Kinetic Ensemble of Tau Protein through the Markov State Model and Deep Learning Analysis.

The ordered assembly of Tau protein into filaments characterizes Alzheimer's and other neurodegenerative diseases, and thus, stabilization of Tau protein is a promising avenue for tauopathies therapy. To dissect the underlying aggregation mechanisms on Tau, we employ a set of molecular simulations and the Markov state model to determine the kinetics of ensemble of K18. K18 is the microtubule-binding domain of Tau protein and plays a vital role in the microtubule assembly, recycling processes, and amyloid fibril formation. Here, we efficiently explore the conformation of K18 with about 150 µs lifetimes in silico. Our results observe that all four repeat regions (R1-R4) are very dynamic, featuring frequent conformational conversion and lacking stable conformations, and the R2 region is more flexible than the R1, R3, and R4 regions. Additionally, it is worth noting that residues 300-310 in R2-R3 and residues 319-336 in R3 tend to form sheet structures, indicating that K18 has a broader functional role than individual repeat monomers. Finally, the simulations combined with Markov state models and deep learning reveal 5 key conformational states along the transition pathway and provide the information on the microsecond time scale interstate transition rates. Overall, this study offers significant insights into the molecular mechanism of Tau pathological aggregation and develops novel strategies for both securing tauopathies and advancing drug discovery.

A spectrally selective visible microbolometer based on planar subwavelength thin films.

In this work, we experimentally demonstrate a new type of compact, low-cost, visible microbolometer based on metal-insulator-metal (MIM) planar subwavelength thin films, which exploits resonant absorption for spectral selectivity without additional filters and has the advantages of compact design, simple structure, cost-efficiency, and large format fabrication. The experimental results show that a proof-of-principle microbolometer exhibits spectrally selective properties in the visible frequency range. At a resonant absorption wavelength of 638 nm, a responsivity of about 10 mV W-1 is achieved at room temperature at a bias current of 0.2 mA, which is about one order of magnitude higher than that of the control device (a bare Au bolometer). Our proposed approach provides a viable solution for the development of compact and inexpensive detectors.

Study of structural effects on the polarization characteristics of subwavelength metallic gratings in short infrared wavelengths.

Applications of subwavelength grating based-polarizers for polarimetric detections are being hindered due to the limited extinction ratio. In this work, the structural effect, including the line edge roughness (LER), of the gratings on the polarizing characteristics was studied by both numerical simulations using finite difference and time domain (FDTD) method and experiments, aiming to figure out the optimal grating profile for achieving high transmittance as well as high extinction ratio. Two different configurations of the gratings, one is dual layer Au lines and the other is parabolic shaped Al lines on structured spin-on-carbon (SOC) films were systematically studied and compared. Nanofabrication of the gratings by electron beam lithography without lift-off process were conducted and optical measurements of their polarization properties demonstrate superior performance of the developed polarizers. The origin of the structural effect was explained by the local surface plasmonic modes, existing in the nano-slits in metallic gratings, which is instructive for further enhancement of the polarization performance.

Theoretical modeling of ice lithography on amorphous solid water.

Due to the perfection of the nanofabrication in nanotechnology and nanoscience, ice lithography (IL) by patterning ice thin-films with a focused electron beam, as a significant derivative technology of electron beam lithography (EBL), is attracting growing attention, evoked by its advantages over traditional EBL with respects of in situ-fabrication, high efficiency, high accuracy, limited proximity effect, three-dimensional (3D) profiling capability, etc. However, theoretical modeling of ice lithography for replicated profiles on the ice resist (amorphous solid water, ASW) has rarely been reported so far. As the result, the development of ice lithography still stays at the experimental stage. The shortage of modeling methods limits our insight into the ice lithography capability, as well as theoretical anticipations for future developments of this emerging technique. In this work, an e-beam induced etching ice model based on the Monte Carlo algorithm for point/line spread functions is established to calculate the replicated profiles of the resist by ice lithography. To testify the fidelity of the modeling method, systematic simulations of the ice lithography property under the processing parameters of the resist thickness, electron accelerating voltage and actual patterns are performed. Theoretical comparisons between the IL on ASW and the conventional EBL on polymethyl methacrylate (PMMA) show superior properties of IL over EBL in terms of the minimum feature size, the highest aspect ratio, 3D nanostructure/devices, etc. The success in developing a modeling method for ice lithography, as reported in this paper, offers a powerful tool in characterizing ice lithography up to the theoretical level and down to molecular scales.

Spectral filter in short-wave infrareds based on a metasurface on silicon-on-insulator with polarizing bandpass.

Spectral filters with polarimetric character in short-wave infrareds are urgently needed because of their broad applications in optic-fiber communications, polarimetric detections, and imaging. Based on our earlier progress in developing polarimetric devices in infrared wavelengths, in this work, a plasmonic-metasurface-based polarization-dependency multi-channel narrowband filter in short-wave infrareds was developed. To meet the requirement by the developing trend of polarimetric detection/spectral imaging in short-wave infrareds, a resonant cavity in the form of the Au hat/elliptical Si/SiO2 pillars/Au layer as the filters was proposed. Numerical simulations by finite-difference time-domain (FDTD) show resonant and polarized transmissions of the designed devices to infrared light in short wavelengths, and the peak positions are relevant to the structural dimensions. Optical characteristics of the filters, fabricated by electron beam lithography/dry-etch technique, agree well with the simulated behavior. To enhance the transmission efficiency to the applicable level, nanoprocessing of the filters still needs to be optimized. Nevertheless, the progress reported is promising for this new type of spectral filters based on modern metasurfaces.

A Broadband Photoelectronic Detector in a Silicon Nanopillar Array with High Detectivity Enhanced by a Monolayer Graphene.

To meet the fast-growing need for broad applications in remote sensing, novel optoelectronic devices with high detectivity in full bands and room temperature operation are urgently desired. This paper reports our progress in developing a specially designed photovoltaic detector by integrating a monolayer graphene onto a silicon-based nanopillar array standing on a p-n junction. Optoelectronic measurements of the fabricated detectors show that the monolayer graphene plays a critical role in device performance. Compared with the one without the graphene covering, the new device demonstrates significant improvements in the specific detectivity of 1.43 × 1013 Jones and the responsivity exceeding ∼106 V/W with a reduced leakage current corresponding to a quantum efficiency of 74.8% at 860 nm wavelength. Moreover, such sensing performance remained unaffected over the entire band from 450 to 1100 nm at room temperature, which is suitable for broadband imaging applications.

Optimization study of metallic hole arrays as the multi-channel spectral filters in long-infrared wavelengths.

The development of miniaturized multi-channel infrared filters based on plasmonic metasurfaces is attracting growing attention, driven by its potential applications in infrared imaging, photodetectors, and spectroscopy. However, the advance of such filters in long-infrared wavelengths has rarely been reported. This paper reports our recent progress on developing multi-channel spectral filters based on micrometer metallic hole arrays in the long-infrared band of 10-15 µm. The effects of structural parameters and the shapes of metallic hole arrays on filtering performance are investigated by numerical simulations with the finite-difference time-domain method and then experimentally verified by optical characterizations of fabricated filters using electron beam lithography. The transmission peaks of the filter on a zinc selenide substrate were optimized with a maximum transmittance of 63%. A comparison of the hole shapes shows that elliptical holes give rise to sharper transmission peak quality than round ones by 28%. The progress achieved in this work should be a promising step in the development of metallic hole-based spectral filters with miniaturized dimensions.

Prognostic Significance of the Hsp70 Gene Family in Colorectal Cancer.

BACKGROUND Colorectal cancer (CRC) is a deadly form of cancer worldwide. Heat shock protein 70 (Hsp70) belongs to the family of human HSPs and plays an essential role in multiple cellular developments and in responding to environmental changes. However, studies on the relationship between CRC and the Hsp70 family are rare. MATERIAL AND METHODS Data pertaining to 438 patients with CRC was downloaded from The Cancer Genome Atlas database. To investigate the prognostic significance of the Hsp70 genes, survival and joint-effect analyses were conducted. The correlation between prognosis-related Hsp70 genes and clinical factors in CRC was analyzed using a nomogram. Gene set enrichment analysis (GSEA) was performed to explore the complex enrichment pathway in CRC with the prognosis-related Hsp70 genes. RESULTS According to multivariate Cox regression survival analysis, low expression levels of HSPA1A, HSPA1B, and HSPA1L were correlated with improved overall survival (OS). According to the joint-effects survival analysis, the joint low expression levels of HSPA1A, HSPA1B, and HSPA1L were related to improved OS. The 1-, 3-, 5-, and 10-year survival rates of patients with CRC were predicted by constructing a nomogram model based on HSPA1A, HSPA1B, HSPA1L, and tumor stage. The GSEA results indicated the biological roles of HSPA1A, HSPA1B, and HSPA1L in CRC. CONCLUSIONS Low expression levels of HSPA1A, HSPA1B, and HSPA1L were strongly correlated with improved prognosis in CRC and might serve as latent prognostic biomarkers in CRC.

Prognostic Value of Enolase Gene Family in Colon Cancer.

BACKGROUND Colorectal cancer (CRC), the most common gastrointestinal cancer, is associated with high mortality rates. Enolase is a major enzyme present in the glycolytic pathway. However, the functional significance of the enolase (ENO) gene family in the pathogenesis of CRC has been unclear. MATERIAL AND METHODS The data associated with 438 CRC patients from The Cancer Genome Atlas database were extracted for analysis. Survival analyses with Cox regression was performed to construct a prognostic signature. We investigated the processes that underlies the correlation between ENO genes and overall survival (OS) using gene set enrichment analysis (GSEA). We then developed a connectivity map to identify candidate target drugs for CRC. RESULTS The multivariate survival analysis showed that low expression of ENO2 and ENO3 had a significant correlation with longer OS. The joint-effects survival analysis indicated that the combined low expression of ENO2 and ENO3 was highly correlated with favorable OS. As indicated by the gene set enrichment analysis (GSEA), the ENO gene is involved in various biological pathways and has multiple roles. Potential pharmacological targets of ENO2 and ENO3 were constructed as well. CONCLUSIONS Low expression levels of both ENO2 and ENO3 were linked to a positive prognosis for CRC. Both ENO2 and ENO3 show promise as prognostic biomarkers for colon cancer patients.

Prognostic value of chloride channel accessory mRNA expression in colon cancer.

Chloride channel accessory (CLCA) is a gene family that encode Ca2+ activated chloride channels, which make a substantial contribution to various diseases. The aim of the present study was to investigate the prognostic value of CLCA expression in colon cancer. In an attempt to elucidate the value of CLCA mRNA expression in the prognosis of patients with colon cancer, the gene expression data of 438 patients with colon cancer were analyzed. The source of the data was The Cancer Genome Atlas, and it was identified that high expression levels of CLCA1 and CLCA2 were associated with a favorable overall survival (OS) time in patients with colon cancer. As revealed by joint effects analysis, the co-occurrence of high expression levels of CLCA1 and CLCA2 was associated with a favorable OS time in patients with colon cancer. CLCA genes were investigated using gene set enrichment analysis. The results of the bioinformatics analysis demonstrated that high expression levels of CLCA1 and CLCA2 were associated with the prognosis of colon cancer. These findings suggest that CLCA1 and CLCA2 are potential prognostic biomarkers for patients with colon cancer. Furthermore, combining CLCA1 and CLCA2 can enhance the sensitivity of the prediction of the OS time of patients with colon cancer.

Rosmarinic Acid Analogue-11 Induces Apoptosis of Human Gastric Cancer SGC-7901 Cells via the Epidermal Growth Factor Receptor (EGFR)/Akt/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND According to the latest statistics from the American Cancer Society, there will be 1.73 million cancer cases and more than 600 000 cancer deaths in the United States in 2018, among which there will be 26 240 new cases of gastric cancer and around 10 800 deaths arising from gastric cancer. The objective of this study was to use RAA-11 to intervene in SGC-7901 cells to understand its effects on cell proliferation and apoptosis, and to explore the apoptosis mechanism. MATERIAL AND METHODS MTT assay was used to detect the survival of human gastric mucosal epithelial GES-1 cells and human gastric cancer SGC-7901 cells. Colony formation assay was used to observe the colony forming ability in SGC-7901 cells. The apoptotic rate of SGC-7901 cells was evaluated by Hoechst33258 staining and flow cytometry. qRT-PCR was used to analyze the epidermal growth factor receptor (EGFR) mRNA expression level in SGC-7901 cells. Western blot was used to examine the expression levels of caspase-3, Bcl-2, BAX, EGFR, Akt, p-Akt, and NF-κB in SGC-7901 cells. RESULTS RAA-11 is capable of inhibiting the proliferation and inducing the apoptosis of SGC-7901 cells in a time- and dose-dependent manner. Western blot showed that the expression levels of caspase-3 and BAX were upregulated, while the expression levels of Bcl-2, EGFR, Akt, p-Akt, and NF-κB in the SGC-7901 cells were downregulated. CONCLUSIONS Apoptosis can be induced in SGC-7901 cells by RAA-11, potentially via the EGFR/Akt/NF-κB pathway, indicating that RAA-11 might be a potent agent for cancer treatment.