Cell Reports Medicine
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2025
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IF 10.6
Wenhua Wang,Xin Li,Rui Hu,Liang Dong,Shiyao Pei,Liping Jin,Qian Gao,Xiang Chen,Mingzhu Yin
Immunotherapy shows remarkable benefits in treating melanoma, yet existing approaches achieve limited overall responses. Here, we show that a combination of bromodomain and extra-terminal protein family inhibitor, NHWD-870, and Bacillus Calmette-Guérin vaccine is a promising therapeutic strategy for melanomas. Single-cell transcriptome analyses and functional experiments show that the combination therapy significantly inhibited tumor growth by reprogramming T cells toward an immune-activated state, enhancing their cytotoxicity, preventing their exhaustion, and increasing the recruitment of them into the tumor microenvironment. We identify the molecule, MT1, as a direct downstream target of BRD4, which is effectively suppressed by NHWD-870. Furthermore, our findings are reinforced by a humanized patient-derived xenograft (PDX) model, which exhibits notable antitumor effects in humanized tumor-bearing mice treated with the combination therapy. Our study underscores the immense potential of this therapeutic approach for clinical practice, offering promising prospects in overcoming the limitations of current treatments.
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高影响因子
ACS Applied Nano Materials
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2024
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IF 5.3
Pingchuan Qin,Yunqing Pang,Lingyuan Kong,Yurong Lv,Hongliang Du,Yan Zhou,Jing Wang
Malignant melanoma, a particularly aggressive and lethal tumor, has traditionally been treated through methods such as surgery, radiation therapy, and chemotherapy. Unfortunately, these methods frequently show some limitations, such as suboptimal therapeutic effectiveness, notable adverse effects, and the propensity for the development of drug resistance. Targeted therapy and immunotherapy hold substantial promise for extending the survival of patients and elevating their overall quality of life. Nevertheless, the prevalence of “cold tumors” continues to hamper the effectiveness of these treatments, resulting in unsatisfactory outcomes for many patients. Facing this challenge, nanomedicine emerges as a good frontier, functioning as an advanced drug delivery system that integrates immunotherapy with additional anticancer strategies. Hence, there is substantial research on malignant melanoma. This study introduces a multifunctional nanoplatform that combines evodiamine, black phosphorus nanosheets, and tumor cell membranes. The tumor cell membrane imparts the nanoplatform immune evasion capabilities and enhances precision in tumor targeting. Simultaneously, the effects of black phosphorus nanosheets and evodiamine synergistically impede tumor cell growth by the combination of photothermal, chemotherapy, and immunotherapy approaches, ultimately leading to an amplified immune response.
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JOURNAL OF POWER SOURCES
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2024
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IF 8.1
Xuxu Wang,Ruxiu He,Ying Bai,Fen Yao,Shuang Gao,Ping Nie,Limin Chang
T-Nb 2 O 5 is a promising anode material for high power density lithium-ion batteries (LIBs) due to its fast lithium storage capacity and safe lithiation potential. However, its practical application is hindered by its low electronic conductivity. In this work, we improved the electrochemical performance of T-Nb 2 O 5 by surface P-doping and the N-doped carbon substrate. Surface P-doping guided by defects enhances the electronic conductivity of the material, which can synergize with N-doped carbon substrates to form a conductive network and accelerate the lithiation/delithiation process. More importantly, surface P-doping does not destroy the internal crystal structure of the material, ensuring the stability of the Nb 2 O 5 during the charge/discharge process. When used as the anode for LIBs, the Nb 2 O 5 -P/N-C exhibits great cycling stability and high-current charge/discharge performance. The specific capacity of Nb 2 O 5 -P/N-C exceeds 116 mAh g −1 after 1000 cycles at 1000 mA g −1 . This work presents a novel approach to improve the electrochemical performance of T-Nb 2 O 5 .
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LANGMUIR
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2024
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IF 3.7
Qianrui Xu,Zhimin Zhao,Xinyu Chen,Wenqian Fan,Yong Jiang
Fe3O4 nanoparticles occupy a pivotal position in the realm of nanobiology due to their nontoxic, biocompatible, and superparamagnetic properties. This study examines the influence of surface modifiers on the properties of magnetic nanoparticles. Poly(methacrylic acid) (PMAA), poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSM), trisodium citrate (TSC), carboxymethylcellulose (CMC), and carboxymethylated-dextran 40 (CMD40) were introduced into a one-pot solvothermal method to synthesize magnetic nanoparticles. TEM, the 4-(bromomethyl)-6,7-dimethoxy coumarin (BMMC) absorption assay, and the Bradford method were employed to characterize the diameter, carboxyl content, and protein immobilization ability of the nanoparticles, respectively. The findings revealed that CMD40-modified magnetic nanoparticles (CMD40-MNPs) exhibited the highest carboxyl content and streptavidin (SA) immobilization content, reaching 6.5 × 10–7 mol/mg and 375 μg/mg, respectively. In contrast, CMC-modified magnetic nanoparticles displayed opposite trends. This is primarily attributed to dextran’s unique molecular structure, which enhances its water solubility and biocompatibility, thereby facilitating contact with Fe3O4 nanoparticles in aqueous solutions. CMD40-MNPs possess a saturation magnetization value of 60.90 emu/g and can be collected within (60 ± 5) s using a standard magnetic separator. Cytotoxicity assays demonstrated that CMD40-MNPs are nontoxic to cells. A cell sorting strategy utilizing the binding of SA-CMD40-MNPs and biotin antihuman CD3 antibody-modified cell suspensions was employed to isolate CD3+T cells. The results indicate that the purity and efficiency of targeted CD3+T cells are 85.2% and 61.5%, respectively.
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ADVANCED MATERIALS
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2025
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IF 26.8
Xiejun Zhao,Xiangchuan Qin,Ruizhe Wang,Yawen Wang,Yinli He,Yuchen Wang,Kefeng Li,Peipei Zhang,Chen Yang,Menghan Wang,Yingtong Dong,Xue Shi,Jia Ma,Jiye Zhang,Xiaojiao Li
Inefficient priming, poor recruitment, and inadequate reinvigoration of T cells challenges the therapy of PD-L1-resistant tumors. Herein, a pH-responsive charge-reversal nanoplatform integrating coactivator-associated arginine methyltransferase 1 (CARM1) inhibitor (iCARM1) and poliovirus receptor siRNA (siPVR) is developed. Upon tumor penetration, iCARM1 released in tumor cells facilitates T cell priming by epigenetically activating cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling-mediated dendritic cell maturation. Meanwhile, in T cells, iCARM1 facilitates their recruitment by upregulating CXC-chemokine receptor 3 (CXCR3) expression. The released siPVR silences pvr to reinvigorate T cells. This epigenetic nanoagonist induces a robust immune response, dramatically suppresses tumor growth, metastasis, and relapse, and confers durable protection against secondary tumor challenge. Multiple PD-L1-resistant models demonstrate the broad applicability of this strategy. This study thus represents an innovative approach for facilitating multilevel T cell responses to combat PD-L1-resistant tumors.
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JOURNAL OF APPLIED TOXICOLOGY
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2025
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IF 2.8
Kai Wang,Aneela Perveen,Jiakun Shen,Niaz Ali Kaka,Yansen Li,Dan Shen,Chunmei Li
T-2 mycotoxin is a highly toxic type A trichothecene mycotoxin that widely contaminates livestock feed, posing a serious threat to animal and human health. Long-term exposure can lead to immunosuppression, growth retardation, and liver damage, causing significant economic losses to the livestock industry. Offspring are particularly susceptible to maternal dietary influences during pregnancy and lactation. This research aimed to evaluate the impact of T-2 mycotoxin exposure on both dams and their pups. Thirty pregnant mice were randomly allocated into three groups ( n = 10). From gestational day 14 to lactational day 21, the dams received gavage doses of T-2 mycotoxin at concentrations of 0, 0.005, and 0.05 mg/kg/day. Randomly selected one male pup and one female pup from each dam were sacrificed on LD 1, 7, and 21; dams were dosed until the day they were sacrificed. T-2 mycotoxin decreased the relative body/organ weights of the dams and offspring ( p < 0.05). Moreover, T-2 mycotoxin-induced oxidative stress in dams and offspring increased the malondialdehyde content, which led to reduced activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, and total antioxidant capacity in the serum and liver ( p < 0.05). T-2 mycotoxin induced histomorphological changes in the liver and early involution of the mammary gland acini in dams. The concentrations of liver-metabolizing enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase increased in offspring ( p < 0.05). The serum insulin-like growth factor-1 level in offspring was decreased, which may impair the development of vital organs such as the liver, kidneys, and spleen in offspring. Consequently, the body weight and length of the offspring of exposed dams decreased. This study revealed that T-2 mycotoxin exposure during late gestation and entire lactation harms dams, damages mammary gland acini, alters liver biochemistry, induces oxidative stress, and delays offspring growth while also impairing maternal weight gain during lactation.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Yu Han,Kai Zhang,Ning Xin,Xintao Gao,Guohua Ma,Jingtong An,Yantao Li
Despite recent advancements in lipid nanoparticles (LNPs)-based messenger RNA (mRNA) delivery, significant challenges persist in the structural optimization and functional modulation of their components for cancer immunotherapy, particularly regarding inadequate organ-specific targeting, and insufficient immune activation. Notably, metal ions have demonstrated emerging immunomodulatory potential, yet their coordinated self-assembly within LNPs as adjuvants to enhance the immunotherapeutic efficacy remains largely unexplored. To address these limitations, we combine newly designed imidazole-based LNPs with functional metal ions (Zn 2+ ) to develop novel Zn-coordinated LNP-based mRNA vaccines. A total of 48 imidazole-based ionizable lipids were designed and synthesized, among which C2–13 LNPs emerged as the top-performing formulation in terms of transfection efficiency. By innovatively incorporating Zn 2+ into C2–13 LNPs via coordination interaction, we further developed the novel metal-coordinated mRNA delivery systems, referred to as Zn-C2–13 LNPs. Compared to their non-metal counterparts, Zn-C2–13 LNPs exhibited markedly improved transfection efficiency and antigen presentation in vitro . Impressively, the synergistic effect of the optimized LNP formulation and Zn 2+ in the Zn-C2–13/mOVA systems (Zn-C2–13 LNPs loading ovalbumin mRNA) resulted in superior spleen-selective expression and immune response, significantly boosting the efficacy of cancer immunotherapy in the B16F10 ovalbumin-expressing (B16F10-OVA) melanoma tumor model. Collectively, this novel metal-coordinated LNPs improve specific organ targeting and immune responses, presenting a promising strategy to advance mRNA vaccine-based cancer immunotherapy.
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TALANTA
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2024
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IF 5.6
Meixiang Xue,Shuangxi Cai,Ye Deng,Fang Luo,Jianhui Huang,Zhenyu Lin
T-2 toxin, a hazardous mycotoxin often present in cereals and products based on cereals, poses a substantial risk to humans and animals due to its high toxicity. The development of uncomplicated, quick and highly sensitive methods for detecting T-2 toxin is imperative. In this work, a portable sensing system was constructed using water column height as a readout device in combination with a controlled release system, which allows for an accurate quantitative analysis of T-2 toxin without the need for expensive instrumentation or skilled technicians. Hyaluronic acid (HA) hydrogel was constructed by double cross-linked DNA/aptamer hybrids with polyethyleneimine (PEI) and embedded with platinum nanoparticles (Pt NPs). The aptamer specifically bound to T-2 toxin in its presence, resulting in the disruption of the hydrogel and subsequent release of the Pt NPs. These Pt NPs were later mixed with a solution of H 2 O 2 in a confined reaction flask, leading to the decomposition of H 2 O 2 into O 2 . A glass capillary tube containing a column of red water had been inserted into the cap of the reaction flask, and the low solubility of O 2 led to an increase in pressure within the reaction unit, causing the red water column to rise. There is a good linear correlation between the height of the capillary liquid level and the T-2 toxin concentration in the range of 20 ng/mL to 6 μg/mL. The system has been successfully used to detect T-2 toxin in samples of barley tea and corn.
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JOURNAL OF MEMBRANE SCIENCE
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2024
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IF 8.4
Na Yang,Keting Li,Yufan Hao,Longfei Zhang,Yongli Sun,Luhong Zhang,Bin Jiang
Polyethyleneimine (PEI) nanofiltration (NF) membranes hold great application prospects in lithium extraction from salt lakes due to their high positive charge properties. However, the poor permeability of the membranes caused by the dense separation layer structure severely hinders their further application. Herein, a functional end-capping strategy was employed to address this problem by adding the effective end-capping reagent, Girard's Reagent T (GRT), to the PEI aqueous phase as the co-reaction reagent. Under the dual functions of the end-capping effect and the quaternary ammonium groups of GRT, the looseness and positive charge of the membrane were simultaneously optimized. After the modification of GRT, the looser structure of the PEI/GRT NF membrane improved its pure water flux (PWF) to 115 L m −2 h −1 at 6 bar, which was around 3.7 times higher than that of the original PEI NF membrane. Meanwhile, the enhanced positive charge (from −8 to 9 mV, pH = 7) of the membrane bottom surface allowed it to maintain the high rejection rate of MgCl 2 at 97.2 %. Besides, the PEI/GRT NF membrane exhibited good Mg 2+ /Li + selectivity (S Mg 2+ /Li + = 22.7, 2000 ppm, Mg 2+ /Li + mass ratio: 20:1). Therefore, this study provides a simple and feasible strategy for the preparation of high-permeable PEI NF membranes with good Mg 2+ /Li + separation performance.
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ANALYTICA CHIMICA ACTA
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2016
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IF 4.712
Hua Sang,Gaoyuan Lu,Yazhong Liu,Qiyue Hu,Weifeng Xing,Dongbing Cui,Fang Zhou,Jingwei Zhang,Haiping Hao,Guangji Wang,Hui Ye
Trastuzumab-MCC-DM1 (T-DM1) is an antibody-drug conjugate (ADC) that consists of a monoclonal antibody (mAb) trastuzumab non-cleavably linked to a cytotoxic drug DM1. During production, the DM1 agents were conjugated to the lysine residues of the mAb in a non-specific manner, yielding a heterogeneous mixture of ADC molecules that differ with respect to both the number and the conjugation sites of DM1 per mAb molecule. Since drug conjugation sites of ADC can significantly impact properties such as stability and pharmacokinetic behaviors, a rapid and reliable approach for conjugation site analysis of ADCs is highly demanded. Herein, we have employed a signature ion fingerprinting approach to specifically determine lysine residues with DM1 conjugation, and developed a normalized peak area quantitation method to characterize the percentage of DM1-conjugated lysine for each putative site using a T-DM1 biosimilar as a model drug. With this integrative approach, 38 lysine residues were identified with DM1 conjugation among 90 possible sites. More interestingly, we found that the T-DM1 biosimilar exhibited a specific preference of DM1-conjugation for several lysine residues, and such preference was consistent among three production batches. A molecular modeling approach was subsequently utilized to analyze all the conjugation sites, and revealed an intriguing correlation of the conjugated residue's microenvironment with the conjugation level. In summary, our study introduced an approach that is widely applicable to ADCs of interest for conjugation site analysis. Moreover, it suggests the necessity of performing conjugation site analysis for product and process characterization and also for routine use in lot release and stability testing of manufactured ADCs.
研究领域:
生物化学
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药物分析
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蛋白质组学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Zhen Yu,Yan Zhang,Dongquan Leng,Tingting Wu,Si-Jia Ge,Dawei Fan,Hongmin Ma,Yu Du,Qin Wei
Human papillomavirus (HPV) infection represents a major global health concern due to its strong association with cervical cancer and other malignancies, underscoring the critical need for highly sensitive detection methods. In this study, an advanced photoelectrochemical biosensing platform was developed for ultrasensitive HPV detection. An In 2 S 3 -sensitized SnO 2 heterostructure substrate that dramatically enhances photogenerated charge separation efficiency, generating extremely significant photocurrent enhancement. Furthermore, a CuFe 2 O 4 @T-COF nanosphere serving as a multifunctional signal quencher through synergistic steric hindrance, competitive oxygen consumption and light absorption effects. Notably, an exonuclease III-powered DNA walker system enabling cyclic signal amplification through programmable target recycling. The biosensor demonstrates exceptional analytical performance, achieving a broad dynamic range of 10 −6 to 10 μmol/L with an ultralow detection limit of 1.37 × 10 −7 μmol/L. This breakthrough sensing platform not only provides a powerful tool for early HPV diagnosis but also opens new possibilities for developing next-generation biosensors with clinical-level sensitivity and specificity.
研究领域:
生物传感器
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纳米技术
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分子诊断
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病毒学
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癌症研究
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分析化学
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高影响因子
CYTOTHERAPY
·
2021
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IF 5.414
Jiao Sun,Wen Zhang,Yi Zhao,Jiang Liu,Fang Wang,Ying Han,Miao Jiang,Shiwu Li,Dongqi Tang
Background aims Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy, adverse effects, including cytokine release syndrome and neurotoxicity , impede its therapeutic application, thus making the modulation of CAR T-cell activity a priority. The destabilizing domain mutated from Escherichia coli dihydrofolate reductase (DHFR) is inherently unstable and degraded by proteasomes unless it is stabilized by its chemical ligand trimethoprim (TMP), a Food and Drug Administration-approved drug . Here the authors reveal a strategy to modulate CAR T-cell activity at the protein level by employing DHFR and TMP as a chemical switch system. Methods First, the system was demonstrated to work in human primary T cells . To introduce the system to CAR T cells, DHFR was genetically fused to the carboxyl terminal of a third-generation CAR molecule targeting CD19 (CD19-CAR), constructing the CD19-CAR-DHFR fusion. Results The CD19-CAR-DHFR molecule level was shown to be modulated by TMP. Importantly, the incorporation of DHFR had no impact on the recognition specificity and normal function of the CAR molecule. Little adverse effect on cell proliferation and apoptosis was detected. It was proved that TMP could regulate cytokine secretion and the in vitro cytotoxicity of CD19-CAR-DHFR T cells. Furthermore, the in vivo anti-tumor efficacy was demonstrated to be controllable through the manipulation of TMP administration. The approach to control CD19-CAR also succeeded in 19-BBZ(71), another CD19-targeting CAR with a different structure. Conclusions The proposed approach based on DHFR and TMP provides a facile strategy to bring CAR T-cell therapy under conditional user control, and the strategy may have the potential to be transplantable.
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