Gigahertz-rate-switchable wavefront shaping through integration of metasurfaces with photonic integrated circuit

Achieving spatiotemporal control of light at high-speeds presents immense possibilities for various applications in communication, computation, metrology, and sensing. The integration of subwavelength metasurfaces and optical waveguides offers a promising approach to manipulate light across multiple degrees of freedom at high-speed in compact photonic integrated circuit (PICs) devices. Here, we demonstrate a gigahertz-rate-switchable wavefront shaping by integrating metasurface, lithium niobite on insulator (LNOI) photonic waveguide and electrodes within a PIC device. As proofs of concept, we showcase the generation of a focus beam with reconfigurable arbitrary polarizations, switchable focusing with lateral focal positions and focal length, orbital angular momentum light beams (OAMs) as well as Bessel beams. Our measurements indicate modulation speeds of up to gigahertz rate. This integrated platform offers a versatile and efficient means of controlling light field at high-speed within a compact system, paving the way for potential applications in optical communication, computation, sensing, and imaging

A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl4-induced injury in rats compared to rhKGF-1

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Effects of Bacterial Motility on Dynamic Succession of Biofilms and Settlement of the Mussel Mytilus coruscus

To study the regulatory role of marine bacterial motility on biofilm formation and settlement of marine bivalves, this study used the economically important marine mussel Mytilus coruscus as the research target, and investigated the wild-type strain and ΔcheW strain of Pseudoalteromonas marina. These bacteria have different motility; thus, the motility analysis of these strains was carried out at various time points, and the differences in the biofilm thickness and composition and bacterial density were also analyzed at different time points. Finally, their effects on dynamic biofilm succession and settlement of M. coruscus were evaluated. This study found that the motility of the wild-type strain and the ΔcheW strain at 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h was significantly different (P < 0.05). It was found that both bacterial circle radii increased with time and reached their maximum at 96 h. Overall, the wild-type strain formed a larger bacterial circle than the ΔcheW strain. The two strains' bacterial density and biofilm thickness increased with time and reached their maximum at 48 h, begging to spread after 72 h. At all time points, the mussel settlement rates on the wild-type strain biofilm were higher than on the ΔcheW biofilm. Initially, the mussel settlement rates increased, but after 72 h a decreasing tendency was observed, reaching the highest value at 48 h. These settlement results were consistent with the changes in the biofilm composition under different time points. Therefore, this study concluded that bacterial motility affects biofilm formation, mainly biofilms thickness, bacterial density, and extracellular compounds during the dynamic succession of biofilms, thereby regulating the settlement of the mussel M. coruscus. This study provides novel insights into the interaction between bacterial motility, biofilm formation, and the settlement of M. coruscus, which may help optimize the production and breeding of economically important marine animals

AMPK Promotes Larval Metamorphosis of Mytilus coruscus

Metamorphosis is a critical process in the transition from planktonic life to benthic life for marine invertebrates, which is accompanied by a large amount of energy consumption. Previous studies have proved that AMP-activated protein kinase (AMPK), as a vital energy regulator, plays a prominent role in mediating the growth and development of terrestrial animals. However, its function in the growth and development of marine invertebrates, especially in metamorphosis, remains elusive. This study explored the function of AMPK in the larval metamorphosis of Mytilus coruscus. The full-length cDNA of AMPK genes in M. coruscus was cloned and characterized, which is composed of three subunits, McAMPK&alpha;, McAMPK&beta;, and McAMPK&gamma;. Pharmacological tests demonstrated that through the application of an AMPK activator, AMP substantially enhanced the larval metamorphosis rate (p &lt; 0.05). By contrast, the larval metamorphosis rate decreased significantly after being treated with the AMPK inhibitor Compound C (p &lt; 0.05). McAMPK gene knock-down resulted in a reduction in McAMPK gene expression (p &lt; 0.05), and the larval metamorphosis of M. coruscus was significantly restrained (p &lt; 0.05). These results indicated that AMPK signaling is vital in the larval metamorphosis of M. coruscus, which advances further understanding in exploring the molecular mechanisms in the metamorphosis of marine invertebrate larvae

The effect of rhKGF-1 PEGylation on MAP kinase activation.

<p>Panel A. NIH 3T3 fibroblasts were stimulated with rhKGF-1 or PEGylated rhKGF-1 at three does 1.5 µM, 3 µM, and 6 µM, and phosphorylation courses of ERK1/2 (p-ERK) were measured by immunoblotting alongside total ERK as loading controls. The blots shown are representative of three independent experiments; Panel B. Semi-quantitative analysis of the protein bands in Panel A. *, p<0.05 <i>vs</i> Normal control; ^#, p<0.05 <i>vs</i> the corresponding non-PEGylated rhKGF-1 group.</p

Validation of the solid-phase PEGylated rhKGF-1.

<p>Panel A, MALDI-TOF mass spectrometry of PEGylated rhKGF-1 showing the molecular mass of PEGylated rhKGF-1 (36997 Da). Panel B, MALDI-TOF mass spectrometry of non-PEGylated rhKGF-1 showing the molecular mass of non-PEGylated rhKGF-1 (16297 Da). Panel C, D. N-terminal sequencing of non-PEGylated and PEGylated rhKGF-1 by Edman degradation method.</p

Effect of solid-phase PEGylated rhKGF-1 on serum AST and ALT levels in rats intoxicated with CCl₄.

<p>48 male SD rats were randomly divided into four groups (12 rats/group): enalpril interventional group A (rhKGF-1-pretreated groups), enalpril interventional group B (PEGylated rhKGF-1-pretreated groups), injury-model group and healthy control group. The test groups were pretreated with non-PEGylated and PEGylated rhKGF-1 24 hours prior to 2.5 mL/kg CCl₄ administration. Four hours after the intraperitoneal injection of CCl₄, rats were killed and their serum AST/ALT levels were determined. *, p<0.05 <i>vs</i> control group; ^#, p<0.05 <i>vs</i> injury-model group; ^ss, p<0.05 between indicated groups.</p

Pharmacokinetics study of solid-phase PEGylated rhKGF-1 in rats.

<p>Panel A. Normal male SD rats were injected intravenously with 100 µg/kg rhKGF-1 (open circle), and PEGylated rhKGF-1 (solid circle). Blood samples were collected at the indicated time points. The amount of rhKGF-1 was measured by Human KGF-basic Mini ELISA Development Kit. A standard curve was made for each rhKGF-1, n = 6. Values are the mean±SD. Panel B. Comparison of half-life of non-PEGylated rhKGF-1 and PEGylated rhKGF-1. *, p<0.01 <i>vs</i> the corresponding non-PEGylated rhKGF-1 group.</p