The mechanical effects of chemical stimuli on neurospheres.

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of the CCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

Crosstalk in monocentric multiscale systems based on an internal stray light stop suppression method.

Monocentric multi-scale (MMS) systems offer the advantages of a high resolution and wide field of view (FOV). These systems can improve the image resolution with a broad FOV by utilizing the stitching of the detectors. In addition to traditional stray light in optical systems, such as ghost reflection, scattering, and diffraction, the crosstalk between relay lenses cannot be ignored as a type of special stray light. Because of the intersection rays between the multiscale relay lenses in MMS systems, the rays enter the adjacent relay lens, which generates rays that do not belong to the corresponding relay lens in the corresponding image plane. Consequently, this crosstalk stray light affects the imaging contrast of the systems. This study aimed to investigate the crosstalk stray light in MMS systems. A simulation model of the MMS system was established. In the object-imaging process, the characteristic rays of a multiscale relay lens are traced using geometrical optics. Factors affecting the crosstalk stray light were studied in detail. The relationships between different parameters and crosstalk stray light were analyzed. A stray light suppression method is proposed based on incorporating a stray light stop in a monocentric (MC) objective to cut the crosstalk stray rays. The simulation results show that the crosstalk stray light can be effectively eliminated with this method, and the image contrast of the MMS systems is greatly improved.

Design methodology for catadioptric zoom panoramic optical systems based on image plane bending matched correction.

Zoom panoramic optical systems incorporate a panoramic peripheral vision zoom imaging function, enabling swift wide-area coarse and localized precise detection. These systems find applicability in examining pipes and other internal structures. This study centers on the catadioptric zoom panoramic optical system and its associated optical design method. A mathematical model of the front mirror was formulated based on the imaging relationship. Subsequently, the bending of the image plane of the front mirror was computed and simplified through curve fitting. The object surface bending of the zoom subsystem was established correspondingly, leveraging the solution for the mirror bending curve matched correction, culminating in deriving the initial structure of the zoom. Integrating the front mirror and zoom subsystems facilitated the comprehensive design realization of the catadioptric zoom panoramic optical system. A catadioptric zoom panoramic optical system was designed to validate the proposed design method. This study introduces a novel, to the best of our knowledge, conceptual approach to crafting catadioptric zoom panoramic optical systems.

An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

A new instrument for interfacial dilational rheology.

We present a new design for an interfacial dilational rheometer that can generate oscillatory dilational strain on a planar air-liquid interface. The strain is generated by a pneumatic mechanism involving a deformable film, which forms a circular barrier that can contract or expand under different pressures. The interfacial stress is measured using a Wilhelmy rod. We carefully examine and demonstrate the effects of potential sources of measurement error, including inertia, drag, buoyancy, flow from the bulk phase, and surface waves. The design avoids mixed deformations present in other instruments and is currently capable of accurate measurements at frequencies up to ∼0.1 Hz and dilational strains below 0.001, with potential for higher frequencies after further theoretical development. We demonstrate the integration of the interfacial dilational rheometer with a Langmuir trough by measuring the compression isotherm of an insoluble surfactant, stearic acid. Furthermore, we verify the capability of the interfacial dilational rheometer to perform frequency and amplitude sweeps and present the storage and loss moduli for a water-soluble surfactant, sodium dodecylbenzenesulfonate, at different concentrations.

Analysis and Suppression of Crosstalk Stray Light in a Microlens Array Scanning and Searching System.

The microlens array (MLA) system can aid in realizing fast beam deflection owing to the lateral displacement between arrays. The MLA system has the advantages of miniaturization and good functionality. However, during system operation, crosstalk beams are generated between each microlens array unit, introducing additional stray light, thus affecting the imaging contrast of the system. Therefore, this study uses the matrix operation method to trace the paraxial ray to trace the optical system and analyzes the generation mechanism of crosstalk stray light in the MLA system. Furthermore, this study proposes a crosstalk suppression method based on a stop array to reasonably suppress stray light. Finally, an example of an infrared array scanning infrared optical system is considered so as to verify the correctness and feasibility of the proposed crosstalk stray light suppression method. Therefore, this paper introduces the stray light suppression principle to guide the optical design process of the system, providing a theoretical basis for the design and analysis of the microlens array scanning and search system.

Panoramic annular image restoration algorithm by prediction based on the lens design characteristics.

A panoramic annular lens optical system is important in circumferential detection. However, a panoramic annular image (PAI) has severe tangential and radial distortion. This study proposes a 3σ guideline-based method, which determines the unwrapping center point of the PAI, and a prediction method based on the lens design characteristics according to the intrinsic distortion of the PAL to correct, respectively, the tangential distortion and the radial distortion. The proposed methods can ensure the restoration ability and simplify the dependence on experimental conditions. The experimental results confirm the effectiveness of the proposed method, thus enabling future panoramic optical image detection.

Analysis and design of a microlens array scanning system based on spherical aberration.

The microlens array (MLA) scanning system is a relatively new solution for beam scanning. The excrescent light generated by overlapping divergent beams from adjacent microlenses increases with the scanning angle, and as a result, the rays do not fill the clear aperture of the MLA. The effect on the detection distance and imaging resolution of the MLA system are analyzed. Based on the principle of minimum spherical aberration, a design method for initial configuration of the MLA system is proposed. The findings of this paper can be beneficial for the design and evaluation of MLA systems.

Manipulate tumor hypoxia for improved photodynamic therapy using nanomaterials.

Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O2 by a photosensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.

Game-Theoretic Frameworks for Epidemic Spreading and Human Decision-Making: A Review.

This review presents and reviews various solved and open problems in developing, analyzing, and mitigating epidemic spreading processes under human decision-making. We provide a review of a range of epidemic models and explain the pros and cons of different epidemic models. We exhibit the art of coupling between epidemic models and decision models in the existing literature. More specifically, we provide answers to fundamental questions in human decision-making amid epidemics, including what interventions to take to combat the disease, who are decision-makers, and when and how to take interventions, and how to make interventions. Among many decision models, game-theoretic models have become increasingly crucial in modeling human responses or behavior amid epidemics in the last decade. In this review, we motivate the game-theoretic approach to human decision-making amid epidemics. This review provides an overview of the existing literature by developing a multi-dimensional taxonomy, which categorizes existing literature based on multiple dimensions, including (1) types of games, such as differential games, stochastic games, evolutionary games, and static games; (2) types of interventions, such as social distancing, vaccination, quarantine, and taking antidotes; (3) the types of decision-makers, such as individuals, adversaries, and central authorities at different hierarchical levels. A fine-grained dynamic game framework is proposed to capture the essence of game-theoretic decision-making amid epidemics. We showcase three representative frameworks with unique ways of integrating game-theoretic decision-making into the epidemic models from a vast body of literature. Each of the three frameworks has their unique way of modeling and analyzing and develops results from different angles. In the end, we identify several main open problems and research gaps left to be addressed and filled.

Anti-tumor effects of an ID antagonist with no observed acquired resistance.

ID proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. ID proteins inhibit basic-HLH transcription factors often blocking differentiation and sustaining proliferation. A small-molecule, AGX51, targets ID proteins for degradation and impairs ocular neovascularization in mouse models. Here we show that AGX51 treatment of cancer cell lines impairs cell growth and viability that results from an increase in reactive oxygen species (ROS) production upon ID degradation. In mouse models, AGX51 treatment suppresses breast cancer colonization in the lung, regresses the growth of paclitaxel-resistant breast tumors when combined with paclitaxel and reduces tumor burden in sporadic colorectal neoplasia. Furthermore, in cells and mice, we fail to observe acquired resistance to AGX51 likely the result of the inability to mutate the binding pocket without loss of ID function and efficient degradation of the ID proteins. Thus, AGX51 is a first-in-class compound that antagonizes ID proteins, shows strong anti-tumor effects and may be further developed for the management of multiple cancers.

Histoplasmosis in an off-trail Hiker receiving ustekinumab: Implications for Preventive and diagnostic strategies for patients receiving anti-IL-12/23 therapy.

Ustekinumab, an IL-12/23 inhibitor, is an important agent in treatment of inflammatory bowel disease and psoriasis. Clinical trials have not demonstrated significantly increased infection risk with ustekinumab. We report a case of disseminated histoplasmosis in the setting of ustekinumab and methotrexate following a hike in the Catskill Mountains, a region not commonly associated with Histoplasma encapsulatum. To our knowledge, this is the first reported case of newly acquired histoplasmosis complicating treatment with ustekinumab.

Astigmatism analysis and correction method introduced by an inclined plate in a convergent optical path.

A plate beam splitter can simultaneously increase the transmittances and reflectances of different split spectrum segments. The splitter has been widely used in optical systems. However, when a beam passes through a beam splitter in a convergent optical path, the image quality may be degraded severely because the tilted plate may introduce aberrations such as astigmatism at the on-axis point. The formula for calculating this astigmatism is established. The calculated results are consistent with the simulated results, and the validity of the formula is verified through experiments. A cylindrical lens curvature calculation formula is derived to correct the on-axis astigmatism, which reduces the aberrations introduced by the tilted plate and improves the imaging performance. The imaging characteristics of the off-axis field of view and the reasons for the changes in image quality are analyzed. The F-number range of the converging light path is calculated, which provides a reference for tilted applications of flat-panel optical elements in converging light paths.

Analysis and calculation of the fill factor for microlens array scanning systems.

Microlens array (MLA) scanning systems are used in numerous applications, such as laser radar and optical communications. Excrescent light generated by overlapping divergent beams from adjacent microlenses increases with scanning angle, thereby reducing the relative aperture and affecting the MLA system resolution. The fill factor is hence proposed to characterize the relative aperture, and its effects on the modulation transfer function are analyzed. The fill factor is calculated from matrix optics paraxial ray tracing using the system parameters. The simulated results of the MLA system and theoretical calculations are in good agreement. This work can benefit the design and evaluation of MLA systems.

Design and analysis of inner focus for a large spectral bandwidth optical system.

In this paper, we present a method of solving the chromatic aberration problem of large spectral bandwidth optical systems encountered during the internal focusing process. Rational selection of the focal length of each lens group and the distance between them retained the achromatic characteristic of the optical system when the inner focus lens group was mobilized. The proposed design was experimentally validated. This paper can be useful to research on internal focusing in wide-band systems.

Modeling and analysis of a monocentric multi-scale optical system.

A monocentric lens combined with a multi-scale form can achieve a large field of view while maintaining the resolution. This report describes an analytical model that is suitable for both Galilean- and Keplerian-type monocentric multi-scale (MMS) systems; this model also analyzes the correlation between the two types of systems. Moreover, the off-axis aberration associated with the analytical model was derived, on this basis, the Galilean- and Keplerian-type MMS systems were compared. It was concluded that the Galilean-type MMS system performs better with respect to aberration performance. This report provides a useful reference for further applications and developments of MC systems.

Development of a cardiac-and-piezoelectric hybrid system for application in drug screening.

In this paper, a cardiac-and-piezoelectric hybrid system is developed for drug screening. The core structure is a polyvinylidene-fluoride piezoelectric membrane that serves as a flexible structure to interact with hiPSC cardiomyocytes and that measures the contraction profile of cardiomyocytes. This design enables the capability of electrically monitoring cardiomyocytes without the aid of an optical system. To guide cardiomyocytes aligning on this circular piezoelectric membrane, concentric rings of polydimethylsiloxane microgrooves are bonded to its surface. Experimental results demonstrate that seeded cardiomyocytes can align and elongate along the circular microgrooves to form a concentric pattern. To promote cardiomyocyte maturation, bipolar stimulation is conducted using a pin and a ring electrode made of a 304 stainless steel sheet. Furthermore, to maintain body temperature and minimize environmental noise, a 304 stainless steel box is constructed to enclose the cardiac-and-piezoelectric hybrid platform. It serves as an incubator and is electrically grounded for electromagnetic interference shielding. Using this system, continuous and repeated contractions of cardiomyocytes can be developed and monitored electrically. The system performance is verified using two commercial drugs: isoproterenol and metoprolol. It is experimentally demonstrated that this system can monitor the dosage effect of both drugs. Our results also show that the measured EC50 and IC50 values of contraction frequency and amplitude are in the same range. These findings suggest that both drugs can influence the beat frequency and contraction force simultaneously. In summary, taking advantage of the electro-mechanical coupling effect of the piezoelectric membrane, this system could be scaled up to perform automatic and parallel screenings for drug discoveries.

L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer.

Metastasis-initiating cells with stem-like properties drive cancer lethality, yet their origins and relationship to primary-tumor-initiating stem cells are not known. We show that L1CAM+ cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and we define their relationship to tissue regeneration. L1CAM is not expressed in the homeostatic intestinal epithelium, but is induced and required for epithelial regeneration following colitis and in CRC organoid growth. By using human tissues and mouse models, we show that L1CAM is dispensable for adenoma initiation but required for orthotopic carcinoma propagation, liver metastatic colonization and chemoresistance. L1CAMhigh cells partially overlap with LGR5high stem-like cells in human CRC organoids. Disruption of intercellular epithelial contacts causes E-cadherin-REST transcriptional derepression of L1CAM, switching chemoresistant CRC progenitors from an L1CAMlow to an L1CAMhigh state. Thus, L1CAM dependency emerges in regenerative intestinal cells when epithelial integrity is lost, a phenotype of wound healing deployed in metastasis-initiating cells.

Publisher Correction: TGF-ß orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.