Clarifying the effect of gut microbiota on allergic conjunctivitis risk is instrumental for predictive, preventive, and personalized medicine: a Mendelian randomization analysis.

Background: Allergic conjunctivitis is an ocular immune disease which affects the conjunctiva, eyelids, and cornea. Growing evidence implicates the gut microbiota in balancing and modulating immunity response, and in the pathogenesis of allergic disease. As a result, gut microbial imbalance could be a useful indicator for allergic conjunctivitis. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of gut microbial imbalance in the development of allergic conjunctivitis could provide a window of opportunity for primary prediction, targeted prevention, and personalized treatment of the disease. Working hypothesis and methodology: In our study, we hypothesized that individuals with microbial dysbiosis may be more susceptible to allergic conjunctivitis due to an increased inflammatory response. To verify the working hypothesis, our analysis selected genetic variants linked with gut microbiota features (N = 18,340) and allergic conjunctivitis (4513 cases, 649,376 controls) from genome-wide association studies. The inverse-variance weighted (IVW) estimate, Mendelian randomization (MR)-Egger, weighted median estimator, maximum likelihood estimator (MLE), and MR robust adjusted profile score (MR.RAPS) were employed to analyze the impact of gut microbiota on the risk of allergic conjunctivitis and identify allergic conjunctivitis-related gut microbes. Ultimately, these findings may enable the identification of individuals at risk of allergic conjunctivitis through screening of gut microbial imbalances, and allow for new targeted prevention and personalized treatment strategies. Results: Genetic liability to Ruminococcaceae_UCG_002 (OR, 0.83; 95% CI, 0.70-0.99; P = 4.04×10-2), Holdemanella (OR, 0.78; 95% CI, 0.64-0.96; P = 2.04×10-2), Catenibacterium (OR, 0.69; 95% CI, 0.56-0.86; P = 1.09×10-3), Senegalimassilia (OR, 0.71; 95% CI, 0.55-0.93; P = 1.23×10-2) genus were associated with a low risk of allergic conjunctivitis with IVW. Besides, we found suggestive associations of a genetic-driven increase in the Oscillospira (OR, 1.41; 95% CI, 1.00-2.00; P = 4.63×10-2) genus with a higher risk of allergic conjunctivitis. Moreover, MLE and MR.RAPS show consistent results with IVW after further validation and strengthened confidence in the true causal associations. No heterogeneity and pleiotropy was detected. Conclusions: Our study suggests that gut microbiota may play a causal role in the development of allergic conjunctivitis and provides new insights into the microbiota-mediated mechanism of the disease. Gut microbiota may serve as a target for future predictive diagnostics, targeted prevention, and individualized therapy in allergic conjunctivitis, facilitating the transition from reactive medical services to PPPM in the management of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00321-9.

Alterations in Macular Microvasculature in Pterygium Patients Measured by OCT Angiography.

Previous studies have reported an association between pterygia and maculopathy, yet the underlying mechanisms and alterations to the macular microvasculature in pterygium patients have yet to be fully elucidated. Our study conducted an analysis of macular superficial vessel length density (VLD) and vessel perfusion density (VPD) to establish associations between the conjunctival and macular microvasculature in patients with unilateral and bilateral pterygia. We revealed a loss of macular microvasculature in the outer nasal (ON) region in both unilateral and bilateral pterygium patients. VLD was significantly decreased in both pterygium groups in the ON region, and VPD was notably lower in bilateral pterygium patients in the same area. Furthermore, in unilateral pterygium patients, the vessel percent pixel coverage (PPC) of the pterygium and the area of the pterygium exhibited a negative correlation with VLD in the ON region. Multiple stepwise linear regression models indicated that the PPC could best predict VLP in the ON region. Taken together, our findings suggest that patients with pterygia may be more susceptible to macular diseases, and this may be due to a compensatory increase in blood perfusion via the anterior ciliary artery. These results underscore the importance of managing maculopathy in patients with pterygia.

Body shape and risk of glaucoma: A Mendelian randomization.

Background: Body size (BS) is one of the risk factors for the development of many clinical diseases, but the relationship between BS and glaucoma is controversial. Herein, we try to use Mendelian randomization (MR) method to study BS causal association with glaucoma risk from the genetic level. Methods: The Body Size was determined through anthropometric traits (ATs), such as body mass index (BMI), waist-to-hip ratio adjusted by body mass index (WHRadjBMI), waist-to-hip ratio (WHR), and waist circumference (WC). Association of single nucleotide polymorphisms (SNPs) with each AT and glaucoma were determined individually from the aggregated data of the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the FinnGen study summary data (8,591 cases with glaucoma and 210,201 controls). To explore the role of BS and glaucoma, a two-sample MR analysis was performed on genome-wide association study (GWAS) data. Besides, three MR methods [inverse variance weighted (IVW), Weighted median, and MR-Egger regression] were used to get the whole causal estimate for multiple instrumental SNPs. Results: BMI (OR = 1.20; 95% CI = 1.02-1.41; P = 0.03) and WC (OR = 1.32; 95% CI =1.04-1.69; P = 0.03) were associated with a risk of glaucoma. Besides, genetically predicted WHRadjBMI (OR = 1.10; 95% CI = 0.88-1.35; P = 0.43) and WHR (OR = 1.22; 95% CI = 0.93-1,572; P = 0.14) were not associated with glaucoma. No heterogeneity and directional pleiotropy were detected. Conclusion: The data of this study revealed that increased BMI and WC are potential risk factors for glaucoma, and WHRadjBMI and WHR are not associated with the occurrence of glaucoma.

Association of mTORC1­dependent circulating protein levels with cataract formation: a mendelian randomization study.

BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development. RESULTS: The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P<5 × 10- 6 and r2<0.05, were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR study. The study revealed causal association between circulating EIF4EBP (OR 1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW estimate. Whereas after correcting outliers, MR robust adjusted profile score (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 95%CI:1.05-1.11, P = 0.007). The observation strengthened the confidence in the true causal associations. However, no association was found for circulating EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No evidence of heterogeneity and unbalanced horizontal pleiotropy was detected. CONCLUSION: The MR study suggests that EIF4EBP is a high-risk factor for cataract development. There may be a potential causal association between the mTORC1/EIF4EBP axis and cataract. This research highlights the potential mechanism for cataract development and a genetic target to prevent as well as treat cataracts.

Robust Electrocatalytic Li2 S Redox of Li-S Batteries Facilitated by Rationally Fabricated Dual-Defects.

The commercialization of lithium-sulfur batteries with ultra-high theoretical energy density is restricted mainly by the notorious polysulfides "shuttle effect" and slow Li2 S redox reaction kinetics. A sulfur host material with high catalytic activity and high conductivity is greatly desired to improve its electrochemical performance. Herein, a sulfur host material, etched cotton@petroleum asphalt carbon (eCPAC), with high specific surface area and excellent catalytic activity, is demonstrated based on a synergistic strategy of introducing intrinsic lattice defects and composite carbon structure. Benefiting from in situ coupling of amorphous and crystalline materials, eCPAC exhibits high conductivity and high sulfur adsorbability. Furthermore, eCPAC containing dual intrinsic defect sites can catalyze the bidirectional sulfur chemistry of Li2 S and capture polysulfides, which is also demonstrated by systematic density functional theory calculations and the potential intermittent titration technique. S@eCPAC/Li cells exhibit excellent cycling stability and rate performance, with an average capacity decay rate of only 0.05% over 1000 cycles at 0.5 C and even 0.03% over 600 cycles at 5 C. Meanwhile, the practicality of eCPAC is proven in high-load batteries and pouch batteries. eCPAC provides a reliable strategy for achieving a win-win situation of capturing polysulfides and accelerating Li2 S redox kinetics.

Emerging Strategies for Gel Polymer Electrolytes with Improved Dual-Electrode Side Regulation Mechanisms for Lithium-Sulfur Batteries.

Although GPE still has the risk of shuttling due to the incomplete removal of liquid electrolytes compared to SPE, which has the most promise of eliminating polysulfide shuttling, researchers have made abundant efforts to eliminate as much of the polysulfide shuttling effect as possible while retaining the unique advantages of GPE. For example, physical barrier to polysulfides by improving the pore size of GPE or fabricating multidimensional structures by different preparation methods. Further chemical adsorption of polysulfides by adding nanofillers to increase polar sites to create polar-polar interactions with polysulfides or to create Lewis acid-base interactions. However, although chemical adsorption can indeed highly immobilize polysulfides, it still brings disadvantages such as loss of active material. Therefore, other researchers have employed GPE with ion-selective permeability that has electrostatic repulsive force or steric hindrance to polysulfides to better inhibit polysulfide shuttling. However, modifying only the cathode side is not enough to enhance this overall properties of Li-S cells. These problems of poor Li+ transport, lithium dendrite growth, and poor SEI due to uneven lithium ion deposit on Li anode side still affect the overall performance of Li-S cells. Therefore, a GPE to improve these problems on the Li anode side is summarized below. Compared with an all-solid electrolyte, GPE, which has a partially liquid electrolyte, clearly has advantages such as strong interfacial contact, good anode interface compatibility, and high flexibility. However, it is still not comparable to the ionic conductivity, etc. of pure liquid electrolyte only. Therefore, the problems on the lithium metal anode side are mainly focused on the lithium ion transport problems and the problems of lithium dendrite growth and inhomogeneous SEI at the lithium anode interface. Facing the problems in these two aspects, researchers have given many improvement solutions respectively. For the lithium ion transport problem, researchers have instead provided pathways for lithium ion transport by adding amorphous nanofibers or nanofillers to reduce the crystallinity of the polymer and improve the ionic conductivity. Alternatively, the migration number of lithium ions can be increased by limiting the anions in the electrolyte. As for the interfacial problems of lithium anodes, researchers have effectively suppressed the growth of lithium dendrites or inhomogeneous lithium plating/stripping phenomena mainly by adding nanofillers to increase the mechanical strength of GPE or by participating in the generation of SEI.

Implicating Causal Brain Magnetic Resonance Imaging in Glaucoma Using Mendelian Randomization.

Background: Glaucoma is hypothesized to originate in the brain but manifests as an eye disease as it possesses the common features of neurodegeneration diseases. But there is no evidence to demonstrate the primary brain changes in glaucoma patients. In the present study, we have used Mendelian randomization (MR) to understand the causal effect of brain alterations on glaucoma. Methods: Our MR study was carried out using summary statistics from genome-wide associations for 110 diffusion tensor imaging (DTI) measurements of white matter (WM) tracts (17,706 individuals), 101 brain region-of-interest (ROI) volumes (19,629 individuals), and glaucoma (8,591 cases, 210,201 control subjects). The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method and verified by two other MR methods, including MR Egger, weighted median, and extensive sensitivity analyses. Results: Genetic liability to fornix fractional anisotropy (FX.FA) (OR = 0.71, 95%CI = 0.56-0.88, P = 2.44 × 10-3), and uncinate fasciculus UNC.FA (OR = 0.65, 95%CI = 0.48-0.88, P = 5.57 × 10-3) was associated with a low risk of glaucoma. Besides, the right ventral diencephalon (OR = 1.72, 95%CI = 1.17-2.52, P = 5.64 × 10-3) and brain stem (OR = 1.35, 95%CI = 1.08-1.69, P = 8.94 × 10-3) were associated with the increased risk of glaucoma. No heterogeneity and pleiotropy were detected. Conclusion: Our study suggests that the fornix and uncinate fasciculus degenerations and injures of the right ventral diencephalon and brain stem potentially increase the occurrence of glaucoma and reveal the existence of the brain-eye axis.

Improved Dry Eye Symptoms and Signs of Patients With Meibomian Gland Dysfunction by a Dietary Supplement.

Purpose: To explore the therapeutic effect of a dietary supplement on dry eye with meibomian gland dysfunction (MGD). Methods: Sixty patients with MGD-related dry eye were included in this prospective and randomized, placebo-controlled study. All the subjects were treated with eye hot compress, artificial tears, and antibiotic ointment. After that, the patients received dietary supplementary or placebo daily for 12 weeks. The dry eye signs, function of MG, and visual quality of the patients were assessed at 4, 8, and 12 weeks after the treatment. Results: Twelve weeks after the treatment, patients who received dietary supplement had a significantly better improvement of dry eye symptoms, in terms of ocular surface diseases index and tear breaking-up time (TBUT), than those who received placebo (P < 0.05). The functions of MG, in terms of meibum quality and MG exclusion and MG obstruction scores, were significantly improved in both dietary supplement and placebo groups (P < 0.05). Patients who received dietary supplement had a significantly better improvement in the MG structure, in terms of acinar diameter and acinar density, than those who received placebo (P < 0.05). The number of inflammatory cells near MG was significantly lower in the dietary supplement group when compared with the placebo group (P < 0.05). The objective visual quality was significantly improved in the dietary supplement group, but not in the placebo group (P < 0.05). Conclusion: The dietary supplement can effectively improve the symptoms and signs of MGD-related dry eye, reduce the inflammatory reaction of MG, restore the gland structure, and indirectly improve the visual quality.

Core-Shell Structured o-LiMnO2@Li2CO3 Nanosheet Array Cathode for High-Performance, Wide-Temperature-Tolerance Lithium-Ion Batteries.

To develop a high-capacity, high-rate, cycle-stable cathode material has long been the focus for lithium-ion battery (LIB) research. Recently, layer-structured orthorhombic-LiMnO2 (o-LMO) has attracted extensive interest owing to its large discharge capacities. However, poor cycle performance greatly hinders its practical application, especially at high temperatures. Conventional strategies to address this issue often lead to sacrificed rate performance and mostly work at low temperatures. Herein, we report a novel core-shell structured, o-LiMnO2@Li2CO3 (o-LMO@Li2CO3) nanosheet array cathode, where the Li2CO3 shell improves cycle performance by preventing o-LMO dissolution in the electrolyte (even at an elevated temperature), the o-LMO core provides high capacities and the nanosheet array architecture ensures rate performance (to the best of our knowledge, this o-LMO nanosheet array architecture is reported for the first time). The above features work synergistically to give well-balanced cycle performance (79% capacity retention at 60 °C, 400 cycles), capacity (207 mAh g(-1) at 0.5C) and rate performance (128 mAh g(-1) at 5C) of the o-LMO@ Li2CO3 cathode as well as remarkable full-cell performance (∼67% capacity retention for 400 cycles at ∼2C, 60 °C). Our work demonstrates that the synergistic effect between the o-LMO core, Li2CO3 coating and the nanoarray structure is an effective strategy for developing high-energy/power density, high-stability LIB cathodes.

[Simultaneous synchronous spectrofluorimetric determination of vitamin B1, B2 and B6 by PARAFAC].

In the present study, a synchronous spectronfluorimetric method has been applied to the simultaneous determination of vitamin B1, B2 and B6. However, their spectra are overlapped so it is difficult to determine them individually. The parallel factor analysis (PARAFAC) was applied to the resolution of the overlapped spectra of mixtures of vitamin B1, B2 and B6. The delta wavelength range used was from 20 to 120 nm, and the excitation wavelength range was selected from 200 to 500 nm. From the measured fluorescence data a four-factor PARAFAC model was established, and was applied to the determination of a set of synthetic validation samples and some commercial samples with satisfactory results. This work shows that PARAFAC method is a powerful chemometric tool to the determination of mixtures of vitamin Bl, B2 and B6.