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Article ; Online: Exploring a novel long-acting glucagon-like peptide-1 receptor agonist built on the albumin-binding domain and XTEN scaffolds

Yan Zhou / Jianhui Li / Guosheng Gao / Yafeng Li / Changzhen Zhang

Heliyon, Vol 10, Iss 2, Pp e24340- (2024)

2024

Abstract: In recent years, glucagon-like peptide-1 (GLP-1) has demonstrated considerable potential in the treatment of type 2 diabetes (T2D) and obesity. However, the half-life of naturally occurring GLP-1 is quite short in vivo. Two common strategies employed for ...

Abstract	In recent years, glucagon-like peptide-1 (GLP-1) has demonstrated considerable potential in the treatment of type 2 diabetes (T2D) and obesity. However, the half-life of naturally occurring GLP-1 is quite short in vivo. Two common strategies employed for half-life extension are the use of the Albumin-binding domain (ABD) and XTEN polypeptide, which operate through different mechanisms. In this study, we designed an innovative GLP-1 receptor agonist with an extended duration of action. This new construct incorporated an albumin binding domain (ABD) and an XTEN sequence (either XTEN144 or XTEN288) as carriers. We referred to these fusion proteins as GLP-ABD-XTEN144 and GLP-ABD-XTEN288. In an E. coli system, the said constructs were efficaciously produced in substantial quantity. It was observed from in vitro studies that the fusion protein GLP-ABD-XTEN144 demonstrated a five times stronger affinity towards human serum albumin (HSA), boasting a binding affinity (Kd) of 5.50 nM. This was in contrast to GLP-ABD-XTEN288, whose Kd value was registered at 27.78 nM. Moreover, GLP-ABD-XTEN144 presented a half-life of 12.9 h in mice, thus exceeding the corresponding value for GLP-ABD-XTEN288, 7.32 h in mice. Both these fusion proteins significantly mitigated non-fasting blood sugar levels and overall food consumption for 48 h subsequent to a one-time injection in mice. Notably, GLP-ABD-XTEN144 exhibited more pronounced hypoglycemic activity and food inhibitory effects than GLP-ABD-XTEN288. The designed GLP-ABD-XTEN144 fusion protein shows promising prospects for clinical application in T2D treatment. Our findings also suggest that ABD and XTEN polypeptides synergistically contribute to half-life extension, further enhancing the pharmacokinetic characteristics of a payload.
Keywords	GLP-1 ; Albumin-binding domain ; Type 2 diabetes ; XTEN ; Half-life ; Bioactivity ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	571
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Design, synthesis, and application in OFET of a small molecule based on π-expanded fused diketopyrrolopyrrole

Jianhui Li / Zhuoting Ji / Aihua He / Haichang Zhang

Frontiers in Chemistry, Vol

2023 Volume 11

Abstract: Diketopyrrolopyrrole (DPP) and its derivatives, as electron deficient units, are widely used as building blocks in organic field-effect transistors, obtaining high performance. However, further modification of the DPP structure is crucial for the ... ...

Abstract	Diketopyrrolopyrrole (DPP) and its derivatives, as electron deficient units, are widely used as building blocks in organic field-effect transistors, obtaining high performance. However, further modification of the DPP structure is crucial for the development of organic semiconductors. In this work, an FDPP is synthesized and characterized. The results show that FDPP exhibited not only a good planar core structure with a good conjugation system, but also strong aggregation in the solid state. As a consequence, FDPP presents p-type behavior with a hole mobility of ∼9.7 × 10−3 cm2 V−1 s−1. This study suggests that FDPP is a promising electron deficient unit for high performance semiconductors.
Keywords	organic field effect transistor (OFET) ; p-type ; charge transport mobility ; semiconductor ; conjugated materials ; DPP ; Chemistry ; QD1-999
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Big Research Data and Data Science

Jianhui Li

Data Science Journal, Vol

2015 Volume 14

Keywords	Science (General) ; Q1-390
Language	English
Publishing date	2015-05-01T00:00:00Z
Publisher	Ubiquity Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aqueous Extract of Sea Squirt ( Halocynthia roretzi ) with Potent Activity against Human Cancer Cells Acts Synergistically with Doxorubicin

Yuting Zhu / Shanhao Han / Jianhui Li / Hongwei Gao / Bo Dong

Marine Drugs, Vol 20, Iss 284, p

2022 Volume 284

Abstract: Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment. Halocynthia roretzi , an edible marine sea squirt, has been demonstrated to have various kinds of ... ...

Abstract	Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment. Halocynthia roretzi , an edible marine sea squirt, has been demonstrated to have various kinds of biological activities, such as anti-diabetic, anti-hypertension, and enhancing immunity. In this study, we reported that aqueous extracts from the edible parts of H. roretzi presented significantly inhibiting the efficiency on HepG-2 cell viability. The separate mixed compound exhibited strong effects of inhibitory proliferation and induced apoptosis via the generation of ROS along with the concurrent loss of mitochondrial membrane potential on tumor cells. Furthermore, we found that there existed a significantly synergistic effect of the ascidian-extracted compound mixture with the anti-cancer drug doxorubicin. In the presence of the extracts from H. roretzi , the dose of doxorubicin at the cellular level could be reduced by a half dose. The extracts were further divided by semipreparative-HPLC and the active ingredients were identified as a mixture of fatty amide, which was composed of hexadecanamide, stearamide, and erucamide by UHPLC-MS/MS. Our results suggest that the potential toxicity of ascidian H. roretzi in tumor cells, and the compounds extracted from H. roretzi could be potentially utilized on functional nutraceuticals or as an adjunct in combination with chemotherapy.
Keywords	ascidian ; Halocynthia roretzi ; anti-tumor ; drug combination ; doxorubicin ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combined Second Harmonic Generation and Fluorescence Analyses of the Structures and Dynamics of Molecules on Lipids Using Dual-Probes

Yi Hou / Jianhui Li / Bifei Li / Qunhui Yuan / Wei Gan

Molecules, Vol 27, Iss 3778, p

A Review

2022 Volume 3778

Abstract: Revealing the structures and dynamic behaviors of molecules on lipids is crucial for understanding the mechanism behind the biophysical processes, such as the preparation and application of drug delivery vesicles. Second harmonic generation (SHG) has ... ...

Abstract	Revealing the structures and dynamic behaviors of molecules on lipids is crucial for understanding the mechanism behind the biophysical processes, such as the preparation and application of drug delivery vesicles. Second harmonic generation (SHG) has been developed as a powerful tool to investigate the molecules on various lipid membranes, benefiting from its natural property of interface selectivity, which comes from the principle of even order nonlinear optics. Fluorescence emission, which is in principle not interface selective but varies with the chemical environment where the chromophores locate, can reveal the dynamics of molecules on lipids. In this contribution, we review some examples, which are mainly from our recent works focusing on the application of combined spectroscopic methods, i.e., SHG and two-photon fluorescence (TPF), in studying the dynamic behaviors of several dyes or drugs on lipids and surfactants. This review demonstrates that molecules with both SHG and TPF efficiencies may be used as intrinsic dual-probes in plotting a clear physical picture of their own behaviors, as well as the dynamics of other molecules, on lipid membranes.
Keywords	second harmonic generation ; two-photon fluorescence ; lipid membrane ; dual-probes ; Organic chemistry ; QD241-441
Subject code	612 ; 541
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification and validation of a novel survival prediction model based on the T-cell phenotype in the tumor immune microenvironment and peripheral blood for gastric cancer prognosis

Jing Ma / Jianhui Li / Nan He / Meirui Qian / Yuanyuan Lu / Xin Wang / Kaichun Wu

Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-

2023 Volume 14

Abstract: Abstract Background The correlation and difference in T-cell phenotypes between peripheral blood lymphocytes (PBLs) and the tumor immune microenvironment (TIME) in patients with gastric cancer (GC) is not clear. We aimed to characterize the phenotypes of ...

Abstract	Abstract Background The correlation and difference in T-cell phenotypes between peripheral blood lymphocytes (PBLs) and the tumor immune microenvironment (TIME) in patients with gastric cancer (GC) is not clear. We aimed to characterize the phenotypes of CD8+ T cells in tumor infiltrating lymphocytes (TILs) and PBLs in patients with different outcomes and to establish a useful survival prediction model. Methods Multiplex immunofluorescence staining and flow cytometry were used to detect the expression of inhibitory molecules (IMs) and active markers (AMs) in CD8+TILs and PBLs, respectively. The role of these parameters in the 3-year prognosis was assessed by receiver operating characteristic analysis. Then, we divided patients into two TIME clusters (TIME-A/B) and two PBL clusters (PBL-A/B) by unsupervised hierarchical clustering based on the results of multivariate analysis, and used the Kaplan–Meier method to analyze the difference in prognosis between each group. Finally, we constructed and compared three survival prediction models based on Cox regression analysis, and further validated the efficiency and accuracy in the internal and external cohorts. Results The percentage of PD-1+CD8+TILs, TIM-3+CD8+TILs, PD-L1+CD8+TILs, and PD-L1+CD8+PBLs and the density of PD-L1+CD8+TILs were independent risk factors, while the percentage of TIM-3+CD8+PBLs was an independent protective factor. The patients in the TIME-B group showed a worse 3-year overall survival (OS) (HR: 3.256, 95% CI 1.318–8.043, P = 0.006), with a higher density of PD-L1+CD8+TILs (P < 0.001) and percentage of PD-1+CD8+TILs (P = 0.017) and PD-L1+CD8+TILs (P < 0.001) compared to the TIME-A group. The patients in the PBL-B group showed higher positivity for PD-L1+CD8+PBLs (P = 0.042), LAG-3+CD8+PBLs (P < 0.001), TIM-3+CD8+PBLs (P = 0.003), PD-L1+CD4+PBLs (P = 0.001), and LAG-3+CD4+PBLs (P < 0.001) and poorer 3-year OS (HR: 0.124, 95% CI 0.017–0.929, P = 0.015) than those in the PBL-A group. In our three survival prediction models, Model 3, ...
Keywords	Inhibitory molecule ; Tumor immune microenvironment ; Peripheral blood lymphocytes ; Survival prediction model ; Gastric cancer ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Transport of Charged Molecules across Three Lipid Membranes Investigated with Second Harmonic Generation

Baomei Xu / Jianhui Li / Shuai Zhang / Johar Zeb / Shunli Chen / Qunhui Yuan / Wei Gan

Molecules, Vol 28, Iss 4330, p

2023 Volume 4330

Abstract: Subtle variations in the structure and composition of lipid membranes can have a profound impact on their transport of functional molecules and relevant cell functions. Here, we present a comparison of the permeability of bilayers composed of three ... ...

Abstract	Subtle variations in the structure and composition of lipid membranes can have a profound impact on their transport of functional molecules and relevant cell functions. Here, we present a comparison of the permeability of bilayers composed of three lipids: cardiolipin, DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol), and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)). The adsorption and cross-membrane transport of a charged molecule, D289 (4-(4-diethylaminostyry)-1-methyl-pyridinium iodide), on vesicles composed of the three lipids were monitored by second harmonic generation (SHG) scattering from the vesicle surface. It is revealed that structural mismatching between the saturated and unsaturated alkane chains in POPG leads to relatively loose packing structure in the lipid bilayers, thus providing better permeability compared to unsaturated lipid bilayers (DOPG). This mismatching also weakens the efficiency of cholesterol in rigidifying the lipid bilayers. It is also revealed that the bilayer structure is somewhat disturbed by the surface curvature in small unilamellar vesicles (SUVs) composed of POPG and the conical structured cardiolipin. Such subtle information on the relationship between the lipid structure and the molecular transport capability of the bilayers may provide clues for drug development and other medical and biological studies.
Keywords	lipid membrane ; molecular transport ; energy barrier ; second harmonic generation ; vesicle ; Organic chemistry ; QD241-441
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quality of Vermicompost and Microbial Community Diversity Affected by the Contrasting Temperature during Vermicomposting of Dewatered Sludge

Hongwei Zhang / Jianhui Li / Yingying Zhang / Kui Huang

International Journal of Environmental Research and Public Health, Vol 17, Iss 5, p

2020 Volume 1748

Abstract: This study aimed to investigate the effects of temperature on the quality of vermicompost and microbial profiles of dewatered sludge during vermicomposting. To do this, fresh sludge was separately vermicomposted with the earthworm Eisenia fetida under ... ...

Abstract	This study aimed to investigate the effects of temperature on the quality of vermicompost and microbial profiles of dewatered sludge during vermicomposting. To do this, fresh sludge was separately vermicomposted with the earthworm Eisenia fetida under different temperature regimes, specifically, 15 °C, 20 °C, and 25 °C. The results showed that the growth rate of earthworms increased with temperature. Moreover, the lowest organic matter content along with the highest electrical conductivity, ammonia, and nitrate content in sludge were recorded for 25 °C indicating that increasing temperature significantly accelerated decomposition, mineralization, and nitrification. In addition, higher temperature significantly enhanced microbial activity in the first 30 days of vermicomposting, also exhibiting the fastest stabilization at 25 °C. High throughput sequencing results further revealed that the alpha diversity of the bacterial community was enhanced with increasing temperature resulting in distinct bacterial genera in each vermicompost. This study suggests that quality of vermicompost and dominant bacterial community are strongly influenced by the contrasting temperature during vermicomposting of sludge, with the optimal performance at 25 °C.
Keywords	earthworms ; microorganisms ; sludge recycling ; temperature ; vermicomposting ; Medicine ; R
Subject code	550
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of Prandtl Number on Mixed Convective Heat Transfer from a Porous Cylinder in the Steady Flow Regime

Shimin Yu / Tingting Tang / Jianhui Li / Peng Yu

Entropy, Vol 22, Iss 2, p

2020 Volume 184

Abstract: The effect of the Prandtl number ( Pr ) on the flow and heat transfer from a porous circular cylinder with internal heat generation in the mixed convection regime is numerically investigated. The steady flow regime is considered over the ranges of the ... ...

Abstract	The effect of the Prandtl number ( Pr ) on the flow and heat transfer from a porous circular cylinder with internal heat generation in the mixed convection regime is numerically investigated. The steady flow regime is considered over the ranges of the Reynolds number ( Re ), Darcy number ( Da ), and Richardson number ( Ri ), varying from 5 to 40, 10 −6 to 10 −2 , and 0 to 2, respectively. The wake structure, the temperature distribution, and the heat transfer rate are discussed. Besides precipitating the growth of the recirculating wake, the Prandtl number is found to have a significant impact on the thermal characteristics. The concave isotherms, resembling a saddle-shaped structure, occur behind the cylinder at larger Pr , resulting in swells of the isotherms pairing off at the lateral sides. These swells are found to have a negative effect on heat transfer owing to a relatively smaller temperature gradient there. Then, the heat transfer rate in terms of the local Nusselt number ( Nu ) and enhancement ratio ( Er ) is calculated, which is closely related to Pr , Re , Da , and Ri. The local minimum heat transfer rate along the cylinder surface is found at the position where the swells of the isotherms form.
Keywords	porous cylinder ; mixed convection ; the prandtl number ; the recirculating wake ; heat transfer ; Science ; Q ; Astrophysics ; QB460-466 ; Physics ; QC1-999
Subject code	532
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Perovskite Chromite With In-Situ Assembled Ni-Co Nano-Alloys

Zhishan Li / Lin Cui / Jingli Luo / Jianhui Li / Yifei Sun

Frontiers in Chemistry, Vol

A Potential Bifunctional Electrode Catalyst for Solid Oxide Cells

2021 Volume 8

Abstract: Solid oxide fuel cell (SOFC) is an advanced electricity generation device with attractive fuel flexibility and conversion efficiency. As its reversed process, solid oxide electrolysis cell (SOEC) can efficiently electrolyze notorious CO2 to valuable ... ...

Abstract	Solid oxide fuel cell (SOFC) is an advanced electricity generation device with attractive fuel flexibility and conversion efficiency. As its reversed process, solid oxide electrolysis cell (SOEC) can efficiently electrolyze notorious CO2 to valuable chemical product such as CO, by utilizing renewable energy. To achieve long-term operation, the development of catalytically active electrode materials in both SOFC/SOEC modes is highly desirable, yet still challenging. In this research, an A-site deficient perovskite oxide (lanthanum chromite) decorated with in-situ exsolved Ni-Co nano-alloy has been fabricated and applied as a potential fuel electrode for both SOFC/SOEC. The influences of A-site non-stoichiometry and B-site dopant concentration on structural properties and in-situ exsolution process have been elaborately studied from various aspects. Diverse characterizations collectively confirm that the existence of A-site deficiency helps the formation of oxygen vacancies and stimulates the exsolution of B-site cations. In addition, the synergistic effect between the dopants of Co and Ni manipulates the reducibility and promotes carbon deposition resistance of the material. The electrolyte-supported SOFC with self-assembled Ni-Co nano-alloy electrode has shown maximum power densities of 329 mW/cm2 (in H2) and 258 mW/cm2 (in syngas, H2 + CO) at 850 °C, which are 50% better than those of the fuel cell with the exsolved Ni nanoparticles only. Also, the nano-alloy decorated electrode catalyst promotes a 30% increase in SOEC performance for CO2 electrolysis with prominently enhanced resistance against carbon deposition, suggesting the versatile functionality of the materials.
Keywords	solid oxide cells ; in-situ exsolution ; perovskite oxide ; nano alloy ; carbon deposition resistance ; Chemistry ; QD1-999
Subject code	660
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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