LncRNA PCAT6 promotes the occurrence of laryngeal squamous cell carcinoma via modulation of the miR-4731-5p/NOTCH3 axis.

Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers that affect the head and neck region. Recent researches have confirmed that long non-coding RNAs (lncRNAs) present an emerging role in diversiform diseases including cancers. Prostate cancer-associated ncRNA transcript 6 (PCAT6) is an oncogene in lung cancer, cervical cancer, colon cancer and gastric cancer, but its role in LSCC is still unknown. In the current study, we attempted to figure out the role of PCAT6 in LSCC. RT-qPCR was to analyze PCAT6 expression in LSCC cells. Functional assays were to uncover the role of PCAT6 in LSCC. Mechanism assays were to explore the regulatory mechanism behind PCAT6 in LSCC. PCAT6 exhibited higher expression in LSCC cells and PCAT6 strengthened cell proliferation and inhibited cell apoptosis. Furthermore, lncRNA PCAT6 modulated notch receptor 3 expression and activated NOTCH signaling pathway via serving as a sponge for miR-4731-5p. Taken together, lncRNA PCAT6 was identified as an oncogene in LSCC, which revealed that PCAT6 might be used as potential therapeutic target for LSCC.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Photoacoustic/Fluorescence Dual-Modality Probe for Biothiol Discrimination and Tumor Diagnosis in Cells and Mice.

Developing probes to simultaneously detect and discriminate biothiols is important, yet challenging. Activatable photoacoustic (PA) probes for discriminating biothiols in vivo are still lacking, and this hinders the diagnosis of thiol-related diseases. Herein we present the first PA and fluorescence dual-modality probe MB-NBD for discriminating different biothiol species. The probe has the advantages of both fluorescence imaging and PA imaging (high sensitivity and deep penetration) with distinct signal patterns toward hydrogen sulfide (H2S), cysteine/homocysteine (Cys/Hcy), and glutathione (GSH) treatment. The biothiol-activated product of MB-NBD exhibits enhancements in near-infrared fluorescence (NIRF) at 690 nm and absorbance/PA at 664 nm upon fast reaction, allowing it to selectively detect biothiol species over other reactive species. On the other hand, MB-NBD displays characteristic absorbance enhancement at 547 nm toward H2S, rendering specific detection of H2S. In addition, the specific enhancements in absorbance/PA at 470 nm and fluorescence at 550 nm toward Cys/Hcy treatment endows the probe with the capability of selectively detecting Cys/Hcy. Furthermore, MB-NBD is able to discriminate Cys and GSH by fluorescent imaging in live-cell and ratiometric PA imaging in mice experiments. MB-NBD has been successfully used to diagnose tumors by dual-channel ratiometric PA imaging.

Controllable Cleavage of C-N Bond-Based Fluorescent and Photoacoustic Dual-Modal Probes for the Detection of H2S in Living Mice.

Hydrogen sulfide (H2S) has been recognized to influence a wide range of physiological and pathological processes. Its underlying molecular events, however, are still poorly understood. An activatable H2S probe for photoacoustic (PA) imaging is desirable to further explore the role of H2S in vivo. Nevertheless, only a few activatable PA probes for H2S detection have been reported. In particular, examples of dual-modal H2S probes with the combined advantages of fluorescence (high sensitivity and resolution) and PA imaging (deep penetration) are very rare. Herein the controllable cleavage of the C-N bond in nitrobenzoxadiazole (NBD) amine derivatives by H2S is presented for the first time. The cleavage reactivity was found to be accelerated by the introduction of an electron-withdrawing group. Through this strategy, a series of fluorescent and PA dual-modal probes (1-3) were developed for H2S detection. Among them, probe 3 shows a high fluorescence on-off response rate (k2 = 4.04 M-1 s-1) and excellent selectivity for H2S over other biothiols. Moreover, probe 3 can also work as an activatable PA H2S probe because of the significant shift of its absorption peak from 468 to 532 nm in the H2S reaction. Importantly, probe 3 demonstrates its capability for fluorescence and PA imaging of H2S in living cells and mice. These results indicate that the controllable cleavage of the C-N bond can serve as an efficient strategy for designing fluorescent and PA dual-modal H2S probes.

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma.

Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.

Effective Phototheranostics of Brain Tumor Assisted by Near-Infrared-II Light-Responsive Semiconducting Polymer Nanoparticles.

Precise diagnosis and effective treatment of gliomas still remain a huge challenge. Photoacoustic-guided photothermal therapy (PTT) has unique advantages over conventional techniques for brain tumor theranostics, but existing nanoagents for photoacoustic imaging (PAI)-guided PTT are mainly organic small molecules or inorganic nanoparticles, which have the limitations of poor photostability and biocompatibility. Besides, the restricted absorption in the first near-infrared window (NIR-I) of the most existing nanoagents compromises their effectiveness for deep tissue PAI and PTT. We herein develop novel semiconducting polymer nanoparticles (SPNs) that are strongly absorptive in the second NIR window (NIR-II) to alleviate these problems. With the merits of excellent photoacoustic and photothermal performance, high photostability, proper size, and low toxicity, SPNs not only show efficient cellular uptake for PAI and PTT toward U87 glioma cells but also demonstrate effective accumulation in both subcutaneous tumors and brain tumors upon intravenous injection, thereby realizing efficient PAI-guided PTT toward gliomas under NIR-II light irradiation.

Rational Design of Conjugated Small Molecules for Superior Photothermal Theranostics in the NIR-II Biowindow.

Extensive recent progress has been made on the design and applications of organic photothermal agents for biomedical applications because of their excellent biocompatibility comparing with inorganic materials. One major hurdle for the further development and applications of organic photothermal agents is the rarity of high-performance materials in the second near-infrared (NIR-II) window, which allows deep tissue penetration and causes minimized side effects. Up till now, there have been few reported NIR-II-active photothermal agents and their photothermal conversion efficiencies are relatively low. Herein, optical absorption of π-conjugated small molecules from the first NIR window to the NIR-II window is precisely regulated by molecular surgery of substituting an individual atom. With this technique, the first demonstration of a conjugated oligomer (IR-SS) with an absorption peak beyond 1000 nm is presented, and its nanoparticle achieves a record-high photothermal conversion efficiency of 77% under 1064 nm excitation. The nanoparticles show a good photoacoustic response, photothermal therapeutic efficacy, and biocompatibility in vitro and in vivo. This work develops a strategy to boost the light-harvesting efficiency in the NIR-II window for cancer theranostics, offering an important step forward in advancing the design and application of NIR-II photothermal agents.

Organic semiconducting polymer amphiphile for near-infrared-II light-triggered phototheranostics.

Development of near-infrared-II (NIR-II) light responsive nano-agents with high photothermal stability, high photothermal conversion efficiency (PCE), and excellent biocompatibility for photoacoustic (PA) imaging-guided photothermal therapy (PTT) is of tremendous significance. In spite of the superiority of organic semiconducting polymer nanoparticles (OSPNs) in PA imaging-guided PTT, the limited absorption in the first NIR (NIR-I) window and metastable nanostructure of OSPNs resulting from commonly used preparation methods based on nanoprecipitation or reprecipitation compromise their in vivo phototheranostic performance. Herein we design and synthesize a novel NIR-II absorbing organic semiconducting polymer amphiphile (OSPA) to enhance the structural stability of OSPNs. With prominent optical properties, low toxicity, and a suitable size, OSPA not only efficiently labels and kills cancer cells under NIR-II irradiation but also accumulates at the tumor of living mice upon intravenous injection, allowing efficient NIR-II light-triggered phototheranostics toward tumor. The developed OSPA has promising potential for fabricating multifunctional nanoplatforms to enable multimodal theranostics.

Corrigendum to "Bioinformatics Analysis of Potential Key Genes in Trastuzumab-Resistant Gastric Cancer".

[This corrects the article DOI: 10.1155/2019/1372571.].

Asymmetric Total Syntheses of the Akuammiline Alkaloids (-)-Strictamine and (-)-Rhazinoline.

Strictamine and rhazinoline are representative methanoquinolizidine-containing akuammiline alkaloids that possess different stereochemistry at the C16 position. A unified approach to the enantioselective total syntheses of these two molecules is described. The key steps in this synthesis include a photocatalytic intra/intermolecular type II radical cascade reaction, a Tsuji-Trost allylation, a palladium- or nickel-mediated cyclization, and a late-stage intramolecular N-alkylation reaction.

Bioinformatics Analysis of Potential Key Genes in Trastuzumab-Resistant Gastric Cancer.

BACKGROUND: This study was performed to identify genes related to acquired trastuzumab resistance in gastric cancer (GC) and to analyze their prognostic value. METHODS: The gene expression profile GSE77346 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained by using GEO2R. Functional and pathway enrichment was analyzed by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, and MCODE were then used to construct the protein-protein interaction (PPI) network and identify hub genes. Finally, the relationship between hub genes and overall survival (OS) was analyzed by using the online Kaplan-Meier plotter tool. RESULTS: A total of 327 DEGs were screened and were mainly enriched in terms related to pathways in cancer, signaling pathways regulating stem cell pluripotency, HTLV-I infection, and ECM-receptor interactions. A PPI network was constructed, and 18 hub genes (including one upregulated gene and seventeen downregulated genes) were identified based on the degrees and MCODE scores of the PPI network. Finally, the expression of four hub genes (ERBB2, VIM, EGR1, and PSMB8) was found to be related to the prognosis of HER2-positive (HER2+) gastric cancer. However, the prognostic value of the other hub genes was controversial; interestingly, most of these genes were interferon- (IFN-) stimulated genes (ISGs). CONCLUSIONS: Overall, we propose that the four hub genes may be potential targets in trastuzumab-resistant gastric cancer and that ISGs may play a key role in promoting trastuzumab resistance in GC.

Organic Semiconducting Polymer Nanoparticles for Photoacoustic Labeling and Tracking of Stem Cells in the Second Near-Infrared Window.

Photoacoustic (PA) imaging and tracking of stem cells plays an important role in the real-time assessment of cell-based therapies. Nevertheless, the limitations of conventional inorganic PA contrast agents and the narrow range of the excitation wavelength in the first near-infrared (NIR-I) window hamper the applications of PA imaging in living subjects. Herein, we report the design and synthesis of a second near-infrared (NIR-II) absorptive organic semiconducting polymer (OSP)-based nanoprobe (OSPN+) for PA imaging and tracking of stem cells. Comparison studies in biological tissue show that NIR-II light excited PA imaging of the OSPN+ has significantly higher signal-to-noise ratio than NIR-I light excited PA imaging, thereby demonstrating the superiority of the OSPN+ for deep tissue imaging. With good biocompatibility, appropriate size, and optimized surface property, the OSPN+ shows enhanced cellular uptake for highly efficient PA labeling of stem cells. In vivo investigations reveal significant NIR-II PA contrast enhancement of the transplanted OSPN+-labeled human mesenchymal stem cells by 40.6- and 21.7-fold in subcutaneous and brain imaging, respectively, compared with unlabeled cases. Our work demonstrates a class of OSP-based nanomaterials for NIR-II PA stem cell imaging to facilitate a better understanding and evaluation of stem cell-based therapies.

Asymmetric Synthesis of an Advanced Tetracyclic Framework of (+)-Sarain A.

An asymmetric synthetic approach to a tetracyclic framework of the marine-derived alkaloid (+)-sarain A has been developed. The key steps to constructing the congested diazatricycloundecane core include an asymmetric Diels-Alder cycloaddition, an Ireland-Claisen rearrangement, and an intramolecular aziridination/ring-opening sequence.

Apigenin inhibits C5a-induced proliferation of human nasopharyngeal carcinoma cells through down-regulation of C5aR.

Complement 5a (C5a) is able to induce the proliferation of human nasopharyngeal carcinoma (NPC) cells. Therefore, an effective method or drug that can specifically inhibit C5a-induced proliferation of human NPC cells needs to be developed. Reportedly, Apigenin has antiproliferative effects on a variety of cancer cells. However, the effect of Apigenin on NPC cell proliferation and its underlying mechanism are still unclear. Herein, the present study aimed to evaluate the effect of Apigenin on C5a-induced proliferation of human NPC cells and its possible mechanism through down-regulation of C5aR. We revealed that Apigenin in vitro could not only inhibit proliferation of NPC cells and but also reduce the expression of C5aR and P300/CBP-associated factor (PCAF) as well as the activation of signal transducer and activator of transcription 3 (STAT3) in NPC cells. Furthermore, Apigenin reduced the proliferation of human NPC cells triggered by C5a through negative regulation of C5aR/PCAF/STAT3 axis. These might provide a new insight into the function of Apigenin in cancer treatment, and also provide a potential strategy for treating human NPC through inhibition of C5aR expression on cancer cells.

Highly compact circulators in square-lattice photonic crystal waveguides.

We propose, demonstrate and investigate highly compact circulators with ultra-low insertion loss in square-lattice- square-rod-photonic-crystal waveguides. Only a single magneto- optical square rod is required to be inserted into the cross center of waveguides, making the structure very compact and ultra efficient. The square rods around the center defect rod are replaced by several right-angled-triangle rods, reducing the insertion loss further and promoting the isolations as well. By choosing a linear-dispersion region and considering the mode patterns in the square magneto-optical rod, the operating mechanism of the circulator is analyzed. By applying the finite-element method together with the Nelder-Mead optimization method, an extremely low insertion loss of 0.02 dB for the transmitted wave and ultra high isolation of 46 dB∼48 dB for the isolated port are obtained. The idea presented can be applied to build circulators in different wavebands, e.g., microwave or Tera-Hertz.

[Application of modified paramedian forehead flap in reconstruction of nasal defect].

OBJECTIVE: To investigate the feasibility and significance of modified paramedian forehead flap for nasal defect and reconstruction. METHODS: Modified paramedian forehead flaps with forehead muscle in the pedicle were used in 2 patients with nasal reconstruction and 7 patients with nasal defects. The flaps were elevated subcutaneously with only forehead muscle in the pedicle at the supraorbital site. The degree of flap axis ranged from 90 degrees to 50 degrees. Inverted L-shape design was used for 3 cases with low hair line. RESULTS: Skin branch of supratrochlear vessel was observed running at the subcutaneous layer during the operation. 8 flaps all survived successfully with good texture and color. Partial necrosis happened in the distal end of one flap with subcutaneous pedicle, which healed through dressing. CONCLUSIONS: Modified paramedian forehead flap, which includes muscle just in the pedicle, is based on the skin branch of supratrochlear vessel. The flap is very flexible and has reliable blood supply, leaving less morbidity in donor site. It also has good texture and skin color.