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The primordial follicle pool established in early life determines the ovarian reserve in the female reproductive lifespan. Premature exhaustion of primordial follicles contributes to primary ovarian insufficiency (POI), that is dependent by the initial size of the primordial follicle pool and by the rate of its activation and depletion. AAI, a powerful nephrotoxin with carcinogenic potential, is present in the Aristolochiaceae species, which can release AAI into soil as a persistent pollutant. In order to assess the potential risk of Aristolochic Acid I (AAI) exposure on mammalian oogenesis, we uncovered its adverse effect on primordial folliculogenesis in the neonatal mouse ovary and its effect on female fertility in adulthood. Pregnant mice were orally administrated with doses of AAI without hepatic or renal toxicity during late-gestation. Ovaries from offspring of administered female displayed gross aberrations during primordial folliculogenesis. Also, unenclosed oocytes in germ-cell cysts showed increased DNA damage. Furthermore, several key factors, including NANOS3, SOX9, KLF4, that govern early gonad’s differentiation were abnormally expressed in the exposed ovary, while the follicle formation was partially restored by knockdown of Nanos3 or sox9. In adulthood, these aberrations evolved into a significant reduction in offspring number and impaired ovarian reserve. Together, our results show that AAI influences primordial folliculogenesis and, importantly, affected female fertility. This study shows that administration of drugs herbs or consumption of vegetables that contain AAs during pregnancy may adversely influence the fertility of offspring.

Objective The purpose of this study was to evaluate the prognostic significance of corrected baseline metabolic parameters in fluorodeoxyglucose positron emission tomography imaging (18 F-FDG PET/CT) for 3-year progression-free survival (PFS) in patients with primary diffuse large B cell lymphoma (DLBCL). Patients and Methods Retrospective clinical and pathological data were collected for 199 patients of DLBCL diagnosed between January 2018 and January 2021. All patients underwent 18 F-FDG PET/CT scans without any form of treatment. The corrected maximum standardized uptake value (corSUVmax), corrected mean standardized uptake value (corSUVmean), corrected whole-body tumor metabolic volume sum (corMTVsum), and corrected total lesion glycolysis of whole body (corTLGtotal) were corrected using the SUVmean in a 1-cm diameter mediastinal blood pool (MBP) from the descending thoracic aorta of patients. Kaplan–Meier survival curves and Cox regression were used to examine the predictive significance of corrected baseline metabolic parameters on 3-year PFS of patients. The incremental values of corrected baseline metabolic parameters were evaluated by using Harrell's C-indices, receiver operating characteristic, and Decision Curve Analysis. Results The multivariate analysis revealed that only the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and corMTVsum had an effect on 3-year PFS of patients (p < 0.05, respectively). The Kaplan–Meier survival analysis demonstrated significant differences in PFS between the risk groups classified by corSUVsum, corMTVsum, and corTLGtotal (log-rank test, p < 0.05). The predictive model composed of corMTVsum and corTLGtotal surpasses the predictive performance of the model incorporating MTVsum and TLGtotal. The optimal performance was observed when corMTVsum was combined with NCCN-IPI, resulting in a Harrell's C index of 0.785 and area under the curve values of 0.863, 0.891, and 0.947 for the 1-, 2-, and 3-year PFS rates, respectively. Conclusion The corMTVsum offers significant prognostic value for patients with DLBCL. Furthermore, the combination of corMTVsum with the NCCN-IPI can provide an accurate prediction of the prognosis. [ABSTRACT FROM AUTHOR]

Oxidative stress plays an important role in aging-related neurodegeneration. This study used littermates of WT and Nox2-knockout (Nox2KO) mice plus endothelial cell-specific human Nox2 overexpression-transgenic (HuNox2Tg) mice to investigate Nox2-derived ROS in brain aging. Compared with young WT mice (3-4 months), aging WT mice (20-22 months) had obvious metabolic disorders and loss of locomotor activity. Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and [gamma]H2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2KO brains. HuNox2Tg brains at middle age (11-12 months) already had high levels of ROS production and activation of stress signaling pathways similar to those found in aging WT brains. The mechanism of Ang II-induced endothelial Nox2 activation in capillary damage was examined using primary brain microvascular endothelial cells. The clinical significance of Nox2-derived ROS in aging-related loss of cerebral capillaries and neurons was investigated using postmortem midbrain tissues of young (25-38 years) and elderly (61-85 years) adults. In conclusion, Nox2 activation is an important mechanism in aging-related cerebral capillary rarefaction and reduced brain function, with the possibility of a key role for endothelial cells., Introduction The brain is a highly metabolic organ requiring a consistent supply of oxygen and nutrients for normal function. Ensuring a sufficient oxygen and nutrition supply to the brain is [...]

We propose an ultracompact parallel label-free biosensor based on concentric silicon-on-insulator microring resonators. Our numerical studies show that the proposed biosensor offers higher sensitivity and a larger detection area than conventional single-ring-based sensors. We analyze the detection sensitivity of the DNA hybridization by immobilizing the probe on top of the double concentric ring resonators and in the ring-ring air gap. For a concentric double-ring system with an area of 27.646 [micro][m.sup.2], the bulk detection sensitivity is 683 nm [RIU.sup.-1]. The sensitive uniformity of the system related to the optical field distribution is also studied. OCIS codes: 130.6010, 230.4555.

The p47phox is a key regulatory subunit of Nox2-containing NADPH oxidase (Nox2) that by generating reactive oxygen species (ROS) plays an important role in Angiotensin II (AngII)-induced cardiac hypertrophy and heart failure. However, the signalling pathways of p47phox in the heart remains unclear. In this study, we used wild-type (WT) and p47phox knockout (KO) mice (C57BL/6, male, 7-month-old, n = 9) to investigate p47phox-dependent oxidant-signalling in AngII infusion (0.8 mg/kg/day, 14 days)-induced cardiac hypertrophy and cardiomyocyte apoptosis. AngII infusion resulted in remarkable high blood pressure and cardiac hypertrophy in WT mice. However, these AngII-induced pathological changes were significantly reduced in p47phox KO mice. In WT hearts, AngII infusion increased significantly the levels of superoxide production, the expressions of Nox subunits, the expression of PKCα and C-Src and the activation of ASK1 (apoptosis signal-regulating kinase 1), MKK3/6, ERK1/2, p38 MAPK and JNK signalling pathways together with an elevated expression of apoptotic markers, i.e., γH2AX and p53 in the cardiomyocytes. However, in the absence of p47phox, although PKCα expression was increased in the hearts after AngII infusion, there was no significant activation of ASK1, MKK3/6 and MAPKs signalling pathways and no increase in apoptosis biomarker expression in cardiomyocytes. In conclusion, p47phox-dependent redox-signalling through ASK1, MKK3/6 and MAPKs plays a crucial role in AngII-induced cardiac hypertrophy and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

Objective: The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD., Methods: One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed., Results: A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the -log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values., Conclusion: The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Yue, Zhang, Li, Hua, Li, Zheng and Liu.)

Objective  The purpose of this study was to evaluate the prognostic significance of corrected baseline metabolic parameters in fluorodeoxyglucose positron emission tomography imaging ( 18 F-FDG PET/CT) for 3-year progression-free survival (PFS) in patients with primary diffuse large B cell lymphoma (DLBCL). Patients and Methods  Retrospective clinical and pathological data were collected for 199 patients of DLBCL diagnosed between January 2018 and January 2021. All patients underwent 18 F-FDG PET/CT scans without any form of treatment. The corrected maximum standardized uptake value (corSUVmax), corrected mean standardized uptake value (corSUVmean), corrected whole-body tumor metabolic volume sum (corMTVsum), and corrected total lesion glycolysis of whole body (corTLGtotal) were corrected using the SUVmean in a 1-cm diameter mediastinal blood pool (MBP) from the descending thoracic aorta of patients. Kaplan-Meier survival curves and Cox regression were used to examine the predictive significance of corrected baseline metabolic parameters on 3-year PFS of patients. The incremental values of corrected baseline metabolic parameters were evaluated by using Harrell's C-indices, receiver operating characteristic, and Decision Curve Analysis. Results  The multivariate analysis revealed that only the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and corMTVsum had an effect on 3-year PFS of patients ( p  < 0.05, respectively). The Kaplan-Meier survival analysis demonstrated significant differences in PFS between the risk groups classified by corSUVsum, corMTVsum, and corTLGtotal (log-rank test, p  < 0.05). The predictive model composed of corMTVsum and corTLGtotal surpasses the predictive performance of the model incorporating MTVsum and TLGtotal. The optimal performance was observed when corMTVsum was combined with NCCN-IPI, resulting in a Harrell's C index of 0.785 and area under the curve values of 0.863, 0.891, and 0.947 for the 1-, 2-, and 3-year PFS rates, respectively. Conclusion  The corMTVsum offers significant prognostic value for patients with DLBCL. Furthermore, the combination of corMTVsum with the NCCN-IPI can provide an accurate prediction of the prognosis., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)