Ultrasmall CuMn-His Nanozymes with Multienzyme Activity at Neutral pH: Construction of a Colorimetric Sensing Array for Biothiol Detection and Disease Identification.

Biothiol assays offer vital insights into health assessment and facilitate the early detection of potential health issues, thereby enabling timely and effective interventions. In this study, we developed ultrasmall CuMn-Histidine (His) nanozymes with multiple enzymatic activities. CuMn-His enhanced peroxidase (POD)-like activity at neutral pH was achieved through hydrogen bonding and electrostatic effects. In addition, CuMn-His possesses laccase (LAC)-like and superoxide dismutase (SOD)-like activities at neutral pH. Based on three different enzyme mimetic activities of CuMn-His at neutral pH, the colorimetric sensing array without changing the buffer solution was successfully constructed. The array was successfully used for the identification of three biothiols, glutathione (GSH), cysteine (Cys), and homocysteine (Hcy). Subsequently, excellent application results were shown in complex serum and cellular level analyses. This study provides an innovative strategy for the development of ultrasmall bimetallic nanozymes with multiple enzymatic activities and the construction of colorimetric sensing arrays.

The antihypertensive effect of Alizarin is achieved by activating VEGFR2/eNOS pathway, attenuating oxidative stress-induced mitochondrial damage and premature senescence.

The primary and initial manifestations of hypertension encompass arterial hypoelasticity and histiocyte senescence. Oxidative stress plays a pivotal role in the progression of senescence. Elevated intracellular oxidative stress levels will directly induce cell damage, disrupt normal physiological signal transduction, which can cause mitochondrial dysfunction to accelerate the process of senescence. Alizarin, an anthraquinone active ingredient isolated from Rubia cordifolia L., has a variety of pharmacological effects, including antioxidant, anti-inflammatory and anti-platelet. Nevertheless, its potential in lowering blood pressure (BP) and mitigating hypertension-induced vascular senescence remains uncertain. In this study, we used spontaneously hypertensive rats (SHR) and human umbilical vein endothelial cells (HUVECs) to establish a model of vascular senescence in hypertension. Our aim was to elucidate the mechanisms underpinning the vascular protective effects of Alizarin. By assessing systolic blood pressure (SBP) and diastolic blood pressure (DBP), H&E staining, SA-ß-Gal staining, vascular function, oxidative stress levels, calcium ion concentration and mitochondrial membrane potential, we found that Alizarin not only restored SBP and increased endothelium-dependent relaxation (EDR) in SHR, but also inhibited oxidative stress-induced mitochondrial damage and significantly delayed the vascular senescence effect in hypertension, and the mechanism may be related to the activation of VEGFR2/eNOS signaling pathway.

The impact of serum BNP on retinal perfusion assessed by an AI-based denoising optical coherence tomography angiography in CHD patients.

Background: To investigate the correlation between retinal vessel density (VD) parameters with serum B-type natriuretic peptide (BNP) in patients with coronary heart disease (CHD) using novel optical coherence tomography angiography (OCTA) denoising images based on artificial intelligence (AI). Methods: OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device in 176 patients with CHD. Baseline information and blood test results were recorded. Results: Retinal VD parameters of the macular and optic nerves on OCTA were significantly decreased in patients with CHD after denoising. Retinal VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC) was strongly correlated with serum BNP levels in patients with CHD. Significant differences were noted in retinal thickness and retinal VD (SCP, DCP and RPC) between the increased BNP and normal BNP groups in patients with CHD. Conclusion: Deep learning denoising can remove background noise and smooth rough vessel surfaces. SCP,DCP and RPC may be potential clinical markers of cardiac function in patients with CHD. Denoising shows great potential for improving the sensitivity of OCTA images as a biomarker for CHD progression.

Evaluation of retinal and choroidal thickness changes in overweight and obese adults without ocular symptoms by swept-source optical coherence tomography.

AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI<25.00 kg/m2), the overweight group (25.00≤BMI<30.00 kg/m2), and the obesity group (BMI≥30.00 kg/m2). The one-way ANOVA and the Chi-square test were used for comparisons. Pearson's correlation analysis was used to evaluate the relationships between the measured variables. RESULTS: This research covered the left eyes of 3 groups of 434 age- and sex-matched subjects each: normal, overweight, and obesity. The mean BMI was 22.20±1.67, 26.82±1.38, and 32.21±2.35 kg/m2 in normal, overweight and obesity groups, respectively. The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group (P<0.05 for all), while the retinal thickness of the three groups did not differ significantly. Pearson's correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness, but no significant correlation was observed between BMI and retinal thickness. CONCLUSION: Choroidal thickness is decreased in people with overweight or obesity. Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.

Associations between the retinal/choroidal microvasculature and carotid plaque in patients with CAD: An OCTA study.

Background: To investigate the associations between retinal/choroidal microvasculature and carotid plaque in patients with CAD assessed by optical coherence tomography angiography (OCTA). Methods: This study included 127 CAD patients with and 79 without carotid plaque. Each patient had both OCTA taken and digitized to determine retinal/choroidal thickness, vessel density and flow area and carotid ultrasound for carotid plaque size and stability measurement. The superficial capillary plexus (SCP), deep capillary plexus (DCP), out retina and choriocapillaris vessel density, out retina and choriocapillaris flow area, and full retina thickness were analyzed in the fovea centered 6 × 6 mm area. The association between OCTA measurements and carotid plaque characteristics in patients with CAD were evaluated. Results: The duration of hypertension and diabetes mellitus (DM) was significantly longer in CAD patients with carotid plaque than that without (p < 0.001). The mean values for vessel density SCP and DCP (except fovea zone), and choriocapillaris nasal zone were significantly lower in plaque group (p < 0.05). Negative correlations between the carotid plaque width and vessel density SCP and DCP (except fovea zone) (p < 0.05) were also found in this study. Conclusions: In patients with CAD, carotid plaque, a risk factor and marker of atherosclerosis and stenosis, is significantly and independently associated with retinal and choroidal microvascular changes by OCTA.

Imaging 3D chemistry at 1 nm resolution with fused multi-modal electron tomography.

Measuring the three-dimensional (3D) distribution of chemistry in nanoscale matter is a longstanding challenge for metrological science. The inelastic scattering events required for 3D chemical imaging are too rare, requiring high beam exposure that destroys the specimen before an experiment is completed. Even larger doses are required to achieve high resolution. Thus, chemical mapping in 3D has been unachievable except at lower resolution with the most radiation-hard materials. Here, high-resolution 3D chemical imaging is achieved near or below one-nanometer resolution in an Au-Fe3O4 metamaterial within an organic ligand matrix, Co3O4-Mn3O4 core-shell nanocrystals, and ZnS-Cu0.64S0.36 nanomaterial using fused multi-modal electron tomography. Multi-modal data fusion enables high-resolution chemical tomography often with 99% less dose by linking information encoded within both elastic (HAADF) and inelastic (EDX/EELS) signals. We thus demonstrate that sub-nanometer 3D resolution of chemistry is measurable for a broad class of geometrically and compositionally complex materials.

The Association of Intraocular Efavirenz Concentrations and HIV-1 Viral Load Among Persons With HIV.

OBJECTIVE: Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies. DESIGN: Observational, retrospective study. METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042). CONCLUSIONS: The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.

Modified technique for reconstruction of large cyclodialysis cleft with capsular tension ring and continuous and cerclage sutures without scleral flaps.

To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.

Determining Gender-Based Differences in Retinal and Choroidal Thickness in Underweight Individuals via Swept-Source Optical Coherence Tomography.

Despite improvements in reducing hunger in recent years, undernutrition remains a global public health problem. This study utilizes the swept-source optical coherence tomography (SS-OCT) technique to assess changes in retinal and choroidal thickness in underweight subjects. Ophthalmic examinations were conducted on all adults participating in this cross-sectional research. Depending on their body mass index (BMI), the participants were divided into two groups: the underweight group and the normal group. The study included the right eyes of the underweight adults and an equal number of age- and gender-matched normal-weight subjects. The retinal thickness showed no significant difference between the underweight and normal groups (P > 0.05 for all). In males, the retina of the center and inner ring in the underweight group was significantly thinner than that in the normal group, while no such results were found in females. The choroid in the underweight group was significantly thinner compared to that in the normal group (all P < 0.05). Being underweight may affect choroidal thickness in both males and females. In comparison with underweight females, underweight males may experience more retinal damage. These findings contribute to a better understanding of the pathogenesis underlying specific ocular diseases in malnourished individuals.

Retinal thickness and fundus blood flow density changes in chest pain subjects with dyslipidemia.

AIM: To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography (OCTA). METHODS: All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination. According to the serum lipid levels, the participants were divided into the control group and the dyslipidemia group. The retina thickness and fundus blood flow density were determined using OCTA. RESULTS: The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age- and sex-matched participants without dyslipidemia. The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior (P=0.004 and P=0.014, respectively) and temporal (P=0.015 and P=0.019, respectively) regions, both inner and outer layers. In terms of blood flow density in the macula or optic disk, there was a decreasing trend in the dyslipidemia group compared with the control group, especially in the inferior and temporal regions. CONCLUSION: Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density. Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.

Idiopathic Epiretinal Membrane Surgery in Patients Aged Over 80 Years: Efficacy and Safety.

Purpose: To evaluate the efficacy and safety of idiopathic epiretinal membrane (ERM) surgery in patients aged over 80 years. Methods: Consecutive patients who underwent pars plana vitrectomy (PPV) combined with ERM and internal limiting membrane (ILM) peeling with retrobulbar anesthesia were recruited. Based on age, the patients were divided into the elderly group (≥ 80 years of age) and the control group (< 80 years of age). The best-corrected visual acuity (BCVA) and surgical complications were regarded as the main measurement indicators. Results: This study included 43 eyes from 43 patients aged 80 to 91 years and 86 eyes from 86 patients aged 54 to 79 years. Surgical intervention substantially improved BCVA both in the elderly and control groups (p = 0.005 and p < 0.001, respectively). Statistical analyses showed no significant difference in the incidence of surgical complications between the two groups (p = 0.631). The operations in either group were not delayed or canceled for the reason of complications of retrobulbar anesthesia, severe anxiety, or physical discomfort in the perioperative period. Moreover, no patient required a second operation. Also, no stroke, myocardial infarction, or death occurred during the follow-up period. All the surgical complications were treated satisfactorily. Conclusion: Our outcomes indicate that PPV combined with ERM and ILM peeling with retrobulbar anesthesia is effective and safe in elderly patients aged 80 years or older. Based on age alone, we believe that advancing age should not be the risk factor for idiopathic ERM surgery.

Tenofovir Concentration Is Not Enough in Intraocular Tissues of Patients With HIV infection.

OBJECTIVE: To determine tenofovir (TFV) penetration into intraocular tissues using ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). METHODS: Nineteen participants taking tenofovir in combination antiretroviral therapy (cART) regimen who underwent pars plana vitrectomy (PPV) surgery were enrolled in the observational retrospective study between January 2019 and August 2021. The participants were divided into mild, moderate, and severe groups according to retinal manifestations. Basic information was recorded during PPV surgery. Paired blood plasma and vitreous humor samples (n = 19) were collected for UHPLC-MS/MS. RESULTS: The median plasma and vitreous tenofovir concentrations were 106.00 ng/mL (interquartile range[IQR], 54.6-142.5) and 41.40 ng/mL (IQR 9.4-91.6), respectively. The median vitreous/plasma concentration ratio from the paired samples was 0.42 (IQR 0.16-0.84). The plasma and vitreous tenofovir concentrations were significantly correlated (r = 0.483, P = 0.036). The median vitreous tenofovir concentration was the lowest in the mild group (4.58 ng/mL). Six vitreous samples were below 50% inhibitory concentration (IC50) (11.5 ng/mL), and 2 of them were undetectable. Significant differences were noted in vitreous/plasma and vitreous tenofovir concentrations ( P = 0.035 and P = 0.045, respectively) among the 3 groups but not in plasma tenofovir concentration ( P = 0.577). No correlation was noted between vitreous HIV-1 RNA and vitreous tenofovir concentrations (r = 0.049, P = 0.845). CONCLUSION: Vitreous tenofovir did not reliably or consistently achieve concentrations sufficient to inhibit viral replication in intraocular tissues due to poor penetration of the blood-retinal barrier (BRB). The higher vitreous tenofovir concentrations were associated with moderate or severe disease compared with mild disease, indicating an association with the severity of BRB disruption.

Choroidal and retinal thickness in patients with vitamin C deficiency using swept-source optical coherence tomography.

BACKGROUND: To investigate the effects of vitamin C on central retinal thickness and choroidal thickness. METHODS: A total of 69 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 69 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT). RESULTS: The average retinal thickness was 269.07 ± 13.51 µm in the vitamin C deficiency group and 276.92 ± 13.51 µm in the control group. The average choroidal thickness was 195.62 ± 66.40 µm in the in the vitamin C deficiency group and 238.86 ± 55.08 µm in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p < 0.001, and = 0.001 respectively). CONCLUSION: The central retinal and choroidal thickness were thinner in vitamin C deficiency group compared with normal individuals. These findings suggested that vitamin C deficiency might play an important role in retinal and choroidal diseases.

Cytomegalovirus-Immune Recovery Retinitis After Initiation of Highly Active Antiretroviral Therapy: A Case Series.

Purpose: To delineate the characteristics and treatment of cytomegalovirus-immune recovery retinitis (CMV-IRR) in human immunodeficiency virus (HIV) patients with immune recovery under effective highly active antiretroviral therapy (HAART) regimen. Methods: We reported four patients with HIV who were diagnosed with CMV-IRR soon after effective HAART. Plasma levels of CD4 T cells, HAART regimen, and other clinical and laboratory characteristics of the four patients were described. Patients were monitored for ocular manifestations and clinical signs under effective ocular and systemic anti-cytomegalovirus (CMV) and corticosteroid treatment for 12 months. Results: With HAART, plasma levels of CD4 T cell counts rose remarkably. The mean baseline CD4 count of the four patients was 14.5 (range from 7 to 33) cells/µl before HAART and 183.25 (range from 153 to 220) cells/µl when diagnosed with CMV-IRR. Ophthalmic examination demonstrated severe vitreous opacities and necrotizing retinitis, intraretinal hemorrhages, and vasculitis. A large number of CMV sequencing was detected by DNA sequencing of vitreous samples. All four patients were recovered from CMV-IRR with anti-CMV and corticosteroid treatment. Conclusions: Cytomegalovirus-immune recovery retinitis is a new diagnosis of HIV-associated ocular complication under HAART. These findings suggest that the immunological effects of HAART may accelerate the CMV retinitis in patients with very low initial CD4 T cell counts. HIV patients are recommended to have a thorough fundus examination before HAART initiation and a close follow-up especially in those with low CD4 counts to avoid the progression of CMV retinitis.

Bilateral iris mass as the first manifestation of NK cell lymphoma: A case report.

INTRODUCTION: Natural killer (NK) cell lymphoma is a progressive non-Hodgkin's lymphoma with rare prevalence. Intraocular involvement of NK cell lymphoma is very rare, with only case reports to date. CASE PRESENTATION: Here, we report a case of intraocular involvement of NK cell lymphoma which was presented with bilateral uveitis, iris mass, and diffuse infiltration into the center nerve system (CNS), skin, and possibly myocardium. CONCLUSIONS: Iris mass and uveitis which is not responsive to steroids may be ocular manifestations of intraocular lymphoma, such as NK cell lymphoma. Ophthalmological and systemic examinations should be required for early diagnosis and treatment.

Backbone-Photodegradable Polymers by Incorporating Acylsilane Monomers via Ring-Opening Metathesis Polymerization.

Materials capable of degradation upon exposure to light hold promise in a diverse range of applications including biomedical devices and smart coatings. Despite the rapid access to macromolecules with diverse compositions and architectures enabled by ring-opening metathesis polymerization (ROMP), a general strategy to introduce facile photodegradability into these polymers is lacking. Here, we report copolymers synthesized via ROMP that can be degraded by cleaving the backbone in both solution and solid states under irradiation with a 52 W, 390 nm Kessil LED to generate heterotelechelic low-molecular-weight fragments. To the best of our knowledge, this work represents the first instance of the incorporation of acylsilanes into a polymer backbone. Mechanistic investigation of the degradation process supports the intermediacy of an α-siloxy carbene, formed via a 1,2-photo Brook rearrangement, which undergoes insertion into water followed by cleavage of the resulting hemiacetal.

Choroidal Thickness in Relation to Bone Mineral Density with Swept-Source Optical Coherence Tomography.

PURPOSE: To assess whether bone mineral density, indicated by the lumbar X-ray scan, is related to changes in choroid thickness in normal subjects. METHODS: This study included 355 patients with decreased bone mineral density and 355 age- and sex-matched healthy subjects. Lumbar BMD was measured by dual-energy X-ray absorptiometry (DXA). Choroidal thickness was measured using swept-source optical coherence tomography (SS-OCT). Blood pressure (BP), cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were recorded on the same day. RESULTS: There was a significant difference in average choroidal thickness between low BMD subjects and normal subjects (p=0.003). The BP, cholesterol, triglyceride, HDL, and LDL showed no significant difference between the two groups. The correlations showed that average choroidal thicknesses were associated with BMD in the entire population (r = 0.125, p=0.001). CONCLUSION: The choroidal thickness is thinner in low BMD populations compared with normal individuals. There is a strong positive correlation of choroidal thickness with BMD, regardless of age, sex, and other demographic and clinical factors.