling effectors that control pyramidal neuron migration and dendritogenesis.
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http://dx.doi.org/10.1073/pnas.2002749117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502717PMC
September 2020

A novel immunochromatographic strips assay for rapid and simple detection of systemic lupus erythematosus.

Sci Rep 2020 08 25;10(1):14178. Epub 2020 Aug 25.

College of Basic Medical Science, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, 116044, Liaoning, China.

Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease. Detection of anti-nuclear antibodies (ANA) is fundamental for the diagnosis of SLE. In the present study, we found that the level of core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) is markedly up-regulated on immunoglobulin G (IgG) in the sera of SLE patients detected by Aspergillus oryzae lectin (AOL) blot. In sandwich Dot enzyme-linked immunosorbent assay (Dot-ELISA), the core fucosylation level was also found significantly increased in the sera from SLE patients with a higher ANA titer. To establish a rapid and sensitive laboratory test for the diagnosis of SLE, we prokaryotically expressed AOL and C3-D1-C3-D2-C3 of protein G (SpG3), and generate AOL-conjugated colloid gold immunochromatographic strips (ICS). The detection limit of core fucosylated IgG was 10 μg/mL for AOL-conjugated colloid gold ICS. As well as indirect immunofluorescence, the AOL-conjugated colloid gold ICS showed reliable results in the serum of 39 SLE patients. Our results indicated that the AOL-conjugated colloid gold ICS could serve as a rapid test for the detection of ANA and suspected cases of SLE.
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http://dx.doi.org/10.1038/s41598-020-71137-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447788PMC
August 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

Core Fucosylation of Intestinal Epithelial Cells Protects Against Typhi Infection via Up-Regulating the Biological Antagonism of Intestinal Microbiota.

Front Microbiol 2020 27;11:1097. Epub 2020 May 27.

College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

The fucosylated carbohydrate moieties on intestinal epithelial cells (IECs) are involved in the creation of an environmental niche for commensal and pathogenic bacteria. Core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is the major fucosylation pattern on the -glycans of the surface glycoproteins on IECs, however, the role of IECs core fucosylation during infection remains unclear. This study was conducted to investigate the interaction between IECs core fucosylation and gut microbiota, and the effects of this interaction on protecting subsp. serovar Typhi ( Typhi) infection. Firstly, the and mice were infected with Typhi. The level of IECs core fucosylation and protein expression of intestinal mucosa were then detected by LCA blot and Western blot, respectively. The gut microbiota of and mice before and after Typhi infection was assessed by 16S rRNA sequencing. Our results showed that core fucosylation was ubiquitous expressed on the intestinal mucosa of mice and had significant effects on their gut microbiota. Fut8 mice was more susceptive to Typhi infection than Fut8 mice. Interestingly, infection of Typhi upregulated the core fucosylation level of IECs and increased the abundances of beneficial microorganisms such as and spp. Further and studies demonstrated that Wnt/β-catenin signaling pathway mediated the elevation of IECs core fucosylation level upon infection of Typhi. Taken together, our data in this study revealed that the IECs core fucosylation plays an important role in protecting against Typhi infection via up-regulating the biological antagonism of intestinal microbiota.
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http://dx.doi.org/10.3389/fmicb.2020.01097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266941PMC
May 2020

Loss of core fucosylation enhances the anticancer activity of cytotoxic T lymphocytes by increasing PD-1 degradation.

Eur J Immunol 2020 11 3;50(11):1820-1833. Epub 2020 Sep 3.

College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

As an immune checkpoint, programmed cell death 1 (PD-1) and its ligand (PD-L1) pathway plays a crucial role in CD8 cytotoxic T lymphocytes (CTL) activation and provides antitumor responses. The N-glycans of PD-1 and PD-L1 are highly core fucosylated, which are solely catalyzed by the core fucosyltransferase (Fut8). However, the precise biological mechanisms underlying effects of core fucosylation of PD-1 and PD-L1 on CTL activation have not been fully understood. In this study, we found that core fucosylation was significantly upregulated in lung adenocarcinoma. Compared to those of Fut8 OT-I mice, the lung adenocarcinoma formation induced by urethane was markedly reduced in Fut8 OT-I mice. De-core fucosylation of PD-1 compromised its expression on Fut8 CTL, resulted in enhanced Fut8 CTL activation and cytotoxicity, leading to more efficient tumor eradication. Indeed, loss of core fucosylation significantly enhanced the PD-1 ubiquitination and in turn led to the degradation of PD-1 in the proteasome. Our current work indicates that inhibition of core fucosylation is a unique strategy to reduce PD-1 expression for the antilung adenocarcinoma immune therapy in the future.
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http://dx.doi.org/10.1002/eji.202048543DOI Listing
November 2020

Obesogenic Effect of Sulfamethoxazole on with Simultaneous Disturbances on Eclosion Rhythm, Glucolipid Metabolism, and Microbiota.

Environ Sci Technol 2020 05 21;54(9):5667-5675. Epub 2020 Apr 21.

State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, P. R. China.

Antibiotics have recently gained attention because they are emerging environmental pollutants with obesogenic properties. In this study, were exposed to sulfamethoxazole (SMX), a sulfonamide antibiotic, and the effects were measured on circadian rhythm (represented by the eclosion rhythm), lipid metabolism, and microbiota. Circadian rhythm disorder was considered due to its connection with lipid metabolism and microbiota in association with obesity. SMX decreased the proportion of adult flies that eclosed in the morning (AM adults) and increased the proportion of PM adults. Moreover, SMX increased the body weight of PM adults, indicating that SMX exposure caused dysrhythmia in eclosion together with obesity. In measurements of key metabolites and metabolic enzymes, SMX exposure stimulated 3 indices in AM adults and 10 indices in PM adults. In AMP-activated protein kinase and insulin/IGF-1 signaling pathways, SMX upregulated six genes in AM adults and nine genes in PM adults. Finally, microbiota analysis demonstrated that SMX increased the Firmicutes/Bacteroides ratios (F/B) by 79.6- and 5.8-fold compared to concurrent controls in AM and PM adults. Collectively, these results suggest that SMX showed obesogenic effects accompanied with dysrhythmia and disturbances in lipid metabolism and microbiota. Further studies on the intrinsic connection are needed.
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http://dx.doi.org/10.1021/acs.est.9b07889DOI Listing
May 2020

[Effect of terlipressin on prognosis of adult septic shock patients: a Meta-analysis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Feb;32(2):134-139

Department of Critical Care Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China. Corresponding author: Yu Xiangyou, Email:

Objective: To investigate the effect of terlipressin on prognosis of adult septic shock patients.

Methods: All randomized controlled clinical trials (RCT) of terlipressin in the treatment of adult septic shock patients from January 1980 to December 2019 were retrieved from CNKI, Wanfang, SinoMed, PubMed, Embase, Springer Link, Cochrane Library, Google Scholar, and etc. Patients in the treatment group received terlipressin while patients in the control group received norepinephrine or other vasopressors. Main outcome indicator was mortality. Secondary outcome indicators included the incidence of severe adverse events, limb peripheral ischemic events and renal complications. Literature screening, data extraction and quality evaluation were conducted by two researchers respectively. Meta-analysis was performed with RevMan 5.3 software. Funnel plot was used to analyze the publication bias.

Results: A total of 507 related literatures were retrieved. According to the inclusion and exclusion criteria, 8 RCT studies were finally included, with a total of 811 patients. One study was considered to have a lower risk of bias, 6 studies had uncertain risk of bias, and 1 study had a higher risk of bias. The Meta-analysis showed that terlipressin did not significantly improve the mortality of septic shock patients compared with the control group [odds ratio (OR) = 0.89, 95% confidence interval (95%CI) was 0.67-1.19, P = 0.45]; increased the incidence of severe adverse events (OR = 2.98, 95%CI was 1.99-4.45, P < 0.000 01); there was a tendency to increase the incidence of limb peripheral ischemic events, but without statistical difference (OR = 10.81, 95%CI was 0.88-133.19, P = 0.06); and reduced the incidence of renal complications (OR = 0.30, 95%CI was 0.09-0.96, P = 0.04). Funnel plot analysis indicated that there might be publication bias in a study on case fatality and incidence of serious adverse events in the included literature. No significant publication bias was found in studies on the incidence of limb peripheral ischemic events and the incidence of kidney-related complications.

Conclusions: The available evidence suggests that terlipressin could not significantly improve mortality in adult's septic shock patients, but it may reduce the incidence of renal complications. A tendency to increase the incidence of limb peripheral ischemic events in the terlipressin-treated group needs to be emphasized.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200210-00025DOI Listing
February 2020

Toll signaling promotes JNK-dependent apoptosis in .

Cell Div 2020 10;15. Epub 2020 Mar 10.

1Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092 China.

Background: Apoptosis plays pivotal roles in organ development and tissue homeostasis, with its major function to remove unhealthy cells that may compromise the fitness of the organism. Toll signaling, with the ancient evolutionary origin, regulates embryonic dorsal-ventral patterning, axon targeting and degeneration, and innate immunity. Using as a genetic model, we characterized the role of Toll signaling in apoptotic cell death.

Results: We found that gain of Toll signaling is able to trigger caspase-dependent cell death in development. In addition, JNK activity is required for Toll-induced cell death. Furthermore, ectopic Toll expression induces the activation of JNK pathway. Moreover, physiological activation of Toll signaling is sufficient to produce JNK-dependent cell death. Finally, Toll signaling activates JNK-mediated cell death through promoting ROS production.

Conclusions: As Toll pathway has been evolutionarily conserved from to human, this study may shed light on the mechanism of mammalian Toll-like receptors (TLRs) signaling in apoptotic cell death.
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http://dx.doi.org/10.1186/s13008-020-00062-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063707PMC
March 2020

A similarity based methodology for machine prognostics by using kernel two sample test.

ISA Trans 2020 Aug 10;103:112-121. Epub 2020 Mar 10.

NSF I/UCR Center for Intelligent Maintenance Systems, Department of Mechanical Engineering, University of Cincinnati, PO Box 210072, Cincinnati, OH 45221-0072, USA.

This paper proposes a novel similarity-based algorithm for Remaining Useful Life (RUL) prediction and a methodology for machine prognostics. In the proposed RUL prediction algorithm, a Similarity Matching Procedure including the Kernel Two Sample Test (KTST) is developed to query similar run-to-failure (R2F) profiles from historical data library. Next, the preliminary predictions of RUL are obtained as remaining time-to-failure from the similar R2F records. In the last step, Weibull analysis is performed to fuse the preliminary predictions and to obtain the probability distribution of RUL. Moreover, a methodology for machine prognostics is developed based on the RUL prediction algorithm. Compared with existing similarity-based methods for RUL prediction, the proposed method holds several advantages: 1) the similarities between sensor readings or feature matrices are directly measured without extra health assessment procedure; 2) the proposed method presents good probabilistic interpretations of the prediction uncertainties; 3) the estimated RUL distribution is statistically sound by applying KTST to prescreening the historical R2F records. The effectiveness and the superiority of the proposed method are justified based on the public aero-engine dataset.
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http://dx.doi.org/10.1016/j.isatra.2020.03.007DOI Listing
August 2020

Loss of core fucosylation suppressed the humoral immune response in Salmonella typhimurium infected mice.

J Microbiol Immunol Infect 2020 Feb 21. Epub 2020 Feb 21.

College of Basic Medical Science, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China. Electronic address:

Background: The humoral immune response is pivotal to protect the host from Salmonella typhimurium (S. typhimurium) infection. Previously, we found that core fucosylation catalyzed by core fucosyltransferase (Fut8) could regulate the immune responses. However, the role of core fucosylation during S. typhimurium infection remains unclear.

Methods: To demonstrate the role of Fut8 in S. typhimurium infection, we infected Fut8 and Fut8 mice using S. typhimurium. The production of antiserum against the S. typhimurium was detected. The expression of T and B cell activation-related genes during S. typhimurium infection was analyzed. The role of core fucosylation on CD4 T-B cell interaction and B cell generation was investigated during S. typhimurium infection. The production of sIgA was compared between Fut8 and Fut8 mice.

Results: Compared to Fut8 mice, the number of S. typhimurium colonized in the cecum was markedly increased in Fut8 mice. The production of the IgG and sIgA specific for S. typhimurium was significantly decreased in Fut8 mice. Moreover, loss of Fut8 decreased the induction of Th2-type cytokines from splenic cells of Fut8 mice during S. typhimurium infection. In addition, we found that the core fucosylation regulated the interaction between B and T cells in the lipid raft formation.

Conclusion: Core fucosylation plays important roles in host defence against S. typhimurium infection.
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http://dx.doi.org/10.1016/j.jmii.2020.02.006DOI Listing
February 2020

Loss of core fucosylation in both ST6GAL1 and its substrate enhances glycoprotein sialylation in mice.

Biochem J 2020 03;477(6):1179-1201

College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning, China.

Fucosyltransferase 8 (FUT8) and β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) are glycosyltransferases that catalyze α1,6-fucosylation and α2,6-sialylation, respectively, in the mammalian N-glycosylation pathway. They are aberrantly expressed in various human diseases. FUT8 is non-glycosylated but is responsible for the fucosylation of ST6GAL1. However, the mechanism for the interaction between these two enzymes is unknown. In this study, we show that serum levels of α2,6-sialylated N-glycans are increased in Fut8-/- mice, whereas the mRNA and protein levels of ST6GAL1 are unchanged in mouse live tissues. The level of α2,6-sialylation on IgG was also enhanced in Fut8-/- mice along with ST6GAL1 catalytic activity increase in both serum and liver. Moreover, it was observed that ST6GAL1 prefers non-fucosylated substrates. Interestingly, increased core fucosylation accompanied by a reduction in α2,6-sialylation, was detected in rheumatoid arthritis patient serum. These findings provide new insight into the interactions between FUT8 and ST6GAL1.
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http://dx.doi.org/10.1042/BCJ20190789DOI Listing
March 2020

Second-harmonic generation of asymmetric Bessel-Gaussian beams carrying orbital angular momentum.

Opt Express 2020 Jan;28(2):2536-2546

Nonlinear processes of laser beams carrying orbital angular momentum (OAM) offer a means to generate new wavelengths and to manipulate OAM charge numbers. We demonstrate the second-harmonic generation (SHG) of asymmetric Bessel-Gaussian (BG) beams carrying OAM of both integer and fractional charge numbers. Experimental results show a good one-to-one correspondence of the charge numbers and compliance with the OAM conservation law. The SHG conversion process and efficiency with different combined charge numbers are also discussed.
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http://dx.doi.org/10.1364/OE.381679DOI Listing
January 2020

Experimental probing of turbulence using a continuous spectrum of asymmetric OAM beams.

Opt Express 2020 Jan;28(2):924-935

Propagation of a continuous spectrum of orbital angular momentum (OAM) states through a realistic and controlled 3-dimensional turbulent condition has not been studied to date to the authors' knowledge. Using the Higher Order Bessel-gauss Beams Integrated in Time (HOBBIT) system and a 60 meter optical path Variable Turbulence Generator (VTG), we demonstrate that by changing the OAM in a continuous scan, a spectrum of OAMs provide an opportunity to take advantage of additional propagation channels within the aperture of the transmitter and optical path to the receiver. Experimental results are provided illustrating the HOBBIT system's ability to position the beam in space and time to exploit eigenchannels in the turbulent medium. This technique can be used to probe the turbulence at time scales much faster than the Greenwood frequency.
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http://dx.doi.org/10.1364/OE.380405DOI Listing
January 2020

Epstein-Barr virus-positive gastric cancer involves enhancer activation through activating transcription factor 3.

Cancer Sci 2020 May 20;111(5):1818-1828. Epub 2020 Mar 20.

Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Epstein-Barr virus (EBV) is associated with particular forms of gastric cancer (GC). We previously showed that EBV infection into gastric epithelial cells induced aberrant DNA hypermethylation in promoter regions and silencing of tumor suppressor genes. We here undertook integrated analyses of transcriptome and epigenome alteration during EBV infection in gastric cells, to investigate activation of enhancer regions and related transcription factors (TFs) that could contribute to tumorigenesis. Formaldehyde-assisted isolation of regulatory elements (FAIRE) sequencing (-seq) data revealed 19 992 open chromatin regions in putative H3K4me1 H3K4me3 enhancers in EBV-infected MKN7 cells (MKN7_EB), with 10 260 regions showing increase of H3K27ac. Motif analysis showed candidate TFs, eg activating transcription factor 3 (ATF3), to possibly bind to these activated enhancers. ATF3 was considerably upregulated in MKN7_EB due to EBV factors including EBV-determined nuclear antigen 1 (EBNA1), EBV-encoded RNA 1, and latent membrane protein 2A. Expression of mutant EBNA1 decreased copy number of the EBV genome, resulting in relative downregulation of ATF3 expression. Epstein-Barr virus was also infected into normal gastric epithelial cells, GES1, confirming upregulation of ATF3. Chromatin immunoprecipitation-seq analysis on ATF3 binding sites and RNA-seq analysis on ATF3 knocked-down MKN7_EB revealed 96 genes targeted by ATF3-activating enhancers, which are related with cancer hallmarks, eg evading growth suppressors. These 96 ATF3 target genes were significantly upregulated in MKN7_EB compared with MKN7 and significantly downregulated when ATF3 was knocked down in EBV-positive GC cells SNU719 and NCC24. Knockdown of ATF3 in EBV-infected MKN7, SNU719, and NCC24 cells all led to significant decrease of cellular growth through an increase of apoptotic cells. These indicate that enhancer activation though ATF3 might contribute to tumorigenesis of EBV-positive GC.
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http://dx.doi.org/10.1111/cas.14370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226279PMC
May 2020

Biohydrogen production through active saccharification and photo-fermentation from alfalfa.

Bioresour Technol 2020 May 11;304:123007. Epub 2020 Feb 11.

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

Studying biohydrogen production from alfalfa is of practical significance to cleaner production and biomass utilization. The performances of biohydrogen production through active/passive saccharification and photo-fermentation were compared. The effects of initial pH, substrate concentration, and cellulase loading on biohydrogen production from alfalfa by photosynthetic bacteria HAU-M1 were presented. It was found that the maximum hydrogen yield of 55.81 mL/g was achieved at initial pH of 6.90, substrate concentration of 31.23 g/mL, and cellulase loading of 0.13 g/g. Hydrogen yield of active saccharification and photo-fermentation was much higher as compare to passive saccharification and photo-fermentation. Initial pH value showed a more significant influence on photosynthetic bacteria in comparison to cellulase in active saccharification and photo-fermentation biohydrogen production. The low yield of propionic acid suggested that it was an efficient photosynthetic hydrogen production. Photo-fermentation hydrogen production from alfalfa provides a novel path for efficient utilization of alfalfa.
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http://dx.doi.org/10.1016/j.biortech.2020.123007DOI Listing
May 2020

High levels of fucosylation and sialylation of milk N-glycans from mothers with gestational diabetes mellitus alter the offspring gut microbiome and immune balance in mice.

FASEB J 2020 03 15;34(3):3715-3731. Epub 2020 Jan 15.

Department of Biochemistry, College of Basic Medical Science, Dalian Medical University, Dalian, China.

Gestational diabetes mellitus (GDM) is significantly associated with allergen sensitization in early childhood, and this may influence the gut microbiome and immune system of the children. In addition to mother-to-child transmission of microbes, milk glycans play a pivotal role in shaping the gut microbiome of infants. A previous study has demonstrated alterations in the major milk N-glycans of mothers with GDM. However, the impact of these changes on the gut microbiome and immune response of the neonates has yet to be studied. Here, we aimed to compare the glycosylation levels of various milk glycans between normal and GDM mice, and to characterize the intestinal microbiome and immune responses of the offspring after weaning. We found that GDM mouse milk contained significantly higher concentrations of fucosylated and sialylated N-glycans than control mice, but there was no difference in the concentration of milk oligosaccharides between the groups. The differences in milk N-glycans had direct effects on the intestinal microbiome of the offspring, which in turn affected their immune response upon challenge with ovalbumin (OVA), with disruptions in the Th1/Th2 and Th17/Treg cell balances. This study lays the foundation for further research and development of specific nutritional care for the offspring of GDM mothers.
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http://dx.doi.org/10.1096/fj.201901674RDOI Listing
March 2020

CHIP modulates APP-induced autophagy-dependent pathological symptoms in Drosophila.

Aging Cell 2020 02 28;19(2):e13070. Epub 2019 Nov 28.

The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China.

Dysregulation of autophagy is associated with the neurodegenerative processes in Alzheimer's disease (AD), yet it remains controversial whether autophagy is a cause or consequence of AD. We have previously expressed the full-length human APP in Drosophila and established a fly AD model that exhibits multiple AD-like symptoms. Here we report that depletion of CHIP effectively palliated APP-induced pathological symptoms, including morphological, behavioral, and cognitive defects. Mechanistically, CHIP is required for APP-induced autophagy dysfunction, which promotes Aβ production via increased expression of BACE and Psn. Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.
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http://dx.doi.org/10.1111/acel.13070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996943PMC
February 2020

Snail modulates JNK-mediated cell death in Drosophila.

Cell Death Dis 2019 11 26;10(12):893. Epub 2019 Nov 26.

Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.
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http://dx.doi.org/10.1038/s41419-019-2135-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879600PMC
November 2019

The roles of Qishen granules recipes, Qingre Jiedu, Wenyang Yiqi and Huo Xue, in the treatment of heart failure.

J Ethnopharmacol 2020 Mar 2;249:112372. Epub 2019 Nov 2.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, PR China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, PR China. Electronic address:

Ethnopharmacological Relevance: Recipes (Qingre Jiedu (QJ), Wenyang Yiqi (WYYQ) and Huo Xue (HX)) in Qishen granules (QSG) are believed to synergistically exert cardio-protective effects. However, the underlying pattern of each decomposed recipe in QSG and their synergistic effects in the treatment of heart failure (HF) are not clear.

Objective: The purpose of this study is to explore the biological contributions of decomposed recipes to therapeutic effects of QSG and reveal the pharmacological mechanism of QSG in treating HF.

Materials And Methods: The therapeutic effects of QSG or its recipes on heart failure were examined in wet-lab at both transcription and phenotypic level using HF Sprague-Dawley rats. Sequencing and transcriptome analyses were performed using in silico approaches including identification of differentially expressed genes, pathway enrichment and protein-protein interaction network studies. Specially, an optimized in silico quantitative pathway analysis that maximally extracted gene expression information was developed to reveal differentially expressed pathways (DEPs) among various groups, and is publicly available as R package QPA on GitHub (https://github.com/github-gs/QPA). Finally, the HF-related genes predicted using DEP approach were validated by quantitative real-time polymerase chain reaction and western blot.

Results: Multiple key genes and the associated signaling pathways were shown to be highly relevant for the therapeutic effect of QSG. Decreased expression of Spp1 gene required for inflammatory signaling and profibrotic signaling were observed in failing hearts treated with QJ, WYYQ and HX. Decreased expression of Cx3cr1 gene required for inflammatory signaling was observed in failing hearts treated with WYYQ and HX. Decreased expression of Myc gene required for oxidative stress and Fgfr2 gene required for profibrotic signaling were observed in failing hearts treated with HX and WYYQ, respectively. Increased expression of Adcy1 gene required for cAMP-PKA signaling cascade was observed in failing hearts treated with WYYQ and HX.

Conclusions: Our study suggests that QJ, WYYQ and HX recipes in QSG achieve synergistic and complementary therapeutic effects through alleviating inflammatory responses, attenuating ventricular remodeling and enhancing myocardial energy supply.
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http://dx.doi.org/10.1016/j.jep.2019.112372DOI Listing
March 2020

Dual-Functionalized Janus Mesoporous Silica Nanoparticles with Active Targeting and Charge Reversal for Synergistic Tumor-Targeting Therapy.

ACS Appl Mater Interfaces 2019 Nov 14;11(47):44582-44592. Epub 2019 Nov 14.

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

Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.
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http://dx.doi.org/10.1021/acsami.9b15434DOI Listing
November 2019

FoxO1 controls the expansion of pre-B cells by regulating the expression of interleukin 7 receptor α chain and its signal pathway.

Immunol Lett 2019 12 20;216:28-35. Epub 2019 Sep 20.

College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning 116044, China. Electronic address:

Forkhead box O1 (FoxO1) has a crucial role in the early B cell development. To understand the functional importance of FoxO1 gene in the early B cell expansion, we established a FoxO1 knockdown model using 70Z/3 pre-B cell line. The FoxO1 knockdown 70Z/3 cells (70Z/3-KD cells) showed the down-regulated expression of interleukin 7 receptor α chain (IL-7Rα). Moreover, the signaling via IL-7Rα was significantly attenuated in the 70Z/3-KD cells, and this alteration was fully rescued by re-expression of FoxO1 gene. Compared to the mock cells, loss of FoxO1 reduced the growth rates in the 70Z/3-KD cells, and was fully rescued by reintroduction of FoxO1 gene. The expansion of pre-B cells (CD45RCD43 fraction) was also reduced by the knockdown of FoxO1 gene. Indeed, FoxO1 induces accumulation in the p27-mediated G0/G1 phase arrest in 70Z/3 cells. FoxO1 bound to the Il7ra locus specifically and regulate the IL-7Rα transcription. In conclusion, FoxO1 regulates the expansion of pre-B cells by regulating the expression of IL-7Rα and its signal transduction.
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http://dx.doi.org/10.1016/j.imlet.2019.09.004DOI Listing
December 2019

Rapid detection of carbon-nitrogen ratio for anaerobic fermentation feedstocks using near-infrared spectroscopy combined with BiPLS and GSA.

Appl Opt 2019 Jun;58(18):5090-5097

Near-infrared spectroscopy (NIRS) is an efficient method for detecting the content of carbon and nitrogen in many materials, which solves the problems of the time-consuming and high-cost traditional chemical analysis method. To quickly detect the carbon-nitrogen ratio (C/N) for the anaerobic fermentation (AF) feedstock using NIRS, a genetic simulated annealing algorithm (GSA) is presented based on a genetic algorithm combined with a simulated annealing algorithm. By combining GSA with backward interval partial least squares (BiPLS), we construct a BiPLS-GSA algorithm to optimize the characteristic wavelength variables of NIRS; this algorithm significantly reduced the number of wavelength variables involved in modeling and effectively improved the detection accuracy and efficiency of the model. The determination coefficients, root mean squared error, mean relative error (MRE) and residual predictive deviation for the validation set in the BiPLS-GSA regression model were 0.9067, 7.6676, 5.5274%, and 3.5626, respectively. Meanwhile, compared to the entire spectrum model, the MRE was decreased by 16.54% in the BiPLS-GSA-based model. The research in this paper improves the adaptability of the prediction model based on optimizing sensitive wavelength variables for C/N, which provides a new way for rapid and accurate measurement of the C/N of AF feedstock.
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http://dx.doi.org/10.1364/AO.58.005090DOI Listing
June 2019