The emerging role of extracellular vesicles in fungi: a double-edged sword.

Fungi are eukaryotic microorganisms found in nature, which can invade the human body and cause tissue damage, inflammatory reactions, organ dysfunctions, and diseases. These diseases can severely damage the patient's body systems and functions, leading to a range of clinical symptoms that can be life-threatening. As the incidence of invasive fungal infections has progressively increased in the recent years, a wealth of evidence has confirmed the "double-edged sword" role of fungal extracellular vesicles (EVs) in intercellular communication and pathogen-host interactions. Fungal EVs act as mediators of cellular communication, affecting fungal-host cell interactions, delivering virulence factors, and promoting infection. Fungal EVs can also have an induced protective effect, affecting fungal growth and stimulating adaptive immune responses. By integrating recent studies, we discuss the role of EVs in fungi, providing strong theoretical support for the early prevention and treatment of invasive fungal infections. Finally, we highlight the feasibility of using fungal EVs as drug carriers and in vaccine development.

The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis.

China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health. In this study, we investigated the toxic effects of YCl3 on mouse testes and four types of testicular cells, including Sertoli, Leydig, spermatogonial and spermatocyte cells. The results showed that YCl3 exposure causes substantial damage to mouse testes and induces apoptosis and autophagy, but not pyroptosis or necrosis, in testicular cells. Genome-wide gene expression analysis revealed that YCl3 induced significant changes in gene expression, with Ca2+ and mitochondria-related genes being the most significantly altered. Mechanistically, YCl3 exposure induced mitochondrial dysfunction in testicular cells, triggering the overproduction of reactive oxygen species (ROS) by impairing the Nrf2 pathway, regulating downstream Ho-1 target protein expression, and increasing Ca2+ levels to activate the CamkII/Ampk signaling pathway. Blocking ROS production or Ca2+ signaling significantly attenuates apoptosis and autophagy, while supplementation with Ca2+ reverses the suppression of apoptosis and autophagy by ROS blockade in testicular cells. Notably, apoptosis and autophagy induced by YCl3 treatment are independent of each other. Thus, our study suggests that YCl3 may impair the antioxidant stress signaling pathway and activate the calcium pathway through the ROS-Ca2+ axis, which promotes testicular cell apoptosis and autophagy independently, thus inducing testicular damage and impairing male reproductive function.

Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels.

Objective: The widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection. Methods: The structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation-reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation. Results: It was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 µg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection. Conclusion: The synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections.

Relationship between Platelet-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Spontaneous Preterm Birth: A Systematic Review and Meta-analysis.

Background: Spontaneous preterm birth is one of the most common pregnancy complications in obstetric clinical practice, and its etiology is complex. The problems of low survival and high morbidity rates of premature infants need to be solved urgently. The platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) are two novel biomarkers of inflammation, and several studies have linked PLR and LMR to spontaneous preterm birth. These systematic review and meta-analysis are aimed at analyzing the relationship between PLR and LMR in patients with spontaneous preterm birth to provide new ideas for the early prevention and treatment of spontaneous preterm births. Methods: Cochrane Library, EMBASE, PubMed, and China National Knowledge Infrastructure databases were inspected to gather PLR and LMR in patients with spontaneous preterm birth, all from the database to February 2022. Interstudy heterogeneity was evaluated using Cochran's Q test and I 2 statistic. Differences in PLR and LMR between patients with spontaneous preterm birth and full-term controls were evaluated by computing standardized mean differences and 95% confidence intervals. Publication bias and sensitivity analyses were also performed. Results: Nine studies were included in the meta-analysis based on the inclusion and exclusion criteria. The meta-analysis showed that serum PLR values were remarkably larger for patients with spontaneous preterm birth than for full-term controls (SMD = 0.49, 95% CI: 0.13 to 0.84, P = 0.007), whereas the difference between serum LMR in patients with spontaneous preterm birth and full-term controls was not statistically significant (SMD: 0.35, 95% CI: -0.18, 0.88, P = 0.199). The results of Begg's and Egger's tests revealed that the publication bias of the meta-analysis was not significant. The outcomes of the sensitivity analysis showed that the individual studies did not influence the meta-analysis results. Conclusions: Current evidence shows that PLR is strongly associated with spontaneous preterm birth, whereas LMR is not. PLR has a certain clinical value in diagnosing and treating spontaneous preterm births, and our research will provide strong theoretical support for clinical work. In the future, it will be necessary to further explore the reasons for the increased PLR in the serum of patients with spontaneous preterm birth and other mechanisms inducing spontaneous preterm birth.