INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
·
IF 5.3
Liqiao Zhang,Xinyu Cao,Jiayi Chen,Yanyan Dong,Wenwen Chen,Yu Gao,Jingjing Guo,Haiqin Huang
Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary pharmaceutical agent for treating recurrent and metastatic breast cancer, the emergence of PTX resistance frequently results in therapeutic shortcomings, representing a substantial obstacle in clinical breast cancer management. In response, we developed a delivery system exhibiting dual specificity for both tumors and mitochondria. This system facilitated the sequential administration of small interfering B-cell lymphoma-2 (siBcl-2) and PTX to the tumor cytoplasm and mitochondria, respectively, with the aim of surmounting PTX resistance in tumor cells through the activation of the mitochondrial apoptosis pathway. Notably, we employed genetic engineering techniques to fabricate a recombinant ferritin containing the H-subunit (HFn), known for its tumor-targeting capabilities, for loading siBcl-2. This HFn-siBcl-2 complex was then combined with positively charged Triphenylphosphine-Liposome@PTX (TL@PTX) nanoparticles (NPs) to formulate HFn/siBcl-2@TL/PTX. Guided by HFn, these nanoparticles efficiently entered cells and released siBcl-2 through the action of triphenylphosphine (TPP)-mediated “proton sponge,” thereby precisely modulating the expression of Bcl-2 protein. Simultaneously, PTX was directed to the mitochondria through the accurate targeting of TL@PTX, synergistically initiating the mitochondrial apoptosis pathway and effectively suppressing PTX resistance both in vitro and in vivo . In conclusion, the development of this dual-targeting delivery system presents a promising therapeutic strategy for overcoming PTX resistance in the clinical treatment of breast cancer.
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MOLECULAR CELL
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2024
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IF 14.5
Wei Luo,Yunyuan Xu,Jie Cao,Xiaoyu Guo,Jingdan Han,Yuanyuan Zhang,Yuda Niu,Meiling Zhang,Yi Wang,Guohua Liang,Qian Qian,Song Ge,Kang Chong
While it is known that temperature sensors trigger calcium (Ca 2+ ) signaling to confer cold tolerance in cells, less is known about sensors that couple with other secondary messengers. Here, we identify a cold sensor complex of CHILLING-TOLERANCE DIVERGENCE 6 (COLD6) and osmotin-like 1 (OSM1), which triggers 2′,3′-cyclic adenosine monophosphate (2′,3′-cAMP) production to enhance cold tolerance in rice. COLD6, which is encoded by a major quantitative trait locus (QTL) gene, interacts with the rice G protein α subunit (RGA1) at the plasma membrane under normal conditions. Upon exposure to chilling, cold-induced OSM1 binds to COLD6, kicking out RGA1 from interaction. This triggers an elevation of 2′,3′-cAMP levels for enhancing chilling tolerance. Genetic data show that COLD6 negatively regulates cold tolerance and functionally depends on OSM1 in chilling stress. COLD6 alleles were selected during rice domestication. Knockout and natural variation of COLD6 in hybrid rice enhanced chilling tolerance, hinting design potential for breeding. This highlighted a module triggering 2′,3′-cAMP to improve chilling tolerance in crops.
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Biosensors-Basel
·
2024
·Vol. 14
·期 4
·195
·
IF 4.9
Youjun Zeng,Dongyun Kai,Zhenxiao Niu,Zhaogang Nie,Yuye Wang,Yonghong Shao,Lin Ma,Fangteng Zhang,Guanyu Liu,Jiajie Chen
SPR biosensors have been extensively used for investigating protein–protein interactions. However, in conventional surface plasmon resonance (SPR) biosensors, detection is limited by the Brownian-motion-governed diffusion process of sample molecules in the sensor chip, which makes it challenging to detect biomolecule interactions at ultra-low concentrations. Here, we propose a highly sensitive SPR imaging biosensor which exploits the coffee ring effect (CRE) for in situ enrichment of molecules on the sensing surface. In addition, we designed a wavelength modulation system utilizing two LEDs to reduce the system cost and enhance the detection speed. Furthermore, a detection limit of 213 fM is achieved, which amounts to an approximately 365 times improvement compared to traditional SPR biosensors. With further development, we believe that this SPR imaging system with high sensitivity, less sample consumption, and faster detection speed can be readily applied to ultra-low-concentration molecular detection and interaction analysis.
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JOURNAL OF MEMBRANE SCIENCE
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2024
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IF 8.4
Nan Sun,Shucheng Mo,Yuanhang Cai,Yingshuai Zhao,Yaling Han,Yijun Zheng,Tao He
Forward osmosis (FO) has shown great promise in concentrating enriched lithium brine during lithium extraction from salt-lake brine due to low energy consumption and ecologically friendliness. The effective utilization of enormous osmotic pressure of freely available MgCl 2 onsite requires highly selective FO membranes with high flux, which calls for thin-film composite forward osmosis (TFC-FO) membranes of highly interconnected substrate and defect-free separation layer. Herein, for the first time, we employed 2-Pyrrolidone (2-PD) as the solvent to prepare FO substrates via the non-solvent induced phase separation (NIPS) for preparing TFC FO membranes. Owing to its weak solubility, the PSf/2-PD polymer solution shows high viscoelasticity, resulting in spinodal demixing and a bicontinuous porous structure, unlike the closed finger-like pore structure observed in the PSf/DMAc binary system. By further reducing the casting humidity and coagulation bath temperature, the substrate surface pore size was optimized to prepare high-performance TFC-FO membranes: the TFC-30%-3 exhibits a water flux of 20.0 LMH and low specific reverse salt flux of 0.23 g/L at AL-FS mode, showing competitive performance compared to the state-of-the-art membranes. These results imply that 2-PD, as an environmentally friendly alternative to traditional solvents, shows significant promise for FO substrate preparation using a simple polymer/solvent binary system.
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MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Xu Yang,Zixuan Liu,Yong Kong,Zheng-Zhi Yin,Guojun Zheng,Hongyu Zhang
An anti-fouling surface molecularly imprinted (SMI) ratiometric electrochemical biosensor was fabricated for the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein (S protein). Polypyrrole (PPy) was electrodeposited on the electrode surface by using ferrous phthalocyanine (PcFe) and sodium alginate (SA) as the dopants, which acted as the molecularly imprinted polymers (MIPs). The SMI electrochemical biosensor could be used for the detection of SARS-CoV-2 S protein based on the ratiometric signals of the internal reference (PcFe) and the external probe ([Fe(CN) 6 ] 3−/4− ). Under optimized conditions, the as-fabricated SMI ratiometric biosensor showed a wide linear range of 100 fg mL −1 ∼ 100 ng mL −1 with a low limit of detection (LOD) of 30.1 fg mL −1 . Nonspecific adsorption of interfering substances onto the SMI biosensor surface could be significantly reduced due to the outstanding anti-fouling ability of SA, as revealed by fluorescence microscopy. Finally, the reliability of the SMI ratiometric electrochemical biosensor was demonstrated by the detection of SARS-CoV-2 S protein in clinical serum samples. The findings of this work open a new avenue in clinical diagnosis of COVID-19.
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CURRENT BIOLOGY
·
2024
·
IF 8.1
Yun Chen,Xia Hua,Siyu Li,Jiamei Zhao,Huan Yu,Dongyao Wang,Jiqiang Yang,Lijun Liu
Rice paddy has been the main source of anthropogenic methane (CH 4 ) emissions, with significant variations among rice varieties. 2-Acetyl-1-pyrroline (2-AP) is the key component of the pleasant aroma in fragrant rice. Here, we show that fragrant rice is metabolically active in nitrogen assimilation and exhibits high levels of 2-AP and that CH 4 fluxes at the booting stage and cumulative emissions are 25.5% and 14.8% lower, respectively, in fragrant rice paddies compared with nonfragrant rice paddies. Three precursors involved in 2-AP synthesis—proline, glutamic acid, and ornithine—are identified as crucial nitrogen compounds that significantly promote CH 4 oxidation in the rhizosphere. Augmenting 2-AP synthesis, either through foliar spraying or by utilizing CRISPR-Cas9 technology to generate knockout lines of BETAINE ALDEHYDE DEHYDROGENASE 2 gene, effectively enhances CH 4 oxidation and reduces CH 4 fluxes. Our findings reveal that the 2-AP metabolic pathway coordinates the carbon/nitrogen cycle to improve nitrogen assimilation along with high 2-AP levels and mitigate CH 4 emissions in paddy ecosystems.
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SYNLETT
·
2011
·Vol. 2012
·期 01
·145-149
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IF 2.447
Wenpeng Mai,Jinwei Yuan,Zhicheng Li,Gangchun Sun,Lingbo Qu
All articles of this category A novel direct arylation of pyridine N -oxideswith arylboronic acids through C-H functionalization hasbeen developed. This new reaction is performed at room temperatureusing catalytic silver(I) nitrate in the presence of potassium persulfateand give 2-pyridyl arylation derivatives of pyridine N -oxides.
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ANALYST
·
2024
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IF 3.6
Lei Han,Bing Wang,Kunhui Sun,Muqadas Sitara,Meifang Li,Ping Wang,Ning Chen,Xie-an Yu,Jiangwei Tian
The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL−1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.
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International Journal of Nanomedicine
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2024
·
IF 6.6
Bin Zheng,Fei Pan,Minfei Shi,Cuiping He,Beibei He,Rongrong Wang,Guolian Ren,Shuang Yang,Shuqiu Zhang
Purpose: Reducing the first-pass hepatic effect via intestinal lymphatic transport is an effective way to increase the oral absorption of drugs. 2-Monoacylglycerol (2-MAG) as a primary digestive product of dietary lipids triglyceride, can be assembled in chylomicrons and then transported from the intestine into the lymphatic system. Herein, we propose a biomimetic strategy and report a 2-MAG mimetic nanocarrier to target the intestinal lymphatic system via the lipid absorption pathway and improve oral bioavailability.Methods: The 2-MAG mimetic liposomes were designed by covalently bonding serinol (SER) on the surface of liposomes named SER-LPs to simulate the structure of 2-MAG. Dihydroartemisinin (DHA) was chosen as the model drug because of its disadvantages such as poor solubility and high first-pass effect. The endocytosis and exocytosis mechanisms were investigated in Caco-2 cells and Caco-2 cell monolayers. The capacity of intestinal lymphatic transport was evaluated by ex vivo biodistribution and in vivo pharmacokinetic experiments.Results: DHA loaded SER-LPs (SER-LPs-DHA) had a particle size of 70 nm and a desirable entrapment efficiency of 93%. SER-LPs showed sustained release for DHA in the simulated gastrointestinal environment. In vitro cell studies demonstrated that the cellular uptake of SER-LPs primarily relied on the caveolae- rather than clathrin-mediated endocytosis pathway and preferred to integrate into the chylomicron assembly process through the endoplasmic reticulum/Golgi apparatus route. After oral administration, SER-LPs efficiently promoted drug accumulation in mesenteric lymphatic nodes. The oral bioavailability of DHA from SER-LPs was 10.40-fold and 1.17-fold larger than that of free DHA and unmodified liposomes at the same dose, respectively.Conclusion: SER-LPs improved oral bioavailability through efficient intestinal lymphatic transport. These findings of the current study provide a good alternative strategy for oral delivery of drugs with high first-pass hepatic metabolism.
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Journal of Orthopaedic Translation
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2024
·
IF 5.9
Peng He,Yanbin Zhao,Bin Wang,Guoyin Liu,Lei Zhang,Mei Li,Bin Xu,Weihua Cai,Chenglin Chu,Yu Cong
Background The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity. Methods In this study, the cement liquid phase base on rhBMP-2 and chitosan solution into MPC were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, and cellular responses and bone regeneration in response to CHI-rhBMP2 MPC were investigated in vitro and in vivo. Results After the chemical component modification, CHI-rhBMP2 MPC possessed controllable degradation rate, moderate setting time, appropriate cuing temperature, good injectability, and improved initial strength. In vitro tests showed that the CHIrhBMP2 MPC could promote cell proliferation and adhesion, as well as that contribute to osteoblast differentiation and mineralization. In addition, cement materials were implanted into the rabbit femoral condyles for in vivo osseointegration evaluation. The results displayed that more new bone grew around CHI-rhBMP2 MPC, verifying improved osseointegration capacity. Transcriptome analysis revealed that focal adhesion, Forkhead box O（FoxO） signaling pathway and P13K/AKT signaling pathway were may involved in CHI-rhBMP2 MPC induced new bone formation. Conclusion This work provides a new strategy for the rational design of potential bone repair candidate materials.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
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2012
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IF 2.237
Hong-Xing Zhang,Jia-Jun Gao,Hong Meng,Ying-zhou Lu,Chun-Xi Li
A novel integrated process is proposed for the catalytic oxidative desulfurization of fuel oil, in which the oxidant H2O2 is in situ generated by oxidizing 2-propanol with oxygen, and its feasibility is evaluated in terms of the S-conversion of 3-methylthiophene (3-MT), benzothiophene (BT), and dibenzothiophene (DBT) in octane under varying conditions. The catalysis of [π-C5H5NC16H33]3[PW4O16] is found to be much superior to H3PW12O40 and [(C4H9)4N]3[PW12O40] due to its good dispersivity in oil and adsorptivity for S-compounds. Some influencing factors for the S-conversion were studied, viz., time, temperature, various S-compounds, and the amount of 2-propanol, initiator, oxygen, and catalyst. All factors that favor the production of the 2-propanol radicals affect the desulfurization rate remarkably. Both BT and DBT can be removed efficiently at mild conditions (1.4 MPa O2, 90 °C) in 6 h with S-conversion above 96%, and the resulting sulfones can be separated via settling or filtration.
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RESEARCH IN MICROBIOLOGY
·
2025
·
IF 3.4
Haoying Zhang,Qi Zhang,Ting Zuo,Ziqi Wang,Jianmin Liao,Yuanyuan Lu
Candida albicans is an opportunistic pathogen, and the formation of its biofilm makes it resistant to traditional antifungal therapy. Anthraquinones have universal antibacterial activity. We evaluated the inhibitory effects of 2-chloromethyl anthraquinone on C. albicans adhesion, mycelial morphology transformation, and biofilm formation. The results showed that 2-chloromethyl anthraquinone could inhibit C. albicans adhesion, mycelium formation, and biofilm formation in a dose-dependent manner at 2 μg/mL. In addition, 2-chloromethyl anthraquinone significantly inhibited the expression of biofilm formation-related genes in C. albicans , including ALS1 , CPH1 , ECE1, HWP1 , TEC1 , BCR1 , and UME6 . In addition, Ras1-cAMP-Efg1 pathway-related genes ( RAC1 , CYR1 , and TPK2) were also significantly down-regulated, indicating that the inhibitory effect of 2-chloromethyl anthraquinone on C. albicans biofilms may be related to the Ras1-cAMP-Efg1 signaling pathway. In summary, the results of this study confirmed the inhibitory mechanism of 2-chloromethyl anthraquinone on the virulence factors of C. albicans , which laid a theoretical foundation for its use as an anti-biofilm agent against C. albicans .
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