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Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in the world, arises from the interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5‐fluorouracil, and paclitaxel have now become the first‐line options for OSCC patients. Nevertheless, most OSCC patients eventually acquire drug resistance, leading to poor prognosis. With the discovery and identification of non‐coding RNAs (ncRNAs), the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized. The mechanisms of drug resistance of OSCC are intricate and involve drug efflux, epithelial‐mesenchymal transition, DNA damage repair, and autophagy. At present, strategies to explore the reversal of drug resistance of OSCC need to be urgently developed. Nano‐delivery and self‐cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting, controlled release, and consistent pharmacokinetic profiles. In particular, the combined application of new technologies (including CRISPR systems) opened up new horizons for the treatment of drug resistance of OSCC. Hence, this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC, elucidated multiple ncRNA‐meditated mechanisms of drug resistance of OSCC, and discussed the potential value of drug delivery platforms using nanoparticles and self‐cells as carriers in drug resistance of OSCC., The mechanisms of drug resistance are intricate and involve drug efflux, epithelial mesenchymal transition, DNA damage repair, and autophagy. Nano‐delivery and self‐cellular drug delivery platforms have a broad prospective for alleviating OSCC drug resistance. In particular, the combined application of new technologies (including CRISPR systems) opens up new horizons for treatment of OSCC drug resistance.

Gene expression noise influences organism evolution and fitness but is poorly understood. There is increasing evidence that the functional roles of components of the translation machinery influence noise intensity. In addition, modulation of the activities of at least some of these same components affects the replicative lifespan of a broad spectrum of organisms. In a novel comparative approach, we modulate the activities of the translation initiation factors eIFG1 and eIF4G2, both of which are involved in the process of recruiting ribosomal 43S preinitiation complexes to the 5’ end of eukaryotic mRNAs. We show that tagging of the cell wall using a fluorescent dye allows us to follow gene expression noise as different yeast strains progress through successive cycles of replicative ageing. This procedure reveals a relationship between global protein synthesis rate and gene expression noise (cell‐to‐cell heterogeneity), which is accompanied by a parallel correlation between gene expression noise and the replicative age of mother cells. An alternative approach, based on microfluidics, confirms the interdependence between protein synthesis rate, gene expression noise and ageing. We additionally show that it is important to characterize the influence of the design of the microfluidic device on the nutritional state of the cells during such experiments. Analysis of the noise data derived from flow cytometry and fluorescence microscopy measurements indicates that both the intrinsic and the extrinsic noise components increase as a function of ageing.\ud \ud

The aim of this study was to analyse 69 Chinese patients with USH2A mutations and to assess the genotype-phenotype correlation.All 36 Usher syndrome type IIA patients and 33 nonsyndromic RP (retinitis pigmentosa) patients underwent clinical examinations. Eye examinations included best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination with dilated pupils, fundus fluorescent angiography, visual field test, full-field electroretinography and optic coherence tomography; audiological assessment included pure tone audiometry and hearing thresholds. The molecular diagnosis of genotype combined the single-gene Sanger sequencing and next-generation sequencing. This study is a retrospective study.The mean age of first symptoms with Usher syndrome type IIa and nonsyndromic RP patients was 13.7 versus 29.8 years (ocular phenotypes, p 0.001); 17.7 versus 29.9 years (nyctalopia, p 0.001); 44.7 versus 54.8 years (low vision based on VF, p 0.001); 41.7 versus 54.7 years (low vision based on VA, p 0.001); and 46.0 versus 56.7 years (legal blindness based on VF, p 0.001). There was significant difference in variants in the two groups (p 0.05). Among patients with mutation c.2802T G (p.Cys934Trp), more (66.7%) presented with normal hearing. All patients (3/3, 100%) with the variant c.8232G C (p.Trp2744Cys) had hearing loss. Furthermore, we identified 23 novel variants in USH2A.Patients with Usher syndrome type IIa had an earlier onset of the disease, inferior visual function and presented with more truncating variants, compared with the nonsyndromic RP patients.

We have specified the synthetic conditions to obtain one-directionally ordered CaSi2 microwall arrays vertically grown on a Si substrate. Our basic concept is based on the utilization of the Kirkendall effect for reactive deposition epitaxy (RDE). We found for the first time that: 1) a much larger Ca vapor supply on the Si substrate than the conventional RDE, 2) the adoption of a two-step heating process, and 3) the selection of the crystal axis of the Si surface are the keys to control the microstructures of CaSi2 on the Si substrate. The CaSi phase was first formed on Si, then the CaSi2 phase was formed at the CaSi/Si interface. Based on the Kirkendall effect, the interdiffusion of Ca and Si was enhanced in the vertical direction rather than in the parallel direction to the Si surface. CaSi2 tends to grow along four equivalent Si{111} planes, however, the specific orientation of the Si surface resulted in CaSi2 microwalls grown along its Si(111‾ ) plane, the only plane directing nearly vertical to the surface among the Si{111} planes. These results suggest that the Kirkendall effect under asymmetric growth of target materials would be a rational strategy to obtain their ordered microstructures.

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by intramolecular crosslinking of isolated single polymer chains. Syntheses of such SCNPs usually need to be performed in a dilute solution. In such a condition, the bonding probability of the two active crosslinking units at a short contour distance along the chain backbone is much higher than those which are far away from each other. Such a reaction condition often results in local spheroidization and, therefore, the formation of loosely packed structures. How to inhibit the local spheroidization and improve the compactness of SCNPs is thus a major challenge for the syntheses of SCNPs. In this study, computer simulations are performed and the fact that a precollapse of the polymer chain conformation in a cosolvent condition can largely improve the probability of the crosslinking reactions at large contour distances is demonstrated, favoring the formations of closely packed globular structures. As a result, the formed SCNPs can be more spherical and have higher compactness than those fabricated in ultradilute good solvent solution in a conventional way. It is believed this simulation work can provide a insight into the effective syntheses of SCNPs with spherical conformations and high compactness.

The adsorption of methane on intrinsic, vacancy and N-doped graphene are investigated using the first-principles method of density functional theory. We build models by placing methane on three different adsorption sites, including the A, B and C sites above the perfect, vacancy and N-doped graphene. The results indicate that the different adsorption sites of methane on the perfect, vacancy and N-doped graphene have little impact on the band structures. The introduction of N atom can possibly make the adsorption of methane on graphene much easier in the case of A adsorption site. The interactions between methane and N-doped graphenes with a vacancy are much stronger than other systems in the case of B and C adsorption sites.

Background The effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines were investigated in Chinese patients with type 2 diabetes mellitus (DM). Methods Ninety-five DM patients were randomly allocated to two groups: 59 to Group A who received antidiabetic treatment that included acarbose 150 mg/day, and 36 to Group B who received similar treatment to Group A but without acarbose. Forty-five healthy volunteers were selected as a control group. Serum concentrations of inflammatory cytokines were determined by ELISA, and the contents of 16S rDNA of gut bacteria were determined by real-time quantitative polymerase chain reaction. General linear analysis for repeated measurements was used to analyze trend differences between the two diabetic groups. Results After 4 weeks of antidiabetic treatment, the gut contents of Bifidobacterium longum and Enterococcus faecalis were significantly increased in both diabetes groups. The increase of Bifidobacterium longum (P = 0.004) and the decrease of lipopolysaccharides (LPS) (P

Proteins have been utilized in numerous photonic and optoelectronic devices, for example, in optical computation, organic light emitting diodes (OLEDs), waveguides, biomicro/nanolasers, organic field effect transistors (OFETs), and memory devices, because their unique optical, mechanical, electrical, and chemical properties are easily tailored to each application. The performance of as-prepared proteinbased photonic devices has been demonstrated to exceed that of devices that are made with currently available organic materials. The underlying motivation for the use of proteins in microdevices is not only abundance, inexpensiveness, and biodegradability, but also biocompatibility and the capacity to tune their properties through appropriate external stimuli. These features are highly desirable for biologically inspired microdevices, for example delicate miniaturized lenses that are similar to the “camera-type” eyes of human beings, the compound eyes of insects, the photosensitive microlens arrays of brittlestars, or the infrared-sensitive microlens receptor arrays of the fire beetle (Melanophila acuminata). Scientists have been highly motivated to fabricate these lens-like micro/nanostructures with the aim of producing small, multifunctional, artificial eyes by using dynamically adjustable and fully biocompatible proteins. However, the preparation of protein microlenses that have controlled geometry and precise positioning still poses a challenge. Herein, we report a promising approach for the production of biomimetic protein microlenses by facile and rapid maskless femtosecond laser direct writing (FsLDW). FsLDW is a well-known method for producing complicated 3D structures with nanometric resolution. Recently, pioneering work from Shear and co-workers demonstrated that protein hydrogel-based microstructures fabricated by FsLDWexhibit a unique responsiveness to chemical signals. This responsiveness could result in rapid and reversible changes in the size and shape of the structures after stimulation by environmental triggers. However, to our knowledge there are few reports on the development of practical and useful devices, such as a tunable microlens, that are made from this class of proteins. In this study, commercial bovine serum albumin (BSA, 300–500 mgmL 1 in aqueous solution) and a photosensitizer (methylene blue, MB, 0.6 mgmL ) were used to fabricate micro/nanoarchitectures. The cross-linking reaction is initiated through the excitation of photosensitive molecules to their triplet states. The photoexcited molecules then react directly with oxidizable moieties (type I process) or transfer the energy to ground state molecular oxygen (type II process) to form a reactive oxygen species, such as singlet oxygen (O2). In either case, excited-state intermediates catalyze the inter or intramolecular covalent cross-linking of oxidizable protein residues (see Scheme S1 in the Supporting Information). In other words, proteins with photooxidizable groups, such as Tyr, Trp, His, Met, and Cys, can absorb infrared or UV light to form reactive or ionized species that are capable of cross-linking with other oxidizable moieties. This mechanism appears to play a role in the formation of some types of cataracts and in the aging of skin. BSA and other proteins with oxidizable side chains “inherit” this photo-cross-linking ability, and can thus be used for multiphoton fabrication (Figure 1). Proof-of-concept protein microlenses were fabricated by using a FsLDW system of our own construction (Figure 1). The system was composed of a femtosecond titanium/ sapphire laser (Spectra Physics 3960-X1BB), a piezo stage with a precision of 1 nm (Physik Instrumente P-622.ZCD), and a set of two galvano mirrors. The 3D shapes of the microstructures were designed by using 3Ds Max and then the designs were converted into computer processing programs. Prior to the photo-cross-linking of the proteins at the focal spot, the beam from the femtosecond laser (80 MHz repetition rate, 120 fs pulse width, 780 nm central wavelength) was tightly focused by a high-numerical-aperture (NA= 1.35) oilimmersion objective lens (60 ). The horizontal and vertical scanning movements of the focused laser spot were achieved simultaneously by the two-galvano-mirror set and the piezo stage. After cross-linking, the sample was rinsed in water several times to remove unreacted proteins. Then the asformed protein microstructures were left on the chip. Surface topography (shape and roughness) plays an important role in the optical properties of protein microoptics. However, the surface roughness of BSA microstruc[*] Y. L. Sun, Prof. Dr. W. F. Dong, R. Z. Yang, X. Meng, L. Zhang, Prof. Dr. Q. D. Chen, Prof. Dr. H. B. Sun State Key Laboratory on Integrated Optoelectronics College of Electronic Science and Engineering Jilin University, 2699 Qianjin Street Changchun 130012 (China) E-mail: dongwf@jlu.edu.cn hbsun@jlu.edu.cn

Interface structure and dynamics properties in an all-polystyrene composite composed of linear chains and one single-chain nanoparticle (SCNP) are investigated by using large-scale molecular dynamics simulations at both coarse-grained and full atomistic level. It is demonstrated that the SCNP adopts a crumpled globular state in composite; it has layered internal structures especially at low temperatures. When temperature decreases, its interior phenyl rings (iPRs) are parallel to each other and scaffold cross-linking bonds undergo a “loose-to-tight” transition, leading to a “soft-to-hard” transition of the SCNP. Such transition provides more interior free volume and therefore results in faster rotational relaxation of inner layer iPRs at low temperature. It also facilitates the infiltration of the matrix monomers, resulting in an enhanced interfacial correlation and therefore a stronger deceleration effect in diffusion of matrix monomers at low temperatures. These results provide new insights into unique structure and dynamics properties at the polymer/SCNP interface region.