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Phototherapy is effective for triggering the immunogenic cell death (ICD) effect. However, its efficacy is limited by low 1O2 generation and photothermal conversion efficacy due to two irreconcilable obstacles, namely the aggregation‐caused‐quenching (ACQ) effect and photobleaching. In this work, a discretely integrated nanofabrication (DIN) platform (Pt‐ICG/PES) is developed by facile coordination coassembly of cisplatin (Pt), photosensitizer molecules (indocyanine green (ICG)), and polymeric spacer (p(MEO2MA‐co‐OEGMA)‐b‐pSS (PES)). By controlling the ICG/PES feeding ratio, the aggregation of ICG can be easily tailored using PES as an isolator to balance the ACQ effect and photobleaching, thereby maximizing the phototherapy potency of Pt‐ICG/PES. With the optimized ratio of each component, Pt‐ICG/PES integrates the complementarity of photodynamic therapy, photothermal therapy, and chemotherapeutics to magnify the ICD effect, exerting a synergistic antitumor immunity‐promoting effect. Additionally, temperature‐sensitive PES enables photothermally guided drug delivery. In a tumor‐bearing mouse model, Pt‐ICG/PES elicits effective release of danger‐associated molecular patterns, dendritic cell maturation, cytotoxic T lymphocytes activation, cytokine secretion, M2 macrophage repolarization, and distal tumor suppression, confirming the excellent in situ tumor ICD effect as well as robust systematic antitumor immunity. Ultimately, a versatile DIN strategy is developed to optimize the phototherapeutic efficacy for improving antitumor effects and strengthening systemic antitumor immunity.

Background/Aims: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms. Methods: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein. Results: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p. Conclusion: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.

Porous metal frameworks offer potentially useful applications for the aerospace, automotive and bio-medical industries. They can be used as electrodes, actuators, or as selective membrane films. The versatility of the physical features (pore size, pore depth, overall porosity and pore surface coverage) as well as the large range of surface chemistries for both metal oxides and pure noble metals offers scope to functionalise metal nano-particles and networks of nano-porous metal structures. As well as traditional routes to producing metal structures, such as metal sintering or foaming, novel high-throughput techniques have recently been investigated. Nanoparticle self-assembly, metal ion reduction and deposition as well as metal alloy de-alloying were identified as sustainable routes to produce large surface areas of such nano-porous metal frameworks. The main limitations of the current fabrication techniques include the difficulty to process stable and homogeneous arrays of nano-scale pores and the control of their morphology due to the high reactivity of nano-structured metal structures. This paper aims at critically reviewing the various fabrication techniques and surface functionalization routes used to produce advanced functional porous metal frameworks. The limitations and advantages of the different fabrication techniques will be discussed in light of the final material properties and targeted applications. Keywordsporous metal frameworks; porous metal fabrication routes; metal surface chemistry; application of metal frameworks; 3

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC.

Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy in adults, the incidence of which continues to increase. The lipid droplet protein perilipin 2 (PLIN2), which was originally considered an RNA transcript, is markedly expressed during adipocyte differentiation. In addition, it has been observed to be elevated in numerous types of cancer, including ccRCC; however, its essential function remains unclear in ccRCC. The present study examined the expression of PLIN2 in ccRCC, and aimed to determine the association between PLIN2 expression and patient survival. The present study mined the transcriptional, clinicopathological and survival data of PLIN2 in patients with ccRCC through The Cancer Genome Atlas. The expression levels of PLIN2 were also detected in human ccRCC tissues and cell lines by western blotting and immunohistochemistry, and its biological role was identified by functional analysis. The results demonstrated that PLIN2 was predominantly elevated in RCC tissues and cells. In addition, the expression levels of PLIN2 were significantly associated with various clinicopathological factors, and high PLIN2 expression was associated with a good prognosis. The results of a multivariate analysis demonstrated that high PLIN2 expression was an independent prognostic indicator of overall survival (hazard ratio, 0.586; P=0.001). Furthermore, PLIN2 knockdown promoted proliferation of ccRCC cells, and enhanced cell invasion and migration. These results suggested that PLIN2 may be considered a novel prognostic factor in ccRCC and a specific diagnostic indicator for patients with ccRCC. Furthermore, it could be a potential novel target for the clinical treatment of ccRCC.

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3D graphene frameworks/Co O composites are produced by the thermal explosion method, in which the generation of Co O nanoparticles, reduction of graphene oxide, and creation of 3D frameworks are simultaneously completed. The process prevents the agglomeration of Co O particles effectively, resulting in monodispersed Co O nanoparticles scattered on the 3D graphene frameworks evenly. The prepared 3D graphene frameworks/Co O composites used as electrodes for supercapacitor display a definite improvement on electrochemical performance with high specific capacitance (≈1765 F g at a current density of 1 A g ), good rate performance (≈1266 F g at a current density of 20 A g ), and excellent stability (≈93% maintenance of specific capacitance at a constant current density of 10 A g after 5000 cycles). In addition, the composites are also employed as nonenzymatic sensors for the electrochemical detection of glucose, which exhibit high sensitivity (122.16 µA mM cm ) and noteworthy lower detection limit (157 × 10 M, S/N = 3). Therefore, the authors expect that the 3D graphene frameworks/Co O composites described here would possess potential applications as the electrode materials in supercapacitors and nonenzymatic detection of glucose.