Efficacy of orthokeratology lens with the modified small treatment zone on myopia progression and visual quality: a randomized clinical trial.

BACKGROUND: To evaluate the long-term effectiveness of orthokeratology (ortho-K) lenses with small treatment zone (STZ) or conventional treatment zone (CTZ) in controlling axial elongation in children with myopia as well as the impact on visual quality. We also sought to determine the effect of retinal visual signal quality on axial elongation. METHODS: This is a prospective randomized controlled study. A total of 140 participants (age ranging from 8 to 12 years) were randomly assigned to wear either STZ or CTZ ortho-K lenses. STZ ortho-K lenses design was achieved by changing the depth of reverse zone and the sagitta height of the optical zone. Using the IOL-Master 500, axial length (AL) was measured at baseline and after 6, 12 and 18 months of ortho-K treatment. Spherical aberration (SA) and corneal topographic parameters were obtained by the Pentacam anterior segment analyzer at baseline and the 1-month follow-up visit, and optical qualities were assessed by optical quality analysis system-II (OQAS-II) at baseline and after 1 month of lens wearing. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, Strehl ratio (SR), objective scattering index (OSI), and predicted visual acuity (PVA). RESULTS: A total of 131 participants completed the study, including 68 in the STZ group and 63 in the CTZ group. The STZ group had significantly reduced AL elongation compared to the CTZ group after treatment (12 months: 0.07 ± 0.11 mm vs. 0.14 ± 0.12 mm, P = 0.002; 18 months: 0.17 ± 0.15 mm vs. 0.26 ± 0.16 mm, P = 0.002). The topography in the STZ group showed a smaller treatment zone (TZ) diameter (2.50 ± 0.23 mm vs. 2.77 ± 0.18 mm, P < 0.001), a wider defocus ring width (2.45 ± 0.28 mm vs. 2.30 ± 0.30 mm, P = 0.006), and larger values of total amount of defocus (119.38 ± 63.71 D·mm2 vs. 91.40 ± 40.83 D·mm2, P = 0.003) and total SA (0.37 ± 0.25 µm vs. 0.25 ± 0.29 µm, P = 0.015), compared with the CTZ group. Objective visual quality decreased in both groups (P < 0.001). This was evidenced by a greater decrease in MTF cutoff (- 14.24 ± 10.48 vs. - 10.74 ± 9.46, P = 0.047) and SR values (- 0.09 ± 0.07 vs. - 0.06 ± 0.07, P = 0.026), and an increase in OSI value (0.84 ± 0.72 vs. 0.58 ± 0.53, P = 0.019). PVA9% decreased significantly in the STZ group but not the CTZ group. A statistically significant negative correlation was found between the changes in total SA and MTF cutoff values (r = - 0.202, P = 0.025). AL changes were associated with sex, change of MTF cutoff value, increment of total SA and TZ area. CONCLUSIONS: Compared with CTZ ortho-K lenses, STZ ortho-K lenses significantly inhibited axial elongation in children with myopia while moderately reducing their objective visual quality. Axial elongation was affected by retinal visual quality, and it may be a possible mechanism for ortho-K slowing myopia progression. Trial registration This trial is registered at Chinese Clinical Trial Registry on November 5, 2019 with trial registration number: ChiCTR1900027218. https://www.chictr.org.cn/showproj.html?proj=45380.

Rational design of anthocyanidins-directed near-infrared two-photon fluorescent probes.

Recently, two-photon fluorescent probes based on anthocyanidin molecules have attracted extensive attention due to their outstanding photophysical properties. However, there are only a few two-photon excited fluorescent probes that really meet the requirements of relatively long emission wavelengths (>600 nm), large two-photon absorption (TPA) cross-sections (300 GM), significant Stokes shift (>80 nm), and high fluorescence intensity. Herein, the photophysical properties of a series of anthocyanidins with the same substituents but different fluorophore skeletons are investigated in detail. Compared with b-series molecules, a-series molecules with a six-membered ring in the backbone have a slightly higher reorganization energy. This results in more energy loss upon light excitation, enabling the reaction products to detect NTR through a larger Stokes shift. More importantly, there is very little decrease in fluorescence intensity as the Stokes shift increases. These features are extremely valuable for high-resolution NTR detection. In light of this, novel 2a-n (n = 1-5) compounds are designed, which are accomplished by inhibiting the twisted intramolecular charge transfer (TICT) effect through alkyl cyclization, azetidine ring and extending π conjugation. Among them, 2a-3 gains a long emission spectrum (λem = 691.4 nm), noticeable TPA cross-section (957 GM), and large Stokes shift (110 nm), indicating that it serves as a promising candidate for two-photon fluorescent dyes. It is hoped that this work will offer some insightful theoretical direction for the development of novel high performance anthocyanin fluorescent materials.

Spontaneously Formed Ratio-Tunable Micro- and Nano-Capsule Coexist System for Precision and on-Demand Fungicide Delivery in Crop Leave.

Multiscale particle size functional pesticide carriers can provide more efficient protection for plants, but this protection is difficult to achieve via single-scale formulation technology. This study presents a novel one-step method for the preparation of lignin-based micro/nanocapsules with controllable proportions within a unified system. This strategy enables the adjustment of the proportion of nanocapsules to between 18.81% and 85.21%. The microcapsules (MCs) vary in diameter from 2 to 3 µm, whereas the nanocapsules (NCs) span from 160 to 220 nm, with an encapsulation efficiency exceeding 90%. An increased proportion of NCs in the system leads to faster release, heightened sensitivity to UV light, and enhanced penetration into the leaves. During Phytophthora capsici (P. capsici) infection, the NCs in the leaves interact with the defensive enzymes of the plant to quickly respond. Moreover, an optimal balance of MCs and NCs is key to effective fungicide use, not just a higher concentration of NCs. A 65:35 ratio of NCs to MCs ensures effective inhibition of P. capsici outside leaves and a rapid response to leaf invasion. This study enhances fungicide efficiency and advances the development of nanoresponsive fungicides to promote sustainable agricultural practices.

A model for electroencephalogram emotion recognition: Residual block-gated recurrent unit with attention mechanism.

Electroencephalogram (EEG) signals, serving as a tool to objectively reflect real emotional states, hold a crucial position in emotion recognition research. In recent years, deep learning approaches have been widely applied in emotion recognition research, and the results have demonstrated their effectiveness in this field. Nevertheless, the challenge remains in selecting effective features, ensuring their retention as the network depth increases, and preventing the loss of crucial information. In order to address the issues, a novel emotion recognition method is proposed, which is named Res-CRANN. In the proposed method, the raw EEG signals are transformed into four dimensional spatial-frequency-temporal information, which can provide a more enriched and complex feature representation. First, the residual block is incorporated into the convolutional layers to extract spatial and frequency domain information. Subsequently, gated recurrent unit (GRU) is employed to capture temporal information from the convolutional neural network outputs. Following GRU, attention mechanisms are applied to enhance awareness of key information and diminish interference from irrelevant details. By reducing attention to irrelevant or noisy temporal steps, it ultimately improves the accuracy and robustness of the classification process. The Res-CRANN method exhibits excellent performance on the DEAP dataset, with an accuracy of 96.63% for valence and 96.87% for arousal, confirming its effectiveness.

Piperazine ferulate inhibits diabetic nephropathy by suppressing AGE/RAGE-mediated inflammatory signaling in rats and podocytes.

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity.

OBJECTIVE: Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity. METHODS: Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson's and Spearman's analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD. RESULTS: The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44-0.67) versus 0.44 (0.34-0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015-1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059-1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008-1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045-1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors. CONCLUSION: The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

Association of lifestyle with sleep health in general population in China: a cross-sectional study.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Cellular RNA-binding proteins LARP4 and PABPC1 synergistically facilitate viral translation of coronavirus PEDV.

Coronaviruses are causing epizootic diseases and thus are a substantial threat for both domestic and wild animals. These viruses depend on the host translation machinery to complete their life cycle. The current paper identified cellular RNA-binding proteins (RBPs), La-related protein 4 (LARP4) and polyadenylate-binding protein cytoplasmic 1 (PABPC1), as critical regulators of efficient translation of the coronavirus porcine epidemic diarrhea virus (PEDV) mRNA. In Vero cells, PEDV infection caused LARP4 to migrate from the nucleus to the cytoplasm in a chromosome region maintenance1 (CRM1)-independent pathway. In the absence of the nuclear export signal of LARP4, viral translation was not promoted by LARP4. A further study unveiled that the cytoplasmic LARP4 binds to the 3'-terminal untranslated region (3'UTR) of PEDV mRNA with the assistance of PABPC1 to facilitate viral translation. LARP4 knockdown reduced the promotion of the PABPC1-induced 3'UTR translation activity. Moreover, the rabbit reticulocyte lysate (RRL) system revealed that the prokaryotic expressed protein LARP4 and PABPC1 enhance PEDV mRNA translation. To our knowledge, this is the first study demonstrating that PEDV induces nucleo-cytoplasmic shuttling of LARP4 to enhance its own replication, which broadens our insights into how viruses use host's RBPs for the efficient translation of viral mRNA.

The heterogeneity of cellular metabolism in the tumour microenvironment of hepatocellular carcinoma with portal vein tumour thrombus.

Given the growing interest in the metabolic heterogeneity of hepatocellular carcinoma (HCC) and portal vein tumour thrombus (PVTT). This study comprehensively analysed the metabolic heterogeneity of HCC, PVTT, and normal liver samples using multi-omics combinations. A single-cell RNA sequencing dataset encompassing six major cell types was obtained for integrated analysis. The optimal subtypes were identified using cluster stratification and validated using spatial transcriptomics and fluorescent multiplex immunohistochemistry. Then, a combined index based meta-cluster was calculated to verify its prognostic significance using multi-omics data from public cohorts. Our study first depicted the metabolic heterogeneity landscape of non-malignant cells in HCC and PVTT at multiomics levels. The optimal subtypes interpret the metabolic characteristics of PVTT formation and development. The combined index provided effective predictions of prognosis and immunotherapy responses. Patients with a higher combined index had a relatively poor prognosis (p <0.001). We also found metabolism of polyamines was a key metabolic pathway involved in conversion of metabolic heterogeneity in HCC and PVTT, and identified ODC1 was significantly higher expressed in PVTT compared to normal tissue (p =0.03). Our findings revealed both consistency and heterogeneity in the metabolism of non-malignant cells in HCC and PVTT. The risk stratification based on cancer-associated fibroblasts and myeloid cells conduce to predict prognosis and guide treatment. This offers new directions for understanding disease development and immunotherapy responses.

Application of PARP inhibitors combined with immune checkpoint inhibitors in ovarian cancer.

The advent of polyadenosine diphosphate ribose polymerase inhibitors (PARPi) has brought about significant changes in the field of ovarian cancer treatment. However, in 2022, Rucaparib, Olaparib, and Niraparib, had their marketing approval revoked for third-line and subsequent therapies due to an increased potential for adverse events. Consequently, the exploration of new treatment modalities remains imperative. Recently, the integration of PARPi with immune checkpoint inhibitors (ICIs) has emerged as a potential remedy option within the context of ovarian cancer. This article offers a comprehensive examination of the mechanisms and applications of PARPi and ICIs in the treatment of ovarian cancer. It synthesizes the existing evidence supporting their combined use and discusses key considerations that merit attention in ongoing development efforts.

Coronary CT Angiography-Based Radiomics to Predict Vessel-Specific Ischemia by Stress Dynamic CT Myocardial Perfusion Imaging.

RATIONALE AND OBJECTIVES: To investigate the predictive value of coronary CT angiography (CCTA)-based radiomics for vessel-specific ischemia by stress dynamic CT myocardial perfusion imaging (MPI). MATERIALS AND METHODS: Patients with typical angina/atypical angina/non-angina chest pain who underwent both stress dynamic CT MPI and CCTA scans were retrospectively enrolled. The following models were constructed for ischemic prediction using logistic regression and CCTA-derived quantitative and radiomic features: plaque quantitative model, lumen quantitative model, CT-fractional flow reserve (CT-FFR) model, integrative quantitative model, plaque radiomic model, peri-coronary adipose tissue (pCAT) radiomic model, integrative radiomic model, and quantitative and radiomic fusion model. A relative myocardial blood flow ≤ 0.75 on stress dynamic CT MPI was considered ischemic. The models' performances were quantified by the area under the receiver-operating characteristic curve (AUC). RESULTS: 386 coronary vessels (stenosis grade: 25%∼75%; training set: 200 [ischemia/non-ischemia=96/104]; test set:186 [ischemia/non-ischemia=79/107]) from 326 patients were included. The plaque radiomic model (training/test set: AUC=0.81/0.80) outperformed (p < .05) both the plaque quantitative (training/test set: AUC=0.71/0.68) model and the lumen quantitative (training/test set: AUC=0.69/0.65) model in identifying ischemia. The integrative radiomic model (training/test set: AUC=0.83/0.82) outperformed (p < .05) the CT-FFR model (training/test set: AUC=0.74/0.73) for ischemic prediction. The quantitative and radiomic fusion model (training/test set: AUC=0.86/0.84) outperformed (p < .05) the integrative quantitative model (training/test set: AUC=0.79/0.77) for ischemic detection. CONCLUSION: The plaque and pCAT radiomic features were superior to the plaque and pCAT quantitative features in predicting ischemia and the addition of the radiomic features to the quantitative features for ischemic identification yielded incremental discriminatory value.

Phosphomolybdates for Dual-Mode Photoelectrochemical Sensing toward Trace Chromium(VI) and Tetracycline.

Highly sensitive photoelectrochemical (PEC) sensors for trace carcinogens, such as heavy metal chromium(VI) [Cr(VI)] and antibiotic tetracycline (TC) are crucial. Herein, by integration of photoactive and redox phosphomolybdates with conjugated organic components, types of dual-mode PEC sensors were synthesized for sensing trace Cr(VI) and TC pollutants, with formulas of (H2bimb)2[Co2(bimb)1.5][Co(H2O)4][Co(P4Mo6O31H6)2]·6H2O (1), (H2bib)2[Co(H2O)3][Co2(H2O)5][Co(P4Mo6O31H6)2]·9H2O (2), and (H2bib)6[Co(Hbib)2(H2O)5][Co(P4Mo6O31H7)2]2·15H2O (3), where bimb represents 1,4-bis(1-imidazolyl)benzene and bib is 4,4'-bis(imidazolyl)bibphenyl. Hybrid 1 consisted of a three-dimensional framework structure constructed by Co{P4Mo6}2 clusters and one-dimensional (1D) {Co-bimb} chains, hybrid 2 exhibited 1D Co ion-bridged Co{P4Mo6}2 chains hydrogen-bonding with [H2bib]2+ cations, and hybrid 3 showed a discrete hybrid structure built upon a Co{P4Mo6}2 cluster modified by the {Co-bib} unit. Hybrids 1-3 displayed wide spectral absorption and excellent electrochemical redox properties, enabling dual-mode PEC responses to Cr(VI) reduction and TC oxidation. For Cr(VI) detection, hybrids 1-3 exhibited high sensitivities of 364.40, 225.72, and 124.29 µA·µM-1 as well as "nM" level detection limits (LODs) of 4.9, 10.0, and 11.0 nM, respectively. For TC detection, the sensitivities of hybrids 1-3 were 494.72, 308.78, and 174.03 µA·µM-1 and the LODs were 5.2, 6.1, and 12.9 nM, respectively. This research offers significant insights into designing efficient PEC sensors for the detection of environmental pollutants.

Current and future research directions in cellular metabolism of colorectal cancer: A bibliometric analysis.

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer (CRC). Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer (version 1.6.18) software and CiteSpace 6.1.R6 (64-bit) Basic. A comprehensive compilation of 4722 English-language publications, covering the period from January 1, 1991 to December 31, 2022, was carefully identified and included in the analysis. Among the authors, "Ogino, Shuji" contributed the most publications in this field, while "Giovannucci, E" garnered the highest number of citations. The journal "Cancer Research" ranked first in both publication volume and citations. Institutionally, "Shanghai Jiao Tong University" emerged as the top contributor in terms of published articles, while "Harvard University" led in citation impact. In country-based analysis, the United States held the top position in both publication output and citations, closely followed by China. The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

Tolerance Mechanisms and Removal Efficiency of Chlorella pyrenoidosa in Treating 3-Fluorophenol Pollution.

This study investigates the growth tolerance mechanisms of Chlorella pyrenoidosa to 3-fluorophenol and its removal efficiency by algal cells. Our results indicate that C. pyrenoidosa can tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed by promotion of growth. In C. pyrenoidosa cells, the activities of superoxide dismutase (SOD) and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were higher than or comparable to the control group. Metabolic analysis revealed that the 3-fluorophenol treatment activated pathways, such as glycerol phospholipid metabolism, autophagy, glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, and phenylpropanoid biosynthesis, contributed to the stabilization of cell membrane structures and enhanced cell repair capacity. After 240 h of treatment, over 50% of 3-fluorophenol was removed by algal cells, primarily through adsorption. Thus, C. pyrenoidosa shows potential as an effective biosorbent for the bioremediation of 3-fluorophenol.

Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Heritability and Genetic Factors of Astigmatism and Corneal Curvature: a Systematic Review and Meta-analysis.

PURPOSE: To systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC. DESIGN: Systematic review and meta-analysis (PROSPERO ID: CRD42023447370). METHODS: Studies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023). Newcastle-Ottawa Scale criteria was used to assess the risk of bias. Meta-analyses of heritability were conducted using random-effects model for mean difference. All current genetic associations were catalogued according to level of statistical significance. RESULTS: Pooled heritabilities were moderate for RA (h2 = 0.46, 95% CI: 0.27 - 0.65), CA (h2 = 0.48, 95% CI: 0.38 - 0.58) and CC (h2 = 0.64, 95% CI: 0.53 - 0.76). Subgroup analyses revealed significant differences between analysis methods (CA: P < 0.01; CC: P = 0.03) and populations (CA: P < 0.01; CC: P < 0.01) in both CA and CC, and between age groups in CA (P < 0.01). Totally 50 single-nucleotide polymorphisms (SNPs) in 10 genes have been reported with overlapping associations with RA, CA and/or CC, with BMP3, FMNL2, HERC2, PROX1-AS1 and ZC3H11B associated with RA and CA, FBN1, NHSL1 and PDGFRA with CA and CC, TRAF3IP1 with RA and CC; and CASC15 with RA, CA and CC. CONCLUSIONS: This study confirms moderate heritabilities of RA, CA and CC. Through evaluating overlapping SNPs or genes between these three phenotypes, we prioritized 50 SNPs in 10 genes as candidate variants for further validation. These findings highlight the complex genetic architecture of astigmatism and indicate shared and distinct genetic markers for different astigmatism-related corneal parameters. Future studies in different populations and functional studies evaluating the roles of the involved genes in astigmatism are warranted.

4D label-free proteomic analysis reveals key potential pathways of Toxoplasma invasion into the central nervous system.

Toxoplasma gondii is a successful parasite capable of infecting a wide range of warm-blooded animals, including people, livestock, and wildlife. In individuals with intact immune function, T. gondii can invade the host brain tissue by altering the blood-brain barrier permeability, leading to chronic infection. Proteins play crucial regulatory roles in disease progression. By monitoring changes in proteins, a deeper understanding of the molecular mechanisms underlying host resistance to infection and the potential pathogenic mechanisms of pathogens can be gained. This study analyzed differential protein expression and associated signaling pathways in mouse brain tissues during acute and chronic T. gondii infection using proteomic and bioinformatics methods. The results showed that during acute and chronic T. gondii infection stages, 74 and 498 differentially expressed proteins (DEPs) were identified in mouse brain tissue, respectively. Among them, 45 and 309 were up-regulated, while 29 and 189 were down-regulated. GO and KEGG analyses revealed that some of these DEPs were implicated in host immunity, pathogen immune evasion, and T. gondii invasion of the central nervous system, particularly interleukin production and secretion, complement system activation, and alterations in tight junction pathways. Notably, the upregulation of Rab13 was identified as a potential molecular mechanism for T. gondii to regulate blood-brain barrier permeability and facilitate central nervous system invasion. Our findings provided fundamental data for understanding host control of Toxoplasmosis infection and offered new insights into parasite immune evasion and invasion mechanisms within the central nervous system. These insights are crucial for developing strategies to prevent the establishment of chronic T. gondii infection.

Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping.

While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors.