Abstract ：

Improving the ecological environment resilience is the key path to continuously improve the ecological environment quality and ensure the steady progress of ecological civilization construction in China. Based on the concept of ecological resilience, this paper constructs an evaluation system of eco...

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Ecological environment resilience Multidimensional difference Q53 Q56 R11 Shapley value decomposition The longitudinal and horizontal pull-out grading method

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This study explores whether green development benefits or suffers from economic growth targets. Although prior research has highlighted various aspects of green development, the impact of performance targets, which are set by authorities as a baton of macroeconomic policy, remains largely unexplored...

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China Economic growth targets Green development O11 Q56 R11 Spatial econometric model Spillover effects

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Introduction: Bladder cancer (BCa) is among the most prevalent cancers worldwide. However, the effectiveness of intravesical therapy for BCa is limited due to the short dwell time and the presence of the permeation barrier.Methods: Nanocomplexes were self-assembled between DNA and hendeca-arginine peptide (R11). Stepwise intravesical instillation of R11 and the generated nanocomplexes significantly enhanced the targeting capacity and penetration efficiency in BCa therapy. The involved mechanism of cellular uptake and penetration of the nanocomplexes was determined. The therapeutic effect of the nanocomplexes was verified preclinically in murine orthotopic BCa models.Results: Nanocomplexes exhibited the best BCa targeting efficiency at a nitrogen-to-phosphate (NP) ratio of 5 but showed a lack of stability during cellular uptake. The method of stepwise intravesical instillation not only increased the stability and target specificity of the DNA component but also caused the delivered DNA to more effectively penetrate into the glycosaminoglycan layer and plasma membrane. The method promotes the accumulation of the delivered DNA in the clathrin-independent endocytosis pathway, directs the intracellular trafficking of the delivered DNA to nonlysosome-localized regions, and enables the intercellular transport of the delivered DNA via a direct transfer mechanism. In preclinical trials, our stepwise method was shown to remarkably enhance the targeting and penetration efficiency of DNA in murine orthotopic BCa models.Conclusion: With this method, a stepwise intravesical instillation of self-assembled nanocomplexes, which are generated from hendeca-arginine peptides, was achieved; thus, this method offers an effective strategy to deliver DNA to target and penetrate BCa cells during gene therapy and warrants further development for future intravesical gene therapy in the clinical context.

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bladder cancer direct transfer DNA delivery intravesical therapy

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Intravesical chemotherapy is generally used in the clinic for treating bladder cancer (BCa), but its efficacy is limited due to the permeation barrier and side effects caused by the off-targeting of normal urothelial cells. In this study, BCa cell-derived membrane nanovesicles were used as drug carriers, and their homologous tumor-targeting capacity was utilized. A BCa-targeting hendeca-arginine peptide was functionalized onto the nanovesicles to impart a mucus-penetrating ability and thus overcome the permeation barrier. The tumor-targeting and mucus-penetrating nanovesicles were stable in urine, were highly permeable to the glycosaminoglycan layer, and specifically targeted BCa. The vesicles were internalized through caveolin-mediated endocytosis, were transported to nonlysosome-localized intracellular regions, and efficiently infiltrated bladder tumor spheroids. In in vivo intravesical chemotherapy, the nanovesicles achieved chemo-resection in murine orthotopic BCa models. This BCa-targeting and mucus-penetrating drug delivery system may be promising for the intravesical chemotherapy of BCa. © 2022 The Authors

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Amino acids Cells Chemotherapy Controlled drug delivery Cytology Diseases Molecular biology Nanoparticles Permeation Targeted drug delivery Tumors

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本发明公开了一种增强宫颈癌放疗敏感性的靶向穿膜肽、修饰纳米颗粒复合物和制药应用。该靶向穿膜肽可特异性、高效性进入宫颈癌中，通过调控PI3K/AKT途径及发挥microRNA“分子海绵”作用，从而提高放疗敏感性、降低放疗副作用。本发明以小分子二硫键(‑SS‑)修饰PEI，使得PEI的毒性得以大大降低；同时，也提高了PEI‑核酸复合物的胶体稳定性，延长了其在体内的循环时间；同时利用肿瘤靶向多肽R11修饰PEI‑核酸复合物，使得其解决了纳米颗粒在基因治疗研究中的靶向性问题。

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One of the critical problems in bladder cancer (BC) management is the local recurrence of disease. However, achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology. Herein, survivin molecular beacon (MB) and R11 peptide-linked spherical nucleic acids (SNAs) were synthesized as nanoprobes (AuNP-MB@R11) for sensitive detection of BC margins. Physicochemical properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs. AuNP-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA (ssDNA) in vitro. According to cytology, R11 peptides could increase the BC targeting ability and membrane penetrability of SNAs. Notably, R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging quality. Further RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated, such as AGPAT5, GPD1L, and GRB2. In orthotopic BC models and a clinical sample from a patient with BC, AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs. R11 peptide-linked SNAs present promising potential to identify BC margin, which may help to improve the R0 resection rate in surgery and improve patients' quality of life.

Keyword ：

bladder cancer lysosome escape molecular beacons R11 peptides spherical nucleic acids tumor targeting

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C4F7N is one of the promising candidates to replace SF6 as insulating medium in power equipment. Meanwhile, the effect of an O atom on C4F7N decomposition is still unclear but it greatly influences the decomposition mechanism and insulating properties of C4F7N. In this paper, the B3LYP method, in conjunction with 6-311G(d,p) basis set, is used to study the decomposition mechanism of C4F7N with an O atom. The molecular structures of reactants, products and transition states (TS) in the C4F7N decomposition pathway, which consists of 25 reactions, are optimized. The potential energy surface of each reaction and the vibrational frequencies of each molecule or TS are studied with same method as the prerequisite for rate constant calculations using transition state theory. The results show that the CN bond breaks with the highest energy of 321.91 kcal mol-1, so reaction (R21) (C4F7NO → C4F7O + N) plays a less important role than (R2) (C4F7NO → C3F4NO + CF3), (R5) (C4F7NO → C3F7O + CN), (R11) (C4F7NO → TS1 → C3F5N + CF2O) and (R15) (C4F7NO → TS2 → C3F3NO + CF4) in the decomposition of C4F7NO. CF2O and CF4, characteristic decomposition products of C4F7N + O which have negative impacts on the insulating gas, are generated in reactions (R11) and (R15) with a higher rate constant at 1500 K above, respectively. CF3 and F3C-O are important in C4F7N with O decomposition because of the high overall-generation rate constants. This work is expected to provide a theoretical basis to evaluate the insulation performance of C4F7N-insulated power equipment and develop novel gas sensors for insulating condition monitoring. © 2019 IOP Publishing Ltd.

Keyword ：

Atoms Condition monitoring Decomposition Density functional theory Insulation Potential energy Quantum chemistry Rate constants SF6 insulation Sulfur hexafluoride Surface reactions

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Objective： To determine the effects of photodynamic therapy (PDT) with R11-SSPEI/miR-145 as photosensitizer on cell death in cervical cancer so as to investigate the underlying mechanisms. Methods： Cell cytotoxic effect was measured by MTT assay. Cellular apoptosis was detected by AnnexinV-PI by flow cytometry. The level of reactive oxygen species (ROS) was observed by DCFH-DA staining. The expressions of Caspase-3, Caspase-9, BIP, and Bcl-2 were assessed by Western blotting. Mitochondrial membrane potential was tested by JC-1 staining. Results： Analysis of cell proliferation evidenced that there was a dramatic inhibition after photodynamictherapy (PDT) with R11-SSPEI/miR-145. We observed increased apoptosis (P=0.014) and demonstrated that the apoptosis was involved of mitochondrial and endoplasmic reticulum death pathway. The expressions of Caspase-3, Caspase-9 and BIP were elevated (P<0.05) and that of Bcl-2 decreased. NAC could decrease the ROS level in photodynamic therapy with R11-SSPEI/miR-145 group and rescue the cell death. Conclusion： Taken together, the present results indicated that PDT with R11-SSPEI/miR-145 suppressed cancer development with Hela cells, suggesting R11-SSPEI/miR-145 as a new photosensitizer in PDT has the potential to become the mainstream of cancer treatment. © 2019, Editorial Board of Journal of Xi'an Jiaotong University (Medical Sciences). All right reserved.

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Cervical cancer; Photodynamic therapy; R11-SSPEI/miR-145

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Radioresistant cervical cancer is likely to give rise to local recurrence, distant metastatic relapse, and decreased survival rates. Recent studies revealed microRNA mediated regulation of tumor aggressiveness and metastasis; however, whether specific microRNAs regulate tumor radioresistance and can be exploited as radiosensitizing agents remains unclear. Here, we find that miR-29b could promote radiosensitivity in radioresistant subpopulations of cervical cancer cells. Notably, therapeutic delivery of miR-29b mimics via R11-SSPEI nanoparticle, whose specificity has been proved by our previous studies, can sensitize the tumor to radiation in a xenograft model. Mechanistically, we reveal a novel function of miR-29b in regulating intracellular reactive oxygen species signaling and explore a potential application for its use in combination with therapies known to increase oxidative stress such as radiation. Moreover, miR-29b inhibits DNA damage repair by targeting phosphate and tension homology deleted on chromsome ten (PTEN), and overexpression of PTEN could partially rescue miR-29b-mediated homologous recombination (HR)-DNA damage repair and increase radiosensitivity. These findings identify miR-29b as a radiosensitizing microRNA and reveal a new therapeutic strategy for radioresistant tumors.

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Condensing heat transfer of R134a on horizontal single plain and integral-fin tubes was investigated by both computational and experimental methods. The VOF model and Lee condensation model were utilized in the simulation. Validation of the model was performed with two different refrigerants. Condensing heat transfer coefficient for plain and integral-fin tubes were calculated in comparison with the experimental data and Nusselt analytical solution. Instantaneous film flow characteristics of condensation on horizontal single plain and integral-fin tubes were discussed respectively. Contours of liquid volume fraction for the plain tube and condensing heat transfer coefficient for the plain tube at different time with T-w = 303 K are presented. For integralfin tubes, contours show that the thickness of liquid film at lateral fin surface is much smaller than that at root fin surface. Comparison between R134a and R11 were made and it was found that different surface tension could lead to different liquid film distribution which could result in different heat transfer performance. Experiments involving the same fin structure were also conducted to verify the theoretical model and a satisfactory agreement between simulation and experimental results was found.

Keyword ：

CFD Condensation Heat transfer enhancement Tube VOF

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