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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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Previous studies have shown that GIGYF2 plays multiple roles, but its overall biological function remains poor-defined. Here we clearly demonstrated that zebrafish (Danio rerio) GIGYF2 has GYF domain and gigyf2 mainly expressed in caudal fin, brain, eyes and testis in a tissue specific manner, and was most abundant in brain and testis. GYF domain of GIGYF2 was a peptidoglycan (PGN), lipopolysaccharide (LPS)- and lipoteichoic acid (LTA)- binding protein abundantly stored in the testis/embryos of zebrafish, acting not only as a pattern recognition receptor, but also as an effector molecule, capable of inhibiting the growth of gram-positive and -negative bacteria. Furthermore, we reveal that the residues of GIGYF2 positioned at 582-601 and 848-865 were indispensable for GIGYF2 antibacterial activity. Additionally, site-directed mutation could improve antibacterial activities. Collectively, our results indicate that zebrafish GYF domain of GIGYF2 recognize bacterial characteristic molecules PGN, LPS and LTA, and directly kill bacteria as an antibacterial effector. This work also provides another angle for understanding the biological roles of GIGYF2.

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As an electrode material, LiFePO4 has been extensively studied in the field of energy conversion and storage due to its inexpensive cost and excellent safety, as well as good cycling stability. However, it remains a challenge to obtain LiFePO4 electrode materials with acceptable discharge capacity at low temperature. Here, micro/nano-structured LiFePO4 electrode materials with grape-like morphology were fabricated via a facile solvothermal approach using ethanol and OA as the co-solvent, the surfactant as well as the carbon source. The structure and electrochemical properties of the LiFePO4 material were investigated with x-ray diffraction (XRD), field emission scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the formation mechanism of the self-assembled micro/nano-structured LiFePO4 was discussed as well. The micro/nano-structured LiFePO4 electrode materials exhibited a high discharge capacity (142 mAh·g-1) at a low temperature of 0 °C, and retained 102 mAh·g-1 when the temperature was decreased to -20 °C. This investigation can provide a reference for the design of micro/nano-structured electrode materials with improvement of the electrochemical performance at low temperature.

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Ischemic stroke is the second leading cause of death worldwide. Therefore, exploring effective and emerging molecular targets for ischemic stroke is a primary task of basic and clinical research. The aim of the present study was to investigate the function of corticotropin-releasing factor (CRF) in ischemic stroke and its related mechanisms, to provide a reference for the treatment of ischemic stroke. CRF, antalarmin, or astressin-2B were used to activate or block the CRF1 (CRF receptor 1) or CRF2 (CRF receptor 2) in BV2 cells and adult male mice, thus constructing a distal middle cerebral artery occlusion (dMCAO) model. CRF not only accelerated microglial activity by promoting transcription and production of inflammatory factors, but also promoted the transformation of activated BV2 cells from a neuroprotective phenotype (M2) to cytotoxic phenotype (M1), and these effects were mediated by the TLR4/NF-κB signaling pathway. These effects can be blocked by antalarmin but not by astressin-2B. CRF significantly aggravated the neurological deficit, increased infarction volume, and exacerbated neuronal injuries. Additionally, CRF significantly improved the levels of TNF-α and phospho-NF-κB in the ischemia penumbra. Finally, CRF significantly increased the number of CD16/Iba-1-positive cells and decreased the number of CD206/Iba-1-positive cells in the ischemia penumbra. These results provide evidence of the proinflammatory role of CRF in an ischemic stroke model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for ischemic stroke.

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OBJECTIVE: To investigate the effects of Fu Fang Yi Mu Cao (FFYMC) capsules combined with Yiqi Xiaoyu (YX) decoction on persistent lochia after birth. METHODS: In this retrospective analysis, 120 patients with lochia treated in our hospital from January 2014 to October 2020 were enrolled as study subjects. Sixty of each were randomly allocated into the study group (60 cases, treated with FFYMC capsules and YX decoction) and the control group (60 cases, treated with YX decoction). The two groups were compared in terms of efficacy, volume of lochia and changes in Traditional Chinese Medicine Syndrome Score (TCMSS) before and after intervention, and the incidence of adverse reactions. RESULTS: (1) The total effective rate in the study group was 100.00%, which was significantly higher than that in the control group (P<0.05); (2) The difference in volume of lochia between two groups before the intervention was not statistically significant (P>0.05), and was significantly lower in the study group than in the control group at day 4 and day 7 of the intervention (P<0.05); (3) The difference in TCMSS between two groups before the treatment was not statistically significant (P>0.05). TCMSS was lower in the study group than in the control group after treatment (P<0.05); (4) The decreased height of uterine fundus in the study group was higher than that in the control group at 5 d after treatment (P<0.05); (5) The plasma viscosity in the study group was significantly lower than that in the control group (P<0.05); (6) The total incidence of adverse reactions in the study group was 8.33%, which was not significantly different from the control group which was 11.67% (P>0.05). CONCLUSION: FFYMC capsule and YX decoction could improve the treatment effect for primiparas with lochia in terms of reducing volume of lochia and improving clinical symptoms with high safety.

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Liver fibrosis, originating from activated hepatic stellate cells (HSCs), is receiving much attention in the treatment of clinical liver disease. In this study, mitochondria-targeted curcumin (Cur) loaded 3-carboxypropyl-triphenylphosphonium bromide-poly(ethylene glycol)-poly(ε-caprolactone) (CTPP-PEG-PCL) micelles were constructed to prolong the systemic circulation of Cur, improve the bioavailability of Cur and play a precise role in anti-fibrosis. The prepared Cur-CTPP-PEG-PCL micelles with a spherical shape had satisfactory dispersion, low critical micelle concentration (CMC) and high encapsulation efficiency (92.88%). The CTPP modification endowed good endosomal escape ability to the CTPP-PEG-PCL micelles, and micelles could be selectively accumulated in mitochondria, thereby inducing the enhanced cell proliferation inhibition of HSC-T6 cells. Mitochondrial Membrane Potential (MMP) was greatly reduced due to the mitochondrial-targeting of Cur. Moreover, the system circulation of Cur was extended and bioavailability was significantly enhanced in vivo. As expected, Cur loaded CTPP-PEG-PCL micelles were more effective in improving liver fibrosis compared with Cur and Cur-mPEG-PCL micelles. In conclusion, the Cur-CTPP-PEG-PCL based micelles can be a potential candidate for liver fibrosis treatment in future clinical applications.

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To synthetize 3-carboxypropyl-triphenylphosponium bromide-polycaprolacton-CTPP-PEG-PC, and prepare curcumin CTPP-PEG-PCL micelles by using the self-assembled emulsion solvent evaporation method, in order to determine the critical micelle concentration (CMC) with the pyrene fluorescent probe technology, detect the particle size, entrapment efficiency (%), morpheme and in vitro release rate, and evaluate the cytotoxicity of hepatic stellate cells with MTT assay. The structure of CTPP-PEG-PCL had been identified by 1H-NMR spectra. Specifically, the CMC of polymer was 2.25 mg x L(-1), the average size was 190 nm, the drug content was (0.66 +/- 0.008) g x L(-1), and the entrapment efficiency was (94 +/- 0.6)%. The in vitro release results showed curcumin micelles had a significant higher inhibition ratio in the growth of hepatic stellate cells than crude curcumin (P < 0.05). This suggested that CTPP-PEG-PCL micelles feature low CMC, high encapsulation efficiency and notable inhibition effect in growth of hepatic stellate cells.

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