Search

Age-associated decreases in follicle number and oocyte quality result in a decline in female fertility, which is associated with increased infertility. Granulosa cells play a major role in oocyte development and maturation both in vivo and in vitro. However, it is unclear whether a reduction in cryptochrome 1 (Cry1) expression contributes to granulosa cell senescence, and further exploration is needed to understand the underlying mechanisms. In this study, we investigated the role of Cry1, a core component of the molecular circadian clock, in the regulation of senescence in ovarian granulosa cells. Western blotting and qRT-PCR showed that Cry1 expression was downregulated in aged human ovarian granulosa cells and was correlated with age and anti-Müllerian hormone (AMH) levels. RNA-seq analysis suggested that ferritinophagy was increased after Cry1 knockdown in KGN cells. MDA, iron, and reactive oxygen species (ROS) assays were used to detect cellular ferritinophagy levels. Ferroptosis inhibitors, iron chelators, autophagy inhibitors, and nuclear receptor coactivator 4 (NCOA4) knockdown alleviated KGN cell senescence induced by Cry1 knockdown. Immunofluorescence, immunoprecipitation, and ubiquitination assays indicated that Cry1 affected NCOA4 ubiquitination and degradation through HERC2, thereby affecting NCOA4-mediated ferritinophagy and causing granulosa cell senescence. KL201, a Cry1 stabilizer, enhanced ovarian function in naturally aged mice by reducing ferritinophagy. Our study reveals the potential mechanisms of action of Cry1 during ovarian aging and provides new insights for the clinical treatment of age-related fertility decline. A proposed molecular model of Cry1 in regulating senescence of human granulosa cells. Cry1 depletion reduced the expression of the E3 ubiquitin ligase HERC2, which reduced the ubiquitination and degradation of NCOA4, thereby promoting ferritinophagy and inducing granulosa cell senescence. [Display omitted] • Cry1 expression is downregulated in aged human ovarian granulosa cells. • Cry1 induces KGN cell senescence through NCOA4-mediated ferritinophagy. • Cry1 affects NCOA4 ubiquitination and degradation through HERC2. • Cry1 stabilizer KL201 enhances ovarian function by reducing ferritinophagy in middle-aged mice. [ABSTRACT FROM AUTHOR]

Objective: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2. Methods: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted. Results: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts. Conclusion: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population. [ABSTRACT FROM AUTHOR]

Aims: In patients with renal disease, high serum phosphate shows a relationship with cardiovascular risk. We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms. Methods: Isolated vessel relaxation, endothelial function, glomerular filtration rate (GFR), oxidative stress status and protein expression were assessed in HP diet mice. Mitochondrial function and protein expression were assessed in HP‐treated human umbilical vein endothelial cells (HUVECs). Results: High phosphate (1.3%) diet for 12 weeks impaired endothelium‐dependent relaxation in mesenteric arteries, kidney interlobar arteries and afferent arterioles; reduced GFR and the blood pressure responses to acute administration of acetylcholine. The PPARα/LKB1/AMPK/eNOS pathway was attenuated in the endothelium of mesenteric arteries from HP diet mice. The observed vasodilatory impairment of mesenteric arteries was ameliorated by PPARα agonist WY‐14643. The phosphate transporter PiT‐1 knockdown prevented HP‐mediated suppression of eNOS activity by impeding phosphorus influx in HUVECs. Endothelium cytoplasmic and mitochondrial reactive oxygen species (ROS) were increased in HP diet mice. Moreover HP decreased the expression of mitochondrial‐related antioxidant genes. Finally, mitochondrial membrane potential and PGC‐1α expression were reduced by HP treatment in HUVECs, which was partly restored by AMPKα agonist. Conclusions: HP impairs endothelial function by reducing NO bioavailability via decreasing eNOS activity and increasing mitochondrial ROS, in which the AMPK‐related signalling pathways may play a key role. [ABSTRACT FROM AUTHOR]

Human endometrium decidualization, which involves endometrial stromal proliferation and differentiation, is a prerequisite for embryo implantation, thus successful pregnancy. The Forkhead Box M1 (FoxM1), previously known as HNF-3, HFH-11, MPP2, Win, and Trident, is a transcriptional factor that plays crucial roles in cell proliferation and cell cycle progression. However, the molecular mechanism of FoxM1 during human endometrial decidualization remains unexplored. In this study, we first found FoxM1 is dynamically expressed in human endometrium during menstrual cycle. Employing a human endometrial stromal cell (HESC) line, we then demonstrated that FoxM1 inhibition downregulates cyclin B1 expression, delaying G2/M phase transition during HESC proliferation. Additionally, loss of FoxM1 expression blocks the differentiation of HESCs in response to estrogen, progesterone, and dbcAMP. Applying chromatin immunoprecipitation (ChIP) technique and luciferase assay, we further approved that FoxM1 can transcriptionally active signal transducer and activator of transcription 3 (STAT3), ensuring normal HESC differentiation. Besides enriching our knowledge on molecular basis underlying stromal decidualization, these findings help to shed light on the potential molecular causes for the endometrial disorders in humans. [ABSTRACT FROM AUTHOR]

Silicon-rich anodes are desired to leverage the energy capacity of lithium-ion batteries (LIBs) towards critical markets. We prepared new silicon-rich composite anodes with a nanofiber-in-microfiber architecture using a co-axial electrospinning setup. A polyvinyl alcohol (PVA) solution that allows high silicon content serves as the central stream, which holds silicon nanoparticles into short, branched composite nanofibers. These nanofibers were wrapped by long, ductile microfibers made of polyacrylonitrile (PAN) that is supplied in the sheath fluid. After carbonization, the received carbon/silicon composites were tested as the anode of LIBs, in which the silicon-rich nanofibers host the majority of lithium ions while their thin carbon skin originated from PVA promotes the conductivity and charge transfer. The outside PAN-derived microfibers provide needed structural support for those encapsulated silicon-rich nanofibers, making the final composites also an integrated, three-dimensional current collector. The nanofibrous morphology and the void space in between help accommodate the notorious volume expansion issues during lithiation/delithiation. The new composites were confirmed on their nanofiber-in-microfiber configuration. With a Si content of 40%, this unique fibrous anode material achieves ∼900 mAh g−1 specific capacity and ∼90% capacity retention from cycle 50 to cycle 250 by effectively balancing some major challenges associated with silicon-rich anodes. [Display omitted] [ABSTRACT FROM AUTHOR]

Human uterine stromal cell undergoes decidualization for pregnancy establishment and maintenance, which involved extensive proliferation and differentiation. Increasing studies have suggested that recurrent spontaneous abortion (RSA) may result from defective endometrial stromal decidualization. However, the critical molecular mechanisms underlying impaired decidualization during RSA are still elusive. By using our recently published single-cell RNA sequencing (scRNA-seq) atlas, we found that MYC-associated factor X (MAX) was significantly downregulated in the stromal cells derived from decidual tissues of women with RSA, followed by verification with immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). MAX knockdown significantly impairs human endometrial stromal cells (HESCs) proliferation as determined by MTS assay and Ki67 immunostaining, and decidualization determined by F-actin, and decidualization markers. RNA-seq together with chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and release using nuclease sequencing (CUT&RUN-seq) analysis were applied to explore the molecular mechanisms of MAX in regulation of decidualization, followed by dual-luciferase reporter assay to verify that MAX targets to (odd-skipped related transcription factor 2) OSR2 directly. Reduced expression of OSR2 was also confirmed in decidual tissues in women with RSA by IHC and qRT-PCR. OSR2 knockdown also significantly impairs HESCs decidualization. OSR2-overexpression could at least partly rescue the downregulated insulin-like growth factor binding protein 1 (IGFBP1) expression level in response to MAX knockdown. Collectively, MAX deficiency observed in RSA stromal cells not only attenuates HESCs proliferation but also impairs HESCs decidualization by downregulating OSR2 expression at transcriptional level directly. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cr3+ lattice doping in r-TiO 2 achieved Ru/Ti 0.95 Cr 0.05 O 2 with much higher activity than Ru/r-TiO 2. • Cr3+ doping led to Ru/Ti 0.95 Cr 0.05 O 2 with higher dispersion of Ru and enhanced MSIs. • The MSIs affected adsorption states of linear-CO*. • The formaiton of Blue-shifted CO* decided the much higher activity. • Ru-CO and C-O bonds were key for CO 2 methanation on supported Ru catalysts. Understanding the correlation between metal–support interactions (MSIs) and the adsorption states of reaction intermediates is critical for developing heterogeneous catalysts. To modulate MSIs and CO adsorption states, various Ru/Ti 1-x Cr x O 2 catalysts were prepared by Cr3+ cation doping and used for CO 2 methanation compared to the rutile TiO 2 -supported Ru catalyst (Ru/r-TiO 2). The activity followed the order: Ru/Ti 0.95 Cr 0.05 O 2 > Ru/Ti 0.97 Cr 0.03 O 2 > Ru/Ti 0.87 Cr 0.13 O 2 ≫ Ru/r-TiO 2. The best Ru/Ti 0.95 Cr 0.05 O 2 catalyst possessed CO 2 turnover frequency (TOF) value at 200 °C 10.2 times higher than that on the Ru/r-TiO 2. Cr3+ doping in the lattice of r-TiO 2 support led to the Ru/Ti 0.95 Cr 0.05 O 2 with higher dispersion of Ru and enhanced MSIs. A linear-CO*-II intermediate formed on the Ru/Ti 0.95 Cr 0.05 O 2 with higher C-O vibrational frequency (2003 cm−1) than the linear-CO*-I at 1972 cm−1 on the Ru/r-TiO 2 , and the blue-shifted CO possessed higher activity for CO hydrogenation to CH 4. The higher activity of the linear-CO* were accounting for the much higher TOF value of the Ru/Ti 0.95 Cr 0.05 O 2. The strength of MSIs was proved to be highly correlated with CO adsorpton states including the balance of the strength of Ru-C and C-O bonds, which were found to be a crucial factor for the activity of supported Ru-based catalysts for CO hydrogenation. [ABSTRACT FROM AUTHOR]

Aims: Reduced A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif member 13 (ADAMTS13) levels are observed in kidney disease. We test whether recombinant human ADAMTS13 (rhADAMTS13) mitigates renal injury in chronic kidney disease (CKD) and the potential mechanisms. Methods: CKD was established 3 months after ischaemia/reperfusion (IR). ADAMTS13 and von Willebrand factor (vWF) levels, renal function and morphological changes were analysed. Afferent arteriolar responses to angiotensin II (Ang II) and acetylcholine (ACh) were measured. Oxidative stress‐related molecules were detected. Results: Higher vWF and lower ADAMTS13 levels were observed in CKD mice, which were markedly attenuated by rhADAMTS13. rhADAMTS13 alleviated renal dysfunction, as documented by decreased blood urea nitrogen (BUN), serum creatinine, kidney injury molecule‐1 (KIM‐1) and neutrophil gelatinase‐associated lipocalin (NGAL) levels in CKD mice. Moreover, rhADAMTS13 attenuated transforming growth factor (TGF)‐β1/Smad3 activation. Plasma vWF: ADAMTS13 ratio showed positive correlations with malondialdehyde (MDA), hydrogen peroxide (H2O2) and proteinuria, and correlated inversely with superoxide dismutase (SOD) and catalase (CAT). Finally, rhADAMTS13 inhibited reactive oxygen species (ROS) levels and improved microvascular functional disorders, accompanied by the inhibition of glycogen synthase kinase (GSK) 3β hyperactivity and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) expression. Conclusions: Acute kidney injury (AKI) reduces the expression of ADAMTS13 that contributes to progressive CKD, microvascular dysfunction, oxidative stress, inhibition of Nrf2 activity and renal histopathological damage. All of which can be alleviated by administration of rhADAMTS13. [ABSTRACT FROM AUTHOR]

• Solid crystallization of dry nanogels into mesoporous ZSM-5 at ambient pressure. • Hierarchical pore structure created by jointing nanocrystals into single zeolites. • Low temperature hydrogenation/deoxygenation of Pd/Meso-ZSM-5 catalyst. • Improved conversion and anti-coking performance in guaiacol hydrodeoxygenation. • Saturated/unsaturated product regulated by hydrodeoxygenation temperature. Mesoporous structure is important to promote mass transport and active site utilization of zeolites when used in reactions involving bulky molecules. However, their conventional hydrothermal synthesis is energy and labor intensive, requiring high-pressure operation, and lengthy heating a huge amount of alkaline liquid. We successfully synthesized new mesoporous zeolites, Meso-ZSM-5, via solid-state crystallization of dry aluminosilicate nanogels. Neighbor developing nanocrystals further joint at edges, creating connected, inter-lattice mesoscale pathway in the finished single crystalline zeolites. Palladium was further loaded on these zeolites to form a bi-functional catalyst (Pd/Meso-ZSM-5). When used in the hydrodeoxygenation (HDO) of guaiacol, a major bio-oil compound with disappointing conversion and severe coking issue over many HDO catalysts, Pd/Meso-ZSM-5 exhibits superior guaiacol conversion and product distribution when compared with those supported on conventional microporous ZSM-5 counterparts. This is attributed to the improved diffusion and accessibility of active sites inside Meso-ZSM-5 with its unique hierarchically porous structure. Ring saturated hydrocarbons are largely produced at 200 °C when hydrogenation dominates while alkaylated aromatics become major HDO products as deoxygenation becomes favorable at 250 °C. These encouraging results may ignite the wide use of these mesoporous zeolites in many other reactions in both traditional fossil fuel and emerging renewable energy fields. [ABSTRACT FROM AUTHOR]

To utilize its rich aromatics, lignin, a high-volume waste and environmental hazard, was depolymerized in supercritical ethanol over various zeolites types with different acidity and pore structures. Targeting at high yield/selectivity of aromatics such as phenols, microporous Beta, Y, and ZSM-5 zeolites were first examined in lignin ethanolysis, followed by zeolites with similar micropore size but different acidity. Further comparisons were made between zeolites with fin-like and worm-like mesoporous structures and their microporous counterparts. Despite depolymerization complexity and diversified ethanolysis products, strong acidity was found effective to cleave both C–O–C and C–C linkages of lignin while mild acidity works mainly in ether bond breakdown. However, when diffusion of gigantic molecules is severe, pore size, particularly mesopores, becomes more decisive on phenol selectivity. These findings provide important guidelines on future selection and design of zeolites with appropriate acidity and pore structure to promote lignin ethanolysis or other hydrocarbon cracking processes. [ABSTRACT FROM AUTHOR]