FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma.

Cisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and BNIP3 in CDDP resistance of OS cells. FoxG1 and BNIP3 expression levels were detected in the CDDP-sensitive and CDDP-resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and BNIP3 showed significant downregulation in the CDDP-resistant OS tumor samples and cell lines. CDDP-resistant OS tumor specimens and cells displayed impaired mitophagy. FoxG1 overexpression promoted BNIP3 expression, enhanced mitophagy in CDDP-resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/BNIP3 axis in regulating mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/BNIP3-dependent mitophagy as a potential strategy to overcome CDDP resistance in OS.

Highly Potent, Selective, Biostable, and Cell-Permeable Cyclic d-Peptide for Dual-Targeting Therapy of Lung Cancer.

The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRASG12D using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRASG12D mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRASG12D-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRASG12D-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRASG12D-driven lung cancer treatment.

Tunable and channel spacing precisely controlled comb filters based on the fused taper technology.

We propose and demonstrate an adjustable all-fiber comb filter with precisely controlled channel spacing by employing a tapered fiber in one arm of a Mach-Zehnder interferometer (MZI) for the first time. Using fused taper technology to draw the fiber, we can precisely control the optical path difference between the two arms of the MZI, thus realizing a precisely controllable channel spacing. By rotating the polarization controller state in the other arm of the MZI, the transmission spectrum wavelength can be continuously tuned. Comb filters with controllable channel spacings from 0.2 to 3.0 nm have been numerically studied and achieved in experiment. Applications of a filter based on a multi-wavelength tunable all-fiber laser source are also demonstrated.

L-band wavelength-tunable dissipative soliton fiber laser.

A tunable L-band dissipative soliton (DS) fiber laser with nonlinear polarization rotation (NPR) playing the roles of both a saturable absorber (SA) and a tunable filter has been demonstrated experimentally and numerically. By appropriate adjustment of the states of the polarization controllers (PCs) and the pump power, DSs with continuously tunable wavelengths have been observed over the wavelength range from 1583.0 to 1602.4 nm with a 3-dB spectral bandwidth of around 20 nm and from 1581.9 nm to 1602.6 nm with a 3-dB spectral bandwidth of around 4 nm. In addition, we have observed that by increasing the pump power, the 3-dB spectral bandwidth of the DS could be increased without pulse breaking. Numerical results for the characteristics of the DSs are in accord with the experimental data.

Different polarization dynamic states in a vector Yb-doped fiber laser.

Different polarization dynamic states in an unidirectional, vector, Yb-doped fiber ring laser have been observed. A rich variety of dynamic states, including group velocity locked polarization domains and their splitting into regularly distributed multiple domains, polarization locked square pulses and their harmonic mode locking counterparts, and dissipative soliton resonances have all been observed with different operating parameters. We have also shown experimentally details of the conditions under which polarization-domain-wall dark pulses and bright square pulses form.

[Application value of multiple phase subtraction imaging of dynamic contrast enhanced magnetic resonance imaging in common breast tumor].

OBJECTIVE: To evaluate the application value of multiple phase subtraction imaging of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in common breast tumor. METHODS: All radiographic and MRI data of 72 patients with histological proved common breast tumor were analyzed retrospectively. Prior to an injection of gadolinium-diethylenetriaminepentaacetate (GD-DTPA), 3D mask scans were performed. Then 9 consecutive phases of imaging were acquired. After the drawing of time-signal intensity curve, he first and second phases were selected to perform subtraction with the mask, rebuild 3D maximum intensity projection and analyze the application value of subtracted and 3D maximum intensity projection (MIP) reformation images. Chi-square test was used for the analyses of benign and malignant breast tumors. RESULTS: There were 83 lesions in 72 patients. Among 18 cases of fibro adenoma, 23 lesions had no tumor vessel. For the detecting ratio of lesions, the first and second phase subtraction imaging had no statistics difference. Only one intraductal papilloma with ductal carcinoma in situ (DCIS) had tumor vessel in 4 intraductal papilloma patients. Among 5 DCIS cases, one of them had small curved tumor vessel. And 51 lesions were found in 45 infiltrating ductal carcinoma (IDC) cases. Tumor vessels could be seen in all IDC cases. And 37 cases had multiple tumor vessels while 8 cases had single tumor vessel. When the first phase was used for subtraction, 36 lesions were found. On the other hand, 51 lesions were found in the second phase subtraction. There were significant differences between them. CONCLUSION: No significant differences exist in benign breast tumor on differential phase subtraction images of DCE-MRI, but there are significant differences in malignant breast tumor. It is very important to detect the lesions and show the tumor vessels by rebuilding multiple phase subtraction.

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases.

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.

Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications.

Long non-protein-coding RNAs (lncRNAs) are emerging as important gene expression regulators that are linked to various biological processes at the post-transcriptional and transcriptional levels. lncRNAs are known to be important in cell proliferation, cell differentiation, apoptosis and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a novel lncRNA, is highly conserved amongst mammals. In addition, it has been considered to act as an oncogene, depending on the tumor system. An increasing number of studies have indicated that MALAT-1 may be detected in certain types of human tumors, including lung and bladder cancer and hepatocellular carcinoma. MALAT-1 silencing may be an effective therapeutic approach against tumors. The present study reviews the current knowledge on the functional role of MALAT-1 in the control of various cancers.

Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region.

To understand the structure and activity relationship of human LL-37, a series of peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as well as drug-sensitive and drug-resistant cancer cells. A 13-residue core antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37, was identified based on total correlated spectroscopy by trimming nonessential regions (TOCSY-trim). Because LL-37 acts on bacterial membranes, three-dimensional structures of its fragments were determined in micelles by NMR, including structural refinement by natural abundance 15N and 13C chemical shifts. Aromatic-aromatic interactions in the N-terminal fragment were proposed to be essential for LL-37 aggregation. The LL-37 core peptide adopts a similar structure in the micelles of SDS or dioctanoyl phosphatidylglycerol. This structure is retained in the C-terminal fragment LL-37(13-37) and very likely in intact LL-37 based on peptide-aided signal assignments. The higher antibacterial activity of the LL-37 core peptide than aurein 1.2 was attributed to additional cationic residues. To achieve selective membrane targeting, D-amino acids were incorporated into LL-37(17-32). While the D-peptide showed similar antibacterial activity to the L-diastereomer, it lost toxicity to human cells. Structural analysis revealed hydrophobic defects in the new amphipathic structure of the D-peptide, leading to a much shorter retention time on a reversed-phase HPLC column. It is proposed that hydrophobic defects as a result of incoherent hydrophobic packing provide a structural basis for the improvement in cell selectivity of the LL-37 fragment.