The Role of Mitochondrial Permeability Transition in Bone Metabolism, Bone Healing, and Bone Diseases.

Bone is a dynamic organ with an active metabolism and high sensitivity to mitochondrial dysfunction. The mitochondrial permeability transition pore (mPTP) is a low-selectivity channel situated in the inner mitochondrial membrane (IMM), permitting the exchange of molecules of up to 1.5 kDa in and out of the IMM. Recent studies have highlighted the critical role of the mPTP in bone tissue, but there is currently a lack of reviews concerning this topic. This review discusses the structure and function of the mPTP and its impact on bone-related cells and bone-related pathological states. The mPTP activity is reduced during the osteogenic differentiation of mesenchymal stem cells (MSCs), while its desensitisation may underlie the mechanism of enhanced resistance to apoptosis in neoplastic osteoblastic cells. mPTP over-opening triggers mitochondrial swelling, regulated cell death, and inflammatory response. In particular, mPTP over-opening is involved in dexamethasone-induced osteoblast dysfunction and bisphosphonate-induced osteoclast apoptosis. In vivo, the mPTP plays a significant role in maintaining bone homeostasis, with many bone disorders linked to its excessive opening. Genetic deletion or pharmacological inhibition of the over-opening of mPTP has shown potential in enhancing bone injury recovery and alleviating bone diseases. Here, we review the findings on the relationship of the mPTP and bone at both the cellular and disease levels, highlighting novel avenues for pharmacological approaches targeting mitochondrial function to promote bone healing and manage bone-related disorders.

A Multifunctional Additive Based on the Cation-Anion Synergistic Effect for Highly Stable Zinc Metal Anodes.

The Zn dendrite and hydrogen evolution reaction have been a "stubborn illness" for the life span of zinc anodes, which significantly hinders the development of aqueous zinc batteries (AZBs). Herein, considering the ingenious molecular structure, a multifunctional additive based on the synergistic regulation of cations and anions at the interface is designed to promote a dendrite-free and stable Zn anode. Theoretical calculations and characterization results verified that the electrostatic shield effect of the cation, the solvation sheath structure, and the bilayer structural solid electrolyte film (SEI) jointly account for the uniform Zn deposition and side reaction suppression. Ultimately, a remarkably high average Coulombic efficiency (CE) of 99.4% is achieved in the Zn||Cu cell for 300 cycles, and a steady charge/discharge cycling over 3000 and 300 h at 1.0 mA cm-2/1.0 mAh cm-2 and 10 mA cm-2/10 mAh cm-2 is obtained in the Zn||Zn cell. Furthermore, the assembled full battery demonstrates a prolonged cycle life of 2000 cycles.

Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants.

Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis in ovarian tissue. When the balance between ROS and antioxidants is disrupted, however, it can cause serious consequences of oxidative stress (OS), and the quantity and quality of oocytes will decline. Therefore, this review discusses the interrelationship between OS and premature ovarian insufficiency (POI), the potential mechanisms and the methods by which antioxidants can improve POI through controlling the level of OS. We found that OS can mediate changes in genetic materials, signal pathways, transcription factors and ovarian microenvironment, resulting in abnormal apoptosis of ovarian granulosa cells (GCs) and abnormal meiosis as well as decreased mitochondrial Deoxyribonucleic Acid(mtDNA) and other changes, thus accelerating the process of ovarian aging. However, antioxidants, mesenchymal stem cells (MSCs), biological enzymes and other antioxidants can delay the disease process of POI by reducing the ROS level in vivo.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia: a propensity score matching analysis.

Objective: Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population. Methods: A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival. Results: During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery. Conclusion: EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility.

Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

An specific photoelectrochemical sensor based on pillar[5]arenes functionalized gold nanoparticles and bismuth oxybromide nanoflowers for bovine hemoglobin recognition.

In this work, the ultrasensitive photoelectrochemical (PEC) sensor for the detection of bovine hemoglobin (BHb) was developed based on water-soluble pillar[5]arenes (WP5) functionalized gold nanoparticles (Au NPs) and bismuth oxybromide (BiOBr) nanoflowers (Au@WP5/BiOBr). The photoelectrical signal of dopamine (DA) was decreased after adding the different concentrations of BHb due to the formation of hydrogen bond between the COOH groups of BHb molecules and the NH2 group of DA, which could achieve the indirect detection of BHb. Benefiting from the photo-generated electron-holes of BiOBr nanoflowers, the localized surface plasmon resonance (LSPR) effect of Au NPs, the host-guest interaction of WP5 between and DA, the PEC sensor showed a specificallyrecognize toward BHb with a wide detection range of 1.0 × 10-11-1.0 × 10-1 mg/mL and a detection limit of 4.2 × 10-12 mg/mL (S/N = 3). Additionally, the proposed PEC sensor also displayed good stability, remarkable selectivity and provided a promising strategy of design pillar[5]arenes functionalized photoelectric activity nanomaterials for PEC sensing application.

Relationship Between INPP5E Gene Expression and Embryonic Neural Development in a Mouse Model of Neural Tube Defect.

BACKGROUND The INPP5E gene encodes for the inositol polyphosphate-5-phosphatase (INPP5E) 72 kDa protein that regulates the phosphoinositide signaling pathway and other cellular activities, but the functional role of this gene in embryonic neurodevelopment and neural tube defect (NTD) remains unclear. The aim of this study was to use a mouse model of NTD to investigate the expression levels of the INPP5E gene during neural development and the occurrence of NTD. MATERIAL AND METHODS In an established NTD mouse model, stereoscopy was used to look for morphological defects. Transcription and expression levels of the INPP5E gene in neural tissues were detected using real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blotting in the NTD mouse embryos and compared with control mouse embryos. RESULTS The expression levels of the INPP5E gene decreased as embryonic development progressed in the neural tissue of control mice embryos, but showed no obvious trend in the neural tissues of the NTD mouse embryos. The expression levels of the INPP5E gene in NTD mouse embryos were significantly lower compared with control embryos, at the time of neural tube closure (gestational day 11.5). CONCLUSIONS The INPP5E gene regulates the process of embryonic neural development. Abnormal levels of expression of the INPP5E gene may contribute to NTDs. Increased knowledge of the expression pattern of the INPP5E gene may lead to an advanced understanding of the molecular mechanism of embryonic neurodevelopment and identify more specific directions to explore potential treatments for NTDs associated with abnormalities in INPP5E gene expression levels.

Interaction between Z-ligustilide from Radix Angelica sinensis and human serum albumin.

Z-ligustilide (LIG), an essential oil extract from Radix Angelica sinensis, has broad pharmaceutical applications in treating cardiovascular and cerebrovascular diseases. Interaction of LIG with the major transport protein of human blood circulation, human serum albumin (HSA) has been investigated by steady-state, UV-vis and circular dichroism (CD) spectroscopic methods, as well as the effect of metal ions (e.g. Zn(2+), Cu(2+), Fe(3+), Co(2+), Ni(2+)) on the LIG-HSA system. Fluorescence results revealed that a moderate binding affinity (1.59 × 10(4) M(-1) at 298 K) between LIG and HSA with a 1:1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +12.96 J mol(-1) K(-1) and ΔH =- 20.11 kJ mol(-1)) suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. The specific binding distance r (3.75 nm) between donor (Trp-214) and acceptor (LIG) was obtained according to fluorescence resonance energy transfer. CD results showed that slight conformational changes occurred in the protein upon complexation with LIG.