GMFB/AKT/TGF-ß3 in Müller cells mediated early retinal degeneration in a streptozotocin-induced rat diabetes model.

Retinal degeneration, characterized by Müller cell gliosis and photoreceptor apoptosis, is considered an early event in diabetic retinopathy (DR). Our previous study proposed that GMFB may mediate diabetic retinal degeneration. This study identified GMFB as a sensitive and functional gliosis marker for DR. Compared to the wild type (WT) group, Gmfb knockout (KO) significantly improved visual function, attenuated gliosis, reduced the apoptosis of neurons, and decreased the mRNA levels of tumor necrosis factor α (Tnf-α) and interleukin-1ß (Il-1ß) in diabetic retinas. Tgf-ß3 was enriched by hub genes using RNA sequencing in primary WT and KO Müller cells. Gmfb KO significantly upregulated the transforming growth factor (TGF)-ß3 protein level via the AKT pathway. The protective effect of TGF-ß3 in the vitreous resulted in significantly improved visual function and decreased the number of apoptotic cells in the diabetic retina. The protection of Gmfb KO in primary Müller cells against high glucose (HG)-induced photoreceptor apoptosis was partially counteracted by TGF-ß3 antibody and administration of TGFBR1/2 inhibitors. Nuclear receptor subfamily 3 group C member 1 (NR3C1) binds to the promoter region of Gmfb and regulates Gmfb mRNA at the transcriptional level. NR3C1 was increased in the retinas of early diabetic rats but decreased in the retinas of late diabetic rats. N'-[(1E)-(3-Methoxyphenyl)Methylene]-3-Methyl-1H-Pyrazole-5-Carbohydrazide (DS-5) was identified as an inhibitor of GMFB, having a protective role in DR. We demonstrated that GMFB/AKT/TGF-ß3 mediated early diabetic retinal degeneration in diabetic rats. This study provides a novel therapeutic strategy for treating retinal degeneration in patients with DR.

Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort.

BACKGROUND: The gut microbiome is central to human health, but the potential impact of ozone (O3) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 exposure and the variations of the human gut microbiome during the first two years of life. DESIGN: A cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16 S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 exposure and gut microbiome features. RESULTS: Prenatal O3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 exposure explained 13.1 % of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 exposure was negatively associated with variations of Streptococcus (p-value = 0.001, q-value = 0.005), Enterococcus (p-value = 0.001, q-value = 0.005), Escherichia-Shigella (p-value = 0.010, q-value = 0.025), and Bifidobacterium (p-value = 0.003, q-value = 0.010). CONCLUSIONS: This study is the first to examine the effects of prenatal O3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.

Postnatal nighttime light exposure and infant temperament at age 12 months: mediating role of genus Akkermansia.

The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.

Highly Efficient Multi-Resonance Thermally Activated Delayed Fluorescence Material with a Narrow Full Width at Half-Maximum of 0.14 eV.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) material, which possesses the ability to achieve narrowband emission in organic light-emitting diodes (OLEDs), is of significant importance for wide color gamut and high-resolution display applications. To date, MR-TADF material with narrow full width at half-maximum (FWHM) below 0.14 eV still remains a great challenge. Herein, through peripheral protection of MR framework by phenyl derivatives, four efficient narrowband MR-TADF emitters are successfully designed and synthesized. The introduction of peripheral phenyl-based moieties via a single bond significantly suppresses the high-frequency stretching vibrations and reduces the reorganization energies, accordingly deriving the resulting molecules with small FWMH values around 20 nm/0.11 eV and fast radiative decay rates exceeding 108 s-1 . The corresponding green OLED based on TPh-BN realizes excellent performance with the maximum external quantum efficiency (EQE) up to 28.9% without utilizing any sensitizing host and a relatively narrow FWHM of 0.14 eV (28 nm), which is smaller than the reported green MR-TADF molecules in current literatures. Especially, the devices show significantly reduced efficiency roll-off and relatively long operational lifetimes among the sensitizer-free MR-TADF devices. These results clearly indicate the promise of this design strategy for highly efficient OLEDs with ultra-high color purity.

Highly Efficient Asymmetric Multiple Resonance Thermally Activated Delayed Fluorescence Emitter with EQE of 32.8 % and Extremely Low Efficiency Roll-Off.

Multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters show great potentials for high color purity organic light-emitting diodes (OLEDs). However, the simultaneous realization of high photoluminescence quantum yield (PLQY) and high reverse intersystem crossing rate (kRISC ) is still a formidable challenge. Herein, a novel asymmetric MR-TADF emitter (2Cz-PTZ-BN) is designed that fully inherits the high PLQY and large kRISC values of the properly selected parent molecules. The resonating extended π-skeleton with peripheral protection can achieve a high PLQY of 96 % and a fast kRISC of above 1.0×105  s-1 , and boost the performance of corresponding pure green devices with an outstanding external quantum efficiency (EQE) of up to 32.8 % without utilizing any sensitizing hosts. Remarkably, the device sufficiently maintains a high EQE exceeding 23 % at a high luminance of 1000 cd m-2 , representing the highest value for reported green MR-TADF materials at the same luminescence.

Waste treats waste: Facile fabrication of porous adsorbents from recycled PET and sodium alginate for efficient dye removal.

Dye-contaminated water and waste plastic both pose enormous threats to human health and the ecological environment, and simultaneously solving these two issues in a sustainable and resource-saving way is highly important. In this work, a sodium alginate-polyethylene terephthalate-sodium alginate (SA@PET) composite adsorbent for efficient dye removal is fabricated using wasted PET bottle and marine plant-based SA via simple and energy-efficient nonsolvent-induced phase separation (NIPS) method. Benefiting from its porous structure and the abundant binding sites, SA@PET shows an excellent methylene blue (MB) adsorption capacity of 1081 mg g-1. The Redlich-Peterson model more accurately describes the adsorption behavior, suggesting multiple adsorption mechanisms. In addition to the electrostatic attractions of SA to MB, polar interactions between the PET matrix and MB are also identified as adsorption mechanisms. It is worth mentioning that SA@PET could be recycled 7 times without a serious decrease in performance, and the trifluoroacetic acid-dichloromethane solvent involved in the NIPS process has the possibility of reuse and stepwise recovery. Finally, the discarded adsorbent could be completely degraded under mild conditions. This work provides not only a composite adsorbent with excellent cationic dye removal performance for wastewater treatment, but also an upcycling strategy for waste PET.

Rational Molecular Design of Phenanthroimidazole-Based Fluorescent Materials toward High-Efficiency Deep-Blue OLEDs by Molecular Isomer Engineering.

Organic light-emitting diodes (OLEDs) have been extensively investigated in full-color displays and energy-saving lighting owing to their unique advantages. However, deep-blue OLEDs based on nondoped emitting layers with a satisfactory external quantum efficiency (EQE) are still rare for applications. In this work, six hot exciton materials, PPIM-12F, PPIM-22F, PPIM-13F, PPIM-23F, PPIM-1CN, and PPIM-2CN, are designed and synthesized via an isomer engineering design strategy and their photophysical properties and OLED performance are systematically investigated. These emitters all possess wide band gaps (3.53-3.69 eV), hybrid local and charge transfer (HLCT) characteristics, and good thermal stabilities. The C2 series compounds, PPIM-22F, PPIM-23F, and PPIM-2CN, all show redder emission peaks than the N1 series counterparts of PPIM-12F, PPIM-13F, and PPIM-1CN. In addition, the LUMO energy levels decrease consecutively in the sequence of PPIM-22F < PPIM-23F < PPIM-2CN and are all lower than their respective N1 series position isomers of PPIM-12F, PPIM-13F, and PPIM-1CN. The CV measurements indicate that such a design strategy renders the fine-tuning of LUMO energy levels, and the incorporation of electron acceptors at the extended C2 position of the PI unit is a better choice to improve the electron injection ability. Theoretical simulations indicate that they may harvest the triplet exciton through an upper-level reverse intersystem crossing process, which decreases the gathering of triplet excitons and allows the OLEDs to be fabricated by nondoping technology. Among them, PPIM-22F with a difluorobenzene substituent at the C2 position manifests the best performance in OLEDs, which exhibits the maximum EQE of 7.87% and Commission Internationale de lEclairage (CIE) coordinates of (0.16, 0.10). This work demonstrates an effective strategy for considerable improvement in device performance by a subtle change in the molecular structure through isomer engineering.

Triphenylene-Based Emitters with Hybridized Local and Charge-Transfer Characteristics for Efficient Nondoped Blue OLEDs with a Narrowband Emission and a Small Efficiency Roll-Off.

Developing high-efficiency nondoped blue organic light-emitting diodes (OLEDs) with high color purity and low-efficiency roll-off is vital for display and lighting applications. Herein, we developed two asymmetric D-π-A blue emitters, PIAnTP and PyIAnTP, in which triphenylene is first utilized as a functional acceptor. The relatively weak charge transfer (CT) properties, rigid molecular structures, and multiple supramolecular interactions in PIAnTP and PyIAnTP can significantly enhance the fluorescence efficiency and suppress the structural relaxations to obtain a narrowband blue emission. The photophysical experiments and theoretical simulations reveal that they both exhibit a typical hybridized local and charge-transfer (HLCT) excited state and achieve high external quantum efficiency (EQE) via a "hot exciton" channel. As a result, PIAnTP- and PyIAnTP-based nondoped devices realize blue emission at 456 and 464 nm, corresponding to CIE coordinates of (0.16, 0.14) and (0.16, 0.19), narrow full width at half-maximums of 52 and 60 nm, and the high EQEs of 8.36 and 8.69%, respectively. More importantly, the PIAnTP- and PyIAnTP-based nondoped devices show small EQE roll-offs of only 5.9 and 2.4% at 1000 cd m-2, respectively. These results signify an advance in designing a highly efficient blue emitter for nondoped OLEDs.

Glia Maturation Factor ß as a Novel Independent Prognostic Biomarker and Potential Therapeutic Target of Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) has the highest mortality rate and potential for invasion among renal cancers. The diagnosis and treatment of KIRC are becoming challenging because of its diverse pathogenic mechanisms. Glia (GMFB) is a highly conserved growth and differentiation factor for glia cells and neurons, and it is closely associated with neurodegenerative diseases. However, its role in KIRC remains unknown. The present study integrated bioinformatics approaches with suitable meta-analyses to determine the position of GMFB in KIRC. There was a significant decrease in Gmfb expression in KIRC kidneys compared with normal controls. Gmfb expression was negatively associated with pathologic stage, T and M stages, and histologic grade. Univariate and multivariate analyses showed that elevated Gmfb expression was an independent factor for a favorable prognosis. Furthermore, the nomogram verified that Gmfb is a low-risk factor for KIRC. Knockdown of Gmfb in Caki-2 cells increased viability and decreased p21 and p27 levels. Overexpression of Gmfb inhibited Caki-2 cell proliferation, migration, and invasion and decreased mitochondrial membrane potential. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses considering Gmfb co-expressed differentially expressed genes (DEGs) showed that collecting duct acid secretion and mineral absorption ranked were the most important upregulated and downregulated DEGs, respectively. The upregulated hub genes for DEGs were mainly involved in nucleosome assembly, nucleosome organization, and chromatin assembly, and the downregulated hub genes were primarily associated with keratinization. The ratio of tumor-infiltrating immune cells in KIRC tissues was evaluated using CIBERSORTx. The results showed that the Gmfb expression was significantly positively correlated with macrophage M2 cells and mast resting cell infiltration levels and negatively correlated with T follicular helper, T regulatory, and B plasma cell infiltration levels. The former cell types were associated with a beneficial outcome, while the latter had a worse outcome in patients with KIRC. In summary, this study identified GMFB as a novel independent biomarker and therapeutic target for KIRC, and it provides a helpful and distinct individualized treatment strategy for KIRC with a combination of molecular targets and tumor microenvironment.