EMBO REPORTS
·
2025
·
IF 6.2
LiYuanyuan,ChengShuyang,JinXu,WuRuoxuan,GuoYiyi,WuDezhi,DongJie
Plants have evolved intricate strategies to cope with various abiotic stresses. Ubiquitin-mediated protein degradation plays a key role in plant development as well as abiotic stress tolerance. In this study, we identify LAO1, an F-box protein with unknown function, as a negative regulator of plant fitness during nitrogen starvation. DOMINANT SUPPRESSOR OF KAR 2 (DSK2) interacts with and mediates the autophagic degradation of LAO1 protein during nitrogen starvation. The loss of LAO1 improves the fitness of an autophagy-deficient mutant, atg5-1, under nitrogen starvation. Intriguingly, mutations in DSK2 facilitate rather than reduce plant growth after nitrogen starvation. This unexpected effect of DSK2 knockout led us to discover that DSK2 also interacts with and degrades a group of class I TCP transcription factors. Phenotypic observations demonstrate that class I TCPs are crucial for plant adaptation to nitrogen starvation. Moreover, genetic analyses indicate that class I TCPs function downstream of LAO1 and counteract its negative effects. Collectively, our findings unveil a previously undescribed regulatory network governing plant fitness during nitrogen starvation.
研究领域:
植物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yuqi Zhen,Quzhen Baima,Shipeng Yang,Yu Cao,XiuPing Meng
Enterococcus faecalis (E. faecalis) is commonly associated with persistent periapical infections. Even after multiple courses of root canal therapy, the infection is difficult to eradicate due to its drug resistance and adaptability. However, root canal treatment will remove nutrients from the root canal and make the remaining E. faecalis near starvation. Iron is an essential element for the growth and metabolism of E. faecalis, but previous studies were mostly based on bacterial nutrient sufficient conditions. Therefore, in this study, the starvation state was used as the breakthrough point to explore the mechanism of iron on the biofilm formation of E. faecalis, so as to be more suitable for clinical practice. In this study, we first constructed a starving E. faecalis model. Subsequently, we found that iron supply promoted biofilm formation in starved E. faecalis, with more eDNA in the biofilm. Iron starvation induced by the iron competitive inhibitor gallium nitrate reduced biofilm formation but increased the proportion of eDNA. In contrast, high iron levels in the environment counteracted this inhibition of biofilm formation. Following DNase I treatment, both the eDNA content and viable bacteria within the biofilm of the iron-supply group exhibited a statistically significant reduction. These results suggest that iron supply may regulate the proliferation of active bacteria by regulating eDNA release, thereby promoting biofilm formation of starved E. faecalis and providing a new perspective on its survival strategy under stress.
研究领域:
微生物学
·
口腔医学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biotechnology for Biofuels and Bioproducts
·
2024
·Vol. 17
·期 1
·1-17
·
IF 3.3
Liu Lin,Wang Zhixing,Fang Yu,Yang Renfei,Pu Yi,Meng Xiangfeng,Liu Weifeng
Background The saprophytic filamentous fungus Trichoderma reesei represents one of the most prolific cellulase producers. The bulk production of lignocellulolytic enzymes by T. reesei not only relies on the efficient transcription of cellulase genes but also their efficient secretion after being translated. However, little attention has been paid to the functional roles of the involved secretory pathway in the high-level production of cellulases in T. reesei. Rab GTPases are key regulators in coordinating various vesicle trafficking associated with the eukaryotic secretory pathway. Specifically, Rab7 is a representative GTPase regulating the transition of the early endosome to the late endosome followed by its fusion to the vacuole as well as homotypic vacuole fusion. Although crosstalk between the endosomal/vacuolar pathway and the secretion pathway has been reported, the functional role of Rab7 in cellulase production in T. reesei remains unknown.Results A TrRab7 was identified and characterized in T. reesei. TrRab7 was shown to play important roles in T. reesei vegetative growth and vacuole morphology. Whereas knock-down of Trrab7 significantly compromised the induced production of T. reesei cellulases, overexpression of the key transcriptional activator, Xyr1, restored the production of cellulases in the Trrab7 knock-down strain (Ptcu-rab7KD) on glucose, indicating that the observed defective cellulase biosynthesis results from the compromised cellulase gene transcription. Down-regulation of Trrab7 was also found to make T. reesei more sensitive to various stresses including carbon starvation. Interestingly, overexpression of Snf1, a serine/threonine protein kinase known as an energetic sensor, partially restored the cellulase production of Ptcu-rab7KD on Avicel, implicating that TrRab7 is involved in an energetic adaptation to carbon starvation which contributes to the successful cellulase gene expression when T. reesei is transferred from glucose to cellulose.Conclusion sTrRab7 was shown to play important roles in T. reesei development and a stress response to carbon starvation resulting from nutrient shift. This adaptation may allow T. reesei to successfully initiate the inducing process leading to efficient cellulase production. The present study provides useful insights into the functional involvement of the endosomal/vacuolar pathway in T. reesei development and hydrolytic enzyme production.
研究领域:
微生物学
·
分子生物学
·
酶工程
✓ 已验证
DOI
高影响因子
Autophagy
·
2023
·
IF 13.3
Chaonan Sun,Yuxin Chen,Qianqian Gu,Yuanyuan Fu,Yao Wang,Cui Liu,Huazhong Xie,Yong Liao,Zhihua Zheng,Peiqing Liu,Min Li
ATG4B is a core protein and essential for cleaving precursor MAP1LC3/LC3 or deconjugating lipidated LC3-II to drive the formation of autophagosomes. The protein stability and activity of ATG4B regulated by post-translational modification (ubiquitination) will directly affect macroautophagy/autophagy. However, the mechanism involved in ATG4B ubiquitination is largely unclear. In this study, a new E3 ligase of ATG4B, UBE3C, was identified by mass spectra. UBE3C mainly assembles K33-branched ubiquitin chains on ATG4B at Lys119 without causing ATG4B degradation. In addition, the increased ubiquitination of ATG4B caused by UBE3C overexpression inhibits autophagy flux in both normal and starvation conditions, which might be due to the reduced activity of ATG4B and ATG4B-LC3 interaction. This reduction could be reversed once the lysine 119 of ATG4B was mutated to arginine. More important, under starvation conditions the interaction between ATG4B and UBE3C apparently decreased followed by the removal of the K33-branched ubiquitin chain of ATG4B. Thus, starvation-induced autophagy could be partially suppressed by an increased ubiquitination level of ATG4B. In conclusion, our research reveals a novel modification mode of ATG4B in which UBE3C can fine tune ATG4B activity by specific ubiquitination regulating autophagy without causing ATG4B degradation.
研究领域:
细胞生物学
·
分子生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Xiyou Du,Yu Zhang,Yanan Zhang,Shan Gao,Xiaoye Yang,Lei Ye,Guangxi Zhai
Tumor microenvironment (TME) featured by dense extracellular matrix (ECM), high interstitial pressure, hypoxia, and immunosuppression hinders the infiltration of nanoparticles (NPs) into tumors, impairing the efficacy of chemotherapy or phototherapy. To overcome these obstacles, we propose a novel biomimetic nano-carrier, B16F10 cell membrane camouflaged heparin-3-bromopyruvate conjugate modified graphene oxide (GO [email protected] , GBM), for the targeted delivery of etoposide (EPT). EPT/GBM accumulates in tumor tissue and is internalized into B16F10 cells relying on homologous targeting ability. GO-mediated hyperthermia could accelerate the release of EPT, destruct ECM, dilate blood vessels, increase oxygen supply, and induce immunogenic cell death (ICD). The acylhydrazone bond-conjugated 3BP is released in acidic environment, suppressing glycolysis for starvation therapy, and reducing lactate efflux to alleviate immunosuppression. The released EPT entered the cell nuclei to exert a chemotherapeutic effect and downregulated the expression of programmed death ligand 1 (PD-L1) by inhibiting epithelial-mesenchymal transition (EMT)/β-catenin/STT3/PD-L1 signaling. EPT/GBM plus near infrared (NIR) laser treatment activated T lymphocytes and downregulated M2 tumor-associated macrophage (TAM), showing significant efficacy against primary tumors, abscopal tumors and lung metastases. In summary, this study presented a novel combinational strategy that integrated PTT, chemotherapy, starvation therapy and immunotherapy in one system, providing a new perspective for targeted-therapy of melanoma.
研究领域:
纳米技术
·
肿瘤学
·
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Hang Wu,Lei Xie,Liang Zhu,Tengbo Yu,Yingze Zhang
As a common malignant bone tumor in adolescents, osteosarcoma (OS) possesses a very poor prognosis and lacks effective treatments. In this study, we developed a multifunctional nanotherapeutic agent (WSe 2 /AIPH/GOx) that can combine photothermal therapy (PTT) /thermodynamic therapy (TDT) /starvation therapy (ST) against OS. The prepared WSe 2 /AIPH/GOx exhibited a high photothermal conversion efficiency of 37.3% under 808 nm near-infrared laser irradiation, which could effectively eliminate tumor cells. In addition, the local high temperature caused by photothermal heat induces the rapid release and decomposition of AIPH, generating oxygen-independent alkyl radicals that promote tumor cell death in the hypoxic microenvironment. More importantly, the introduction of GOx depletes glucose to starve tumor cells on the one hand, and on the other hand can indirectly increase the thermal sensitivity of cells. In vivo experiments have demonstrated that WSe 2 /AIPH/GOx can effectively inhibit tumor growth in mice due to the combined effects of multiple therapies. Overall, this work provides an effective strategy for potential osteosarcoma treatment based on combination therapies.
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Zhanlin Zhang,Kun Wei,Jie Meng,Junwu Wei,Yupeng Su,Huan Tan,Xiaohong Li
Piezoelectrodynamic therapy (PEDT) is compromised by hypoxia dilemma of tumors, while starvation therapy is constrained by insufficient enzyme activities. To address these challenges, Janus piezoelectric nanoparticles (NPs) are proposed to spatially immobilize glucose oxidase (GOx) and catalase (CAT), enabling piezoelectric potential-amplified enzyme activities and synergistic PEDT-starvation tumor therapy. Here hollow barium titanate (hBT) NPs are synthesized using SiO 2 templates, followed by partial Au deposition via the Pickering emulsion-masking method to create Janus hBT@Au NPs, which are then conjugated with GOx and CAT on opposing sides to yield C-hBT@Au-G NPs. The hollow structure of hBT enhances flexibility and deformation under ultrasonication, while Schottky heterojunctions with Au layers promote charge carrier transfer, amplifying piezoelectric effects and free electron transfer to boost GOx activities. Piezoelectric field-enhances selective tumor cell internalization of NPs and PEDT generation of reactive oxygen species (ROS), coupled with self-propagated GOx/CAT cascades, intensify tumor cytotoxicities and deplete intracellular adenosine triphosphate. The Janus architecture, ultrasonic cavitation, and O 2 generation collaboratively drive robust propulsion for efficient NP accumulation and deep ROS penetration into tumor tissues, thereby achieving full tumor suppression with negligible systemic toxicity. This design overcomes delivery barriers of tumor accumulation, intratumoral penetration, and cellular uptake and synergizes PEDT-starvation tumor therapy.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 43
·9933-9942
·
IF 5.344
Xinhe Liu,Jing Liu,Shangyu Chen,Yuxin Xie,Quli Fan,Jiahong Zhou,Jianchun Bao,Tianxiang Wei,Zhihui Dai
The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙−) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.
研究领域:
肿瘤学
·
生物医学工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Linjie Huang,Yina Su,Xueqi Hu,Yichao Zhang,Guizhen Xu,Simin Chen,Jiaqiong Wu,Siyu Wang,Dongdong Zhang,Zheng Zeng,Shanni Hong,Xiahui Lin
Sonodynamic therapy (SDT) is a promising ultrasound (US)-triggered therapeutic modality for anticancer treatments due to its high penetration, safety, and noninvasiveness. Its therapeutic efficiency is closely related to the performance of sonosensitizers and the oxygen concentration of the tumor microenvironment (TME). Herein, inspired by the adhesion of cocklebur, a rough-surface sonosensitizer gold platinum encapsulated with magnesium silicate loaded with glucose oxidase (AuPt@MgSiO3@GOx, APMS-GOx) with an enzymatic cascade activity was designed to improve delivery capability, produce reactive oxygen species, and reduce the glucose concentration in tumor tissue. The rough surface of APMS-GOx can improve the ability of nanomaterials to deliver to tumor areas. The enzymatic cascade reaction of APMS-GOx can induce starvation therapy and improve the level of oxygen. Adequate oxygen can not only alleviate hypoxia TME but also further convert to singlet oxygen (1O2) by APMS-GOx under US activation. Moreover, the activity of GOx increases due to the involvement of US, resulting in a positive effect on starvation therapy. Furthermore, APMS-GOx exhibits near-infrared absorption properties, providing a photoacoustic imaging-guided combination breast tumor therapy strategy.
研究领域:
肿瘤学
·
生物医学工程
·
影像医学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yang Wang,Shulong Wang,Min He,Yanli Luo,Fanggui Ye,Jianniao Tian,Shulin Zhao
Integrating imaging-guided diagnoses with therapeutic strategies holds significant potential in the treatment of cancer and other diseases. Herein, we developed a dual stimulus-responsive nanoagent that is responsive to two specific stimuli, and demonstrated its application to the diagnosis and photothermal-starvation therapy of colon cancer. The elevated levels of H 2 S and glucose in colon cancer cells are used as targets for a dual stimulus-responsive, self-assembled copper-albumin-glucose oxidase@polyaniline (Cu 2 + -BSA-GO x @PANI) nanoplatform. Upon entering colon cancer cells, GO x oxidizes glucose to produce gluconic acid, which leads to the protonation of PANI and the red-shifting of the wavelength of maximum absorbance of the nano-platform from 680 nm to 780 nm. Concurrently, Cu 2+ reacts with H 2 S to form CuS, which further induces a redshift from 780 nm to 830 nm, and significantly enhancing the near-infrared II region absorption intensity and enabling photoacoustic imaging under 1064 nm laser irradiation. Additionally, the consumption of glucose within cancer cells inhibits the generation of ATP, achieving starvation therapy while reducing the expression of tumor heat-shock protein 90 to weaken tumoral thermo-tolerance, resulting in a synergistic anti-tumor effect. In vitro and in vivo analyses indicate that the Cu 2+ -BSA-GOx@PANI nano-platform possesses specific visual diagnostic and therapeutic capabilities for colon cancer, providing a novel strategy for the design of highly effective nanodiagnosis-treatment agents.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2019
·
IF 7.65
Zong-Yao Qian,Xiao Chen,He-Te Zhu,Jun-zhe Shi,Ting-Ting Gong,Qi-Ming Xian
In this study, the biosynthesis of microcystins (MCs) was investigated after long-term nitrogen-starved conditions in cyanobacterium Microcystis aeruginosa . The results demonstrated that the algal cells were able to survive in a non-growing state with nitrogen starvation for more than one month. The physiological properties of the algal cells were studied to elucidate the mechanisms of viability under nitrogen-deprivation conditions. After the state of nitrogen chlorosis, new toxins could be resynthesized and tracked using 15 N-stable isotope-labelled nitrogen. Nitrogen starvation of nutritionally replete cells resulted in a significant increase of microcystin-LY (MC-LY), thereby suggesting that MC-LY may undergo catabolism to provide nitrogen or that MC-LY may be produced to play an important role in the cell in response to nitrogen deprivation. The rank order of different types of nitrogen in algal cells assimilation was N-ammonium > N-urea > N-nitrate > N-alanine. The relationship between the production of toxin variants and various environmental conditions is an interesting issue for future research and may help improve the understanding of the ecological role of cyanobacterial toxins .
研究领域:
环境科学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FISH BIOLOGY
·
2021
·Vol. 99
·期 6
·1843-1856
·
IF 2.051
Liping Yang,Shaoyang Zhi,Guokun Yang,Chaobin Qin,Xiao Yan,Mingming Niu,Wenlei Zhang,Mingyu Liu,Mengjuan Zhao,Guoxing Nie
Glucose transporter 4 (GLUT4) is comprehensively investigated in mammals, while the comparative research of GLUT4 in common carp is deficient. To investigate the function of GLUT4, carp glut4 was first isolated. The open reading frame of carp glut4 was 1518 bp in length, encoding 505 amino acids. A high-sequence homology was identified in carp and teleost, and the phylogenetic tree displayed that the carp GLUT4 was clustered with the teleost. A high level of glut4 mRNA was analysed in fat, red muscle and white muscle. After fasting treatment, glut4 mRNA expression was increased significantly in muscle. In the oral glucose tolerance test experiment, glut4 mRNA was also significantly elevated in muscle, gut and fat. Furthermore, intraperitoneal injection of insulin resulted in the upregulation of glut4 gene expression significantly in white muscle, gut and fat. On the contrary, the glut4 mRNA level in the white muscle, gut and fat was markedly downregulated after glucagon injection. These results suggest that GLUT4 might play important roles in food intake and could be regulated by nutrient condition, insulin and glucagon in common carp. Our study is the first to report on GLUT4 in common carp. These data provide a basis for further study on fish GLUT4.
研究领域:
分子生物学
·
鱼类生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）