Vision Improvement in Keratoconus Patients Trained With Perceptual Learning: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness and maintenance of perceptional learning (PL) on vision improvement in keratoconus (KC) patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. METHODS: Non-progressive KC patients 9 years of age or older who had best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and who were contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs 0.02 ± 0.06 logMAR; P = .0006). Eight of 17 (47.06%) patients in the PL group reached CDVA improvement ≥2 lines (P = .0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs 0.01 ± 0.07 logMAR; P = .0011). The increase in CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = .009). No side effects were observed, and no subjects withdrew from the study because of training difficulties. CONCLUSIONS: Three-month PL improved vision in KC patients, and the improvement was maintained after 3 months of treatment cessation. The results indicate that PL may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

Full-Length Transcriptome Construction and Systematic Characterization of Virulence Factor-Associated Isoforms in Vairimorpha (Nosema) Ceranae.

Vairimorpha (Nosema) ceranae is a single-cellular fungus that obligately infects the midgut epithelial cells of adult honeybees, causing bee microsporidiosis and jeopardizing bee health and production. This work aims to construct the full-length transcriptome of V. ceranae and conduct a relevant investigation using PacBio single-molecule real-time (SMRT) sequencing technology. Following PacBio SMRT sequencing, 41,950 circular consensus (CCS) were generated, and 25,068 full-length non-chimeric (FLNC) reads were then detected. After polishing, 4387 high-quality, full-length transcripts were gained. There are 778, 2083, 1202, 1559, 1457, 1232, 1702, and 3896 full-length transcripts that could be annotated to COG, GO, KEGG, KOG, Pfam, Swiss-Prot, eggNOG, and Nr databases, respectively. Additionally, 11 alternative splicing (AS) events occurred in 6 genes were identified, including 1 alternative 5' splice-site and 10 intron retention. The structures of 225 annotated genes in the V. ceranae reference genome were optimized, of which 29 genes were extended at both 5' UTR and 3' UTR, while 90 and 106 genes were, respectively, extended at the 5' UTR as well as 3' UTR. Furthermore, a total of 29 high-confidence lncRNAs were obtained, including 12 sense-lncRNAs, 10 lincRNAs, and 7 antisense-lncRNAs. Taken together, the high-quality, full-length transcriptome of V. ceranae was constructed and annotated, the structures of annotated genes in the V. ceranae reference genome were improved, and abundant new genes, transcripts, and lncRNAs were discovered. Findings from this current work offer a valuable resource and a crucial foundation for molecular and omics research on V. ceranae.

Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort.

OBJECTIVE: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation. METHODS: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed. RESULTS: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05). CONCLUSIONS: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Seasonal variations and the prevalence of phenolic profiles in ambient fine particulate matter and their impact on oxidative potential.

Exposure to fine particulate matter (PM2.5) poses numerous health risks, with oxidative potential (OP) serving as a critical marker of its toxicity. Synthetic phenolic antioxidants (SPAs) and bisphenols (BPs) influence reactive oxygen species (ROS) levels in PM2.5, and exposure to these compounds induces oxidative stress in organisms, thereby potentially affecting the OP of PM2.5. We detected 26 phenols (including 12 SPAs, 5 transformation products (TPs), and 9 BPs) in PM2.5 sample collected from October 2018 to September 2021 in Wuhan, China. Among them, 19 substances were detected at a detection frequency greater than 50 % in PM2.5 sample. AO 2246 and BHT were the main components of SPAs, and BHT-Q and BPA had the highest concentrations in TPs and BPs, respectively. PM2.5 mass concentrations and phenolic levels were higher in winter and autumn. Substances within groups were strongly correlated, suggesting the same or similar source of exposure. This finding aid in more precise pollution source identification and is crucial for comprehensively evaluating their combined health effects. Furthermore, we determined the OP of PM2.5 and found that BPs were related to increased OP and ROS. This suggests that the toxicity of PM2.5 is influenced not only by its concentration but also by its chemical composition, with BPs potentially enhancing its toxic effects. These factors should be fully considered when assessing the health impacts of PM2.5.

NMC3D: Non-Overlapping Multi-Camera Calibration Based on Sparse 3D Map.

With the advancement of computer vision and sensor technologies, many multi-camera systems are being developed for the control, planning, and other functionalities of unmanned systems or robots. The calibration of multi-camera systems determines the accuracy of their operation. However, calibration of multi-camera systems without overlapping parts is inaccurate. Furthermore, the potential of feature matching points and their spatial extent in calculating the extrinsic parameters of multi-camera systems has not yet been fully realized. To this end, we propose a multi-camera calibration algorithm to solve the problem of the high-precision calibration of multi-camera systems without overlapping parts. The calibration of multi-camera systems is simplified to the problem of solving the transformation relationship of extrinsic parameters using a map constructed by multiple cameras. Firstly, the calibration environment map is constructed by running the SLAM algorithm separately for each camera in the multi-camera system in closed-loop motion. Secondly, uniformly distributed matching points are selected among the similar feature points between the maps. Then, these matching points are used to solve the transformation relationship between the multi-camera external parameters. Finally, the reprojection error is minimized to optimize the extrinsic parameter transformation relationship. We conduct comprehensive experiments in multiple scenarios and provide results of the extrinsic parameters for multiple cameras. The results demonstrate that the proposed method accurately calibrates the extrinsic parameters for multiple cameras, even under conditions where the main camera and auxiliary cameras rotate 180°.

Characterizing Retinal Sensitivity and Structure in Congenital Stationary Night Blindness: A Combined Microperimetry and OCT Study.

Purpose: To investigate the characteristics of microperimetry and optical coherence tomography (OCT) in congenital stationary night blindness (CSNB), as well as their structure-function association. Methods: This cross-sectional study included 32 eyes from 32 participants with CSNB, comprising 18 with complete CSNB and 14 with incomplete CSNB, along with 36 eyes from 36 CSNB-unaffected controls matched for age, sex, and spherical equivalent. Using MP-3 microperimetry, central retinal sensitivity was assessed within a 20° field, distributed across six concentric rings (0°, 2°, 4°, 6°, 8°, and 10°). OCT was used to analyze retinal and choroidal thickness. The study aimed to assess the overall and ring-wise retinal sensitivity, as well as choroidal and retinal thickness in CSNB and CSNB-unaffected controls, with a secondary focus on the relationship between retinal sensitivity and microstructural features on OCT. Results: In comparison with CSNB-unaffected subjects, the overall and ring-wise retinal sensitivity as well as choroidal thickness were reduced in patients with CSNB (P < 0.001). Moreover, the central sensitivity in incomplete CSNB group was lower than in complete CSNB group (25.72 ± 3.93 dB vs. 21.92 ± 4.10 dB; P < 0.001). The retinal thickness in the CSNB group was thinner outside the fovea compared with the CSNB-unaffected group. Multiple mixed regression analyses revealed that point-to-point retinal sensitivity was significantly correlated with BCVA (P = 0.002) and the corresponding retinal thickness (P = 0.004). Conclusions: Examination of retinal sensitivity and OCT revealed different spatial distribution profiles in CSNB and its subtypes. In CSNB eyes, retinal sensitivity on microperimetry was associated with retinal thickness on OCT.

Chitosan-based packaging films with antibacterial-sterilization integrated continuous activity for extending the shelf life of perishable foods.

The current food packaging films can be preservative but lack the function of combining antibacterial and sterilization which lead to films can not maximize prolong shelf life of perishable foods. This study provided a new strategy to realize prolonging shelf life of perishable foods by integrating antibacterial and sterilization which focused on applying photodynamic inactivation to films with continuous activity, where curcumin (CUR) and sodium copper chlorophyll (SCC) were loaded into chitosan (CS) films. Compared to pure CS films, the barrier capacity (oxygen permeability and water vapor permeability) and mechanical properties of composite films were improved by introducing CUR and SCC. In addition, the composite film can effectively against food-borne pathogenic bacteria and significantly prolong the shelf life of cherries and pork. The provided strategy has potential application prospects in food preservation packaging.

Prognostic biomarker NRG2 correlates with autophagy and epithelial­mesenchymal transition in breast cancer.

Breast cancer (BRCA) is a leading cause of death in women worldwide, accounting for 31% of female cancer. Autophagy plays a crucial role in cancer progression, however, the function of autophagy-related gene neuroregulatory protein 2 (NRG2) in BRCA and its underlying molecular mechanisms remain unclear. In the present study, the expression of the NRG2 gene in BRCA was significantly down-regulated compared with the normal controls. The low expression level of NRG2 was related to poor survival rate of BRCA. The receiver operating characteristic curve of NRG2 showed a good diagnostic value for distinguishing BRCA from normal tissues (AUC=0.932). GO-KEGG analysis and GSEA enrichment analysis showed that NRG2 and its regulated genes were enriched in autophagy-related and immune-related pathways, and NRG2 was positively correlated with a number of immune cells and immune checkpoint genes. In addition, knockdown of NRG2 significantly promoted the proliferation, invasion and migration of BRCA cells. The autophagy marker, LC3-II and epithelial-mesenchymal transition (EMT) marker, vimentin were increased, while P62 and E-cadherin were decreased in response to NRG2 depletion. The findings of the present study demonstrated that NRG2 acts as a tumor suppressor factor that contributes to the immune escape and anti-tumor immunity inhibition by regulating the pathological process of autophagy and EMT, suggesting that NRG2 could be used as a prognostic biomarker and clinical target for BRCA therapy.

Prevalence of synthetic phenolic antioxidants in food contact materials from China and their implications for human dietary exposure through take-away food.

The application of disposable tableware has increased substantially in recent times due to the rapidly growing food delivery business in China. Synthetic phenolic antioxidants (SPAs) are widely used in food contact materials (FCMs) to delay the process of oxidation; however, their compositions, concentrations, and potential health hazards remain unclear. Therefore, FCMs comprised of five materials obtained from 19 categories (n = 118) in China were analyzed for SPAs concentrations. FCMs have been found to contain a variety of SPAs, with ∑SPAs concentrations ranging from 44.18 to 69,485.12 µg/kg (median: 2615.63 µg/kg). The predominant congeners identified in the sample include 2,4-di-tert-butylphenol (2,4-DTBP), 2,6-di-tert-butylphenol (2,6-DTBP), and 2,6-di-tert-butyl-p-benzoquinone (BHT-Q) with a median concentration of 885.75, 555.45 and of 217.44 µg/kg, respectively. Milky tea paper cups, instant noodle buckets, milky teacups, and disposable cups showed high levels of SPAs. 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (AO 2246) was predominantly detected in polyethylene and polyethylene terephthalate-based products. The migration test identified disposable plastic cups and bowls as the predominant FCMs and 2,4-DTBP as the dominant SPA. The exposure risk of SPAs decreased with age. In children, the estimated daily intake of ∑SPAs from FCMs was determined to be 17.56 ng/kg body weight/day, which was 8.3 times higher than that of phthalic acid esters. The current findings indicate the potential ingestion risk of SPAs during the daily life application of multiple FCM categories.

Human Biomonitoring of Environmental Chemicals among Elderly in Wuhan, China: Prioritizing Risks Using EPA's ToxCast Database.

In line with the "healthy aging" principle, we aim to assess the exposure map and health risks of environmental chemicals in the elderly. Blood samples from 918 elderly individuals in Wuhan, China, were analyzed using the combined gas/liquid-mass spectrometry technology to detect levels of 118 environmental chemicals. Cluster analysis identified exposure profiles, while risk indexes and bioanalytical equivalence percentages were calculated using EPA's ToxCast database. The detection rates for 87 compounds exceeded 70%. DEHP, DiBP, naphthalene, phenanthrene, DnBP, pyrene, anthracene, permethrin, fluoranthene, and PFOS showed the highest concentrations. Fat-soluble pollutants varied across lifestyles. In cluster 2, which was characterized by higher concentrations of fat-soluble substances, the proportion of smokers or drinkers was higher than that of nonsmokers or nondrinkers. Pesticides emerged as the most active environmental chemicals in peroxisome proliferator-activated receptor gamma antagonist, thyroid hormone receptor (TR) antagonist, TR agonist, and androgen receptor (AR) agonist activity assays. Additionally, PAEs and polycyclic aromatic hydrocarbons played significant roles as active contaminants for the corresponding targets of AR antagonists and estrogen receptor alpha. We proposed a list of priority pollutants linked to endocrine-disrupting toxic effects in the elderly, which may provide the groundwork for further research into environmental etiology.

Prediction of breast cancer and axillary positive-node response to neoadjuvant chemotherapy based on multi-parametric magnetic resonance imaging radiomics models.

PURPOSE: Accurate identification of primary breast cancer and axillary positive-node response to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategies. We aimed to develop combining models based on breast multi-parametric magnetic resonance imaging and clinicopathologic characteristics for predicting therapeutic response of primary tumor and axillary positive-node prior to treatment. MATERIALS AND METHODS: A total of 268 breast cancer patients who completed NAC and underwent surgery were enrolled. Radiomics features and clinicopathologic characteristics were analyzed through the analysis of variance and the least absolute shrinkage and selection operator algorithm. Finally, 24 and 28 optimal features were selected to construct machine learning models based on 6 algorithms for predicting each clinical outcome, respectively. The diagnostic performances of models were evaluated in the testing set by the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: Of the 268 patients, 94 (35.1 %) achieved breast cancer pathological complete response (bpCR) and of the 240 patients with clinical positive-node, 120 (50.0 %) achieved axillary lymph node pathological complete response (apCR). The multi-layer perception (MLP) algorithm yielded the best diagnostic performances in predicting apCR with an AUC of 0.825 (95 % CI, 0.764-0.886) and an accuracy of 77.1 %. And MLP also outperformed other models in predicting bpCR with an AUC of 0.852 (95 % CI, 0.798-0.906) and an accuracy of 81.3 %. CONCLUSIONS: Our study established non-invasive combining models to predict the therapeutic response of primary breast cancer and axillary positive-node prior to NAC, which may help to modify preoperative treatment and determine post-NAC surgery strategy.

Vimentin inhibits peste des petits ruminants virus replication by interaction with nucleocapsid protein.

The Peste des petits ruminant virus (PPRV) is a member of the Paramyxoviridae family and is classified into the genus Measles virus. PPRV predominantly infects small ruminants, leading to mortality rates of nearly 100%, which have caused significant economic losses in developing countries. Host proteins are important in virus replication, but the PPRV nucleocapsid (N) protein-host interacting partners for regulating PPRV replication remain unclear. The present study confirmed the interaction between PPRV-N and the host protein vimentin by co-immunoprecipitation and co-localization experiments. Overexpression of vimentin suppressed PPRV replication, whereas vimentin knockdown had the opposite effect. Mechanistically, N was subjected to degradation via the ubiquitin/proteasome pathway, where vimentin recruits the E3 ubiquitin ligase NEDD4L to fulfill N-ubiquitination, resulting in the degradation of the N protein. These findings suggest that the host protein vimentin and E3 ubiquitin ligase NEDD4L have an anti-PPRV effect.

Hydrogen sulfide improves endothelial barrier function by modulating the ubiquitination degradation of KLF4 through TRAF7 S-sulfhydration in diabetic aorta.

Anomalous vascular endothelium significantly contributes to various cardiovascular diseases. VE-cadherin plays a vital role in governing the endothelial barrier. Krüppel-like factor 4(KLF4), as a transcription factor, which binds the VE-cadherin promoter and enhances its transcription. Tumor necrosis factor receptor-associated factor 7 (TRAF7) is an E3 ubiquitin ligase that has been shown to modulate the degradation of KLF4. H2S can covalently modify cysteine residues on proteins through S-sulfhydration, thereby influencing the structure and functionality of the target protein. However, the role of S-sulfhydration on endothelial barrier integrity remains to be comprehensively elucidated. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates endothelial integrity and its underlying mechanism. In this study, we observed that protein S-sulfhydration was reduced in the endothelium during diabetes and TRAF7 was the main target. Overexpression of TRAF7-Cys327 mutant could mitigate the endothelial barrier damage by weakening TRAF7 interaction with KLF4 and reducing ubiquitination degradation of KLF4. In conclusion, our research demonstrates that H2S plays a pivotal role in regulating S-sulfhydration of TRAF7 at Cys327. This regulation effectively inhibits the ubiquitin-mediated degradation of KLF4, resulting in an upregulation of VE-cadherin levels. This molecular mechanism contributes to the prevention of endothelial barrier damage.

Characterization of Lower Paleozoic Water and Gas Distribution in Yan'an Gas Field, Ordos Basin.

The distribution of gas and water in the tight gas reservoirs is complex. This limits exploration and development compared to conventional resources. Elucidating the characteristics that control fluid distribution is critical to unlocking the tight gas potential. This study combines geologic analysis with production data to reveal the water chemistry, gas-water distribution, and factors controlling zoning in the study area. The results show that (a) extracted water includes formation brines, condensate, and residual drilling fluids; (b) formation water dominates production, and the salinity of Lower Paleozoic brines is as high as 169,689 mg/L; (c) low NaCl and high metamorphic coefficients indicate that the water bodies are disconnected and the hydrocarbons are well-preserved in several gas-water systems; and (d) paleomorphological features, tectonics, and lithologies control the distribution of gas water. Discrete water bodies are widely distributed.

Developments in Negative-Strand RNA Virus Reverse Genetics.

Many epidemics are caused by negative-stranded RNA viruses, leading to serious disease outbreaks that threaten human life and health. These viruses also have a significant impact on animal husbandry, resulting in substantial economic losses and jeopardizing global food security and the sustainable livelihoods of farmers. However, the pathogenic and infection mechanism of most negative-stranded RNA viruses remain unclear. Reverse genetics systems are the most powerful tools for studying viral protein function, viral gene expression regulation, viral pathogenesis, and the generation of engineered vaccines. The reverse genetics of some negative-strand viruses have been successfully constructed, while others have not. In this review, we focus on representative viruses from the Orthomyxoviridae family (IAV), the Filoviridae family (EBOV), and the Paramyxoviridae family (PPRV) to compile and summarize the existing knowledge on reverse genetics techniques for negative-strand viruses. This will provide a theoretical foundation for developing reverse genetics techniques for some negative-strand viruses.

Exogenous hydrogen sulfide prevents SOD2 degradation to safeguard renal function in diabetic kidney disease.

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease. Hydrogen sulfide (H2S) serves as an endogenous gaseous signaling molecule capable of safeguarding renal function within the context of DKD. However, the underlying mechanisms need to be elucidated. This study was undertaken to unveil the mechanisms by which H2S counteracts against DKD. Utilizing mice and human renal tubular epithelial (HK-2) cells, we demonstrated a reduction in cystathionine-γ-lyase/H2S levels within renal tissues of db/db mice and in HK-2 cells subjected to hyperglycemic and hyperlipidemic environments. Notably, we observed that sodium hydrosulfide (NaHS) supplementation could serve as an exogenous source of H2S. Exogenous H2S exhibited the capacity to mitigate the accumulation of reactive oxygen species and attenuate the degradation of superoxide dismutase 2 (SOD2) by Lon protease homolog 1 induced by hyperglycemia and hyperlipidemia, thus affording cellular protection against mitochondrial apoptosis. Consequently, NaHS treatment led to decreased serum levels of blood urea nitrogen and serum creatinine, reflecting alleviated renal damage and thereby preserving renal function in db/db mice. Based on these findings, we propose that exogenous H2S exerts a protective role against DKD by inhibiting SOD2 degradation.

[Effect of signal peptide optimized by site-directed mutagenesis on the function of chimeric antigen receptor T cells].

Signal peptides (SP) are involved in regulating the secretion level and transmembrane translocation of chimeric antigen receptors (CAR), which is crucial for CAR-T cells. This study aimed to optimize the SP sequence by site-directed mutagenesis and investigate its impact on the killing function of CD19-CAR-T. Firstly, CAR vectors targeting CD19 containing wild-type SP (SP-wtY) or two mutant SP (SP-muK or SP-muR) were constructed using gene synthesis and molecular cloning techniques. The successfully constructed vector was packaged with lentivirus, and T cells were infected. The transfection efficiency of T cells was detected by flow cytometry, while the killing effect on target cells was assessed using the calcein release method. The secretion levels of cytokines interferon-γ (IFN-γ) and interferon-α (TNF-α) were measured using enzyme linked immunosorbent assay (ELISA). The results showed that successful construction of recombinant lentivirus plasmids with wild type and signal peptide mutation. After the transferring the lentivirus into T cells, the transfection efficiency of CD19-CAR carrying three signal peptides (SP-wtY, SP-muK, or SP-muR) were 33.9%, 35.5%, and 36.8%, respectively. Further killing assay showed that the tumor-killing effect of SP-muR cells was significantly higher than that of SP-muK and SP-wtY cells. When the ratio of effector to target was 10:1, the secretion levels of cytokines IFN-γ and TNF-α of CAR-T cells of the SP-muR group were significantly higher than those in SP-muK and SP-wtY groups. In summary, this study revealed that increasing the N-terminal positive charge of the signal peptide can improve the expression efficiency of CAR and promote the killing of CD19+ target cells. These findings provide a scientific basis the optimization and clinical application of CAR structure.

Long-term effect of orthokeratology on choroidal thickness and choroidal contour in myopic children.

PURPOSE: To investigate the long-term effect of orthokeratology (ortho-k) on the choroidal thickness and choroidal contour in myopic children. METHODS: Subjects were from a conducted 2-year randomised clinical trial. Children (n=80) aged 8-12 years with spherical equivalent refraction of -1.00 to -6.00D were randomly assigned to the control group (n=40) and ortho-k group (n=40). Optical coherence tomography images were collected at the baseline, 1-month, 6-month, 12-month, 18-month and 24-month visits, then the choroidal thickness and choroid contour were calculated. Axial length (AL) and other ocular biometrics were also measured. RESULTS: During 2 years, in the control group, the choroidal thickness became thinning and the choroidal contour became prolate with time at all visits (all p<0.001). Ortho-k can improve the choroidal thickness (all p<0.001) and maintain the choroidal contour at all visits (all p<0.05). In the ortho-k group, the choroidal contour was less changed in the temporal than nasal (p=0.008), and the choroidal thickness was more thickening in the temporal 3 mm (p<0.001). Two-year change in choroidal thickness was significantly associated with the 2-year AL change in the control group (r=-0.52, p<0.001), however, this trend was broken by ortho-k (r=-0.05, p=0.342). After being adjusted by other variables in the multivariable regression model, the effect of ortho-k on choroidal thickness was stable. CONCLUSIONS: In the current 2-year prospective study, ortho-k can improve the choroidal thickness and maintain the choroidal contour, but this effect diminished in a long term. Further study with larger sample size and longer follow-up is warranted to refine this issue.

Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment.

Ferroptosis, a novel form of cell death triggered by iron-dependent phospholipid peroxidation, presents significant therapeutic potential across diverse cancer types. Central to cellular metabolism, the metabolic pathways associated with ferroptosis are discernible in both cancerous and immune cells. This review begins by delving into the intricate reciprocal regulation of ferroptosis between cancer and immune cells. It subsequently details how factors within the tumor microenvironment (TME) such as nutrient scarcity, hypoxia, and cellular density modulate ferroptosis sensitivity. We conclude by offering a comprehensive examination of distinct immunophenotypes and environmental and metabolic targets geared towards enhancing ferroptosis responsiveness within the TME. In sum, tailoring precise ferroptosis interventions and combination strategies to suit the unique TME of specific cancers may herald improved patient outcomes.