Synthesis and Evaluation of a Novel c-Met-Targeting Cyclic Peptide as a Potential Diagnostic Agent for Colorectal Cancer.

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase linked to the proliferation, survival, invasion, and metastasis of several types of cancers, including colorectal cancer (CRC), particularly when aberrantly activated. Our study strategically designs peptides derived from interactions between c-Met and the antibody Onartuzumab. By utilizing a cyclic strategy, we achieved significantly enhanced peptide stability and affinity. Our in vitro assessments confirmed that the cyclic peptide HYNIC-cycOn exhibited a higher affinity (KD = 83.5 nM) and greater specificity compared with its linear counterpart. Through in vivo experiments, [99mTc]Tc-HYNIC-cycOn displayed exceptional tumor-targeting capabilities and minimal absorption in nontumor cells, as confirmed by single-photon emission computed tomography. Notably, the ratios of tumor to muscle and tumor to intestine, 1 h postinjection, were 4.78 ± 0.86 and 3.24 ± 0.47, respectively. Comparable ratios were observed in orthotopic CRC models, recording 4.94 ± 0.32 and 3.88 ± 0.41, respectively. In summary, [99mTc]Tc-HYNIC-cycOn shows substantial promise as a candidate for clinical applications. We show that [99mTc]Tc-HYNIC-cycOn can effectively target and visualize c-Met-expressing tumors in vivo, providing a promising approach for enhancing diagnostic accuracy when detecting c-Met in CRC.

Dynamical deformed Airy beams with arbitrary angles between two wings.

We study both numerically and experimentally the acceleration and propagation dynamics of 2D Airy beams with arbitrary initial angles between their "two wings." Our results show that the acceleration of these generalized 2D Airy beams strongly depends on the initial angles and cannot be simply described by the vector superposition principle (except for the normal case of a 90° angle). However, as a result of the "Hyperbolic umbilic" catastrophe (a two-layer caustic), the main lobes of these 2D Airy beams still propagate along parabolic trajectories even though they become highly deformed. Under such conditions, the peak intensity (leading energy flow) of the 2D Airy beams cannot be confined along the main lobe, in contrast to the normal 90° case. Instead, it is found that there are two parabolic trajectories describing the beam propagation: one for the main lobe, and the other for the peak intensity. Both trajectories can be readily controlled by varying the initial wing angle. Due to their self-healing property, these beams tend to evolve into the well-known 1D or 2D Airy patterns after a certain propagation distance. The theoretical analysis corroborates our experimental observations, and explains clearly why the acceleration of deformed Airy beams increases with the opening of the initial wing angle.

Repurposing GnRH-A as a Near-Infrared Fluorescent Probe for Diagnosis and Surgical Navigation of Breast Cancer Tumors and Metastases.

Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast's appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN-n) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity (Kd of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7's effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.

Generation of linear and nonlinear propagation of three-Airy beams.

We report the first experimental demonstration of the so-called three-Airy beams. Such beams represent a two-dimensional field that is a product (rather than simple superposition) of three Airy beams. Our experiments show that, in contrast to conventional Airy beams, this new family of Airy beams can be realized even without the use of truncation by finite apertures. Furthermore, we study linear and nonlinear propagation of the three-Airy beams in a photorefractive medium. It is found that a three-Airy beam tends to linearly diffract into a super-Gaussian-like beam, while under nonlinear propagation it either turns into three intensity spots with a self-defocusing nonlinearity or evolves into a self-trapped channel with a self-focusing nonlinearity.

Repositioning and steering laser beam power via coherent combination of multiple Airy beams.

We study numerically and experimentally laser coherent combination (LCC) with multiple one- or two-dimensional Airy beams. It is shown that the method of LCC using Airy beams leads to a higher combining efficiency and a better feature of propagation than that using conventional Gaussian beams. Based on such coherent Airy beams combination, we propose a laser steering approach that could achieve large-angle beam steering (over 0.6°) without the need of using any mechanical steering component.

HAT therapy for sepsis: A review of the therapeutic rationale and current clinical evaluation status.

Vitamin C-based cluster therapy, which involves the combined application of hydrocortisone, vitamin C, and thiamine (HAT), is a recently proposed new treatment option for sepsis on top of conventional treatment. This therapy has a strong theoretical basis, but its clinical efficacy remains inconclusive. This review summarizes the rationale for HAT therapy for sepsis and describes the evaluation of its efficacy in clinical observational studies and randomized controlled trials, with the aim of providing a reference for the future clinical practice application of HAT therapy in sepsis.

PDGFRß targeted innovative imaging probe for pancreatic adenocarcinoma detection.

The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, making it one of the most lethal forms of cancer. Early-stage diagnosis and resection of the incipient lesions could increase the 4-year survival rate of PA up to 78%. Platelet-derived growth factor receptor ß (PDGFRß), an oncogenic key regulator for migration, proliferation and angiogenesis of cancer cells, has been proved to be aberrantly expressed in the majority of PA. Herein, by amino acid substitution strategy and surface plasmon resonance (SPR) analysis, we designed a novel PDGFRß-targeting peptide (YQGX-10) with high affinity (Kd = 227.7 nM) and coupled it with a near-infrared fluorescent (NIRF) dye MPA for precisely detection of PA. Great binding affinity and specificity were displayed in a series of in vitro assays. NIRF imaging experiments demonstrated that the synthesized probe could be highly accumulated in xenograft and orthotopic BxPC-3 tumors and provide favorable tumor contrast in the mice, offering a potential novel approach for the early diagnosis of PA. Moreover, YQGX-10 could visualize tumor boundaries and minor lesions in BxPC-3 xenograft mice, shedding a new light on NIRF-guided tumor resection of PA. In addition, we successfully constructed the radioactive probe 99mTc-HYNIC-YQGX-10 for the diagnosis of PA with high specificity and sensitivity. In summary, the probe warrants further exploration for clinical translation in the early diagnosis and NIRF-guided surgery of PA.

Acceleration control of Airy beams with optically induced refractive-index gradient.

We demonstrate both experimentally and theoretically controlled acceleration of one- and two-dimensional Airy beams in optically induced refractive-index potentials. Enhancement as well as reduction of beam acceleration are realized by changing the index gradient, while the beam shape is maintained during propagation through the linear optical potential. Our results of active acceleration manipulation in graded media are pertinent to Airy-type beam propagation in various environments.

Self-trapping of optical vortices at the surface of an induced semi-infinite photonic lattice.

We demonstrate self-trapping of singly-charged vortices at the surface of an optically induced two-dimensional photonic lattice. Under appropriate conditions of self-focusing nonlinearity, a singly-charged vortex beam can self-trap into a stable semi-infinite gap surface vortex soliton through a four-site excitation. However, a single-site excitation leads to a quasi-localized state in the first photonic gap, and our theoretical analysis illustrates that such a bandgap surface vortex soliton is always unstable. Our experimental results of stable and unstable topological surface solitons are corroborated by direct numerical simulations and linear stability analysis.