The unique properties of tear film breakup process in patients with nasal unilateral pterygium.

SIGNIFICANCE: This study found that the unique properties of tear film breakup process in eyes with pterygium, combined with ocular surface parameters, further revealed specific dynamic mechanism. It suggested that the thickness of pterygium was especially valuable in deciding the necessity of surgical management. PURPOSE: This study aimed to explore the dynamic mechanism of tear film instability in eyes with pterygium. METHODS: A paired-eye controlled cross-sectional study was conducted. Seventy-eight patients with nasal pterygium were enrolled. Fluorescein tear film breakup was observed. Several key parameters related to tear film quality were defined and analyzed, including total breakup area (mathematically derived from pixel size using MATLAB), breakup velocity, fluorescein breakup time, breakup location and pattern, tear meniscus height, score of fluorescein corneal staining, and meiboscore. RESULTS: With comparable tear meniscus height, score of fluorescein corneal staining, and meiboscore between paired eyes (p > 0.05), eyes with pterygium had shorter breakup time, larger breakup area, and faster breakup velocity (p < 0.05). In eyes with pterygium, a positive correlation between meiboscore and pterygium parameters including length, thickness, and size was observed (p > 0.001). As the thickness increased, difference of breakup time and area between paired eyes increased (p = 0.02 and 0.046). Eyes with pterygium had more fixed inferonasal breakup location and often presented as dimple break (60%), whereas random break was the most common in contralateral normal eyes (62%). A unique breakup pattern named pterygium-induced local dimple break was found. It displayed as an irregular but vertical line-like shape appearing after lipid layer spreading, which was adjacent to the lower margin of pterygium and presented with unique properties including inferonasal breakup location, local breakup area, shorten breakup time, and faster breakup velocity. CONCLUSIONS: Eyes with pterygium showed a unique tear film breakup process and novel breakup pattern named pterygium-induced local dimple break . Dynamic mechanism played a significant role in tear film instability of eyes with pterygium rather than aqueous deficiency and increased evaporation.

Nanomechanical-based classification of prostate tumor using atomic force microscopy.

BACKGROUND: The loss of mechanical homeostasis between tumor cells and microenvironment is an important factor in tumor metastasis. In the process, mechanical forces affect cell proliferation, differentiation, migration and tissue development. AIMS: Using high spatial resolution of Atomic force microscopy (AFM) technology, our study provides the direct measurement of the nanomechanical properties of prostate cancer clinical tissue specimens. MATERIALS AND METHODS: AFM was used to determine the biomechanical properties of prostate tissue with different grade scores. K-means clustering method and fuzzy C-means were used to distinguish the cellular component in prostate tissue from non-cellular component based on their viscoelasticity. Futhermore, AFM measurements in vitro cells, including metastatic prostate cells (PC-3) and normal human prostate cells (PZ-HPV-7) were carried out. RESULTS: The Young's modulus was decreased in prostate cancer progression, and the elasticity of cellular component in prostate cancer tissue was smaller than that of normal prostate tissue. PC-3 cells were softer than PZ-HPV-7 cells. Further mechanism investigation showed that the difference in modulus between cancerous and normal prostate tissue may be associated with a greater actin cytoskeleton distribution inside the cancer cells. CONCLUSION: The results suggests that the nanomechanical properties can classify the prostate tumor, which could be used as an index for the identification and classification of cancer at cellular level.

Action Sites and Clinical Application of HIF-1α Inhibitors.

Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the physiological and pathological processes of the body, so it is a focus of biomedical research. In recent years, various types of HIF-1α inhibitors have been designed and synthesized and are expected to become a new class of drugs for the treatment of diseases such as tumors, leukemia, diabetes, and ischemic diseases. This article mainly reviews the structure and functional regulation of HIF-1α, the modes of action of HIF-1α inhibitors, and the application of HIF-1α inhibitors during the treatment of diseases.

Time-course of the visual Impact on presbyopes of a low dose miotic.

PURPOSE: To examine the pupil and visual impact of a single early morning drop of a low concentration miotic. METHODS: Pupil size, refraction, visual acuity (VA), near reading performance and intraocular pressure were monitored for 8 h at a wide range of light levels following bilateral instillation of single drops of 0.1% brimonidine tartate in 19 early presbyopes (40-50 years) and 11 mature presbyopes (>50 years). RESULTS: Pupil miosis did not alter distance VA or refraction. Significant pupil miosis peaked at 1-2 h after dosing, which expanded the depth of focus of mature presbyopes with the mean improvement in near logMAR VA of -0.15, -0.07 and -0.03, at 20, 200 and 2000 lux, respectively. One hour after instillation, near reading speed improved by 21, 24 and 5 words per min for text size commonly seen in US newspaper and cellphone text messages, 18, 21 and 19 words per min for text size of grocery labels and 12, 13 and 30 words per min for text size of over-the-counter medications at light levels of 20, 200 and 2000 lux, respectively. No such improvements in near VA and near reading speed were observed in the young presbyopes having some residual accommodation. Most of the pupil miosis remained 8 h after instillation, whereas near VA improvements disappeared after 4 h. CONCLUSION: Low dose miotics can enhance near vision in presbyopic subjects while retaining high quality distance vision over a wide range of light levels. Significant improvements in near vision were observed only during the 1-2 h period after dosing when miosis peaked.

Ricco's law and absolute threshold for foveal detection of black holes.

Visual detection of small black objects surrounded by a light background depends on background luminance, pupil size, optical blur, and object size. Holding pupil and optics fixed, we measured the minimum background luminance needed for foveal detection of small black targets as a function of target size. For all three observers, absolute threshold varied inversely with target area when disk diameter subtended less than 10' of visual angle. For target diameter ≥10', threshold remained constant at about 0.3 Td, which was also the absolute threshold for detecting light spots 10' or larger in diameter on a black background. These results are consistent with Ricco's law of spatial summation: a "black hole" is just detectable when the background luminance is sufficiently high for its absence inside the Ricco area to reduce 555 nm photon flux by 7500 photons/s, which is the same change needed to detect light spots on a black surround. These results can be accounted for by a differential pair of Ricco detectors, each about the size of the receptive field center of magocellular retinal ganglion cells when projected into object space through the eye's weakly aberrated optical system. Statistical analysis of the model suggests the quantum fluctuations due to internal, biological noise (i.e., "scotons") are a greater handicap than the photon fluctuations inherent in the light stimulus at absolute foveal threshold.

Psychophysical study of the optical origin of starbursts.

Starbursts seen around small bright lights at night have been attributed to optical scatter, diffraction, or aberrations. We manipulated pupil aperture and aberrations to investigate the entopic appearance of perceived starbursts. The impact of circular, annular, and wedge-shaped pupil apertures, and spherical aberration sign and magnitude were used to identify pupil sub-apertures responsible for each radial perceived starburst line. Local intensity distributions within the starbursts mapped onto unique sub-regions of the pupil of both phakic and pseudophakic eyes, consistent with the hypothesis that ocular aberrations are the cause of starbursts. In paraxially focused eyes, the size of starbursts is predicted by the amount of spherical aberration, and starburst orientation is either the same or 180 deg rotated from the pupil region that creates each starburst line. No starbursts are seen when the pupil diameter is smaller than 3 mm. Replacing the eye's natural lens with a radially symmetric and optically homogeneous intraocular lens reduced the observed number of starbursts by 50%. Geometrical optics modeling including the measured aberrations of an individual eye can reveal point spread function structure that captures some of the key elements of the entopic perceptions.

Small Text on Product Labels Poses a Special Challenge for Emerging Presbyopes.

SIGNIFICANCE: Approximately 10% of the lowercase text on nonprescription drug labels is smaller than the 1 mm required by the Food and Drug Administration. The small size, combined with the progressive decline in accommodative amplitude and gain, poses a reading challenge for middle-aged emerging presbyopes. PURPOSE: The purpose of this study was to evaluate the impact of progressing presbyopia and near adds on the ability of middle-aged patients to read small text routinely encountered on product labels. METHODS: Geometrical optics was used to determine the impact of changing viewing distance, accommodation, and pupil size on retinal blur size. We photographed 261 consumer product labels in grocery, personal care, and nonprescription (over-the-counter) drug categories and used character recognition software to identify and size 255,298 printed letters. We computed the impact of viewing distance on the ratio of blur to letter detail and used published blur ratios of ≤4 and ≤2 to identify the conditions that allowed for letter recognition and proficient reading, respectively. RESULTS: Median/mode lowercase letter heights (in millimeters) were 1.39/1.16, 1.29/1.15, and 1.18/1.01, respectively, for groceries, personal care, and over-the-counter drug categories. Despite the increased angular subtense of approaching letters, blur ratios generally increased with reduced viewing distance because of increased defocus. Increased viewing distance decreased blur, but small (e.g., 1 mm) letters became too small to read proficiently (angular size <10 arcminutes) for distances beyond 37 cm. With larger pupils, blur ratios were too large to support proficient reading when accommodative amplitude dropped to ≤3 diopters. An add power sufficient to bring the far point closer than 37 cm was required to proficiently read small text. CONCLUSIONS: Product labels, especially nonprescription drug packages, typically use fonts that are too small to be read proficiently by unaided emmetropes with emerging presbyopia. This problem can be ameliorated by correction of presbyopia at an earlier age and with higher add powers.

Reducing starbursts in highly aberrated eyes with pupil miosis.

PURPOSE: To test the hypothesis that marginal ray deviations determine perceived starburst sizes, and to explore different strategies for decreasing starburst size in highly aberrated eyes. METHODS: Perceived size of starburst images and visual acuities were measured psychophysically for eyes with varying levels of spherical aberration, pupil sizes, and defocus. Computationally, we use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-LASIK eyes to quantify the image quality (the visually weighted Strehl ratio derived from the optical transfer function, VSOTF) with different pupil sizes at both photopic and mesopic light levels. RESULTS: For distance corrected post-LASIK and keratoconic eyes with a night-time pupil (e.g., 7 mm), the starburst diameter is about 1.5 degrees (1 degree for normal presbyopic eyes), which can be reduced to ≤0.25 degrees with pupil sizes ≤3 mm. Starburst size is predicted from the magnitude of the longitudinal spherical aberration. Refracting the eye to focus the pupil margin also removed starbursts, but, unlike small pupils, significantly degraded visual acuity. Reducing pupil diameter to 3 mm improved image quality for these highly aberrated eyes by about 2.7 ×  to 1.7 ×  relative to the natural pupils when light levels were varied from 0.1 to 1000 cd m-2 , respectively. CONCLUSION: Subjects with highly aberrated eyes observed larger starbursts around bright lights at night predictable by the deviated marginal rays. These were effectively attenuated by reducing pupil diameters to ≤3 mm, which did not cause a drop in visual acuity or modelled image quality even at mesopic light levels.

Interaction of aberrations, diffraction, and quantal fluctuations determine the impact of pupil size on visual quality.

Our purpose is to develop a computational approach that jointly assesses the impact of stimulus luminance and pupil size on visual quality. We compared traditional optical measures of image quality and those that incorporate the impact of retinal illuminance dependent neural contrast sensitivity. Visually weighted image quality was calculated for a presbyopic model eye with representative levels of chromatic and monochromatic aberrations as pupil diameter was varied from 7 to 1 mm, stimulus luminance varied from 2000 to 0.1 cd/m2, and defocus varied from 0 to -2 diopters. The model included the effects of quantal fluctuations on neural contrast sensitivity. We tested the model's predictions for five cycles per degree gratings by measuring contrast sensitivity at 5 cyc/deg. Unlike the traditional Strehl ratio and the visually weighted area under the modulation transfer function, the visual Strehl ratio derived from the optical transfer function was able to capture the combined impact of optics and quantal noise on visual quality. In a well-focused eye, provided retinal illuminance is held constant as pupil size varies, visual image quality scales approximately as the square root of illuminance because of quantum fluctuations, but optimum pupil size is essentially independent of retinal illuminance and quantum fluctuations. Conversely, when stimulus luminance is held constant (and therefore illuminance varies with pupil size), optimum pupil size increases as luminance decreases, thereby compensating partially for increased quantum fluctuations. However, in the presence of -1 and -2 diopters of defocus and at high photopic levels where Weber's law operates, optical aberrations and diffraction dominate image quality and pupil optimization. Similar behavior was observed in human observers viewing sinusoidal gratings. Optimum pupil size increases as stimulus luminance drops for the well-focused eye, and the benefits of small pupils for improving defocused image quality remain throughout the photopic and mesopic ranges. However, restricting pupils to <2 mm will cause significant reductions in the best focus vision at low photopic and mesopic luminances.

Liquid Crystal Spatial Light Modulators for Simulating Zonal Multifocal Lenses.

SIGNIFICANCE: To maximize efficiency of the normally lengthy and costly multizone lens design and testing process, it is advantageous to evaluate the potential efficacy of a design as thoroughly as possible prior to lens fabrication and on-eye testing. The current work describes an ex vivo approach of optical design testing. PURPOSE: The aim of this study was to describe a system capable of examining the optical characteristics of multizone bifocal and multifocal optics by subaperture stitching using liquid crystal technologies. METHODS: A liquid crystal spatial light modulator (SLM) was incorporated in each of two channels to generate complementary subapertures by amplitude modulation. Additional trial lenses and phase plates were placed in pupil conjugate planes of either channel to integrate the desired bifocal and multifocal optics once the two optical paths were recombined. A high-resolution Shack-Hartmann aberrometer was integrated to measure the optics of the dual-channel system. Power and wavefront error maps as well as point spread functions were measured and computed for each of three multizone multifocal designs. RESULTS: High transmission modulation was achieved by introducing half-wavelength optical path differences to create two- and five-zone bifocal apertures. Dual-channel stitching revealed classic annular rings in the point spread functions generated from two-zone designs when the outer annular optic was defocused. However, low efficiency of the SLM prevented us from simultaneously measuring the eye + simulator aberrations, and the higher-order diffraction patterns generated by the cellular structure of the liquid crystal arrays limited the visual field to ±0.45 degrees. CONCLUSIONS: The system successfully simulated bifocal and multifocal simultaneous lenses allowing for future evaluation of both objective and subjective evaluation of complex optical designs. However, low efficiency and diffraction phenomena of the SLM limit the utility of this technology for simulating multizone and multifocal optics.

Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes.

PURPOSE: To quantify the optimum pupil diameters for presbyopic eyes when environmental light levels vary from high photopic to low mesopic. METHODS: We computed the white light visual Strehl ratio from the polychromatic optical transfer function (VSOTF). The impact on image quality of retinal illuminance and the accompanying changes in photon noise were reflected in changing neural contrast sensitivity. VSOTF was calculated for focused and -2D defocused images, over a wide range of photopic and mesopic target luminances, and for pupil diameters ranging from 1 to 7 mm. We compare these modeling data to logMAR visual acuity measured under the same conditions. RESULTS: Optimum pupil depends on the relative gain of optical factors (diffraction and aberrations) and neural thresholds (photon noise effect). When light levels are reduced from 1000 to 2 cd/m, the pupil size that optimizes VSOTF for a well-focused presbyopic eye model also maximizes visual acuity and it increases from 2.5 to 4 mm. A 1-mm-diameter pupil maximizes VSOTF at all light levels when -2D of defocus are included, but at 2 cd/m the optimum pupil diameter for acuity increases slightly to 1.4 mm. At 0.2 cd/m, the pupil size that optimizes VSOTF remains 4 and 1 mm for a focused and -2D defocused eye, respectively, but significantly larger pupils are needed for maximal visual acuity. Reducing pupils to 30% of their natural size is beneficial for distance and near image quality and visual acuity at all light levels, producing more gains for near than for distance. CONCLUSIONS: A fixed 2- to 3-mm small pupil or a 30% pupil miosis can both produce near visual acuity gains without significant losses to distance acuity or image quality, and therefore can be considered as optimal for a presbyope experiencing a wide range of light levels.

Can Down-gaze During Near Work Cause Peripheral Deprivation in Asian Eyes?

PURPOSE: We hypothesize that the typically narrower palpebral apertures of East Asian eyes in combination with the narrowing of this aperture during down-gaze combine to reduce light levels and image contrast in the inferior retina during near work, thus creating peripheral deprivation in these eyes that could generate deprivation myopia in children culturally encouraged to perform near work. METHODS: We photographed the right eyes of 53 Chinese children during down-gaze (from 10 to 40 degrees) from the fixation point and the primary gaze position. From these images, we determined the size and shape of the effective foveal and superior field entrance pupil at different down-gaze angles. By using an eye model with typical levels of off-axis higher-order aberrations, we quantified the impact of eyelid and eyelash vignetting of the pupil on both retinal illuminance and image quality using Visual Strehl Ratio (VSOTF), and the non-visually weighted Strehl Ratio (SROTF). RESULTS: The effective aperture for the superior visual field is vignetted during down-gaze by lids and lashes, producing reductions in retinal illuminance of 30% and >60% at 20 and 40 degrees, respectively. However, the aperture vignetting effect on peripheral image modulation is small, with neural and aberration changes dominating image quality in the superior field during down-gaze. CONCLUSIONS: Occlusion of the pupil by eyelid and eyelashes during down-gaze is unlikely to produce significant superior field deprivation in East Asian eyes.

IURead: a new computer-based reading test.

PURPOSE: To develop a computer-based single sentence reading test especially designed for clinical research enabling multiple repeat trials without reusing the same sentences. METHODS: We initially developed 422 sentences, with an average of 60 characters and 12 words. Presentation controls were improved by employing computer-based testing and the oral reading was recorded by visual inspection of digital audio recordings. Variability in reading speed of normally sighted adults between sentences, between charts, between subjects, between formats, and between display devices was quantified. The impact of display size and pixel resolution on test geometry was assessed, and the impact of reduced retinal image quality and retinal illuminance were compared for reading and standard letter acuities. Eleven visually normal subjects (age: 18-60 years) participated in this study. RESULTS: Stopwatch timing of sentences reliably underestimated reading times by about 0.3 s, and exhibited coefficients of repeatability 17 times larger than those estimated from visual inspection of digital recordings. A slight relaxing of the lexical content constraints had no effect on reading speed; neither did sentence format (single vs three lines) or display size or distance. Within subject standard deviations of reading speed for different sentences were small (between 6% and 9% of the mean speed) requiring only small samples sizes to achieve typical statistical reliability and power when comparing conditions within individual subjects. The greater variability associated with stopwatch timing necessitates larger sample sizes. As defocus and light level were varied, reading acuity and standard letter acuity were highly correlated (r(2)  = 0.99), and reading acuity was slightly better. DISCUSSION: A computer-based IURead reading test provides a useful reading speed and reading acuity tool for clinical research involving multiple conditions and repeat testing of individual subjects. Ready to use IURead files for use with a computer, tablet or cell phone can be downloaded from our lab website (https://www.opt.indiana.edu/Bradley/Downloads.aspx).

Modelling the effects of secondary spherical aberration on refractive error, image quality and depth of focus.

PURPOSE: To examine the role of Zernike secondary spherical aberration and its component terms on refraction, image quality and depth of focus. METHODS: Computational methods were used to define wavefronts with controlled levels of r(6) , r(4) and r(2) terms, and image quality associated with these terms for a range of target vergences. Target vergences that generated maximum image quality were used as an objective measures of refractive error. RESULTS: Unlike primary Zernike spherical aberration, which generates peak image quality with a near paraxial focus, in the absence of other higher order aberrations, peak image quality with secondary spherical aberration is achieved with a near marginal focus. When alone, positive primary and secondary spherical aberration induce small hyperopic shifts in refraction, but in the presence of other higher order aberrations, secondary spherical aberration can induce significant myopic shifts in refractive error, as predicted by the combined lower order r(4) & r(2) component of Z60. The predicted expansion in depth of focus associated with increased primary or secondary spherical aberration is mostly absent if a strict image quality criterion is applied. The expansion of depth of focus observed with a low image quality criterion when opposite sign Z40 and Z60 are combined is primarily due to the elevated r(4) term. CONCLUSIONS: Secondary Zernike spherical aberration can have a significant impact on refractive error, image quality and depth of focus, but mostly due to the lower order components within this polynomial. Our analysis shows that the r(6) term that defines secondary spherical aberration actually narrows rather than expands depth of focus, when in the presence of the r(4) term within Z60. Therefore, a multifocal lens generated with exclusively primary spherical aberration is likely to be more effective than one that includes opposite sign of primary and secondary spherical aberration.

Impact of contact lens zone geometry and ocular optics on bifocal retinal image quality.

PURPOSE: To examine the separate and combined influences of zone geometry, pupil size, diffraction, apodisation and spherical aberration on the optical performance of concentric zonal bifocals. METHODS: Zonal bifocal pupil functions representing eye + ophthalmic correction were defined by interleaving wavefronts from separate optical zones of the bifocal. A two-zone design (a central circular inner zone surrounded by an annular outer-zone which is bounded by the pupil) and a five-zone design (a central small circular zone surrounded by four concentric annuli) were configured with programmable zone geometry, wavefront phase and pupil transmission characteristics. Using computational methods, we examined the effects of diffraction, Stiles Crawford apodisation, pupil size and spherical aberration on optical transfer functions for different target distances. RESULTS: Apodisation alters the relative weighting of each zone, and thus the balance of near and distance optical quality. When spherical aberration is included, the effective distance correction, add power and image quality depend on zone-geometry and Stiles Crawford Effect apodisation. When the outer zone width is narrow, diffraction limits the available image contrast when focused, but as pupil dilates and outer zone width increases, aberrations will limit the best achievable image quality. With two-zone designs, balancing near and distance image quality is not achieved with equal area inner and outer zones. With significant levels of spherical aberration, multi-zone designs effectively become multifocals. CONCLUSION: Wave optics and pupil varying ocular optics significantly affect the imaging capabilities of different optical zones of concentric bifocals. With two-zone bifocal designs, diffraction, pupil apodisation spherical aberration, and zone size influence both the effective add power and the pupil size required to balance near and distance image quality. Five-zone bifocal designs achieve a high degree of pupil size independence, and thus will provide more consistent performance as pupil size varies with light level and convergence amplitude.

Influence of spherical aberration, stimulus spatial frequency, and pupil apodisation on subjective refractions.

PURPOSE: To test competing hypotheses (Stiles Crawford pupil apodising or superior imaging of high spatial frequencies by the central pupil) for the pupil size independence of subjective refractions in the presence of primary spherical aberration. METHODS: Subjective refractions were obtained with a variety of test stimuli (high contrast letters, urban cityscape, high and low spatial frequency gratings) while modulating pupil diameter, levels of primary spherical aberration and pupil apodisation. Subjective refractions were also obtained with low-pass and high-pass stimuli and using 'darker' and 'sharper' subjective criteria. RESULTS: Subjective refractions for stimuli containing high spatial frequencies focus a near paraxial region of the pupil and are affected only slightly by level of Seidel spherical aberration, degree of pupil apodisation and pupil diameter, and generally focused a radius of about 1-1.5 mm from the pupil centre. Low spatial frequency refractions focus a marginal region of the pupil, and are significantly affected by level of spherical aberration, amount of pupil apodisation, and pupil size. Clinical refractions that employ the 'darker' or 'sharper' subjective criteria bias the patient to use lower or higher spatial frequencies, respectively. CONCLUSIONS: In the presence of significant levels of spherical aberration, the pupil size independence of subjective refractions occurs with or without Stiles Crawford apodisation for refractions that optimise high spatial frequency content in the image. If low spatial frequencies are optimised by a subjective refraction, spherical refractive error varies with spherical aberration, pupil size, and level of apodisation. As light levels drop from photopic to scotopic, therefore, we expect a shift from pupil size independent to pupil size dependent subjective refractions. Emphasising a 'sharper' criterion during subjective refractions will improve image quality for high spatial frequencies and generate pupil size independent refractions.

Ferried Albumin-Inspired Bioadhesive With Dynamic Interfacial Bonds for Emergency Rescue.

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m-2), and favorable tissue-adhesion is maintained after ten cycles. IFA hydrogel shows unchangeable adhesive performance after 1 month of storage based on the internal oxidation-reduction mechanism. It not only can efficiently seal various organs but also achieves effective hemostasis in models of the rat femoral artery and rabbit-ear artery. This work also proposes an effective strategy for controllable adhesion, enabling the production of asymmetric adhesives with on-demand detachment. Importantly, IFA hydrogel has sound antioxidation, antibacterial property, hemocompatibility, and cytocompatibility. Hence, the HSA-inspired bioadhesive emerges as a promising first-aid supply for human-machine interface-based health management and non-invasive wound closure.

Impact of primary spherical aberration, spatial frequency and Stiles Crawford apodization on wavefront determined refractive error: a computational study.

PURPOSE: We tested the hypothesis that pupil apodization is the basis for central pupil bias of spherical refractions in eyes with spherical aberration. METHODS: We employed Fourier computational optics in which we vary spherical aberration levels, pupil size, and pupil apodization (Stiles Crawford Effect) within the pupil function, from which point spread functions and optical transfer functions were computed. Through-focus analysis determined the refractive correction that optimized retinal image quality. RESULTS: For a large pupil (7 mm), as spherical aberration levels increase, refractions that optimize the visual Strehl ratio mirror refractions that maximize high spatial frequency modulation in the image and both focus a near paraxial region of the pupil. These refractions are not affected by Stiles Crawford Effect apodization. Refractions that optimize low spatial frequency modulation come close to minimizing wavefront RMS, and vary with level of spherical aberration and Stiles Crawford Effect. In the presence of significant levels of spherical aberration (e.g. C(4)(0) = 0.4 µm, 7 mm pupil), low spatial frequency refractions can induce -0.7 D myopic shift compared to high SF refraction, and refractions that maximize image contrast of a three cycle per degree square-wave grating can cause -0.75 D myopic drift relative to refractions that maximize image sharpness. DISCUSSION: Because of small depth of focus associated with high spatial frequency stimuli, the large change in dioptric power across the pupil caused by spherical aberration limits the effective aperture contributing to the image of high spatial frequencies. Thus, when imaging high spatial frequencies, spherical aberration effectively induces an annular aperture defining that portion of the pupil contributing to a well-focused image. As spherical focus is manipulated during the refraction procedure, the dimensions of the annular aperture change. Image quality is maximized when the inner radius of the induced annulus falls to zero, thus defining a circular near paraxial region of the pupil that determines refraction outcome.

Contribution of HIF-1α/BNIP3-mediated autophagy to lipid accumulation during irinotecan-induced liver injury.

Irinotecan is a topoisomerase I inhibitor which has been widely used to combat several solid tumors, whereas irinotecan therapy can induce liver injury. Liver injury generally leads to tissue hypoxia, and hypoxia-inducible factor-1α (HIF-1α), a pivotal transcription factor, mediates adaptive pathophysiological responses to lower oxygen condition. Previous studies have reported a relationship between HIF-1α and autophagy, and autophagy impairment is a common characteristic in a variety of diseases. Here, irinotecan (50 mg/kg) was employed on mice, and HepG2 and L-02 cells were cultured with irinotecan (10, 20 and 40 µM). In vivo study, we found that irinotecan treatment increased final liver index, serum aminotransferase level and hepatic lipid accumulation. Impaired autophagic flux and activation of HIF-1α/BNIP3 pathway were also demonstrated in the liver of irinotecan-treated mice. Moreover, irinotecan treatment significantly deteriorated hepatic oxidative stress, evidenced by increased MDA and ROS contents, as well as decreased GSH-Px, SOD and CAT contents. Interestingly, protein levels of NLRP3, cleaved-caspase 1 and IL-1ß were enhanced in the liver of mice injected with irinotecan. In vitro study, irinotecan-treated HepG2 and L-02 cells also showed impaired autophagic flux, while HIF-1α inhibition efficaciously removed the accumulated autophagosomes induced by irinotecan. Additionally, irinotecan treatment aggravated lipid accumulation in HepG2 and L-02 cells, and HIF-1α inhibition reversed the effect of irinotecan. Furthermore, HIF-1α inhibition weakened irinotecan-induced NLRP3 inflammasome activation in HepG2 cells. Taken together, our results suggest that irinotecan induces liver injury by orchestrating autophagy via HIF-1α/BNIP3 pathway, and HIF-1α inhibition could alleviate irinotecan-induced lipid accumulation in HepG2 and L-02 cells, which will provide a new clue and direction for the prevention of side effects of clinical chemotherapy drugs.

Robust but On-Demand Detachable Wet Tissue Adhesive Hydrogel Enhanced with Modified Tannic Acid.

Adhesives with robust but readily detachable wet tissue adhesion are of great significance for wound closure. Polyelectrolyte complex adhesive (PECA) is an important wet tissue adhesive. However, its relatively weak cohesive and adhesive strength cannot satisfy clinical applications. Herein, modified tannic acid (mTA) with a catechol group, a long alkyl hydrophobic chain, and a phenyl group was prepared first, and then, it was mixed with acrylic acid (AA) and polyethylenimine (PEI), followed by UV photopolymerization to make a wet tissue adhesive hydrogel with tough cohesion and adhesion strength. The hydrogel has a strong wet tissue interfacial toughness of ∼1552 J/m2, good mechanical properties (∼7220 kPa cohesive strength, ∼873% strain, and ∼33,370 kJ/m3 toughness), and a bursting pressure of ∼1575 mmHg on wet porcine skin. The hydrogel can realize quick and effective adhesion to various wet biological tissues including porcine skin, liver, kidney, and heart and can be changed easily with triggering urea solution to avoid tissue damage or uncomfortable pain to the patient. This biosafe adhesive hydrogel is very promising for wound closure and may provide new ideas for the design of robust wet tissue adhesives.