MOLECULAR AND CELLULAR BIOCHEMISTRY
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2026
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IF 4.7
Yang Di,Liu Jia,Gao Yan,Guan Xin,Tong Rui
Cervical cancer (CC) is a prevalent malignancy in women; however, the efficacy of immunotherapy in this disease is suboptimal, highlighting the need for novel therapeutic targets. We found that low RNF125 expression correlated with poor prognosis in CC patients. In vitro and in vivo, RNF125 inhibited proliferation and induced apoptosis of CC cells. In immunocompetent mice, RNF125 suppressed tumor growth, increased CD8⁺ T cell infiltration, elevated IFN-γ secretion, and reduced PD-1 expression on CD8⁺ T cells. Co-culture experiments confirmed that tumor cells overexpressing RNF125 enhanced CD8⁺ T cell proliferation and function. Further mechanistic investigation revealed that RNF125 promoted CD8⁺ T cell activity by ubiquitinating and degrading PD-L1. Additionally, RNF125 was identified as a direct target of miR-574-5p. This study demonstrates that RNF125 exhibits tumor-suppressive functions in CC by enhancing anti-tumor immunity, highlighting its therapeutic potential.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Min Cai,Congyu Wu,Muqing Wang,Qian Chen,Yilin Guo,Yu Liu,Xin Huang,Yuan Gao,Yun Qi
Ethnopharmacological relevance Elephantopus scaber L. ( E. scaber ) is a heat-clearing and detoxifying traditional Chinese medicine. Clinically, it is used for treating some immuno-inflammatory diseases associated with excessive T cell activation. However, its action and mechanism on T cells are still ambiguous. Aim of the study This study aims to investigate the molecular mechanism of the ethanol extract of E.scaber (ESE) in ConA-induced T cell activation models. Materials and methods IL-2 transcription and translation levels were determined by RT- q PCR and ELISA. CD4 + naïve T cells were sorted using the flow cytometer. Western blot assay was used for determining intracellular protein levels. Cytoplasmic and mitochondrial Ca 2+ concentrations were measured by fluorometric assays. Results ESE not only dampened the proliferation of splenic lymphocytes, but also decreased IL-2 production in ConA-activated T cells without affecting its mRNA stability. It could inhibit the activation of NFAT and NF-κB pathways, showed as impeding the nuclear translocation of NFAT and p65. Regarding the upstream signaling, ESE significantly decreased cytoplasmic Ca 2+ (Ca 2+ [c] ) level in a model-independent manner. Although it failed to affect plasma membrane Ca 2+ -ATPase, Na + /Ca 2+ exchanger, and mitochondrial Ca 2+ uptake, it affected sarco/endoplasmic Ca 2+ -ATPase (SERCA) pathway. It also hindered IκBα phosphorylation and subsequent degradation. In vivo , ESE reduced IL-2 levels in local and systemic T cell activation models. Conclusion Through inhibiting the activation of SERCA/Ca 2+ [c] /NFAT and NF-κB pathways, ESE markedly decreased ConA-induced IL-2 production in vitro and in vivo . This study provides not only a modern explanation for the traditional uses of E. scaber , but also a scientific guidance for clinical practice.
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Saeed Ghasemzade Bariki,Salman Movahedirad
Liquid-liquid–liquid (L/L/L) flows in microchannels involving three-phase interactions are important in various chemical applications that entail liquid–liquid–liquid reactions. This work comprehensively investigates core (silicone oil)/shell (Polycaprolactone) microdroplet formation using a continuous third phase (distilled water) in a double T-junction microchannel with a diameter of 600 µm, employing Volume-of-Fluid (VOF) simulations and high-speed imaging experimental observation. Due to the satisfactory agreement between computational and experimental techniques, the theoretical flow patterns were identified and categorized into three distinct categories at various flow rates of three phases: core/shell dripping, core/shell slug, and core/shell jetting. The shell thickness increases as the ratio of shell to core phase velocity ( u shell : u core ) increases. Based on the continuous phase Capillary number ( Ca c ) and core and shell phases Weber number ( We core , s h e l l ), a flow pattern map was generated that segregates the distinct flow patterns into different regions. When the flow of the core and shell phases fails to form a droplet due to the inertia of the continuous phase, a core/shell dripping/slug pattern is observed. The channel walls encompass the droplets that form in the slug pattern ( 2 × 10 - 5 ≤ Ca c ≤ 5 × 10 - 4 , 0 < We shell ≤ 1.5 × 10 - 3 , and 0 < We core ≤ 5 × 10 - 5 ) because the continuous phase has less inertia, whereas, in the dripping pattern ( 5.5 × 10 - 5 ≤ Ca c ≤ 9 × 10 - 4 , 7 × 10 - 5 ≤ We shell ≤ 2.5 × 10 - 4 , and 1 × 10 - 5 ≤ We core ≤ 7 × 10 - 5 ), the shell phase fluid is enclosed by the continuous phase. The transition from dripping to jetting ( Ca c ≥ 0.5 , 0 < We shell ≤ 0.15 , and 1 × 10 - 2 ≤ We core ≤ 8 × 10 - 2 ) occurs as the flow rate of a continuous fluid or shell fluid increases. A dimensionless correlation for shell thickness estimation with a 12 % tolerance was proposed with a core/shell/continuous phase's physical properties, surface tensions, and microdroplet size, using Buckingham's theory based on 200 CFD simulations. Additionally, the flow rate and viscosity substantially impact the internal fluid velocity and vorticity of core/shell microdroplets, whereas the influence of interfacial tension can be disregarded. This research lays the groundwork for future studies on mass transfer and reaction behaviors in liquid–liquid–liquid three-phase flow in double T-junction microchannels by exploring various hydrodynamic characteristics under different operating conditions for core/shell microdroplet formation.
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JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Yuchan You,Feiyang Jin,Yan Du,Luwen Zhu,Di Liu,Minxia Zhu,Yuyin Du,Jialu Lang,Weishuo Li,Jian-Song Ji,Yong-Zhong Du
The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength . Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e. , signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy .
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Yanhua Lei,Mengchao Ding,Sha Cheng,Da Huo,Fei Zhang,Tao Liu,Yuliang Zhang
The transition metal sulfide MoS 2 has attracted great interest from the scientific community as an excellent co-catalyst for promoting Fe 2+ /Fe 3+ cycling in advanced oxidation processes to enhance the efficiency of H 2 O 2 decomposition. A photothermal-enhanced photo-Fenton pollutant degradation strategy was proposed. Hybrids of magnetically recyclable Fe 3 O 4 fabricated 1 T-2 H MoS 2 (1 T-2 H MoS 2 @Fe 3 O 4 ) with excellent photothermal conversion efficiency were fabricated to overcome the limitations of relatively low catalytic activity and cycling stability in Fenton reaction. XRD , Raman, TEM and hysteresis loop were employed to evaluate the heterogeneous phase 1 T-2 H MoS 2 nanoflowers as well as the magnetic property . The 1 T-2 H MoS 2 @Fe 3 O 4 hybrids with excellent photothermal conversion efficiency not only enhance the reaction temperature of the Fenton reaction occurring on the material surface, but also demonstrate an effective interfacial photothermal water evaporation efficiency. Due to the synergistic effect of photocatalysis and photo-Fenton catalytic reaction , a quick degradation of simulated pollution were achieved in 5 mins with 98.3% degradation, which could be further improved to 99% due to the photothermal promoting reaction. The 1 T-2 H MoS 2 @Fe 3 O 4 hybrids exhibit good magnetic recyclability, cyclic stability and photothermal performance, which endow it a wide potential application in the field of environmental remediation and the field of water evaporation at the photothermal interface, etc.
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Open Medicine
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2023
·Vol. 18
·期 1
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IF 2.1
Yangfa Chao,Wenting Huang,Zhiheng Xu,Ping Li,Shaodong Gu
Lymphocyte apoptosis is a latent factor for immunosuppression in sepsis. Forkhead box protein P3 (FOXP3) can interact with RUNX family transcription factor 1 (RUNX1) in regulatory T cells. Our research was to probe whether RUNX1/FOXP3 axis affects immunosuppression in the process of sepsis by modulating T and B lymphocyte apoptosis. We constructed sepsis model in mice and mouse CD4 + T and CD19 + B lymphocytes. RUNX1 and FOXP3 expressions and apoptosis in cells were assessed by western blot, quantitative real-time PCR, and flow cytometer. Inflammation of serum and pathological damage was assessed by ELISA and H&E staining. Relationship between RUNX1 and FOXP3 was assessed by co-immunoprecipitation. The findings showed that RUNX1 ameliorated the survival rate, pathological damage, and decreased inflammation-related factors, and inhibited apoptosis of CD4 + T and CD19 + B cells in cecal ligation and puncture mice. Furthermore, RUNX1 up-regulated the viability and down-regulated apoptotic rate with the changed expressions of apoptosis-related molecules in lipopolysaccharide (LPS)-mediated CD4 + T and CD19 + B cells. Additionally, FOXP3 interacted with RUNX1, and its silencing decreased RUNX1 expression and reversed the inhibitory effect of RUNX1 on apoptosis of LPS-mediated CD4 + T and CD19 + B cells. In summary, the RUNX1/FOXP3 axis alleviated immunosuppression in sepsis progression by weakening T and B lymphocyte apoptosis.
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Polymers
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2022
·Vol. 14
·期 24
·5419
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IF 4.967
Puyu Jin,Aimin Pang,Rongjie Yang,Xiaoyan Guo,Jiyu He,Jinxian Zhai
To improve the mechanical properties of polyurethane cross-linked poly (ethylene oxide-co-tetrahydrofuran) (P(E-co-T)) elastomers at room temperature, using poly (ethylene oxide-co-tetrahydrofuran) and high-molecular-weight polyethylene glycol (PEG) as raw materials and polyisocyanate N100 as curing agent, a series of polyurethane cross-linked blended polyether elastomers were prepared by changing the elastomer-curing parameter R value (n(-NCO)/n(-OH)) and P(E-co-T)/PEG ratio. Equilibrium swelling measurements showed that the chemical cross-linkage of the elastomers tended to decrease with the decreasing R value, the average molecular weight (Mc) of the network chain increased, and the density of the network chain (N0) decreased. Wide-angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) tests showed that PEG chain segments within the elastomers crystallized at room temperature, while the crystallinity increased with decreasing R value and increasing PEG content. The mechanical property tests showed that the elongation at break tended to decrease with increasing R value; the tensile strength first increased and then decreased. At R value 0.9, the elastomer presented good comprehensive mechanical properties. In addition, the mechanical properties of polyurethane cross-linked P(E-co-T)/PEG blended polyether elastomer showed an increasing trend with the increase in PEG content when the curing parameter of 0.9 remained unchanged.Keywords:polyurethane cross-linked elastomer;polyether blend;crystallinity;mechanical properties
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ACS Applied Materials & Interfaces
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2022
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IF 10.383
He Ren,Jiexin Li,Gengqi Liu,Yaping Sun,Xingyue Yang,Zhen Jiang,Jingyu Zhang,Jonathan F. Lovell,Yumiao Zhang
The development of nanocarriers capable of codelivering antigens and immune-activating adjuvants is an emerging area of research and is relevant for cancer vaccines that target induction of antigen-specific CD8+ T-cell responses. Here, we report a system for delivery of short peptide antigens to dendritic cells for strong cellular immune responses, based on block copolymers chemically modified with a hydrophobic and self-immolative linker. After modification, micelles effectively and reversibly capture antigens and adjuvants via a covalent bond within several minutes in an aqueous solution. After uptake in antigen presenting cells, the polymer disulfide bond is cleaved by intracellular glutathione, leading to release of pristine antigens, along with the upregulated expression of costimulatory molecules. The induced antigen-specific CD8+ T cells have strong tumor cell killing efficacy in the murine B16OVA and human papilloma virus-E6/E7 subcutaneous and lung metastasis tumor models. In addition, delivery to lymph nodes can be imaged to visualize vaccine trafficking. Taken together, multifunctional self-immolative micelles represent a versatile class of a vaccine delivery system for the generation of a cellular immune response that warrants further exploration as a component of cancer immunotherapy.
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BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Yan Zhao,Changtong Lu,Xian-En Zhao,Weiheng Kong,Shuyun Zhu,Fengli Qu
DNA-templated silver nanoclusters (DNA/AgNCs) serve as a useful electrochemical sensing nanomaterial characterized by excellent electroactivity and good stability, while the effect of surrounding nucleotides on their electroactivity has not been studied. Herein, we validated a nucleotide-assisted enhancement mechanism of the DNA/AgNCs electroactivity caused by T-rich nucleic acid sequences in the vicinity of AgNCs. Based on the T-rich nucleic acid-enhanced AgNCs (NAE-AgNCs) combined with hybrid chain reaction (HCR), a novel signal-enhanced electrochemical biosensing platform was established for the ultrasensitive detection of miRNA . In the presence of target miRNA-155, HCR could be triggered to generate duplex strands containing both numerous AgNC synthesis sites and T-rich overhang strands upon the electrode. With the electrodeposition of adjacent AgNCs on the electrode, the larger oxidation potential of T-rich nucleic acid leaded to stronger electron-accepting capacity, which could contribute to increased current responses. The T-rich NAE HCR electrochemical strategy resulted in a detection limit of 0.39 fM for miRNA-155 detection, one order of magnitude lower than conventional HCR-based electrochemical sensors . This T-rich nucleic acid-assisted enhancement mechanism provided a new direction to construct highly sensitive, label-free, low-cost, and simple sensing platforms for applications in biomarker assays and clinic diagnosis.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2022
·Vol. 414
·期 20
·6149-6156
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IF 4.478
Qin Shanshan,Chen Xuliang,Xu Zhichen,Li Tao,Zhao Shuhong,Hu Rui,Zhu Jiang,Li Ying,Yang Yunhuang,Liu Maili
Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence. Accordingly, an ht-G3-based molecular beacon was successfully designed against the corresponding RNA sequence of the SARS-CoV-2 N-gene. The sensitivity for the non-amplified RNA target achieves 0.01 nM, improved 100 times over the conventional ThT–based method. We believe this ht-G3/ThT–based label-free strategy could be widely applied for RNA detection.
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CHEMISTRY OF MATERIALS
·
2021
·
IF 9.811
Jiexin Li,He Ren,Yaping Sun,Gengqi Liu,Xingyue Yang,Qian Qiu,Yuanmeng Ding,Jonathan F. Lovell,Yumiao Zhang
Cancer peptide vaccines face challenges for antigen delivery and presentation. In the present work, we develop a self-assembled magnetic micelle delivery system for CD8+ T-cell epitopes that produces strong cellular immune responses. Hydrophobically modified imiquimod R837 and Zn1.15Fe1.85O4 are coencapsulated in the core of Pluronic F127 block copolymer micelles. Magnetic Zn1.15Fe1.85O4 enables externally targeted delivery and enrichment of micelles in lymph nodes. Furthermore, metal ions are found to enhance vaccine immunogenicity. F127 micelles were chemically modified by a self-immolative linker so that antigens are rapidly and reversibly grafted on micelles in an aqueous solution. With the assistance of an external magnetic field, once the magnetic micelles are delivered to lymph nodes and taken up by immune cells, intracellular glutathione cleaves the disulfide bond and releases pristine short peptide antigen. Delivery to lymph nodes is tracked by magnetic resonance and fluorescence imaging. The use of this vaccine system eradicated tumors in a murine tumor model. Thus, integrating multiple functionalities in a single micellar delivery system, including responsive linkage, multiple immunostimulatory molecules, targeted delivery, and bimodal imaging, demonstrates the potential for theranostic approaches to develop a new generation of cancer vaccines.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY
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2020
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IF 7.143
Xiaoxuan Yu,Hui Li,Mengyuan Zhu,Po Hu,Xiao Liu,Yingjie Qing,Xiangyuan Wang,Hongzheng Wang,Zhanyu Wang,Jingyan Xu,Renxiang Tan,Qinglong Guo,Hui Hui
Cutaneous T-cell lymphomas (CTCLs) represent a rare form of non-Hodgkin lymphomas characterized by an accumulation of malignant CD4 + T cells in the skin. TP53 genetic alteration is one of the most prevalent genetic abnormalities in CTCLs. Therefore, it is a promising target for innovative therapeutic approaches. We found that p53 could physically interact with histone deacetylase (HDAC) 1 and HDAC8, and was subsequently deacetylated to lose its function in CTCL cells, and the p53 downstream apoptosis-associated genes were repressed. Thus, the anti-CTCL activity displayed by HDAC inhibitors depends on p53 status. However, recent studies have reported that HDAC inhibitors could induce a wide variety of drug-resistant characteristics in cancer cells by regulating ATP-binding cassette transporters. Moreover, we discovered that Baicalein, a natural product, exhibited an inhibitory effect on HDAC1 and HDAC8. Though the inhibition of HDAC1 was mild, Baicalein could induce the degradation of HDAC1 through the ubiquitin proteasome pathway, thereby markedly upregulating the acetylation of histone H3 without promoting ATP-binding cassette transporter gene expression. In terms of the mechanism, Baicalein showed better growth inhibition than traditional HDAC inhibitors in CTCLs. This study indicates a special mechanism of HDAC1 and HDAC8 and p53 in T-cell lymphoma cells and identifies a potential and safe natural HDAC inhibitor for the treatment of CTCLs.
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