The Molecular Mechanism of ferroptosis and Its Relationship with Parkinson's Disease.

Neurodegenerative diseases such as Parkinson's disease (PD) have complex pathogenetic mechanisms. Genetic, age, and environmental factors are all related to PD. Due to the unclear pathogenesis of PD and the lack of effective cure methods, it is urgent to find new targets for treating PD patients. Ferroptosis is a form of cell death that is reliant on iron and exhibits distinct morphological and mechanistic characteristics compared to other types of cell death. It encompasses a range of biological processes, including iron/lipid metabolism and oxidative stress. In recent years, research has found that ferroptosis plays a crucial role in the pathophysiological processes of neurodegenerative diseases and stroke. Therefore, ferroptosis is also closely related to PD, This article reviews the core mechanisms of ferroptosis and elucidates the correlation between PD and ferroptosis. In addition, new compounds that have emerged in recent years to exert anti PD effects by inhibiting the ferroptosis signaling pathway were summarized. I hope to further elaborate the relationship between ferroptosis and PD through the review of this article, and provide new strategies for developing PD treatments targeting ferroptosis.

Interlayer Fermi Polarons of Excited Exciton States in Quantizing Magnetic Fields.

The study of exciton polarons has offered profound insights into the many-body interactions between bosonic excitations and their immersed Fermi sea within layered heterostructures. However, little is known about the properties of exciton polarons with interlayer interactions. Here, through magneto-optical reflectance contrast measurements, we experimentally investigate interlayer Fermi polarons for 2s excitons in WSe2/graphene heterostructures, where the excited exciton states (2s) in the WSe2 layer are dressed by free charge carriers of the adjacent graphene layer in the Landau quantization regime. First, such a system enables an optical detection of integer and fractional quantum Hall states (e.g., ν = ±1/3, ±2/3) of monolayer graphene. Furthermore, we observe that the 2s state evolves into two distinct branches, denoted as attractive and repulsive polarons, when graphene is doped out of the incompressible quantum Hall gaps. Our work paves the way for the understanding of the excited composite quasiparticles and Bose-Fermi mixtures.

Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways.

Interactions between cells are of fundamental importance in affecting cell function. In vivo, endothelial cells and islet cells are close to each other, which makes endothelial cells essential for islet cell development and maintenance of islet cell function. We used endothelial cells to construct 3D pseudo-islets, which demonstrated better glucose regulation and greater insulin secretion compared to conventional pseudo-islets in both in vivo and in vitro trials. However, the underlying mechanism of how endothelial cells promote beta cell function localized within islets is still unknown. We performed transcriptomic sequencing, differential gene analysis, and enrichment analysis on two types of pseudo-islets to show that endothelial cells can promote the function of internal beta cells in pseudo-islets through the BTC-EGFR-JAK/STAT signaling pathway. Min6 cells secreted additional BTC after co-culture of endothelial cells with MIN6 cells outside the body. After BTC knockout in vitro, we found that beta cells functioned differently: insulin secretion levels decreased significantly, while the expression of key proteins in the EGFR-mediated JAK/STAT signaling pathway simultaneously decreased, further confirming our results. Through our experiments, we elucidate the molecular mechanisms by which endothelial cells maintain islet function in vitro, which provides a theoretical basis for the construction of pseudo-islets and islet cell transplants for the treatment of diabetes mellitus.

Can major public health emergencies increase the participation of commercial insurance? Evidence from China.

Background: Public health emergencies have a lasting impact on a country's economic and social development. However, commercial insurance can disperse these negative consequences and reduce risk losses. Method: Based on the Chinese Household Tracking Survey and Peking University Digital Inclusive Finance Index, this study employed a difference-in-differences model to test the impact of the COVID-19 outbreak on commercial insurance participation and the impact mechanism. Results: The analysis showed that the outbreak of COVID-19 improved residents' risk perception, risk preference and digital finance and promoted their participation in commercial insurance, commercial endowment insurance, and commercial medical insurance. Conclusion: Major public health emergencies can increase commercial insurance participation, but the promotional effect of commercial insurance on rural and low-income individuals is relatively limited. To tap into potential customers, financial institutions should focus on vulnerable societal groups. This study supplements the relevant literature on the impact of major public health emergencies on commercial insurance participation.

Synergistic Biofilter Tube for Promoting Scarless Tendon Regeneration.

Inspired by the imbalance between extrinsic and intrinsic tendon healing, this study fabricated a new biofilter scaffold with a hierarchical structure based on a melt electrowriting technique. The outer multilayered fibrous structure with connected porous characteristics provides a novel passageway for vascularization and isolates the penetration of scar fibers, which can be referred to as a biofilter process. In vitro experiments found that the porous architecture in the outer layer can effectively prevent cell infiltration, whereas the aligned fibers in the inner layer can promote cell recruitment and growth, as well as the expression of tendon-associated proteins in a simulated friction condition. It was shown in vivo that the biofilter process could promote tendon healing and reduce scar invasion. Herein, this novel strategy indicates great potential to design new biomaterials for balancing extrinsic and intrinsic healing and realizing scarless tendon healing.

Invasive assessment of coronary microvascular dysfunction and cardiovascular outcomes across the full spectrum of CAD: a meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary artery disease (CAD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CAD has not been systemically quantified. METHODS: We searched electronic databases for studies on patients with CAD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. RESULTS: We included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P < .01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P < .01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value = .95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P < .01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P < .01) (interaction P value < .01). CONCLUSIONS: CMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CAD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CAD populations.

Risk factor evaluation of cuff pressure of >30 cmH2O to stop air leakage during mechanical ventilation: A prospective observational study.

AIM: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. DESIGN: A multi-centre prospective observational study. METHODS: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. RESULTS: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.

Plant-Derived Exosomes as Novel Nanotherapeutics Contrive Glycolysis Reprogramming-Mediated Angiogenesis for Diabetic Ulcer Healing.

Reversal of endothelial cell (EC) dysfunction under high-glucose (HG) conditions to achieve angiogenesis has remained a big challenge in diabetic ulcers. Herein, exosomes derived from medicinal plant ginseng (GExos) were shown as excellent nanotherapeutics with biomimetic cell membrane-like structures to be able to efficiently transfer the encapsulated active substances to ECs, resulting in a marked reprogramming of glycolysis by up-regulating anaerobic glycolysis and down-regulating oxidative stress, which further restore the proliferation, migration, and tubule formation abilities of ECs under HG conditions. In vivo, GExos enhance the angiogenesis and nascent vessel network reconstruction in full-thickness diabetic complicated skin ulcer wounds in mice with high biosafety. GExos were shown as promising nanotherapeutics in stimulating glycolysis reprogramming-mediated angiogenesis in diabetic ulcers, possessing wide application potential for reversing hyperglycemic dysangiogenesis and stimulating vascular regeneration.

Efficacy of tacrolimus monotherapy in primary membranous nephropathy.

Objective: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

Biomedical application of materials for external auditory canal: History, challenges, and clinical prospects.

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

Realization of high-performance biosensor through sandwich analysis utilizing weak value amplification.

A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications.

Exploration of the Existence Forms and Patterns of Dissolved Oxygen Molecules in Water.

The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.

Purification and characterization of limonin D-ring lactone hydrolase from sweet orange (Citrus sinensis (L.) Osbeck) seeds.

BACKGROUND: Citrus products often suffer from delayed bitterness, which is generated from the conversion of non-bitter precursors (limonoate A-ring lactone, LARL) to limonin under the catalysis of limonin D-ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high-performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH. RESULTS: Purified LDLH (25.22 U mg-1) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca2+) intervention was 108% of that in the blank group, and that of zinc ion (Zn2+) intervention was 71%. CONCLUSION: LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3-9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca2+ and significantly inhibited by Zn2+. These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry.

Genetic polymorphism of IL-17 influences susceptibility to recurrent pregnancy loss in a Chinese population.

The current research aims to investigate the relationship between Interleukin-17 (IL-17) polymorphism and the risk of recurrent pregnancy loss (RPL) within a Chinese population. Totally, 120 patients with RPL were selected and enrolled as the experiment group. Additionally, 210 healthy individuals undergoing routine physical examinations during the same period served as the control group. The IL-17 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism method. The IL-17 rs2275913 polymorphism exhibited 3 genotypes: GG, GA, and AA. Significant associations were observed with the AA genotype and A allele (all P < .05), indicating women with the AA genotype were 2.06 times more likely to experience RPL compared to those with the GG genotype. Similarly, women carrying the A allele faced a 1.63 times higher risk of RPL than those with the G allele. Regarding the IL-17 rs763780 polymorphism, which also presented 3 genotypes (TT, TC, CC), significant associations were noted for the CC genotype and C allele (all P < .05). Women with the CC genotype had a 1.84 times greater risk of suffering from RPL compared to those with the TT genotype, and those with the C allele were 1.51 times more likely to experience RPL than those with the T allele. The IL-17 rs2275913 and rs763780 polymorphisms contribute an increased risk to RPL in the Chinese population. Further studies, with larger sample sizes and more rigorous designs, are necessary to validate or replicate our current results.

A novel controllable capacitor commutation based superconducting hybrid direct current breaker.

Featuring low power loss and high reliability, voltage source converter medium voltage direct current (VSC-MVDC) systems have been widely employed for grid-tied renewable energy applications. To maintain high operational safety, circuit breakers are needed to isolate faulted powerlines by comprehensively considering response speed and installation cost. Research efforts have been put to realizing DC fault isolation by coordinating resistive type superconducting fault current limiter (R-SFCL) and integrated-gate-commutated-thyristor (IGCT) based hybrid DC circuit breaker. In this paper, a controllable current commutation based superconducting DC circuit breaker (CCCB-SDCCB) is proposed. By integrating R-SFCL with IGCT based hybrid DC circuit breakers, the current interrupting capacity can be greatly enlarged with the advantage of low cost and fast speed, and hence the overall cost for suppress large fault currents can be greatly reduced for MVDC systems. In addition, a new current injection circuit branch using H-bridge structure is designed to recycle the residual capacitor voltage from the previous fault stage to trigger the IGCTs without the capacitor pre-charging process. Simulation results show that the fault current can be successfully suppressed from 24.2 to 2.1 kA and fully interrupted within 4.11 ms by the proposed CCCB-SDCCB.

Antioxidant and anti-inflammatory function of Eupatorium adenophora Spreng leaves (EASL) on human intestinal Caco-2 cells treated with tert-butyl hydroperoxide.

Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1ß using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC-MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1ß. Through LC-MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial.

Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18-60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7-87.9 vs. 67.8% 95% CI 60.0-76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6-78.8 vs. 57.6%, 95% CI 49.6-67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0-12.2 vs. 30.3%, 95% CI 30.1-30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3-4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.