[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

[Renal mucinous tubular and spindle cell carcinoma: clinicopathological and whole exome sequencing analyses].

Objective: To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of renal mucinous tubular and spindle cell carcinoma (MTSCC), and to explore the all-exon mutations, microsatellite stability and tumor mutational burden (TMB) in MTSCC cases. Methods: The data of 5 patients with MTSCC that were submitted to the Department of Pathology, First Affiliated Hospital of Soochow University, China from January 2008 to May 2020, were reviewed and analyzed. The whole exome sequencing (WES) was conducted in all patients, while 3 of them were subject to the analyses of microsatellite stability and TMB. Results: Among the 5 patients, 3 were males and 2 were females. They were 37-76 years old. The maximum diameter of the tumor was 3.5-6.0 cm. The borders of the tumors were well defined. Microscopically, MTSCC was characterized by tubular structure, spindle cell and mucinous stroma, and the nuclear grade of tumor cells was overall low. The average follow-up was 15 months, and no recurrence or metastasis was found. Immunohistochemistry showed that all 5 cases were positive for broad-spectrum cytokeratin (CKpan), cytokeratin (CK)7, CK19, vimentin, PAX8, and P504s (varying expression levels), and the Ki-67 positive index was low. The WES of 5 cases showed that NF2 and PTPN14 exhibited higher mutation rates, which were 3/5 and 2/5, respectively. The microsatellite stability analysis indicated that the 3 cases were all microsatellite stable, and the TMB analysis showed that the TMB of the 3 cases were all <9 mut/Mb. Conclusions: MTSCC is a unique, low-grade pleomorphic kidney tumor. The WES analyses suggest that NF2 and PTPN14 have a higher mutation rate, indicating that the occurrence and development of MTSCC may be closely related to the Hippo pathway. The analysis of microsatellite stability indicates that there is no significant relationship between microsatellite stability and MTSCC, and the TMB analysis suggests that MTSCC patients may not benefit from immunotherapy.

[Clinicopathologic features with collecting duct carcinoma of kidney: report of 10 cases].

Objective: To study the pathological features, immunophenotypes, differential diagnoses and prognostic parameters of collecting duct carcinoma of the kidney (CDC). Methods: Clinical imaging, histopathology, immunohistochemistry, and survival data of 10 patients at First Affiliated Hospital of Nanjing Medical University from January 2009 to August 2017 were retrospectively analyzed along with a review of literatures. Results: The clinical symptoms of CDC were not specific, and image examinations showed space-occupying mass lesions. Tumors were mainly located in renal medulla with grey and firm cut face and the presence of focal hemorrhage and necrosis. Microscopically, there were predominant tubular or tubular-papillary structures with associated focal sarcomatoid areas, desmoplastic stromal reaction and lymphoplasmacytic cells infiltration. Tumor cells had marked cytological atypia with high grade nuclei, conspicuous nucleolus and numerous mitoses. Immunohistochemically, tumor cells were strongly positive for CK19, E-cadherin, vimentin, HCK, CK7 and PAX8. The main treatment was radical nephrectomy in the patients. Seven cases died of CDC with median survival of 10 months. Conclusions: CDC is a rare, highly aggressive malignancy of kidney with poor prognosis. Definitive diagnosis should be made by histology and immunohistochemistry. Differential diagnoses include papillary renal cell carcinoma(type Ⅱ), renal medullary carcinoma, infiltrating high grade urothelial carcinoma, renal pelvis adenocarcinoma and metastatic adenocarcinomas.

The Kirkendall effect towards oxynitride nanotubes with improved visible light driven conversion of CO2 into CH4.

Functional hollow nanomaterials are of great interest due to their unique physical-chemical properties. Oxynitride photocatalysts are a kind of promising material for solar energy conversion. However, nanoscale design of hollow oxynitrides was difficult to achieve due to the thermal instability of oxide precursors at high temperature. Here, single crystal zinc gallium oxynitride nanotubes were successfully synthesized via the Kirkendall effect with ZnO nanorods and Ga2O3 nanosheets as precursors, which can be attributed to the high diffusion rate of ZnO and the high melting point of oxynitride. Enhanced photocatalytic performance in CO2 reduction was achieved over the as-prepared ZnGaNO nanotubes, due to their higher specific surface area and less recombination of the photogenerated carriers. These results are expected to provide new guidance in the design and preparation of highly efficient nano-scaled oxynitride photocatalysts.

A porous ZnGaNO photoanode for efficient water oxidation modified by a Co-based electrocatalyst.

Porous ZnGaNO microrods were synthesized by a single crystal internal decomposition route, and exhibited high performance in photoelectrochemical water splitting due to the high specific area and short charge transfer distance of the microstructure.

Photodegradation of rhodamine B and methyl orange over boron-doped g-C3N4 under visible light irradiation.

Graphitic carbon nitride (g-C(3)N(4)) and boron-doped g-C(3)N(4) were prepared by heating melamine and the mixture of melamine and boron oxide, respectively. X-ray diffraction, X-ray photoelectron spectroscopy, and UV-vis spectra were used to describe the properties of as-prepared samples. The electron paramagnetic resonance was used to detect the active species for the photodegradation reaction over g-C(3)N(4). The photodegradation mechanisms for two typical dyes, rhodamine B (Rh B) and methyl orange (MO), are proposed based on our comparison experiments. In the g-C(3)N(4) photocatalysis system, the photodegradation of Rh B and MO is attributed to the direct hole oxidation and overall reaction, respectively; however, for the MO photodegradation the reduction process initiated by photogenerated electrons is a major photocatalytic process compared with the oxidation process induced by photogenerated holes. Boron doping for g-C(3)N(4) can promote photodegradation of Rh B because the boron doping improves the dye adsorption and light absorption of catalyst.

Organic-inorganic composite photocatalyst of g-C(3)N(4) and TaON with improved visible light photocatalytic activities.

Organic-inorganic composite photocatalyst g-C(3)N(4)-TaON with visible-light response was prepared by a milling-heat treatment method. The photocatalyst was characterized by X-ray diffraction, high-resolution transmission electron microscopy and UV-vis diffuse reflection spectroscopy. The activity of composite photocatalyst g-C(3)N(4)-TaON for photodegradation of rhodamine B is higher than that of either single-phase g-C(3)N(4) or TaON. The obviously increased performance of g-C(3)N(4)-TaON is ascribed mainly to enhancement of electron-hole separations both at the interface and in the semiconductors.

Photodegradation performance of g-C3N4 fabricated by directly heating melamine.

The g-C(3)N(4) photocatalyst was synthesized by directly heating the low-cost melamine. The methyl orange dye (MO) was selected as a photodegrading goal to evaluate the photocatalytic activity of as-prepared g-C(3)N(4). The comparison experiments indicate that the photocatalytic activity of g-C(3)N(4) can be largely improved by the Ag loading. The strong acid radical ion (SO(4)(2-) or NO(3)(-)) can promote the degrading rate of MO for g-C(3)N(4) photocatalysis system. The MO degradation over the g-C(3)N(4) is mainly attributed to the photoreduction process induced by the photogenerated electrons. Our results clearly indicate that the metal-free g-C(3)N(4) has good performance in photodegradation of organic pollutant.