Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Effects of Total Intravenous Anesthesia on Circadian Rhythms in Patients Undergoing Cardiac Transcatheter Closure.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

Comparison of different sedatives in children before general anaesthesia for selective surgery: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: It is estimated that 60% of children undergoing anaesthesia develop severe preoperative anxiety. The anxiety is associated with adverse reactions. Sedatives such as dexmedetomidine, midazolam, clonidine, ketamine, and melatonin can be used as premedication against preoperative anxiety. However, no consensus has been reached on the choice of pre-anaesthetic sedatives in children before selective surgery. Therefore, the current network meta-analysis (NMA) was carried out to evaluate different sedatives in children aged between 1 and 7 before general anaesthesia for selective surgery. METHODS: Randomized clinical trials (RCTs) were retrieved from Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from inception to October 22, 2021. Primary outcomes showed satisfactory sedation at parent separation and also at induction or mask acceptance. Secondary outcomes were those related to added benefits and side effects. The present NMA was conducted using the R software. Results of the study were reported as Relative Risk (RR) or Mean Difference (MD) at a 95% credible intervals (CrIs). RESULTS AND DISCUSSION: A total of 48 trials were included in the present study. It was found that the effectiveness of dexmedetomidine, midazolam, clonidine, and ketamine were superior to that of placebo in satisfactory sedation at parent separation and induction or mask acceptance. There was no significant difference between melatonin and placebo in satisfactory sedation at induction or mask acceptance. Dexmedetomidine, ketamine, clonidine, and melatonin were superior to placebo in reducing emergence delirium (ED). In addition, midazolam prolonged the length of stay in the post anaesthesia care unit (PACU) as compared with placebo. Dexmedetomidine caused a significant reduction in systolic blood pressure (SBP) and heart rate (HR). Nevertheless, it was noted that the hemodynamic changes were roughly within safety limits. WHAT IS NEW AND CONCLUSION: It was evident that the studied drugs can provide effective sedation with exception of melatonin and placebo. However, it was found that midazolam, ketamine, and clonidine lead to several side effects. The findings of the present study supported that dexmedetomidine, especially intranasal administration, has potential in the optimal selection of the sedatives for premedication in children. This is because the drug has effective sedation, reduced incidence of ED, side effects, and onset time.

Construction of Molecular Sensing and Logic Systems Based on Site-Occupying Effect-Modulated MOF-DNA Interaction.

Interactions between metal-organic frameworks (MOFs) and nucleic acids are of great importance in molecular assembly. However, current MOF-nucleic acid interactions lack diversity and are normally realized in an uncontrollable manner. Herein, the interaction of zirconium-based MOFs (Zr-MOFs) with nucleic acids is enabled by the formation of Zr-O-P bonds and further manipulated by a phosphate-induced site-occupying effect. Covering Zr ions in clusters of MOFs with phosphates impedes the formation of Zr-O-P bonds with nucleic acids, rendering the MOF-nucleic acid interaction tunable and stimulus-responsive. Notably, the experimental results demonstrate that various phosphates, Zr-MOFs, and nucleic acids can all be adopted in the tunable interaction. On the basis of these findings, fluorescent DNA and typical Zr-MOFs are proposed as functional probe-quencher pairs to establish molecular sensing and logic systems. Accordingly, alkaline phosphatase and inorganic pyrophosphatase can be quantified simultaneously, and the overall relation of different phosphates and phosphatases is facilely displayed. The work provides a general strategy for modulating MOF-nucleic acid interactions, which is conducive to the development of molecular intelligent systems.

Principal component analysis-assisted zirconium-based metal-organic frameworks/DNA biosensor for the analysis of various phosphates.

Considering the diversity of phosphates and their pivotal roles in physiological processes, detection of various phosphates related to their metabolism is urgent but challenging. Herein, we design a biosensor with zirconium-based MOFs (Zr-MOFs) and fluorophore-modified single-stranded DNA (F-ssDNA) for the analysis of phosphates. Relying on the interaction between Zr clusters and phosphate backbone, F-ssDNA is anchored on the surface of Zr-MOFs, inducing fluorescence resonance energy transfer (FRET) and subsequently quenching the fluorescence of F-ssDNA. Meanwhile, phosphates with different numbers of phosphate groups, molecular structures and coordination environments are able to adjust the FRET between Zr-MOFs and F-ssDNA via a site-occupying effect, recovering the fluorescence of F-ssDNA in distinct cases, which may result in diverse fluorescence signals. Consequently, seventeen phosphates and four phosphate mixtures are discriminated with the assistance of principal component analysis. These results provide new insight into the application of Zr-MOFs and broaden the path for the development of analytical methods for phosphates.

Pan­cancer analysis identified ARHGAP23 as a potential biomarker for pancreatic adenocarcinoma.

Rho GTPASE-activating protein 23 (ARHGAP23) is known to activate RHO-GTPase and has an important role in the infiltration and metastasis of tumors. Although previous studies suggested its involvement in certain human cancers, its role in pan-cancer remains unclear. In the present study, the expression, prognosis and potential functions of ARHGAP23 in pan-cancer were evaluated through various public databases such as Human Protein Atlas, Tumor IMmune Estimation Resource, Gene Set Co-Expression Analysis, Gene Expression Profiling Interactive Analysis, cBio Cancer Genomics Portal, Tumor-Immune System Interactions Database (TISIDB) and others. Through these data combined with a variety of biological information analysis methods, the potential role of ARHGAP23 as a carcinogenic gene was explored in the present study. The present analysis revealed that ARHGAP23 expressed abnormalities in >10 tumors, which was associated with differences in prognosis. Furthermore, the findings of the present study indicated that ARHGAP23 is associated with DNA methylation and multiple immune cell infiltrations in these tumors. ARHGAP23 expression was related to clinical prognosis, DNA methylation and immune infiltration. These findings support the potential of ARHGAP23 as a prognostic biomarker and a molecular target for cancer treatment.

Hyperaccumulation Route to Ca-Rich Hard Carbon Materials with Cation Self-Incorporation and Interlayer Spacing Optimization for High-Performance Sodium-Ion Batteries.

The hard carbon (HC) has been emerging as one of the most promising anode materials for sodium-ion batteries (SIBs). Incorporation of cations into the HC lattice proved to be effective to regulate their d-interlayer spacing with a modified SIB performance. However, the complexity and high cost of current synthetic processes limited its large-scale application in SIBs. Through the natural hyperaccumulation process, a cost-effective and scale-up-driven procedure to produce Ca-ion self-incorporated HC materials was proposed by applying tamarind fruits as the precursor with the enrichment of Ca ions. In virtue of one-step pyrolysis, the self-incorporated and well-distributed Ca ions in tamarind fruits had successfully served as the buffer layer to expand the d-interlayer spacing of HC materials. Furthermore, the natural porosity hierarchy could be largely preserved by the optimization of calcination temperature. As a result, the Ca-rich HC material had exhibited the optimized cycling performance (326.7 mA h g-1 at 50 mA g-1 and capacity retention rate of 89.40% after 250 cycles) with a high initial Coulombic efficiency of 70.39%. This work provided insight into applying the hyperaccumulation effect of biomass precursors to produce doped HC materials with ion self-incorporation and the optimized d-interlayer spacing, navigating its large-scale application for high-performance SIBs.

Synthesis and properties of novel ester-containing gemini imidazolium surfactants.

Novel ester-containing gemini imidazolium surfactants were synthesized from various aliphatic acids (C12, C14, C16), 1-methylimidazol, and 2,2-bis (bromomethyl)-1,3-propanediol with a two step reaction. The surfactants are abbreviated as [Cnim]2 (n=12, 14, 16). The chemical structures of the prepared compounds were confirmed by (1)H NMR, IR spectra, and elemental analysis. Thermal properties of these new surfactants were studied with thermogravimetry (TG) and differential scanning calorimetry (DSC). Their critical micelle concentrations (cmc) in the aqueous solutions were determined by surface tension and electrical conductivity methods. Surface tension parameters including Γcmc, Amin, and γcmc were obtained. The parameters ß (degree of counterion binding to micelles), ΔGads(0) (Gibbs free energy of adsorption), and ΔGmic(0) (Gibbs free energy change of micellization) were also derived. The results indicated that these novel gemini surfactants exhibited very low cmcs and a good efficiency in lowering the surface tension of water. Dynamic light scattering (DLS) measurements showed that [C12im]2 and [C14im]2 can easily form vesicles at very low concentration, and that the self-assembly of [C14im]2 is more well-organized than for [C12im]2. The use of DOSY and DLS as a complementary technique shows that a dynamic micelle-vesicle equilibrium exists in solution.