Coenzyme Q10 eyedrops conjugated with vitamin E TPGS alleviate neurodegeneration and mitochondrial dysfunction in the diabetic mouse retina.

Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rod-bipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy.

Compensatory Interactions between Corneal and Internal Astigmatism despite Lifestyle Changes.

This study explores whether children's refractive errors and visual behaviors reverted to pre-COVID-19 levels a year after normal schooling resumed in Hong Kong as well as the impact of corneal and internal astigmatism on refractive astigmatism development. Vision survey data and questionnaire results collected in 2022 (n = 119) and 2020 (n = 173) were compared. Cross-sectional data showed similar proportions of astigmatism (cylindrical power ≥ 0.75 D) in the 2020 (49.1%) and 2022 cohorts (55.5%). Despite a 0.28 D increase in corneal astigmatism, a compensatory 0.24 D increase in internal astigmatism of opposite direction kept refractive astigmatism relatively stable. The questionnaire data showed that children spent an additional 0.5 h/day outdoors on weekends post-resumption of normal schooling but engaged in more near-work activities, especially non-screen near-work, by approximately 1 h/day on both weekdays and weekends. These findings were supported by longitudinal data from 72 children who participated in both surveys. This study highlights the significant role of corneal and internal astigmatism in refractive astigmatism changes. Despite the return to in-person classes, children's total near-work time increased and astigmatism remained high. These findings underscore the need for comprehensive strategies to reduce the high environmental risks for refractive error development in children.

Synchronous myopia development induced by bilateral form deprivation in chicks.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

Characteristics of ciliary muscle profile in high myopes measured by swept-source anterior segment optical coherence tomography.

OBJECTIVE: To characterize and compare the ciliary muscle thickness (CMT) between low and high myopes using swept-source anterior segment optical coherence tomography (AS-OCT). METHODS: Forty visually healthy young Chinese adults aged 18-25 years were divided into two groups based on refractive errors: low myopia (n = 20, spherical-equivalent refractive error (SER) between -0.50 D to -3.00 D) and high myopia (n = 20, SER ≤ -6.00 D). Cycloplegic refractions were performed before axial length (AL) and CMT were measured using a partial coherence laser interferometer and an AS-OCT respectively. CMT was measured perpendicularly to the sclera-ciliary muscle interface at 1 mm (CMT_1), 2 mm (CMT_2), and 3 mm (CMT_3) posterior to the scleral spur, and at the location with maximal thickness (CMT_MAX). RESULTS: High myopes demonstrated thicker CMT at 2 mm (CMT_2, p = 0.035) and 3 mm (CMT_3, p = 0.003) posterior to the scleral spur, but thinner maximal CMT (CMT_MAX, p = 0.005) than low myopes. The apical CMT_1 and CMT_MAX were also thinner in high myopes than in low myopes (both p< 0.001). CMT_MAX, apical CMT_1, and apical CMT_MAX correlated directly with SER and inversely with AL; in contrast, CMT_2 and CMT_3 showed inverse correlations with SER but direct correlations with AL. CONCLUSION: Our findings revealed significant differences in CMT between low and high myopes, with high myopes showing thicker CMT at 2 mm and 3 mm posterior to the scleral spur, but thinner maximal CMT. These results provide new evidence of the potential structural differences in ciliary muscles during myopia development and progression.

Brief Adaptation to Astigmatism Reduces Meridional Anisotropy in Contrast Sensitivity.

Purpose: To investigate the effect of visual adaptation to orientation-dependent optical blur on meridional contrast sensitivity function in artificially imposed astigmatism. Methods: The study adopted a top-up adapt-test paradigm. During the blur adaptation process, the 18 non-astigmatic young adult participants were briefly presented with natural scene images (first trial, 10 minutes; subsequent trials, 6 seconds). Contrast sensitivities for horizontal and vertical gratings at spatial frequencies ranging from 1 to 8 cycles per degree (cpd) were measured immediately before and after adaptation to +3.00 diopters cylinder (DC) with-the-rule or against-the-rule astigmatism. Meridional anisotropy was measured to quantify the contrast sensitivity difference between the two grating orientations. Results: Adapting to astigmatic blur enhanced contrast sensitivity at the blurred power meridian but reduced contrast sensitivity at the least affected axis meridian. In with-the-rule conditions, contrast sensitivity for horizontal gratings was significantly increased, whereas that for vertical gratings was significantly decreased. Similarly, in against-the-rule conditions, contrast sensitivity for vertical gratings was significantly increased, whereas that for horizontal gratings was significantly decreased. These two factors together resulted in a substantial systematic reduction, averaging 34%, in meridional anisotropy of contrast sensitivity across the spatial frequency spectrum. Conclusions: Astigmatism adaptation occurs in natural scene viewing. Brief exposure to astigmatic blur altered contrast sensitivity in the opposite direction at the two principal meridians, indicating that the mature visual system possesses functional plasticity to recalibrate the response characteristics of orientationally tuned cortical filters and thus promote substantial reductions of meridional anisotropy in astigmatic vision, to some extent counterbalancing the elongated oval shape of astigmatic blur.

Size of living space as a moderator for central and peripheral refractions in children.

Undesirable living environment may impose risk on myopia development. Furthermore, peripheral refractive error was suggested to contribute to juvenile eye growth modulation. This study aimed to investigate the interaction between peripheral refractive error and living environment in relation to central refractive status in Hong Kong schoolchildren. Central and peripheral refractive errors, axial length (AL), and corneal radius of curvature (CR) were measured in 573 schoolchildren (age 9.5 ± 0.9 years). The AL/CR ratio was used to represent the central refractive status, accounting for non-cycloplegic refraction. The relative peripheral refractive errors (RPRE) up to ± 20° eccentricities were converted into power vectors: spherical-equivalent error (SER) and J0 astigmatic components and fitted with quadratic equations. The second-order coefficients of SER (aSER) and J0 astigmatism (aJ0) and home size reported by parental questionnaires were analyzed to indicate their relationships with AL/CR. Our results showed that children with higher AL/CR lived in smaller homes (p = 0.01) and had a more hyperopic (p < 0.001) but less astigmatic RPRE (p = 0.01). We further analyzed the relationship between AL/CR with RPRE for children living in small (< 300 ft2), moderate (300-600 ft2), and large home sizes (> 600 ft2). Regardless of the home size, a higher AL/CR remained moderately correlated with a more hyperopic aSER (all p < 0.001). However, a higher AL/CR was associated with a more positive aJ0 only in children living in large homes, and the relationships were not significant for small and moderate home sizes. Linear regression models further indicated that home size was a significant moderator contributing to the relationship between AL/CR and aJ0. In conclusion, our results were consistent with previous studies, showing that children with axial myopia usually lived in smaller homes and had more hyperopic defocus and more positive J0 astigmatism. However, the relationship between peripheral astigmatism and axial refraction was modulated by the home size of Hong Kong schoolchildren. While peripheral astigmatism is hypothesized as a visual cue for axial refractive development in children, extrinsic environmental factors, such as home size, might interfere with the relationship and dominate refractive development.

Measuring Retinal Thickness and Visual Acuity in Eyes with Different Types of Astigmatism in a Cohort of Hong Kong Chinese Adults.

Purpose: The purpose of this study was to investigate optical coherence tomography (OCT)-measured retinal thickness (RT) and best-corrected distance visual acuity (BCDVA) in eyes with different types of astigmatism. Methods: This is a case-control study of 101 participants stratified into With-The-Rule (WTR; n = 41), Against-The-Rule (ATR; n = 25), and control (n = 35) groups by noncycloplegic subjective refraction. Inclusion criteria were ages between 18 and 45 years, spherical-equivalent (SE) refraction ≥-10.00 diopters (D), negative cylindrical power (CYL) ≤-0.75 D with axes of 0 to 30 degrees/150 to 180 degrees for WTR and 60 to 120 degrees for ATR, or CYL ≥-0.25 D for controls. Participants suffering from ocular diseases related to retinal defects, having a history of ocular surgery, with BCDVA >0.10 LogMAR, or poor OCT imaging quality were excluded. Fovea-centered scans were performed using spectral-domain OCT (SD-OCT), and RT automatically measured by the inbuilt software. Only right eyes were analyzed. Groups were matched for age, gender, SE, axial length, and corneal curvature. Results: One-way ANOVA showed a significant difference in both BCDVA (P = 0.039) and macular RT (P = 0.028) among the three groups. Bonferroni's post hoc test revealed statistically significant between-group differences in BCDVA (WTR vs. controls, P = 0.041), as well as in RT at inner-nasal (WTR vs. ATR, P = 0.034) and outer-temporal subfields (WTR vs. controls, P = 0.042). BCDVA was positively associated with macular RT (r = 0.206, P = 0.041) after adjusting for age, gender, and axial length. Conclusions: Greater RT and poorer BCDVA were found in eyes with WTR astigmatism. Our findings suggest that the effect of astigmatism on retinal thickness and BCDVA may vary depending on not only magnitude, but also axis of astigmatism.

Significant increase in astigmatism in children after study at home during the COVID-19 lockdown.

CLINICAL RELEVANCE: Evaluating changes in refractive astigmatism after 'study at home' during the COVID pandemic may shed light on the aetiology of refractive errors. BACKGROUND: To investigate whether there has been a change in the proportion of astigmatism among primary school children after the school closure period during the COVID-19 pandemic. METHODS: This observational study compared cross-sectional (2018: n = 112; 2020: n = 173) and longitudinal data (n = 38) collected from two vision screenings, one in 2018 and the other after the school closure period in 2020, in the same primary school for children aged 8-10 years. Non-cycloplegic refraction and axial length were measured using an open-field auto-refractometer and IOL Master, respectively. A questionnaire focusing on demographic information, near-work time, and outdoor activities was administered to parents of all participants. RESULTS: While there were no significant differences in age, gender, or monthly family income between the two cohorts, astigmatism proportion (Cyl ≥ 0.75 D) in 2020 was 1.5-fold higher than that in 2018 (49.1% vs. 33.9%). The median cylindrical power was significantly higher in 2020 in older children (9 or 10 years old). More importantly, the children participating in both vision screenings had cylindrical power and J0 astigmatism significantly increased by 0.35 ± 0.40 D and 0.21 ± 0.25 D, respectively. CONCLUSION: A significant increase in astigmatism (both proportion and magnitude) was found after the school closure period. Further studies are needed to investigate the origin of this increased astigmatism.

Experimentally induced myopia and myopic astigmatism alter retinal electrophysiology in chickens.

Myopia (or "short-sightedness") and astigmatism are major causes of visual impairment worldwide. Significant amounts of astigmatism are frequently observed in infants and have been associated with myopia development. Although it is well established that both myopia and astigmatism are associated with ocular structural changes from anterior to posterior segments, very little is known on how these refractive errors alter retinal functions. This study investigated the effects of experimentally induced myopia and myopic-astigmatism on retinal electrophysiology by using an image-guided, multifocal global flash stimulation in chickens, a widely used animal model for refractive error development. Myopia and myopic-astigmatism were experimentally induced, respectively, by wearing spherical (- 10 D, n = 12) and sphero-cylindrical lenses (- 6.00 DS/- 8.00 DCx90: Hyperopic With-The Rule, H-WTR, n = 15; - 6.00 DS/- 8.00 DCx180: Hyperopic Against-The-Rule, H-ATR, n = 11) monocularly for a week (post-hatching day 5 to 12). An aged-matched control group without any lens treatment provided normal data (n = 12). Multifocal electrophysiological results revealed significant regional variation in the amplitude of induced component (IC) (central greater than peripheral; both p < 0.05) in the normal and H-ATR groups, but not in the - 10 D and H-WTR groups. Most importantly, for the first time, our results showed that both H-WTR and H-ATR groups exhibited a significantly longer implicit time of the inner retinal response at the central region when compared to the normal and - 10 D groups, highlighting a significant role of astigmatism in retinal physiology.

Bi-directional Refractive Compensation for With-the-Rule and Against-the-Rule Astigmatism in Young Adults.

Purpose: The purpose of this study was to investigate the short-term effect of imposing astigmatism on the refractive states of young adults. Methods: Nineteen visually healthy low-astigmatic young adults (age = 20.94 ± 0.37 years; spherical-equivalent errors [M] = -1.47 ± 0.23 diopters [D]; cylindrical errors = -0.32 ± 0.05 D) were recruited. They were asked to wear a trial frame with treated and control lenses while watching a video for an hour. In three separate visits, the treated eye was exposed to one of three defocused conditions in random sequence: (1) with-the-rule (WTR) astigmatism = +3.00 DC × 180 degrees; (2) against-the-rule (ATR) astigmatism = +3.00 DC × 90 degrees; and (3) spherical defocus (SPH) = +3.00 DS. The control eye was fully corrected optically. Before and after watching the video, non-cycloplegic autorefraction was performed over the trial lenses. Refractive errors were decomposed into M, J0, and J45 astigmatism. Interocular differences in refractions (treated eye - control eye) were analyzed. Results: After participants watched the video with monocular astigmatic defocus for an hour, the magnitude of the J0 astigmatism was significantly reduced by 0.25 ± 0.10 D in both WTR (from +1.53 ± 0.07 D to +1.28 ± 0.09 D) and 0.39 ± 0.15 D in ATR conditions (from -1.33 ± 0.06 D to -0.94 ± 0.18 D), suggesting an active compensation. In contrast, changes in J0 astigmatism were not significant in the SPH condition. No compensatory changes in J45 astigmatism or M were found under any conditions. Conclusions: Watching a video for an hour with astigmatic defocus induced bidirectional, compensatory changes in astigmatic components, suggesting that refractive components of young adults are moldable to compensate for orientation-specific astigmatic blur over a short period.

High Prevalence of Astigmatism in Children after School Suspension during the COVID-19 Pandemic Is Associated with Axial Elongation.

During the COVID-19 pandemic, the Hong Kong Government enforced a "school from home" policy between February and September 2020. This cross-sectional epidemiological study was conducted to investigate the prevalence of astigmatism and visual habits after the home confinement period. Vision screenings were conducted at three local government-funded primary schools in Hong Kong from October 2020 to December 2020. A total of 418 ethnically Chinese primary school children completed the eye examination and returned questionnaires concerning demographic information and visual habits. It was found that 46.5% (95% CI, 41.7−61.4%) of the children aged 8 to 11 years had astigmatism ≥ 0.75 D, which was predominately With-The-Rule astigmatism. The prevalence of astigmatism reported in these children is generally higher than that of studies conducted before COVID. Compared to their non-astigmatic peers, astigmatic children had a longer axial length (p < 0.001) and engaged in fewer outdoor activities (p = 0.04). Multiple linear regression analyses also revealed significant relationships between axial length and both cylindrical error and J0 astigmatism. Due to the high astigmatism prevalence, there is a pressing need for further studies on the long-term impact of the pandemic on children's vision.

Centipeda minima Extract Attenuates Dextran Sodium Sulfate-Induced Acute Colitis in Mice by Inhibiting Macrophage Activation and Monocyte Chemotaxis.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease affecting the gastrointestinal tract. IBD is characterized by courses of relapse and remission, and remains incurable. Although multiple factors are related to the pathogenesis of IBD, disruption of intestinal mucosa homeostasis has been proposed to be a major contributor to IBD, and abnormal activation of immune cells is key for initiation of the inflammatory response. Macrophages are the most abundant immune cells in the intestine. Once activated, they are responsible for secretion of pro-inflammatory cytokines and chemokines to attract circulating monocytes to inflammatory sites, exacerbating the inflammatory response, and leading to tissue damage. Therefore, the suppression of activated macrophages, cytokine/chemokine production, and subsequent monocyte chemotaxis possesses great potential for the treatment of IBD. In our study, we have demonstrated the inhibitory effect of Centipeda minima total extract (CME) on the activation of NF-κB, STAT3, and MAPK signaling in LPS-stimulated RAW264.7 macrophages. In addition, we identified the significant suppressive effect of CME on CCL8 expression in activated macrophages, which potentially contributed to inhibition of monocyte chemotaxis. In the DSS-induced acute colitis mouse model, we have demonstrated the suppressive effect of CME on intestinal macrophage infiltration and its ameliorative effect in IBD. Altogether, we have provided evidence of the therapeutic effect of CME in IBD and the potential of CME for the treatment of IBD.

Meridional Anisotropy of Foveal and Peripheral Resolution Acuity in Adults With Emmetropia, Myopia, and Astigmatism.

Purpose: To quantify astigmatism-related meridional anisotropy in visual resolution at central, nasal, and inferior visual fields. Methods: Three groups of young adults (range, 18-30 years) with corrected-to-normal visual acuity (logMAR 0) were recruited: (1) myopic astigmats (MA): spherical-equivalent error (SE) < -0.75D, with-the-rule astigmatism ≥ 2.00D, n = 19; (2) simple myopes (SM): SE < -0.75D, astigmatism ≤ 0.50D, n = 20; and (3) emmetropes (EM): SE ± 0.50D, astigmatism ≤ 0.50D, n = 14. Resolution acuity was measured for the horizontal and vertical gratings at central and peripheral visual fields (eccentricity: 15°) using a 3-down 1-up staircase paradigm. On- and off-axis refractive errors were corrected by ophthalmic lenses. Results: The MA group exhibited meridional anisotropy preferring vertical gratings. At the central field, the MA group had better resolution acuity for vertical than horizontal gratings, and their resolution acuity for horizontal gratings was significantly worse than the SM and EM groups. At peripheral visual fields, both the SM and EM groups showed better resolution acuity for the radial (i.e., nasal field: horizontal gratings; inferior field: vertical gratings) than tangential orientation. However, the MA group tended to have better resolution acuity for the tangential orientation (i.e., vertical gratings), and their resolution acuity for horizontal gratings was significantly lower than the SM and EM groups at the nasal field. No significant differences were found in the inferior field among the three groups. Conclusions: This study provided evidence of astigmatism-related meridional anisotropy at the fovea and nasal visual fields, underscoring the significant impact of astigmatism on orientation-dependent visual functions.

Changes in corneal astigmatism and near heterophoria after smartphone use while walking and sitting.

BACKGROUND/AIMS: Smartphone use has become an indispensable part of our daily life. The handy design and powerful processor allow smartphone users to perform diversified tasks even when walking. This study aimed to investigate and compare the optical aftereffect and vergence adaptation of using a smartphone while walking and sitting. METHODS: Twenty-nine young healthy adults (aged 19 to 24 years old) with normal binocular and accommodative functions were recruited. Participants were asked to watch a movie for 30 minutes using a smartphone while either walking on a treadmill or sitting on a chair. Corneal aberrations and near heterophoria were measured before and after smartphone use by a corneal topographer and modified Thorington heterophoria test, respectively. RESULTS: Using the smartphone while walking induced a change in corneal H/V astigmatism, becoming 0.11±0.03 µm less negative (two-way ANOVA repeated measures, Bonferroni post-hoc test, p = 0.001). This optical aftereffect was significantly higher than after smartphone use while sitting by 0.10±0.03 µm (paired t-test, p = 0.003). Although smartphone use did not result in a significant change in near heterophoria (Bonferroni post-hoc test, p > 0.15), the vergence adaptation showed relatively more eso- or less exo-deviation by 0.79±0.36Δ in the walking than the sitting condition (paired t-test, p = 0.037). CONCLUSIONS: Eyecare practitioners should be cautious of the potential optical after effect and vergence adaptation after prolonged smartphone usage.

Synthesis and Evaluation of Novel Anticancer Compounds Derived from the Natural Product Brevilin A.

Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways.

Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

Effects of Progressive Addition Lens Wear on Digital Work in Pre-presbyopes.

SIGNIFICANCE: Growing popularity of handheld digital devices imposes significant challenges to our visual system and clinical management. This study aimed to determine the effects of lens design on parameters that may influence the refractive management of pre-presbyopic adult computer users. PURPOSE: To determine the effects of wearing conventional single-vision lenses (SVL) versus progressive addition lenses (PAL) on the working distance and refractive status. METHODS: Adult computer users, recruited from two age cohorts (18 to 25 years, n = 19; 30 to 40 years, n = 45), were prescribed SVLs and PALs designed for use with handheld digital devices. For each lens type, the working distance and refractive shift (post-task - pre-task) were measured immediately after lens delivery (T0) and after 1 month of lens wear (T1). Working distances were recorded with an automatic ultrasound device while the participants were playing a video game. Refractive status through the subjects' glasses was measured before (pre-task) and after playing the game (post-task). Questionnaires assessing the frequencies of 10 digital work-related visual symptoms were conducted for both lens types at T1. RESULTS: Switching from SVL to PAL increased the working distance in both cohorts (mean ± SEM = 1.88 ± 0.60 cm; P = .002) and induced a small but significant positive refractive shift (+0.08 ± 0.04 D, P = .021) in the older cohort at T1. In the younger cohort, the changes in working distance due to the switching lens design were correlated with myopic error (r = +0.66, P = .002). In the older cohort, the changes in refractive shift due to switching lens design were correlated with amplitude of accommodation at both time points (r for T0 and T1 = -0.32 and -0.30, respectively; both P < .05). Progressive addition lens was rated as causing less "increased sensitivity to light" compared with SVL. CONCLUSIONS: Switching from SVL to PAL increased the working distance and induced a positive refractive shift in the majority of pre-presbyopic adults.

Blue-Light Filtering Spectacle Lenses: Optical and Clinical Performances.

PURPOSES: To evaluate the optical performance of blue-light filtering spectacle lenses and investigate whether a reduction in blue light transmission affects visual performance and sleep quality. METHODS: Experiment 1: The relative changes in phototoxicity, scotopic sensitivity, and melatonin suppression of five blue-light filtering plano spectacle lenses were calculated based on their spectral transmittances measured by a spectrophotometer. Experiment 2: A pseudo-randomized controlled study was conducted to evaluate the clinical performance of two blue-light filtering spectacle lenses (BF: blue-filtering anti-reflection coating; BT: brown-tinted) with a regular clear lens (AR) serving as a control. A total of eighty computer users were recruited from two age cohorts (young adults: 18-30 yrs, middle-aged adults: 40-55 yrs). Contrast sensitivity under standard and glare conditions, and colour discrimination were measured using standard clinical tests. After one month of lens wear, subjective ratings of lens performance were collected by questionnaire. RESULTS: All tested blue-light filtering spectacle lenses theoretically reduced the calculated phototoxicity by 10.6% to 23.6%. Although use of the blue-light filters also decreased scotopic sensitivity by 2.4% to 9.6%, and melatonin suppression by 5.8% to 15.0%, over 70% of the participants could not detect these optical changes. Our clinical tests revealed no significant decrease in contrast sensitivity either with (95% confidence intervals [CI]: AR-BT [-0.05, 0.05]; AR-BF [-0.05, 0.06]; BT-BF [-0.06, 0.06]) or without glare (95% CI: AR-BT [-0.01, 0.03]; AR-BF [-0.01, 0.03]; BT-BF [-0.02, 0.02]) and colour discrimination (95% CI: AR-BT [-9.07, 1.02]; AR-BF [-7.06, 4.46]; BT-BF [-3.12, 8.57]). CONCLUSION: Blue-light filtering spectacle lenses can partially filter high-energy short-wavelength light without substantially degrading visual performance and sleep quality. These lenses may serve as a supplementary option for protecting the retina from potential blue-light hazard. TRIAL REGISTRATION: ClinicalTrials.gov NCT02821403.

Sharpening coarse-to-fine stereo vision by perceptual learning: asymmetric transfer across the spatial frequency spectrum.

Neurons in the early visual cortex are finely tuned to different low-level visual features, forming a multi-channel system analysing the visual image formed on the retina in a parallel manner. However, little is known about the potential 'cross-talk' among these channels. Here, we systematically investigated whether stereoacuity, over a large range of target spatial frequencies, can be enhanced by perceptual learning. Using narrow-band visual stimuli, we found that practice with coarse (low spatial frequency) targets substantially improves performance, and that the improvement spreads from coarse to fine (high spatial frequency) three-dimensional perception, generalizing broadly across untrained spatial frequencies and orientations. Notably, we observed an asymmetric transfer of learning across the spatial frequency spectrum. The bandwidth of transfer was broader when training was at a high spatial frequency than at a low spatial frequency. Stereoacuity training is most beneficial when trained with fine targets. This broad transfer of stereoacuity learning contrasts with the highly specific learning reported for other basic visual functions. We also revealed strategies to boost learning outcomes 'beyond-the-plateau'. Our investigations contribute to understanding the functional properties of the network subserving stereovision. The ability to generalize may provide a key principle for restoring impaired binocular vision in clinical situations.

Ocular Aberrations and Corneal Shape in Adults with and without Astigmatism.

PURPOSE: To characterize and compare the corneal shapes and monochromatic aberrations in Chinese myopic adults with and without astigmatism. METHODS: Forty-six Hong Kong Chinese aged 50 to 70 years with compound against-the-rule myopic astigmatism (n = 18) or simple myopia (n = 28) were recruited. Corneal shapes were measured by a Scheimpflug-based corneal topographer: the semimeridian corneal shape factors at the nasal, temporal, inferior, and superior corneal quadrants measured from the corneal apex to 3 mm midperiphery were analyzed. The ocular aberrations were measured by the COAS (Complete Ophthalmic Analysis System) Shack-Hartmann wavefront aberrometer; the corneal aberrations were computed using the corneal topographic map data measured by the Medmont E300 corneal topographer; and the internal aberrations were calculated from the ocular and corneal aberrations. RESULTS: Compared with simple myopia, myopic astigmatism had more oblate nasal and temporal corneal shapes and showed significantly more negative Y trefoil and more positive vertical coma. The asymmetry in corneal shape along the vertical principal meridian (inferior - superior) was significantly associated with the Y trefoil and vertical coma of the cornea, suggesting that this regional asymmetry in corneal shape may contribute to the ocular aberrations. CONCLUSIONS: The significant relationships found between astigmatism, corneal shapes, and monochromatic aberrations underscore the importance of taking corneal shape into account when correcting the optical defects in myopic Chinese adults with astigmatism.