Predicting 24-hour intraocular pressure peaks and averages with machine learning.

Purpose: Predicting 24-hour peak and average intraocular pressure (IOP) is essential for the diagnosis and management of glaucoma. This study aimed to develop and assess a machine learning model for predicting 24-hour peak and average IOP, leveraging advanced techniques to enhance prediction accuracy. We also aimed to identify relevant features and provide insights into the prediction results to better inform clinical practice. Methods: In this retrospective study, electronic medical records from January 2014 to May 2024 were analyzed, incorporating 24-hour IOP monitoring data and patient characteristics. Predictive models based on five machine learning algorithms were trained and evaluated. Five time points (10:00 AM, 12:00 PM, 2:00 PM, 4:00 PM, and 6:00 PM) were tested to optimize prediction accuracy using their combinations. The model with the highest performance was selected, and feature importance was assessed using Shapley Additive Explanations. Results: This study included data from 517 patients (1,034 eyes). For predicting 24-hour peak IOP, the Random Forest Regression (RFR) model utilizing IOP values at 10:00 AM, 12:00 PM, 2:00 PM, and 4:00 PM achieved optimal performance: MSE 5.248, RMSE 2.291, MAE 1.694, and R2 0.823. For predicting 24-hour average IOP, the RFR model using IOP values at 10:00 AM, 12:00 PM, 4:00 PM, and 6:00 PM performed best: MSE 1.374, RMSE 1.172, MAE 0.869, and R2 0.918. Conclusion: The study developed machine learning models that predict 24-hour peak and average IOP. Specific time point combinations and the RFR algorithm were identified, which improved the accuracy of predicting 24-hour peak and average intraocular pressure. These findings provide the potential for more effective management and treatment strategies for glaucoma patients.

Latent profiles of multi-dimensional sleep characteristics and association with overweight/obesity in Chinese preschool children.

OBJECTIVES: To examine the association between latent profiles of multi-dimensional sleep characteristics and overweight/obesity (OWO) in Chinese preschool children. STUDY DESIGN: The cross-sectional analysis included 3204 preschool children recruited from 24 kindergartens in Shanghai. Parents reported children's demographics and sleep characteristics, including sleep duration, timing and disturbances. Latent profile analysis (LPA) was used to identify sleep subtypes. Logistic regression models were used to evaluate the associations between sleep characteristics/subtypes and OWO. RESULTS: Short sleep duration, late bedtime, long social jetlag and sleep disturbances were significantly associated with increased OWO. However, when considering the interplay of sleep duration and timing, there was no significant association between sleep duration and OWO for children sleeping later than 22:00. Three sleep subtypes were identified based on children's sleep duration, timing and disturbances: "Average Sleepers" (n = 2107, 65.8 %), "Good Sleepers" (n = 481, 15.0 %), and "Poor Sleepers" (n = 616, 19.2 %). "Good Sleepers" had reduced odds of being OWO (AOR, 0.72; 95 % CI, 0.56-0.93) compared to "Average Sleepers", while "Poor Sleepers" showed an increased risk of OWO (AOR, 1.36; 95 % CI, 1.11-1.67). CONCLUSIONS: These findings highlight that improving multiple sleep characteristics simultaneously is a promising option to prevent and intervene childhood obesity.

Lung-Targeted Lipid Nanoparticle-Delivered siUSP33 Attenuates SARS-CoV-2 Replication and Virulence by Promoting Envelope Degradation.

As a structural protein of SARS-CoV-2, the envelope (E) protein not only plays a key role in the formation of viral particles, but also forms ion channels and has pathogenic functions, including triggering cell death and inflammatory responses. The stability of E proteins is controlled by the host ubiquitin-proteasome system. By screening human deubiquitinases, it is found that ubiquitin-specific protease 33 (USP33) can enhance the stability of E proteins depending on its deubiquitinase activity, thereby promoting viral replication. In the absence of USP33, E proteins are rapidly degraded, leading to a reduced viral load and inflammation. Using lipid nanoparticle (LNP) encapsulation of siUSP33 by adjusting the lipid components (ionizable cationic lipids), siUSP33 is successfully delivered to mouse lung tissues, rapidly reducing USP33 expression in the lungs and maintaining knockdown for at least 14 days, effectively suppressing viral replication and virulence. This method of delivery allows efficient targeting of the lungs and a response to acute infections without long-term USP33 deficiency. This research, based on the deubiquitination mechanism of USP33 on the E protein, demonstrates that LNP-mediated siRNA delivery targeting USP33 plays a role in antiviral and anti-inflammatory responses, offering a novel strategy for the prevention and treatment of SARS-CoV-2.

A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication.

The ORF9b protein, derived from the nucleocapsid's open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host-virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

Anion-Bridged Dual Hydrogen Bond Enabled Concerted Addition of Phenol to Glycal.

A noncovalent organocatalytic concerted addition of phenol to glycal is developed for the stereoselective and regioselective construction of biologically important phenolic 2-deoxyglycosides, featuring wide substrate tolerance. The method relies on an anion-bridged dual hydrogen bond interaction which is experimentally proved by Nuclear Magnetic Resonance (NMR), Ultraviolet and visible (UV-vis), and fluorescence analysis. Experimental evidence including kinetic analysis, Kinetic Isotope Effect (KIE) studies, linear free energy relationship, Hammett plot, and density functional theory (DFT) calculations is provided for a concerted mechanism where a high-energy oxocarbenium ion is not formed. In addition, the potential utility of this method is further demonstrated by the synthesis of biologically active glycosylated flavones. The benchmarking studies demonstrate significant advances in this newly developed method compared to previous approaches.

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.

HAT-Mediated Electrochemical C(sp2)-H Acylation of Quinolines with Alcohols.

Herein, an electrochemical hydrogen atom transfer (HAT) strategy for C(sp2)-H formylation of electron-deficient quinolines and isoquinolines is described. The cheap methanol acts as a formyl source with a catalytic amount of N-hydroxyphthalimide (NHPI) as the hydrogen atom transfer (HAT) catalyst. The advantages of this reaction are transition-metal-catalyst- and chemical-oxidant-free conditions, and the protocol could also be applied to the direct C(sp2)-H acetylation or propionylation of quinolines.

Identification and Validation of Genes Related to RNA Methylation Modification in Diabetic Retinopathy.

PURPOSE: To identify and validate the differentially expressed genes related to RNA methylation modification in diabetic retinopathy. METHODS: The data sets GSE12610 and GSE111465 related to diabetic retinopathy in the Gene Expression Omnibus were selected. The R software package was used to identify differentially expressed genes related to RNA methylation modification in diabetic retinopathy. Protein-protein interaction network was constructed to explore the interactions between proteins and predict proteins. Then, Gene Ontology annotation analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the potential enrichment pathways and clarify the biological functions of these genes. In addition, the correlation between them and immune cells was visualized, and receiver operating characteristic curves were drawn to evaluate the diagnostic performance of each one of them for diabetic retinopathy. To verify the differentially expressed genes, the mRNA expression of rat retinal vascular endothelial cells cultured in low and high glucose medium separately were detected by RT-qPCR. RESULTS: The expression of Lrpprc, Nsun4, Nsun6 and Trdmt1 were significantly up-regulated in diabetic retinopathy samples, while the expression of Cbll1, Hnrnpc, Mettl3 and Wtap were significantly down-regulated. Differentially expressed genes were mainly enriched in the RNA-methylation-medication pathways and biological function. The results of immune infiltration analysis proved that eosinophils aggregated more in diabetic group, while T cells follicular helper aggregated more in normal samples. These genes of Cbll1 (AUC = 0.986), Hnrnpc (AUC = 0.819), Lrpprc (AUC = 0.806), Mettl3 (AUC = 0.917), Nsun4 (AUC = 0.819), Nsun6 (AUC = 0.819), Trdmt1 (AUC = 0.972) and Wtap (AUC = 0.972) were respectively used as the diagnostic basis of diabetic retinopathy. According to the RT-qPCR results, the expression of Mettl3 was significantly down-regulated (p < 0.0005) in cells cultured in high glucose, while Trdmt1 (p < 0.05), Nsun4 (p < 0.05) and Nsun6 (p < 0.05) were significantly up-regulated. CONCLUSION: Differentially expressed genes such as Mettl3, Nsun4, Nsun6, and Trdmt1 should be conducted to explore, and the role of RNA methylation in the process of diabetic retinopathy would be revealed in-depth.

Unique Cluster-Support Effect of a Co3O4/TiO2-3DHS Nanoreactor for Efficient Plasma-Catalytic Oxidation Performance.

For environmental catalysis, a central topic is the design of high-performance catalysts and advanced mechanism studies. In the case of the removal of flue gas pollutants from coal-fired power plants, highly selective nanoreactors have been widely utilized together with plasma discharge characteristics, such as the catalytic oxidation of NO. Herein, a novel reactor with a three-dimensional hollow structure of TiO2 confining Co3O4 nanoclusters (Co3O4/TiO2-3DHS) has been developed for plasma-catalytic oxidation of NO, whose performance was compared with that of the commercial TiO2 confining Co3O4 cluster (Co3O4/TiO2). Specifically, Co3O4/TiO2-3DHS presented a higher efficiency (almost 100%) within lower peak-peak voltage (VP-P). More importantly, the NO oxidation efficiency was between 91.5 and 94.5% after a long time of testing, indicating that Co3O4/TiO2-3DHS exhibits more robust sulfur and water tolerance. Density functional theory calculations revealed that such impressive performance originates from the unique cluster-support effect, which changes the distribution of the active sites on the catalyst surface, resulting in the selective adsorption of flue gas. This investigation provides a new strategy for constructing a three-dimensional hollow nanoreactor for the plasma-catalytic process.

Online PGC-LC-ESI-MS/MS comparative analysis of variations in human milk O-glycopatterns from different secretor status.

O-glycome is one of the important components of glycoconjugates in human milk which is speculated to provide protective features similar to those observed in free oligosaccharides. The effects of maternal secretor status on free oligosaccharides and N-glycome in milk have been well researched and documented. Currently, milk O-glycome of secretors (Se+) and nonsecretors (Se-) was investigated through reductive ß-elimination combined with porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry. A total of 70 presumptive O-glycan structures were identified, of which 25 O-glycans (including 14 sulfated O-glycans) were reported for the first time. Notably, 23 O-glycans exhibited significant differences between Se+ and Se- samples (p < 0.05). Compared to Se- group, the O-glycans of the Se+ group was two times more abundant in the total glycosylation, sialylation, fucosylation, and sulfation (p < 0.01). In conclusion, approximately one-third of the milk O-glycosylation was influenced by maternal FUT2-related secretor status. Our data will lay a foundation for the study of O-glycans structure-function relationship.

High-sensitivity qualitative and quantitative analysis of human, bovine and goat milk glycosphingolipids using HILIC-MS/MS with internal standards.

Glycosphingolipids (GSLs) in human milk regulate the immune system, support intestinal maturation, and prevent gut pathogens. The structural complexity and low abundance of GSLs limits their systematic analysis. Here, we coupled the use of monosialoganglioside 1-2-amino-N-(2-aminoethyl) benzamide (GM1-AEAB) derivatives as internal standards with HILIC-MS/MS to qualitatively and quantitatively compare GSLs in human, bovine, and goat milk. One neutral glycosphingolipid (GB) and 33 gangliosides were found in human milk, of which 22 were newly detected and three were fucosylated. Five GB and 26 gangliosides were identified in bovine milk, of which 21 were newly discovered. Four GB and 33 gangliosides were detected in goat milk, 23 of them newly reported. GM1 was the main GSL in human milk; whereas disialoganglioside 3 (GD3) and monosialogangloside 3 (GM3) were dominant in bovine and goat milk, respectively; N-acetylneuraminic acid (Neu5Ac) was detected in >88 % of GSLs in bovine and goat milk. N-hydroxyacetylneuraminic acid (Neu5Gc)-modified GSLs were 3.5 times more abundant in goat than in bovine milk; whereas GSLs modified with both Neu5Ac and Neu5Gc were 3 times more abundant in bovine than in goat milk. Given the health benefits of different GSLs, these results will facilitate the development of custom-designed human milk-based infant formula.

The complete chloroplast genome of Eastern Asian fern Bolbitis laxireticulata (Dryopteridaceae).

Bolbitis laxireticulata is a potential ornamental plant, which is restricted to eastern Asia. Here, we sequenced the complete chloroplast (cp) genome of B. laxireticulata and constructed a phylogenetic cp tree of Dryopteridaceae to study their relationships. The cp genome of B. laxireticulata is 153,093 bp in length, being made up of large single-copy (LSC, 83,169 bp), small single-copy (SSC, 21,538 bp), and a pair of region inverted repeats (IRs, 24,193 bp). It has 124 genes including 83 protein-coding genes, 33 tRNA genes, and eight rRNA genes. With the maximum-likelihood tree indicating, B. laxireticulata is more closely related to B. subcordata.

Public Concern about Haze and Ozone in the Era of Their Coordinated Control in China.

In China, due to the implementation of the Action Plan for Prevention and Control of Air Pollution (APPCAP), the concentrations of PM2.5 (fine particulate matter) and severe haze in most cities have decreased significantly. However, at present, haze pollution in China has not been completely mitigated, and the problem of O3 (ozone) has become prominent. Therefore, the prevention and control of haze and O3 pollution have become important and noticeable issues in the field of atmospheric management. We used the Baidu search indices of "haze" and "ozone" to reflect public concerns about air quality and uncover different correlations between level of concern and level of pollution, and then we identified regions in China that require public attention. The results showed that (1) over the last decade, the search index of haze had a rapid trend of variation in line with changes in haze pollution, but that of O3 had a relatively slowly increasing trend; (2) the lag days between the peaks of public concern and the peaks of air pollution became increasingly shorter according to daily data analysis; and (3) 96 polluted cities did not receive sufficient public attention. Although periods of heavily haze-polluted weather, which affects visibility, have generated much public concern, periods of slight pollution have not received enough public attention. Public health protection and environmental participation regarding these periods of slight pollution in China deserve appropriate levels of attention.

Phylogeny, character evolution, and biogeography of the fern genus Bolbitis (Dryopteridaceae).

Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae, B. ser. Egenolfianae, and B. ser. Heteroclitae, are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America.

Varying Coefficient Mediation Model and Application to Analysis of Behavioral Economics Data.

This article is concerned with causal mediation analysis with varying indirect and direct effects. We propose a varying coefficient mediation model, which can also be viewed as an extension of moderation analysis on a causal diagram. We develop a new estimation procedure for the direct and indirect effects based on B-splines. Under mild conditions, rates of convergence and asymptotic distributions of the resulting estimates are established. We further propose a F-type test for the direct effect. We conduct simulation study to examine the finite sample performance of the proposed methodology, and apply the new procedures for empirical analysis of behavioral economics data.

UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b.

Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.

M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma.

BACKGROUND: Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. RESULTS: Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (ß-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. CONCLUSIONS: CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC.

Daily Food Insecurity Predicts Lower Positive and Higher Negative Affect: An Ecological Momentary Assessment Study.

Food insecurity (FI) is a dynamic phenomenon, and its association with daily affect is unknown. We explored the association between daily FI and affect among low-income adults during a 2-seasonal-month period that covered days both pre- and during the COVID-19 pandemic. A total of 29 healthy low-income adults were recruited during fall in 2019 or 2020, 25 of whom were followed in winter in 2020 or 2021. Daily FI (measured once daily) and affect (measured 5 times daily) were collected over the 2nd-4th week in each month. Time-Varying-Effect-Models were used to estimate the association between daily FI and positive/negative affect (PA/NA). Overall, 902 person-days of daily-level data were collected. Daily FI was associated with lower PA in the 3rd and 4th week of fall and winter and with higher NA in the second half of winter months. Similar patterns of FI-affect relations were found pre- and during COVID-19 in the second half of a given month, while unique patterns of positive affect scores in the 2nd week and negative scores in the 1st week were only observed during COVID days. Our study supports a time-varying association between FI and affect in low-income adults. Future large studies are needed to verify the findings; ultimately, better understanding such associations may help identify, target, and intervene in food insecure adults to prevent adverse mental health outcomes.

DNMT1-Mediated DNA Methylation Targets CDKN2B to Promote the Repair of Retinal Ganglion Cells in Streptozotocin-Induced Mongolian Gerbils during Diabetic Retinopathy.

Objective: DNA methylation played a vital role in the progression of diabetic retinopathy. In this study, we aimed to explore the role of DNA cytosine-5-methyltransferase 1 (DNMT1) in the development of early diabetic retinopathy and its potential underlying mechanism. Methods: Eight-week-old healthy Mongolian gerbils were used to establish type 1 diabetes using streptozotocin (STZ). Alteration of weight, fasting blood glucose, density of RGCs (Tuj1-labeled), and H&E-stained retinal cross sections were applied to evaluate the diabetic retinopathy mouse model. The global DNA methylation level of the retina at different time points after STZ injection was measured using the global methylation assay. Western blot was used to detect the protein expression of DNMT1, DNA methyltransferase 3A (DNMT3A), and 3B (DNMT3B). Quantitative reverse transcription-polymerase chain reactions (qRT-PCR) and western blot were used to determine the expression of CDKN2B. Cell proliferation and cell cycle were evaluated by the MTS assay and flow cytometry. Results: STZ injection caused the increased global DNA methylation level, which reached a maximum at 6 weeks after injection. Moreover, STZ injection caused the damage of RGCs. At 6 weeks after STZ injection, the expression levels of DNMT1 and DNMT3B were significantly increased in the STZ group. DNMT1-induced DNA hypermethylation inhibited the expression of CDKN2B (a negative regulator of cell cycle). DNMT1-mediated DNA methylation facilitated RGC proliferation via regulating the expression of CDKN2B. Conclusion: DNMT1-mediated DNA methylation played an important role in STZ-induced diabetic retinopathy via modulating CDKN2B expression.

Hetero-Shelled Hollow Structure Coupled with Non-Thermal Plasma Inducing Spatial Charge Rearrangement for Superior NO Conversion and Sulfur Resistance.

Facilitating the mass transfer and spatial charge separation is a great challenge for achieving efficient oxidation of NO and outstanding sulfur resistance. Herein, a hydrothermal-assisted confinement growth technique is used to fabricate well-defined three-dimensional CuOx@MnOx hetero-shelled hollow-structure catalysts. By integrating the coupled plasma space reactor and the porous hierarchical structure of the catalyst, excellent stability (10 h) and high conversion of NO (93.86%) are reached under the concentration of SO2 (1000 mg m-3 ) and NO (200 mg m-3 ). Impressively, precise surface characterization and detailed density functional theory calculations show that the spatial hetero-shelled micro-reactor can orient the redox pairs transportation, facilitating the combination of NO with the surface coordinately unsaturated O atoms, and also prevent the poisoning of SO2 molecules due to the curvature and surface charge effect in the non-thermal plasma equipment.