Low expression of TGF-ß2 and matrilin2 in human aqueous humour with acute primary angle closure.

Primary angle-closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label-free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor-ß2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.

Conjugated Nitroxide Radical Polymer with Low Temperature Tolerance Potential for High-Performance Organic Polymer Cathode.

Low-temperature operation poses a significant challenge for current commercial rechargeable lithium-ion batteries (LIBs). Organic polymer electrode materials, exhibiting a nonintercalation redox mechanism, offer a viable solution to mitigate the decline in electrochemical performance at low temperatures in LIBs. Herein, a radical polymer P(DATPAPO-TPA) with a conjugated nitrogen-rich triphenylamine derivative as the backbone and high-density nitroxide pendants has been synthesized. Due to the large interstitial spaces between adjacent structural units and polymer chains, resulting from the significant torsion angle between the benzene rings in the P(DATPAPO-TPA) skeleton, ions could effectively transport. This structural feature demonstrated a notable discharge capacity of 143.3 mA h·g-1 and a high charge-discharge plateau at ∼3.75 V vs Li+/Li, outperforming most reported radical polymer cathode materials. In addition, its capacity retention could reach 83.1% after 2000 cycles at an ultrahigh current density of 50 C, showing excellent rate capability and promising cyclability. Also notable was P(DATPAPO-TPA)'s favorable low-temperature performance that maintains a high discharge capacity of 139.2 mA h·g-1 at 0 °C. The synthesized P(DATPAPO-TPA) is a tangible illustration of a viable design strategy for low-temperature electrode materials, thereby contributing to broadening applications for radical polymer electrode materials.

Proteomic characteristics of the aqueous humor in Uyghur patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma.

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.

SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis. METHODS: We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin-eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT-related markers, pERK1/2, pGSK3ß and ß-catenin. RESULTS: SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3ß and the expression of ß-catenin. CONCLUSION: SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3ß/ß-catenin pathways. Video Abstract SB431542 inhibits EMT in RPE cells under high glucose conditions.

Acceptability, Preferred Medium, and Components of Nurse-Led Cardiac Telerehabilitation: A Cross-Sectional Study.

Cardiac rehabilitation (CR) is a comprehensive and multidisciplinary secondary prevention care in coronary heart disease (CHD). There are barriers at the patient and health system levels that prevent CR from being utilized. Cardiac telerehabilitation led by nurses (Ne-CTR) can alleviate the obstacles to participation in CR. A patient perspective can improve CR access. This study was the first pre-program investigation to clarify the status of knowledge and participation in CTR. We sought to clarify the acceptability, the reasons for rejection, the desired form, components, and associated factors with the components needed for (Ne-CTR) in patients with CHD. The study aimed to help develop a protocol for Ne-CTR for Chinese patients with CHD. A cross-sectional study was conducted between 2020 and 2021. Hospitals in four provinces in China were included. The participants were 671 patients with CHD in hospitals located in three regions of China. A self-administered questionnaire collected information about demographics, knowledge, and participation in CTR, acceptability, preferred medium, and components of Ne-CTR. Student's t-test, analysis of variance, and multiple linear regression analyzed the factors associated with component needs. All the analyses were conducted using IBM SPSS version 25.0. Most participants (n = 434, 66.77%) had a poor understanding and participation in CTR. In addition, 65.38% (n = 439) of participants were willing to accept the Ne-CTR program, and 43.56% (n = 98) identified safety as reasons for not accepting such a program. In the group accepting Ne-CTR, 35% chose hospital-designed professional applications as a medium for Ne-CTR when offered. Education (4.44 ± 1.056) and drug information (4.44 ± 1.040) had the highest average need score. Education, monthly income, marital status, previous CTR participation, and health insurance were associated with the demand level scores of Ne-CTR. This study demonstrated high levels of need for Ne-CTR among patients with CHD and identified the desired medium, components, and associated factors of Ne-CTR. These findings provide reference information for the construction of a Ne-CTR program.

An Ionic Liquid Supramolecular Gel Electrolyte with Unique Wide Operating Temperature Range Properties for Zinc-Ion Batteries.

Zinc-ion batteries are promising candidates for large-scale energy storage. The side reactions of the hydrogen evolution reaction (HER) and zinc dendrite growth are major challenges for developing high-performance zinc-ion batteries. In this paper, a supramolecular gel electrolyte (BLO-ILZE) was self-assembled in an ionic liquid (EMIMBF4) with zinc tetrafluoroborate (Zn(BF4)2) on the separator in situ to obtain a gel electrolyte used in zinc-ion batteries. BLO-ILZE is demonstrated to significantly enhance conductivity over a broad temperature range between -70 and 100 °C. Interestingly, through testing and fitting, it is found that the supramolecular gel electrolyte satisfies the liquid state law over a wide temperature range, and even achieves high conductivity (2.12 mS cm-1) at -40 °C. It is equivalent to the conductivity of aqueous zinc-ion batteries (ZnSO4/H2O) at -10 °C, which is 2.33 mS cm-1. Moreover, the supramolecular gel electrolyte can effectively inhibit the HER, thus exhibiting a longer lifetime in Zn/Zn cells for 3470 h at 1 mA cm-2 compared to the aqueous zinc-ion batteries with the Zn(BF4)2 aqueous electrolyte (400 h at 1 mA cm-2). The assembled V2O5/BLO-ILZE/Zn full cells also showed cycling performance, with 5000 cycles at 0.5 mA g-1 at room temperature, a capacity of 98%, and a coulombic efficiency of about 100%.

Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

Prioritizing de novo potential non-canonical splicing variants in neurodevelopmental disorders.

BACKGROUND: Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown. METHODS: We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein-protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing. FINDINGS: We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants (CSVs) and NCSVs contributed to an equal proportion of patients with NDD (0.76% vs. 0.82%). The candidate genes carrying NCSVs were associated with glutamatergic synapse and chromatin remodelling. Minigene successfully validated 59 of 79 (74.68%) NCSVs that led to abnormal splicing in 40 candidate genes, and 9 of the genes (ARID1B, KAT6B, TCF4, SMARCA2, SHANK3, PDHA1, WDR45, SCN2A, SYNGAP1) harboured recurrent NCSVs with the same variant present in more than two unrelated patients with NDD. Moreover, 36 of 59 (61.02%) NCSVs are novel clinically relevant variants, including 34 unreported and 2 clinically conflicting interpretations or of uncertain significance NCSVs in the ClinVar database. INTERPRETATION: This study highlights the common pathology and clinical importance of NCSVs in unsolved patients with NDD. FUNDING: The present study was funded by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Hunan Youth Science and Technology Innovation Talent Project, the Provincial Natural Science Foundation of Hunan, The Scientific Research Program of FuRong laboratory, and the Natural Science Project of the University of Anhui Province.