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GENE · 2015 · IF 2.138

Role of GTP-CHI links PAH and TH in melanin synthesis in silkworm, Bombyx mori

Ping Chen,Jiying Wang,Haiyin Li,Yan Li,Peng Chen,Tian Li,Xi Chen,Junjie Xiao,Liang Zhang

In insects, pigment patterns are formed by melanin, ommochromes, and pteridines. Here, the effects of pteridine synthesis on melanin formation were studied using 4th instar larvae of a wild-type silkworm strain, dazao ( Bombyx mori ), with normal color and markings. Results from injected larvae and in vitro integument culture indicated that decreased activity of guanosine triphosphate cyclohydrolase I (GTP-CH I, a rate-limiting enzyme for pteridine synthesis), lowers BH4 (6R- l -erythro-5,6,7,8-tetrahydrobiopterin, a production correlated with GTP-CH I activity) levels and eliminates markings and coloration. The conversion of phenylalanine and tyrosine to melanin was prevented when GTP-CH I was inhibited. When BH4 was added, phenylalanine was converted to tyrosine , and the tyrosine concentration increased. Tyrosine was then converted to melanin to create normal markings and coloration. Decreasing GTP-CH I activity did not affect L-DOPA (3,4- l -dihydroxyphenylalanine). GTP-CH I affected melanin synthesis by generating the BH4 used in two key reaction steps: (1) conversion of phenylalanine to tyrosine by PAH (phenylalanine hydroxylase) and (2) conversion of tyrosine to L-DOPA by TH (tyrosine hydroxylase). Expression profiles of BmGTPCH Ia , BmGTPCH Ib , BmTH , and BmPAH in the integument were consistent with the current findings.

研究领域: 昆虫学 · 生物化学
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Science China-Chemistry · 2025 · IF 9.7

Amplified circularly polarized luminescence in assembly of terpyridine-ZnII and GTP induced by silver(I) ion

Fan Huahua,Wang Runjia,Zhang Li,Liu Minghua

The G-quartet, a hydrogen-bonded macrocycle formed by cation-templated assembly of guanosine derivative, plays a vital role in areas ranging from structural biology to supramolecular chemistry and nanotechnology. Herein, we show a zinc-terpyridine derivative (Ftpy) that could form complex with various guanosine phosphates, exhibiting relatively weak circularly polarized luminescence CPL (dissymmetry factor, g lum ≈ 1 × 10 −3 ). Interestingly, when Ag + ions are involved, significantly boosted circularly polarized luminescence (CPL) is obtained in the assemblies of Ftpy with GTP, which the g lum can reach to 0.15. In contrast, no significant difference is observed in the presence of other cations (Na + , K + , Rb + , NH 4 + , Cu 2+ , and Sr 2+ ). It reveals that CPL signal is amplified due to the formation of G-quartet in the presence of Ag + ions, which further hierarchically self-associate into helically stacked supramolecular aggregates with the cooperation and π - π of Ftpy, contributing to the expression of chirality information. Furthermore, the co-assemblies of Ftpy/GTP/Ag + exhibit an enantioselective recognition of enantiomeric penicillamine by CPL spectra. This work provides a straightforward avenue to fabricate supramolecular assemblies with strong CPL based on G-quartet formation.

研究领域: 超分子化学 · 纳米技术 · 结构生物学
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IEEE SENSORS JOURNAL · 2025 · IF 4.5

GTP-Modified Gold Nanoparticle-Based Four-Core Fiber Sensor for Ultrasensitive Detection of Chlorothalonil in Environmental and Food Safety Monitoring

Zhenpeng Men,Ragini Singh,Qi Zhang,Huibo Han,Sandeep Boddu,Jyothsna Vaadaala,Yesudasu Vasimalla,Bingyuan Zhang,Santosh Kumar

In this study, an ultrasensitive, and glyceraldehyde-3-phosphate dehydrogenase (GTP)-modified gold nanoparticles (AuNPs)-based localized surface plasmon resonance (LSPR) sensor for detection of chlorothalonil (CTL) in environmental and food safety applications. As a widely used fungicide, CTL plays an important role in agricultural production. However, its residues pose a potential threat to environmental ecology and human health. Therefore, it is particularly urgent and significant to develop an efficient and sensitive detection method for CTL. In this study, an innovative detection method of CTL is proposed based on LSPR sensor. A highly sensitive LSPR sensor was successfully constructed by carefully synthesizing AuNPs and modifying them with GTP. The sensor demonstrates high sensitivity, evidenced by its low limit of detection (LoD) for CTL and exhibits excellent selectivity and stability. More importantly, the recovery rate of the detection method in actual samples reached more than 90 %, which fully proved its broad application prospects in the field of environmental monitoring and food safety. The linear range of the sensor is 0-1000 μM, and the LoD is 75.41 μM. The sensitivity is as high as 0.0037 nm/(μM), which verifies that the sensor provides an indispensable technology and a cost-effective and portable solution for CTL-specific detection.

CAS / MDL: 7758-02-3
研究领域: 分析化学 · 环境科学 · 食品安全检测 · 纳米生物技术 · 光学传感 · 农药残留检测
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Nano Today · 2023 · IF 17.4

A universal strategy of facilitating intracellular delivery of nanomedicines based on tuning ARF6 GTPase to its GTP-bound form

Siyang Song,Xiangfu Guo,Zibin Zhang,Shumin Fan,Runyu Zhang,Zhicheng Yan,Qing Chen,Yang Song,Peiyao Wu,Chunling Wang,Yuxi Cheng,Lan Yuan,Hua Zhang,Wenbing Dai,Xueqing Wang,Bing He,Qiang Zhang

Intracellular delivery crossing the endomembrane barrier is the “last mile to target” for nano delivery systems carrying biomacromolecules, including genetic medicines . Nevertheless, a mass of nanomedicines is currently restricted by their equivocal safety and delivery efficiency. Here, we establish a universal strategy independent of nanomaterials . Such a policy broadly facilitates the intracellular delivery of all kinds of tested nanomedicines, subtly by inducing ARF6 GTPases to their overactivated GTP-bound state. ARF6, one member of ARF subfamily in small GTPases , is verified to regulate intracellular vesicle transport and lipid metabolism through GTP/GDP conversion. ARF6 biased to GTP-bound state causes the increased endocytosis and reduced exocytosis of eleven types of nanoparticles . This universal effect is derived from the formation of a hybrid type of endosomes triggered by overactivated ARF6 via regulating cholesterol-associated vesicles and lipid raft/caveolae pathways. Due to the mild microenvironment in hybrid endosomes, the internalized protein and nanoparticles are steadily delivered to the cytoplasm, avoiding the intensive degradation in lysosomes . Based on these findings, we identify QS11, a safe small molecule inhibitor of ARF GTPase-activating proteins, significantly enhances the antitumor efficacy of siEGFR-loaded nanoparticles by inducing ARF6 overactivation. In sum, these findings reveal that the tactics of tuning ARF6 GTPases to GTP-bound form will widely benefit cellular nano delivery.

CAS / MDL: 38215-36-0 68-04-2
研究领域: 药理学 · 纳米技术 · 细胞生物学 · 分子生物学
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MATERIALS & DESIGN · 2026 · IF 8.2

A 3D-printed GTP@PTH composite scaffold with synergistic immunomodulatory and osteogenic capabilities for osteoporotic bone regeneration

Xiaofeng Chen,Zhengzhe Han,Xin Qi,Gaofeng Huang,Junjie Zheng,Yongfeng Li,Shiqiang Zhuo,Jinying Wang,Lin Huang,Qinci Xie,Xiaolin Li

A composite scaffold containing PTH- and proanthocyanidin (PC)-loaded microspheres (GTP@PTH) was successfully developed. • The GTP@PTH retains mechanical stability and provides sustained release of PTH. • The scaffold promotes M2 macrophage polarization via Nrf2/HO-1 activation and NF-κB inhibition. • The GTP@PTH enhances osteogenesis, angiogenesis, and inhibits osteoclast activity in vivo . The treatment of osseous deficiencies in osteoporotic patients continues to pose significant clinical difficulties, requiring scaffolds that can simultaneously modulate the regenerative immune microenvironment and restore bone homeostasis. Here, we fabricated porous microspheres capable of the sustained release of the immunomodulator proanthocyanidin (PC) and the bone‑anabolic regulator PTH(1‑34). These microspheres were then integrated into a 3D‑printed organic–inorganic composite scaffold that exhibited high compressive strength and modulus. The scaffold’s interconnected porosity supported tissue in‑growth, while its high modulus and inorganic salt composition promoted osteogenic differentiation of stem cells. In parallel, surface‑grafted alendronate (ALN) regulated osteoblast/osteoclast activity and chelated calcium ions on the bone surface to form stable interfacial structures. Both in vitro and in vivo studies indicate that the GTP@PTH scaffold, leveraging the combined actions of PC and PTH (1–34), modulates the immune microenvironment and skeletal homeostasis to support bone regeneration. This system restrains M1 macrophage polarization, promotes an M2 phenotype, and limits osteoclast over-differentiation, thus enhancing osteogenic activity. Such a multifunctional platform shows considerable promise for repairing bone defects under osteoporotic conditions, offering a viable approach for developing clinically applicable biomaterial solutions. Download: Download high-res image (124KB) Download: Download full-size image

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BIOMACROMOLECULES · 2023 · IF 6.2

Multifunctional and Tunable Coacervate Powders to Enable Rapid Hemostasis and Promote Infected Wound Healing

Shiying Lang,Yangrui Du,Li Ma,Yangjing Bai,Ying Ji,Gongyan Liu

Hemostatic powders provide an important treatment approach for time-sensitive hemorrhage control. Conventional hemostatic powders are challenged by the lack of tissue adhesiveness, insufficient hemostatic efficacy, limited infection control, and so forth. This study develops a hemostatic powder from tricomponent GTP coacervates consisting of gelatin, tannic acid (TA), and poly(vinyl alcohol) (PVA). The physical cross-linking by TA results in facile preparation, good storage stability, ease of application to wounds, and removal, which provide good potential for clinical translation. When rehydrated, the coacervate powders rapidly form a cohesive layer with interconnected microporous structure, competent flexibility, switchable wet adhesiveness, and antibacterial properties, which facilitate the hemostatic efficacy for treating irregular, noncompressible, or bacteria-infected wounds. Compared to commercial hemostats, GTP treatment results in significantly accelerated hemostasis in a liver puncture model (∼19 s, >30% reduction in the hemostatic time) and in a tail amputation model (∼38 s, >60% reduction in the hemostatic time). In the GTP coacervates, gelatin functioned as the biodegradable scaffold, while PVA introduced the flexible segments to enable shape-adaptability and interfacial interactions. Furthermore, TA contributed to the physical cross-linking, adhesiveness, and antibacterial performance of the coacervates. The study explores the tunability of GTP coacervate powders to enhance their hemostatic and wound healing performances.

CAS / MDL: 9002-89-5
研究领域: 生物医学工程 · 材料科学 · 创伤护理
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CELLULAR AND MOLECULAR LIFE SCIENCES · 2022 ·Vol. 79 ·期 8 ·1-15 · IF 9.207

Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation

Chang Chia-Chun,Peng Min,Zhong Jiale,Zhang Ziheng,Keppeke Gerson Dierley,Sung Li-Ying,Liu Ji-Long

The cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.

研究领域: 细胞生物学 · 分子生物学 · 生物化学
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CELL BIOLOGY INTERNATIONAL · 2019 ·Vol. 43 ·期 8 ·875-889 · IF 2.127

Vrl1 relies on its VPS9-domain to play a role in autophagy in Saccharomyces cerevisiae

Wenjing Li,Zulin Wu,Yongheng Liang

Autophagy is an intracellular degradation process involving many Atg proteins, which are recruited hierarchically to regulate this process. Rab/Ypt GTPases and their activators, guanine nucleotide exchange factors (GEFs), which are critical for regulating vesicle trafficking, are also involved in autophagy. Previously, we reported that yeast Vps21 and its GEF Vps9 are required for autophagy. Later, a third yeast VPS9-domain-containing protein, V A R P- l ike 1 (Vrl1), which was identified as a mutant in major laboratory strains, had partially overlapping functions with Vps9 in trafficking. In this study, we showed that Vrl1 performed roles in autophagy, and its VPS9-domain was crucial for its role in autophagy. We found that localization of Vrl1 differed from the other two VPS9-domain-containing proteins, Vps9 and Muk1, and only Vrl1 changed from multipoint to diffusion after starvation. Like Vps9, Vrl1 suppressed autophagic defects caused by the VPS9 deletion. We further showed that these VPS9-domain-containing proteins, Vps9, Muk1, and Vrl1, all co-localized with Atg8 on autophagosomes in cells blocked in any late step of starvation-induced autophagy, with Vrl1 most often co-localizing with Atg8. A small portion (<25%) of these VPS9-domain-containing proteins were degraded through autophagy. However, a large portion (>60%) of Vrl1 decreased independently of autophagy. We propose that Vrl1 may regulate autophagy in a similar way as Vps9, and the level of Vrl1 partly decreases through both autophagy-dependent and -independent routes.

CAS / MDL: 133407-82-6
研究领域: 分子生物学 · 细胞生物学 · 酵母遗传学
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Cell Death & Disease · 2018 ·Vol. 9 ·期 10 ·1-16 · IF 5.638

GRP75 modulates oncogenic Dbl-driven endocytosis derailed via the CHIP-mediated ubiquitin degradation pathway

Niu Xiuran,Su Linjia,Qi Shanshan,Gao Zhihui,Zhang Qing,Zhang Sihe

Chaperone-assisted proteasome degradation of oncogenic protein acts as an upstream signal controlling tumorigenesis and progression. The understanding of the co-regulation of chaperone and oncoprotein of endocytosis pathways is extremely limited. In this study, we showed for the first time that proto-Dbl ( dbl proto-oncogene product) is co-enriched with mitochondrial chaperone GRP75 in endocytosis vesicles from ovarian cancer cells. onco-Dbl, produced by oncogenic mutation/degradation of proto-Dbl, markedly enhanced cellular macropinocytosis but suppressed clathrin-mediated endocytosis and clathrin-independent endocytosis pathways, presenting a derailed endocytosis phenotype. GRP75 was associated with proto-Dbl inside cells and modulated Dbl-driven endocytosis derailed by a co-regulatory mode. In spite of not being a component of the Hsc70/Hsp90/proto-Dbl complex, the degradation of proto-Dbl was promoted by GRP75 through the CHIP-mediated ubiquitin–proteasome pathway, of which GRP75 acts as a cooperator with CHIP but also acts as a competitor to Hsc70 and Hsp90 in the multiple chaperones-assisted pro-folding/pro-degradation machinery. Knockdown or inhibition of GRP75 attenuated proto-Dbl degradation and reduced the onco-Dbl level, which differentially impaired Rho GTPases activation and therefore shifted the endocytosis-derailed phenotype. Our data uncovered a novel GRP75-Dbl endocytosis regulatory axis and provided an alternative using chaperone inhibitor to shut down the oncoprotein-driven endocytosis derailment mechanism.

CAS / MDL: 133407-82-6
研究领域: 肿瘤学 · 细胞生物学 · 分子生物学 · 癌症研究
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NEW JOURNAL OF CHEMISTRY · 2014 ·Vol. 38 ·期 8 ·3673-3677 · IF 3.159

Water-soluble luminescent copper nanoclusters reduced and protected by histidine for sensing of guanosine 5′-triphosphate

Xi Juan Zhao,Cheng Zhi Huang

A one step synthesis of water-soluble luminescent copper nanoclusters (CuNCs) reduced and protected by histidine is reported. When excited at 350 nm, the as-synthesized CuNCs exhibit luminescence centered at 456 nm with a quantum yield of 1.6%, which is different from that of histidine alone under the same experimental conditions. Upon addition of guanosine 5′-triphosphate (GTP), the emission of CuNCs is gradually quenched. While other nucleoside triphosphates including ATP, CTP and UTP as well as some inorganic anions such as P2O74−, PO43−, and CH3COO− have no such quenching effect, which indicates that the nucleobase instead of the phosphate anion plays an important role in the emission quenching of CuNCs. The most efficient quenching of the CuNCs induced by GTP can be ascribed to the most reducing ability of guanine among the other nucleobases. This interesting experimental result demonstrates that the as-synthesized CuNCs can be applied to sensing of GTP.

研究领域: 纳米材料 · 分析化学 · 生物传感器 · 纳米技术
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FREE RADICAL BIOLOGY AND MEDICINE · 2022 · IF 8.101

MTH1 suppression enhances the stemness of MCF7 through upregulation of STAT3

Jin Li,Zi-Hui Wang,Ya-Min Dang,Dan-Ni Li,Zhen Liu,Da-Peng Dai,Jian-Ping Cai

MTH1 protein can sanitize the damaged (d)NTP pool and MTH1 inhibitors have been developed to impede the growth of rapidly proliferating tumor cells; however, the effect of MTH1 inhibition on breast cancer stemness has not been reported yet. Here, we constructed breast cancer cell lines with the stable depletion of MTH1. MTH1 suppression clearly increased the ratio of CD44 + CD24 −/low subpopulations and promoted the formation of tumorspheres in MCF7 and T47D cells. RNA expression profiling, RT–qPCR and Western blotting showed the upregulation of master stem cell transcription factors Sox2 , Oct4 and Nanog in MTH1 knockdown cells. GSEA suggested and Western blotting verified that MTH1 knockdown increased the expression of phosphorylated STAT3 (Tyr705). Furthermore, we indirectly demonstrated that the increased concentration of 8-oxo-dGTP and 8-oxo-GTP in MTH1 -knockdown cells and exogenous 8-oxoGTP, rather than 8-oxo-dGTP, could significantly increase the phosphorylation of STAT3. In conclusion, this work indicates that MTH1 inhibition increased the proportion of breast cancer stem cells (BCSCs) and promoted stemness properties in MCF7 cells.

CAS / MDL: 890764-63-3
研究领域: 肿瘤学 · 分子生物学 · 癌症研究
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EMBO REPORTS · 2025 · IF 6.2

CDC42 supports HBV entry by NTCP translocation to the plasma membrane and macropinocytosis

Shuzhi Cui,Wei Gao,Yuxin Chen,Yi Xu,Zhifang Li,Yu Wei,Yaming Jiu

CDC42 is a member of Rho GTPase family that regulates various biological processes and its activity can be hijacked by invading pathogens. Here, we discovered that the level of active CDC42 in hepatocytes positively correlates with the entry capacity of hepatitis B virus (HBV). Mechanistically, CDC42 activation effectively promotes the transport of the viral receptor sodium taurocholate co-transporting polypeptide (NTCP) to the plasma membrane via Rab11 dependent recycling endosomal pathway. NTCP interacts with Rab11 and activation of CDC42 signaling reinforces the interaction between NTCP and Rab11. We further show that clathrin mediated endocytosis (CME), the known HBV entry pathway, is independent of CDC42 activity. Intriguingly, we reveal that CDC42 dependent macropinocytosis is a route for HBV entry, which is equally essential for viral infection as CME. Together, our findings uncover new mechanisms for HBV entry that involve unrecognized functions of CDC42 and suggest that Rho GTPase signaling might represent a potential target for antiviral therapy.

CAS / MDL: 81-24-3
研究领域: 病毒学 · 分子生物学 · 细胞生物学 · 感染性疾病 · 肝脏病学 · 信号转导 · 药理学 · 转化医学
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