DANCR Induces Cisplatin Resistance of Triple-Negative Breast Cancer by KLF5/p27 Signaling.

An increasing body of evidence suggests that long noncoding RNAs play critical roles in human cancer. Breast cancer is a heterogeneous disease and the potential involvement of long noncoding RNAs in breast cancer remains poorly understood. Herein, the study identified a long noncoding RNA, DANCR, which promotes cisplatin chemoresistance in triple-negative breast cancer (TNBC) cells. Mechanistically, binding of DANCR to Krüppel-like factor 5 (KLF5) induced acetylation of KLF5 at lysine 369 (K369), and DANCR knockdown resulted in down-regulation of KLF5 protein levels. Furthermore, DANCR/KLF5 signaling pathway induced hypersensitivity to cisplatin in chemoresistant patients by inhibiting p27 transcription. In summary, this study reinforced the potential presence of a growth regulatory network in TNBC cells, and documented a DANCR/KLF5/p27 signaling pathway mediating cisplatin chemoresistance in TNBC.

TRIM proteins in breast cancer: Function and mechanism.

Breast cancer is the most prevalent malignancy in the world, and despite tremendous progress in current treatment strategies, recurrence, metastasis and drug resistance of breast cancer remain the major causes of death in patients. Tripartite motif (TRIM) family proteins play a critical role in the tumor progression such as cell proliferation, migration, invasion, and metastasis. Accumulating evidence suggests that the TRIM protein family serve as cancer suppressor proteins or oncoproteins in breast cancer. This review focused on the roles and molecular mechanisms of TRIM protein in breast cancer. Importantly, it provides new insights that TRIM proteins may be ideal targets to treat breast cancer.

Highly discriminative and adaptive feature extraction method based on NMF-MFCC for event recognition of Φ-OTDR.

To enhance the capability of phase-sensitive optical time domain reflectometers (Φ-OTDR) to recognize disturbance events, an improved adaptive feature extraction method based on NMF-MFCC is proposed, which replaces the fixed filter bank used in the traditional method to extract the mel-frequency cepstral coefficient (MFCC) features by a spectral structure obtained from the Φ-OTDR signal spectrum using nonnegative matrix factorization (NMF). Three typical events on fences are set as recognition targets in our experiments, and the results show that the NMF-MFCC features have higher distinguishability, with the corresponding recognition accuracy reaching 98.47%, which is 7% higher than that using the traditional MFCC features.

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma.

PURPOSE: Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. RESULTS: Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. CONCLUSIONS AND CLINICAL RELEVANCE: Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Analyzing Peak-to-Average Power Ratio Characteristics in Multi-Channel Intensity Modulation and Direct Detection Flexible Transceivers Deploying Inverse Fast Fourier Transform/Fast Fourier Transform-Based Processing.

Cascaded inverse fast Fourier transform/fast Fourier transform (IFFT/FFT)-based multi-channel aggregation/de-aggregation offers a promising solution in constructing highly desirable flexible optical transceivers for considerably improving optical networks' elasticity, flexibility, and adaptability. However, the multi-channel aggregation operation unavoidably results in generated signals having high peak-to-average power ratios (PAPRs). To solve this technical challenge, this paper first explores the PAPR characteristics of the corresponding flexible transceivers in optical back-to-back (B2B) and 20 km intensity modulation and direct detection (IMDD) transmission systems, and then numerically investigates the feasibility and effectiveness of utilizing the conventional clipping techniques in reducing their PAPR reductions. The results show that the last IFFT operation size is the primary factor determining the PAPRs rather than the channel count and modulation format. For a given last IFFT operation size, the optimal clipping ratio can be identified, which is independent of channel count. With the identified optimal clipping ratio, when the channel count is >4, every two-channel increase in the channel count can only lead to <1.2 Gb/s decreases in the maximum aggregated signal transmission capacity.

Multi-constraint Gerchberg-Saxton iteration algorithms for linearizing IM/DD transmission systems.

Chromatic dispersion-enhanced signal-signal beating interference (SSBI) considerably affects the performance of intensity-modulation and direct-detection (IM/DD) fiber transmission systems. For recovering optical fields from received double sideband signals after propagating through IM/DD transmission systems, Gerchberg-Saxton (G-S) iterative algorithms are promising, which, however, suffers slow convergence speeds and local optimization problems. In this paper, we propose a multi-constraint iterative algorithm (MCIA) to extend the Gerchberg-Saxton-based linearized detection. The proposed technique can accelerate the convergence speed and realize nonlinear-equalization-free detection. Based on the data-aided iterative algorithm (DIA) and the decision-directed data-aided iterative algorithm (DD-DIA), the proposed technique reuses redundant bits from channel coding to not only correct decision errors but also enforce the constraints on the task function to further accelerate the whole optical field retrieval processing. Simulation results show that, compared with the DD-DIA, the MCIA reduces the received optical power (ROP) by about 1.5-dB for a 100-Gb/s over 50-km SSMF PAM-4 signal transmission at the symbol error rate (SER) of 2×10-2. For a 100-Gb/s over 400-km SSMF transmission system, just 30 MCIA iterations is needed, which is 30% reduction in iteration count compared with the DD-DIA. For further increased transmission capacities, the MCIA can improve the SER by two orders of magnitude compared with the conventional IA. To validate the effectiveness of the MCIA, we also conduct experiments to transmit 92-Gb/s PAM-4 signals over 50-km IM/DD fibre systems. We find that the MCIA has a 1-dB ROP improvement compared with the DD-DIA. Compared with Volterra nonlinear equalization, the BERs of the MCIA with a simple linear equalizer are reduced by more than one order of magnitude with only 52 MCIA iterations.

Dimethyl fumarate ameliorates stress urinary incontinence by reversing ECM remodeling via the Nrf2-TGF-ß1/Smad3 pathway in mice.

INTRODUCTION AND HYPOTHESIS: Mechanical trauma and oxidative injury are involved in the pathogenesis of stress urinary incontinence (SUI), and oxidative stress (OS) is considered a potential therapeutic target. The antioxidant properties of dimethyl fumarate (DMF), a potent activator of Nrf2, have been highlighted recently. We therefore predicted that DMF might have therapeutic effects on mechanical trauma-induced SUI. METHODS: The SUI mice model was established by vaginal distension (VD). Leak point pressure (LPP), serum OS biomarkers, cell proliferation and apoptosis, collagen, elastin, matrix metalloproteinases (MMP), Nrf2, the TGF-ß1/Smad3 signaling pathway, and the associated tissue growth factors in the anterior vaginal wall were measured in either wild-type or Nrf2-knockout (Nrf2-/-) female C57BL/6 mice. RESULTS: The results showed that DMF improved the VD-induced LPP reduction, alleviated oxidative injury, stimulated cell proliferation and inhibited apoptosis in the anterior vaginal wall tissue of mice. Moreover, DMF treatment reduced the hydrolysis of ECM proteins by MMP2 and MMP9. The above effects may be mediated by a series of tissue growth factors, including α-SMA, PAI-1, and TIMP-2, with the TGF-ß1/Smad3 signaling pathway as the core regulatory mechanism. In further study, Nrf2-/- mice were used to replicate the SUI model. And the difference is that DMF failed to reactivate the TGF-ß1/Smad3 pathway, nor did it improve LPP. CONCLUSIONS: Dimethyl fumarate can ameliorate urethra closure dysfunction in the VD-induced SUI mice model, and the therapeutic effect of DMF is mediated by the Nrf2-dominated antioxidant system and its downstream TGF-ß1/Smad3 signaling pathway.

CASC9 plays a role in salivary adenoid cystic carcinoma in vitro by upregulation of ACLY.

OBJECTIVE: The study was designed to explore the role of cancer susceptibility candidate 9 (CASC9) in salivary adenoid cystic carcinoma (SACC) (SACC-83 and SACC-LM) cell malignant phenotypes. METHODS: Colony formation assay was used to measure cell proliferation. Transwell assay was used to detect cell migration and invasion. Flow cytometry analysis was applied to determine cell cycle distribution and apoptosis. FISH assay revealed the subcellular location of CASC9. RESULTS: Downregulation of CASC9 inhibited SACC cell proliferation, migration, and invasion, led to cell arrest at G0/G1 phase, and facilitated cell apoptosis. In mechanism, CASC9 bound with microRNA 146b-5p (miR-146b-5p) and negatively modulated miR-146b-5p expression. MiR-146b-5p directly targeted 3' untranslated region of ATP-Citrate Lyase (ACLY) to degrade ACLY in SACC cells. CASC9 upregulated ACLY expression through competitively binding with miR-146b-5p. Furthermore, rescue assays indicated that ACLY overexpression counteracted the effects triggered by CASC9 knockdown on cell proliferation, migration, invasion, and apoptosis in SACC cells. CONCLUSION: CASC9 facilitated the malignant phenotypes of SACC cells by the regulation of the miR-146b-5p/ACLY axis. These findings might lay foundation for SACC research.

Immunogenetic determinants of heterosexual HIV-1 transmission: key findings and lessons from two distinct African cohorts.

Immunogenetic studies in the past three decades have uncovered a broad range of human genetic factors that seem to influence heterosexual HIV-1 transmission in one way or another. In our own work that jointly evaluated both genetic and nongenetic factors in two African cohorts of cohabiting, HIV-1-discordant couples (donor and recipient pairs) at risk of transmission during quarterly follow-up intervals, relatively consistent findings have been seen with three loci (IL19, HLA-A, and HLA-B), although the effect size (i.e., odds ratio or hazards ratio) of each specific variant was quite modest. These studies offered two critical lessons that should benefit future research on sexually transmitted infections. First, in donor partners, immunogenetic factors (e.g., HLA-B*57 and HLA-A*36:01) that operate directly through HIV-1 viral load or indirectly through genital coinfections are equally important. Second, thousands of single-nucleotide polymorphisms previously recognized as "causal" factors for human autoimmune disorders did not appear to make much difference, which is somewhat puzzling as these variants are predicted or known to influence the expression of many immune response genes. Replicating these observations in additional cohorts is no longer feasible as the field has shifted its focus to early diagnosis, universal treatment, and active management of comorbidities.

TTK inhibitor promotes radiosensitivity of liver cancer cells through p21.

The monopolar spindle 1 ((hMps1/TTK) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To explore the possible relationship between TTK inhibition and radiosensitivity, we examined whether TTK inhibition influences cellular susceptibility of radiation. And we further revealed its mechanisms. We found that the expression of TTK was obviously higher in liver cancer tissues compared to the normal liver tissues. Kaplan-Meier Plotter demonstrated that patients with low TTK expression levels had a longer overall survival than patients with high TTK expression levels. TTK inhibitor AZ3146 could simulated liver cancer cells to accumulate in the G2/M phase, which ultimately enhances DNA damage with more γ-H2AX foci and more apoptosis and necrosis induced by radiation, which prompted that TTK inhibition sensitized liver cancer cells to radiation. In addition, TTK inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced mitotic catastrophe (MC) induced by radiation in a p21-mediated manner. In this study, we present evidences that the TTK inhibitor promotes the radiosensitivity of liver cancer cells through regulating cell cycle in p21-mediated manner in vitro, indicating that TTK inhibitor may be an attractive radiosensitizer for the patients with liver cancer.

Heparin-binding growth factor (HDGF) drives radioresistance in breast cancer by activating the STAT3 signaling pathway.

Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.

Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.

Despite extensive research on the mechanisms of HLA-mediated immune control of HIV-1 pathogenesis, it is clear that much remains to be discovered, as exemplified by protective HLA alleles like HLA-B*81 which are associated with profound protection from CD4+ T cell decline without robust control of early plasma viremia. Here, we report on additional HLA class I (B*1401, B*57, B*5801, as well as B*81), and HLA class II (DQB1*02 and DRB1*15) alleles that display discordant virological and immunological phenotypes in a Zambian early infection cohort. HLA class I alleles of this nature were also associated with enhanced immune responses to conserved epitopes in Gag. Furthermore, these HLA class I alleles were associated with reduced levels of lipopolysaccharide (LPS) in the plasma during acute infection. Elevated LPS levels measured early in infection predicted accelerated CD4+ T cell decline, as well as immune activation and exhaustion. Taken together, these data suggest novel mechanisms for HLA-mediated immune control of HIV-1 pathogenesis that do not necessarily involve significant control of early viremia and point to microbial translocation as a direct driver of HIV-1 pathogenesis rather than simply a consequence.

Long Noncoding RNA DANCR Regulates Cell Proliferation by Stabilizing SOX2 mRNA in Nasopharyngeal Carcinoma.

The long noncoding RNA DANCR (differentiation antagonizing non-protein coding RNA) displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in nasopharyngeal carcinoma (NPC) remain poorly understood. We found that DANCR is dramatically up-regulated in human NPC, and that it is an indicator for poor survival prognosis. DANCR knockdown suppressed cell proliferation, colony formation in vitro, and tumorigenicity in vivo. Mechanistic analyses demonstrated that DANCR could bind to RNA-binding protein 3 (RBM3) protein and stabilize SOX2 mRNA, resulting in NPC cell proliferation. Our findings indicate that DANCR functions as an oncogene and a potential therapeutic target for NPC.

TGF-ß-activated lncRNA LINC00115 is a critical regulator of glioma stem-like cell tumorigenicity.

Long non-coding RNAs (lncRNAs) are critical regulators in cancer. However, the involvement of lncRNAs in TGF-ß-regulated tumorigenicity is still unclear. Here, we identify TGF-ß-activated lncRNA LINC00115 as a critical regulator of glioma stem-like cell (GSC) self-renewal and tumorigenicity. LINC00115 is upregulated by TGF-ß, acts as a miRNA sponge, and upregulates ZEB1 by competitively binding of miR-200s, thereby enhancing ZEB1 signaling and GSC self-renewal. LINC00115 also promotes ZNF596 transcription by preventing binding of miR-200s to the 5'-UTR of ZNF596, resulting in augmented ZNF596/EZH2/STAT3 signaling and GBM tumor growth. Inhibition of EZH2 by genetic approaches or a small molecular inhibitor markedly suppresses LINC00115-driven GSC self-renewal and tumorigenicity. Moreover, LINC00115 is highly expressed in GBM, and LINC00115 expression or correlated co-expression with ZEB1 or ZNF596 is prognostic for clinical GBM survival. Our work defines a critical role of LINC00115 in GSC self-renewal and tumorigenicity, and suggests LINC00115 as a potential target for GBM treatment.

An unusual tracheal foreign body in a middle-aged male with a 15-year history of coal use: a case report.

BACKGROUND: Long-term exposure to coal dust causes respiratory disease. In chest computer tomography (CT), pulmonary nodules, pulmonary interstitial fibrosis and emphysema manifest themselves. However, tracheal foreign bodies caused by coal dust are rarely reported. In this study, we report a special case of a tracheal coal foreign body, in which the patient has neither a history of coal work nor foreign body inhalation. CASE PRESENTATION: A 49-year-old man was diagnosed with chronic obstructive pulmonary disease (COPD) due to chronic cough and exertional dyspnoea. His symptoms gradually worsened despite treatment for COPD. Chest radiograph and CT images showed an irregular high-density nodule inserting fromthe trachea into the right thyroid at approximately the level of the 7th cervical vertebra. Fiberoptic bronchoscopy revealed that the tracheal lumen was mostly blocked. After the surgery, the energy spectrum CT quantitative analysis showed that the foreign body was likely that of a bituminous coal specimen. CONCLUSIONS: For cases in which a foreign body in the airway is highly suspected, early fiberoptic bronchoscopy and radiographic examinations should be performed as soon as possible to avoid misdiagnosis and ensure timely treatment.

DFT-Spread Spectrally Overlapped Hybrid OFDM-Digital Filter Multiple Access IMDD PONs.

A novel transmission technique-namely, a DFT-spread spectrally overlapped hybrid OFDM-digital filter multiple access (DFMA) PON based on intensity modulation and direct detection (IMDD)-is here proposed by employing the discrete Fourier transform (DFT)-spread technique in each optical network unit (ONU) and the optical line terminal (OLT). Detailed numerical simulations are carried out to identify optimal ONU transceiver parameters and explore their maximum achievable upstream transmission performances on the IMDD PON systems. The results show that the DFT-spread technique in the proposed PON is effective in enhancing the upstream transmission performance to its maximum potential, whilst still maintaining all of the salient features associated with previously reported PONs. Compared with previously reported PONs excluding DFT-spread, a significant peak-to-average power ratio (PAPR) reduction of over 2 dB is achieved, leading to a 1 dB reduction in the optimal signal clipping ratio (CR). As a direct consequence of the PAPR reduction, the proposed PON has excellent tolerance to reduced digital-to-analogue converter/analogue-to-digital converter (DAC/ADC) bit resolution, and can therefore ensure the utilization of a minimum DAC/ADC resolution of only 6 bits at the forward error correction (FEC) limit (1 × 10-3). In addition, the proposed PON can improve the upstream power budget by >1.4 dB and increase the aggregate upstream signal transmission rate by up to 10% without degrading nonlinearity tolerances.

Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China.

To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019-nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019-nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019-nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48-89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6-41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6-19] days) than those aged less than 70 years (20 [range 10-41] days; P = .033). The 2019-nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.

Flat broadband chaos generation in a discrete-mode laser subject to optical feedback.

Chaos generation in a discrete-mode (DM) laser subject to optical feedback is experimentally explored. The results show that a DM laser with only optical feedback can produce flat broadband chaos under an optimized feedback ratio. The effect of the laser bias current on the bandwidth and flatness of chaos is also investigated. It shows that the higher bias current, the better the flatness that can be obtained at the optimal feedback ratio.

Mechanical Stretching induces the apoptosis of parametrial ligament Fibroblasts via the Actin Cytoskeleton/Nr4a1 signalling pathway.

The anatomical positions of pelvic floor organs are maintained mainly by ligaments and muscles. Long-term excessive mechanical tension stimulation of pelvic floor tissue beyond the endurance of ligaments or muscles will lead to the occurrence of pelvic organ prolapse (POP). In addition, cytoskeletal reconstitution is a key process by which cells respond to mechanical stimulation. The aim of the present study was to investigate the protective effect of actin cytoskeleton to resist mechanical stretching (MS)-induced apoptosis in parametrial ligament fibroblasts (PLFs) and the underlying mechanisms. MS provided by a four­point bending device could significantly induce apoptosis of PLFs from non-POP patients, which exhibited an apoptosis rate close to that of PLFs from POP patients, and the apoptosis rate was higher following latrunculin A (Lat-A, a potent inhibitor of actin) treatment. In addition, Nr4a1 and Bax expression was increased while Bcl-2 and caspase-3 expression was clearly decreased after treatment with MS and Lat-A. However, the apoptosis induced by MS was reduced when the expression of Nr4a1 was downregulated by siRNA. These outcomes reveal a novel mechanism that links the actin cytoskeleton and apoptosis in PLFs by Nr4a1; this mechanism will provide insight into the clinical diagnosis and treatment of POP.

A Computer Vision-Based Navigation and Localization Method for Station-Moving Aircraft Transport Platform with Dual Cameras.

In order to develop equipment adapted to the aircraft pulse final assembly line, a vision-based aircraft transport platform system is developed. This article explores a guiding method between assembly stations which is low-cost and easy to change routes by using two-dimensional code and two complementary metal oxide semiconductor (CMOS) cameras. The two cameras installed on the front and back of the platform read the two-dimensional code containing station information to guide the platform. In the process of guiding, the theoretical position and posture of the platform at each assembly station are known, but there is a difference between the actual and theoretical values due to motion errors. To reduce the influence of the deviation on the navigation route, a localization method is proposed based on the two-dimensional images captured by the cameras. Canny edge detection is applied to the processed image to obtain the position of the two-dimensional code in the image, which can measure the angle/distance deviation of the platform. Then, the computer can locate the platform precisely by the information in the two-dimensional code and the deviation measured by the image. To verify the feasibility of the proposed method, experiments have been performed on the developed platform system. The results show that the distance and angle errors of the platform are within ±10 mm and ±0.15° respectively.