Neuronal survival factor VGF promotes chemoresistance and predicts poor prognosis in lung cancers with neuroendocrine feature.

High-grade neuroendocrine tumors (NETs) of the lung consist of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Both exhibit aggressive malignancy with poor prognosis. The transformation of lung adenocarcinoma (ADC) to SCLC or LCNEC also contributes to acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Despite initially being responsive to chemotherapy, high-grade NET patients inevitably develop drug resistance; thus, novel therapeutic targets are urgently needed for these patients. Our study reported that VGF (nerve growth factor inducible), a factor mainly expressed in neurons during neural development, is highly expressed in SCLC and LCNEC as well as in a subset of ADCs, whereas targeting VGF attenuates cancer cell growth and tumor formation. High VGF expression was associated with advanced stage SCLC and predicted poor prognosis in lung ADC. In addition, EGFR-TKI selection enriched VGF expression in TKI-resistant ADC under epigenetic control. The VGF locus possessed the HDAC1 binding site, and treatment of ADC cells with the HDAC1 inhibitor induced VGF expression. High VGF expression was associated with chemoresistance, and silencing VGF induced BMF and BCL2L11 expression and rendered lung cancer cells sensitive to chemotherapy drugs. These findings suggested the potential of VGF as a prognostic factor and therapeutic target in lung cancers with neuroendocrine feature.

LC3A-mediated autophagy regulates lung cancer cell plasticity.

ABBREVIATIONS: ATG14: autophagy related 14; CDH2: cadherin 2; ChIP-qPCR: chromatin immunoprecipitation quantitative polymerase chain reaction; CQ: chloroquine; ECAR: extracellular acidification rate; EMT: epithelial-mesenchymal transition; EPCAM: epithelial cell adhesion molecule; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; NDUFV2: NADH:ubiquinone oxidoreductase core subunit V2; OCR: oxygen consumption rate; ROS: reactive oxygen species; RT-qPCR: reverse-transcriptase quantitative polymerase chain reaction; SC: scrambled control; shRNA: short hairpin RNA; SNAI2: snail family transcriptional repressor 2; SOX2: SRY-box transcription factor 2; SQSTM1/p62: sequestosome 1; TGFB/TGF-ß: transforming growth factor beta; TOMM20: translocase of outer mitochondrial membrane 20; ZEB1: zinc finger E-box binding homeobox 1.

The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance.

The cerebellum plays an important role in cognitive functions through connecting with the cerebral cortical areas. However, the relationship between the resting-state functional connectivity (FC) pattern of human cerebro-cerebellar circuits and cognition is not fully understood. The present study investigated the FC patterns of human cerebro-cerebellar circuits and their associations with verbal working memory performance (an n-back task with three subtasks: 0-back, 1-back, and 2-back) through resting-state functional magnetic resonance imaging (fMRI) data from 34 healthy subjects. The whole-brain connectivity analysis was used to identify the cortical hubs as regions of interest (ROI). Then ROI-based FC analysis was performed to investigate the connectivity characteristics within the key cortical hubs and their associations with n-back task performance. The results showed that the bilateral cerebellum lobule VI as central hubs had increased FC with the default mode network (DMN) node (e.g., right posterior cingulate cortex) and salient network (SN) node (e.g., right anterior cingulate cortex), while decreased FC with the executive control network (ECN) node (e.g., the bilateral superior frontal gyrus). Furthermore, FC values of the cerebellum lobule VI with DMN and ECN nodes correlated with verbal working memory performance (response time of 2-back task). The results suggest that the cerebro-cerebellar circuits involve the underlying neural basis of verbal working memory processing during the resting state.

Dual-band and polarization-independent metamaterial terahertz narrowband absorber.

A dual-band terahertz metamaterial narrowband absorber is investigated based on a single simple windmill-shaped structure. The proposed metamaterial absorber achieves near-perfect absorption at 0.371 THz and 0.464 THz. The full width at half-maximum is 0.76% and 0.31% relative to absorption frequency. The multireflection interference theory is used for analyzing the absorption mechanism at low absorption frequency. The theoretical predictions of the decoupled model have excellent agreement with simulation results. By investigating the absorber's distribution of electric field and surface current density at high absorption frequency, the absorber's near-perfect absorption at the high absorption frequency originating from the magnetic resonance formed between the top metal structure and the bottom metal plane is explained. Besides, the absorber proposed is independent of the polarization angle. It is significant to various applications such as narrowband thermal radiation, photoelectric detection, biological sensing, and other fields.

Individual separation of surface, bulk and Begrenzungs effect components in the surface electron energy spectra.

We present the first theoretical recipe for the clear and individual separation of surface, bulk and Begrenzungs effect components in surface electron energy spectra. The procedure ends up with the spectral contributions originated from surface and bulk-Begrenzungs excitations by using a simple method for dealing with the mixed scatterings. As an example, the model is applied to the reflection electron energy loss spectroscopy spectrum of Si. The electron spectroscopy techniques can directly use the present calculation schema to identify the origin of the electron signals from a sample. Our model provides the possibility for the detailed and accurate quantitative analysis of REELS spectra.

Cross-talk between SOX2 and TGFß Signaling Regulates EGFR-TKI Tolerance and Lung Cancer Dissemination.

Regulation of the stemness factor, SOX2, by cytokine stimuli controls self-renewal and differentiation in cells. Activating mutations in EGFR are proven therapeutic targets for tyrosine kinase inhibitors (TKI) in lung adenocarcinoma, but acquired resistance to TKIs inevitably occurs. The mechanism by which stemness and differentiation signaling emerge in lung cancers to affect TKI tolerance and lung cancer dissemination has yet to be elucidated. Here, we report that cross-talk between SOX2 and TGFß signaling affects lung cancer cell plasticity and TKI tolerance. TKI treatment favored selection of lung cancer cells displaying mesenchymal morphology with deficient SOX2 expression, whereas SOX2 expression promoted TKI sensitivity and inhibited the mesenchymal phenotype. Preselection of EGFR-mutant lung cancer cells with the mesenchymal phenotype diminished SOX2 expression and TKI sensitivity, whereas SOX2 silencing induced vimentin, but suppressed BCL2L11, expression and promoted TKI tolerance. TGFß stimulation downregulated SOX2 and induced epithelial-to-mesenchymal transdifferentiation accompanied by increased TKI tolerance, which can interfere with ectopic SOX2 expression. SOX2-positive lung cancer cells exhibited a lower dissemination capacity than their SOX2-negative counterparts. Tumors expressing low SOX2 and high vimentin signature were associated with worse survival outcomes in patients with EGFR mutations. These findings provide insights into how cancer cell plasticity regulated by SOX2 and TGFß signaling affects EGFR-TKI tolerance and lung cancer dissemination. SIGNIFICANCE: These findings suggest the potential of SOX2 as a prognostic marker in EGFR-mutant lung cancer, as SOX2-mediated cell plasticity regulated by TGFß stimulation and epigenetic control affects EGFR-TKI tolerance and cancer dissemination.

Association of Divergent Carcinoembryonic Antigen Patterns and Lung Cancer Progression.

Changes in expression patterns of serum carcinoembryonic antigen at initial diagnosis (CEAIn) and disease progression (CEAPd) in lung cancer patients under EGFR-tyrosine kinase inhibitors (TKI) treatment may reflect different tumor progression profiles. Of the 1736 lung cancer patients identified from the cancer registry group between 2011 to 2016, we selected 517 patients with advanced stage adenocarcinoma, data on EGFR mutation status and CEAIn, among whom were 288 patients with data on CEAPd, eligible for inclusion in the correlation analysis of clinical characteristics and survival. Multivariable analysis revealed that CEAIn expression was associated with poor progression-free survival in patients harboring mutant EGFR. Moreover, CEAIn and CEAPd were associated with the good and poor post-progression survival, respectively, in the EGFR-mutant group. Cell line experiments revealed that CEA expression and cancer dissemination can be affected by EGFR-TKI selection. EGFR-mutant patients, exhibiting high CEAIn (≥5 ng/mL) and low CEAPd (<5 ng/mL), showed a potential toward displaying new metastasis. Taken together, these findings support the conclusion that EGFR mutation status is a critical factor in determining prognostic potential of CEAIn and CEAPd in patients under EGFR-TKI treatment, and CEAIn and CEAPd are associated with distinct cancer progression profiles.

Active control of noise in a duct using the sparsely coded time-domain underdetermined multichannel inverse filters.

A time-domain underdetermined multichannel inverse filtering (TUMIF) technique is proposed for active feedforward control of noise in ducts. Traditionally, feedforward active control is formulated as an overdetermined inverse filtering problem which generally leads to non-zero residual noise. In this work, a multichannel control approach is presented from the perspectives of vector subspaces and model-matching framework. By introducing multiple secondary sources, the problem can be reformulated into an underdetermined system, which admits infinite number of exact solutions with zero residual noise. However, the finite impulse response filter obtained using the least-square method tends to be prohibitively long for real-time implementation. To tackle this problem, two sparse coding techniques, the least absolute shrinkage and selection operator algorithm and the orthogonal matching pursuit algorithm, are exploited to reduce the controller orders. Simulation and experiment results obtained using a digital signal processor demonstrated that a two-channel reduced-order TUMIF controller has achieved significantly higher noise reduction than the filtered-x least-mean-squares algorithm.

Observation of Plasmon Energy Gain for Emitted Secondary Electron in Vacuo.

Plasmon gain by core-level electrons or elastic electrons observed in past studies seems to be of no practical value in material characterization, mainly because of their ultralow signal intensities. Nevertheless, in the emission spectra of Au samples, we have observed plasmon gain in secondary electrons. The electrons gain energy from surface plasmons after escaping from the surface and thereby only carry surface-plasmon information in the vacuum above the surface. Because the intensity of the emitted SEs is strong, rivaling that of core-level or elastic electrons, the observed phenomenon has in practice the potential to image directly in space the surface plasmon near but exterior to the metal surface.