TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method.

BACKGROUND: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. METHODS: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. RESULTS: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL. CONCLUSIONS: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

Exosome-derived circTFDP2 promotes prostate cancer progression by preventing PARP1 from caspase-3-dependent cleavage.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown. METHODS: We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA-immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT-PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2-containing exosomes on PCa cell progression. RESULTS: circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) protein in its DNA-binding domain to prevent it from active caspase-3-dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA-binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome-derived circTFDP2 promoted PCa cell progression. CONCLUSIONS: In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

Bladder cancer is one of the most common and deadly cancer worldwide. Current chemotherapy has shown limited efficacy in improving outcomes for patients. Nitroxoline, an old and widely used oral antibiotic, which was known to treat for urinary tract infection for decades. Recent studies suggested that nitroxoline suppressed the tumor progression and metastasis, especially in bladder cancer. However, the underlying mechanism for anti-tumor activity of nitroxoline remains unclear. Methods: CircRNA microarray was used to explore the nitroxoline-mediated circRNA expression profile of bladder cancer lines. Transwell and wound-healing assay were applied to evaluate the capacity of metastasis. ChIP assay was chosen to prove the binding of promotor and transcription factor. RNA-pulldown assay was performed to explore the sponge of circRNA and microRNA. Results: We first identified the circNDRG1 (has_circ_0085656) as a novel candidate circRNA. Transwell and wound-healing assay demonstrated that circNDRG1 inhibited the metastasis of bladder cancer. ChIP assay showed that circNDRG1 was regulated by the transcription factor EGR1 by binding the promotor of host gene NDRG1. RNA-pulldown assay proved that circNDRG1 sponged miR-520h leading to the overexpression of smad7, which was a negative regulatory protein of EMT. Conclusions: Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

circPDE5A regulates prostate cancer metastasis via controlling WTAP-dependent N6-methyladenisine methylation of EIF3C mRNA.

BACKGROUND: Circular RNA (circRNA) is a novel class noncoding RNA (ncRNA) that plays a critical role in various cancers, including prostate cancer (PCa). However, the clinical significance, biological function, and molecular mechanisms of circRNAs in prostate cancer remain to be elucidated. METHODS: A circRNA array was performed to identified the differentially expressed circRNAs. circPDE5A was identified as a novel circRNA which downregulated in clinical samples. Functionally, the in vitro and in vivo assays were applied to explore the role of circPDE5A in PCa metastasis. Mechanistically, the interaction between circPDE5A and WTAP was verified using RNA pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP) assays. m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) was then used to identified the downstream target of circPDE5A. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were used to identified transcriptional factor which regulated circPDE5A expression. RESULTS: circPDE5A was identified downregulated in PCa tissues compared to adjacent normal tissue and was negatively correlated with gleason score of PCa patients. circPDE5A inhibits PCa cells migration and invasion both in vitro and in vivo. circPDE5A blocks the WTAP-dependent N6-methyladenisine (m6A) methylation of eukaryotic translation initiation factor 3c (EIF3C) mRNA by forming the circPDE5A-WTAP complex, and finally disrupts the translation of EIF3C. Moreover, the circPDE5A-dependent decrease in EIF3C expression inactivates the MAPK pathway and then restrains PCa progression. CONCLUSIONS: Our findings demonstrate that FOXO4-mediated upregulation of circPDE5A controls PCa metastasis via the circPDE5A-WTAP-EIF3C-MAPK signaling pathway and could serve as a potential therapeutic targer for PCa.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Simultaneous Enhancement of the Long-Wavelength NIR-II Brightness and Photothermal Performance of Semiconducting Polymer Nanoparticles.

Theranostic agents with fluorescence in the second near-infrared (NIR-II) window, especially in its long-wavelength region, and NIR-II-excitable photothermal effect is promising but challenging in tumor diagnosis and therapy. Here, we report a simple but effective strategy to develop semiconducting polymer nanoparticles-based theranostic agents (PBQx NPs) and demonstrate their applications for long-wavelength NIR-II fluorescence imaging beyond 1400 nm and photothermal therapy (PTT) of tumors upon excitation at 1064 nm. Both experimental results and theory calculations show that the brightness and photothermal performance of PBQx NPs can be simultaneously improved by simply increasing the repeating unit number of semiconducting polymers. For example, PBQ45 NPs have 5-fold higher brightness than PBQ5 NPs and 6.7-fold higher photothermal effect (based on PCE × Îµ) than PBQ3 NPs, and exhibit promising applications in long-wavelength NIR-II fluorescence abdomen imaging, image-guided tumor resection, and image-guided PTT. This study demonstrates the effectiveness and importance of repeating unit numbers in regulating the theranostic performance, which has not received enough attention before.

Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2.

Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/-) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/- mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.

Hot-band absorption of indocyanine green for advanced anti-stokes fluorescence bioimaging.

Bright anti-Stokes fluorescence (ASF) in the first near-infrared spectral region (NIR-I, 800 nm-900 nm) under the excitation of a 915 nm continuous wave (CW) laser, is observed in Indocyanine Green (ICG), a dye approved by the Food and Drug Administration for clinical use. The dependence of fluorescence intensity on excitation light power and temperature, together with fluorescence lifetime measurement, establish this ASF to be originated from absorption from a thermally excited vibrational level (hot-band absorption), as shown in our experiments, which is stronger than the upconversion fluorescence from widely-used rare-earth ion doped nanoparticles. To test the utility of this ASF NIR-I probe for advanced bioimaging, we successively apply it for biothermal sensing, cerebral blood vessel tomography and blood stream velocimetry. Moreover, in combination with L1057 nanoparticles, which absorb the ASF of ICG and emit beyond 1100 nm, these two probes generate multi-mode images in two fluorescent channels under the excitation of a single 915 nm CW laser. One channel is used to monitor two overlapping organs, urinary system & blood vessel of a live mouse, while the other shows urinary system only. Using in intraoperative real-time monitoring, such multi-mode imaging method can be beneficial for visual guiding in anatomy of the urinary system to avoid any accidental injury to the surrounding blood vessels during surgery.

Biologically Excretable Aggregation-Induced Emission Dots for Visualizing Through the Marmosets Intravitally: Horizons in Future Clinical Nanomedicine.

Superb reliability and biocompatibility equip aggregation-induced emission (AIE) dots with tremendous potential for fluorescence bioimaging. However, there is still a chronic lack of design instructions of excretable and bright AIE emitters. Here, a kind of PEGylated AIE (OTPA-BBT) dots with strong absorption and extremely high second near-infrared region (NIR-II) PLQY of 13.6% is designed, and a long-aliphatic-chain design blueprint contributing to their excretion from an animal's body is proposed. Assisted by the OTPA-BBT dots with bright fluorescence beyond 1100 nm and even 1500 nm (NIR-IIb), large-depth cerebral vasculature (beyond 600 µm) as well as real-time blood flow are monitored through a thinned skull, and noninvasive NIR-IIb imaging with rich high-spatial-frequency information gives a precise presentation of gastrointestinal tract in marmosets. Importantly, after intravenous or oral administration, the definite excretion of OTPA-BBT dots from the body is demonstrated, which provides influential evidence of biosafety.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life-threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4-LBD) and induces a conformational change in the secondary structure of TR4-LBD. Bexarotene suppressed AtT-20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4-increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5' promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH-secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.

Transperineal single-port robot-assisted radical prostatectomy with Si da Vinci surgical system: initial experience and description of technique.

BACKGROUND: Single-port robotic-assisted radical laparoscopic prostatectomy has emerged as a novel robotic-assisted radical laparoscopic prostatectomy in recent years, arousing wide attention. However, single-port robotic-assisted radical laparoscopic prostatectomy using Si da Vinci surgical system has been rarely reported, especially via the transperineal approach. METHODS: We retrospectively collected 9 cases of prostate cancer patients who underwent transperineal single-port robot-assisted radical prostatectomy (t-spPARP) using Si da Vinci surgical system in our center from May 2020 to June 2020. The operation time, estimated blood loss (EBL), complications, changes in prostate-specific antigen (PSA) 3 months after surgery, and urinary continence recovery 6 months after surgery were analyzed. RESULTS: No perioperative complications were recorded. The median [interquartile range (IQR)] operation time was 350 [150] min and the median [IQR] EBL was 300 [100] mL. PSA levels were less than 0.01 ng/mL at 3 months postoperatively in all cases (undetectable in 8 cases). All the 9 patients recovered their urinary continence 6 months after surgery and merely two patients required pads during the day. CONCLUSIONS: t-spRARP was verified as a safe and feasible surgical alternative to treat patients with localized prostate cancer, especially for those whose prostate is small-volume or who had abdominal surgery history.

Oncometabolite L-2-hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma.

Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L-2-hydroxyglurate (L-2HG). L-2HG has been reported to inhibit the activity of some α-ketoglutarate-dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L-2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L-2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L-2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L-2HG-induced VM formation. In conclusion, these findings highlighted the pathogenic link between L-2HG and VM and suggested a novel therapeutic target for RCC.

The prognostic value of miRNA-18a-5p in clear cell renal cell carcinoma and its function via the miRNA-18a-5p/HIF1A/PVT1 pathway.

Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Extrahepatic cholangiography in near-infrared II window with the clinically approved fluorescence agent indocyanine green: a promising imaging technology for intraoperative diagnosis.

Rationale: Biliary tract injury remains the most dreaded complication during laparoscopic cholecystectomy. New intraoperative guidance technologies, including near-infrared (NIR) fluorescence cholangiography with indocyanine green (ICG), are under comprehensive evaluation. Previous studies had shown the limitations of traditional NIR light (NIR-I, 700-900 nm) in visualizing the biliary tract structures in specific clinical situations. The aim of this study was to evaluate the feasibility of performing the extrahepatic cholangiography in the second NIR window (NIR-II, 900-1700 nm) and compare it to the conventional NIR-I imaging. Methods: The absorption and emission spectra, as well as fluorescence intensity and photostability of ICG-bile solution in the NIR-II window were recorded and measured. In vitro intralipid® phantom imaging was performed to evaluate tissue penetrating depth in NIR-I and NIR-II window. Different clinical scenarios were modeled by broadening the penetration distance or generating bile duct injuries, and bile duct visualization and lesion site diagnosis in the NIR-II window were evaluated and compared with NIR-I imaging. Results: The fluorescence spectrum of ICG-bile solution extends well into the NIR-II region, exhibiting intense emission value and excellent photostability sufficient for NIR-II biliary tract imaging. Extrahepatic cholangiography using ICG in the NIR-II window obviously reduced background signal and enhanced penetration depth, providing more structural information and improved visualization of the bile duct or lesion location in simulated clinical scenarios, outperforming the NIR-I window imaging. Conclusions: The conventional clinically approved agent ICG is an excellent fluorophore for NIR-II bile duct imaging. Fluorescence cholangiography with ICG in the NIR-II window could provide adequate visualization of the biliary tract structures with increased resolution and penetration depth and might be a valid option to increase the safety of cholecystectomy in difficult cases.

Semiconducting Polymer Nanoparticles as Theranostic System for Near-Infrared-II Fluorescence Imaging and Photothermal Therapy under Safe Laser Fluence.

Theranostic systems combining fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) and photothermal therapy (PTT) under safe laser fluence have great potential in preclinical research and clinical practice, but the development of such systems with sufficient effective NIR-II brightness and excellent photothermal properties is still challenging. Here we report a theranostic system based on semiconducting polymer nanoparticles (L1057 NPs) for NIR-II fluorescence imaging and PTT under a 980 nm laser irradiation, with low (25 mW/cm2) and high (720 mW/cm2) laser fluence, respectively. Taking into consideration multiple parameters including the extinction coefficient, the quantum yield, and the portion of emission in the NIR-II region, L1057 NPs have much higher effective NIR-II brightness than most reported organic NIR-II fluorophores. The high brightness, together with good stability and excellent biocompatibility, allows for real-time visualization of the whole body and brain vessels and the detection of cerebral ischemic stroke and tumors with high clarity. The excellent photothermal properties and high maximal permissible exposure limit at 980 nm allow L1057 NPs for PTT of tumors under safe laser fluence. This study demonstrates that L1057 NPs behave as an excellent theranostic system for NIR-II imaging and PTT under safe laser fluence and have great potential for a wide range of biomedical applications.

Development and verification of a nomogram for prediction of recurrence-free survival in clear cell renal cell carcinoma.

Nowadays, gene expression profiling has been widely used in screening out prognostic biomarkers in numerous kinds of carcinoma. Our studies attempt to construct a clinical nomogram which combines risk gene signature and clinical features for individual recurrent risk assessment and offer personalized managements for clear cell renal cell carcinoma. A total of 580 differentially expressed genes (DEGs) were identified via microarray. Functional analysis revealed that DEGs are of fundamental importance in ccRCC progression and metastasis. In our study, 338 ccRCC patients were retrospectively analysed and a risk gene signature which composed of 5 genes was obtained from a LASSO Cox regression model. Further analysis revealed that identified risk gene signature could usefully distinguish the patients with poor prognosis in training cohort (hazard ratio [HR] = 3.554, 95% confidence interval [CI] 2.261-7.472, P < .0001, n = 107). Moreover, the prognostic value of this gene-signature was independent of clinical features (P = .002). The efficacy of risk gene signature was verified in both internal and external cohorts. The area under receiver operating characteristic curve of this signature was 0.770, 0.765 and 0.774 in the training, testing and external validation cohorts, respectively. Finally, a nomogram was developed for clinicians and did well in the calibration plots. This nomogram based on risk gene signature and clinical features might provide a practical way for recurrence prediction and facilitating personalized managements of ccRCC patients after surgery.

Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals.

BACKGROUND: Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. METHODS: We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. RESULTS: Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. CONCLUSION: Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.

Deciphering of cerebrovasculatures via ICG-assisted NIR-II fluorescence microscopy.

Benefiting from high spatial resolution and large penetration depth, NIR-II (second near-infrared spectral region, 900-1700 nm) fluorescence imaging based on US Food and Drug Administration (FDA)-approved indocyanine green (ICG) is expected to be a good approach for clinical applications. As of now, nearly all reported works on ICG-assisted NIR-II fluorescence imaging are macro-imaging while micro-angiography is also a significant imaging modality, especially during the diagnosis and treatment of cerebrovascular diseases. Herein, based on NIR-II fluorescence wide-field microscopy, the high-resolution observation of cerebral vasculature was performed at deep brain tissues in mice via intramuscular (IM) injection of ICG. Altered cerebral vessels in mice after brain embolism were further noticed by means of noninvasive through-skull NIR-II fluorescence microscopy. Moreover, ICG-assisted NIR-II fluorescence confocal microscopy was executed to observe cerebral vasculature, presenting optical sectioning capability and higher spatial resolution.