Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative damage. The molecular regulatory mechanisms are related to iron metabolism, lipid peroxidation, and glutathione metabolism. Additionally, some immunological signaling pathways, such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis, the Janus kinase-signal transducer and activator of transcription 1 axis, and the transforming growth factor beta 1-Smad3 axis, may also participate in the regulation of ferroptosis. Studies have shown that ferroptosis is significantly associated with many diseases such as cancer, neurodegenerative diseases, inflammatory diseases, and autoimmune diseases. Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases, the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of aforementioned conditions.

Intracranial hemorrhage (ICH) causes numerous neurological deficits and deaths worldwide each year, leaving a significant health burden on the public. The pathophysiology of ICH is complicated and involves both primary and secondary injuries. Hematoma, as the primary pathology of ICH, undergoes metabolism and triggers biochemical and biomechanical alterations in the brain, leading to the secondary injury. Past endeavors mainly aimed at biochemical-initiated mechanisms for causing secondary injury, which have made limited progress in recent years, although ICH itself is also highly biomechanics-related. The discovery of the mechanically-activated cation channel Piezo1 provides a new avenue to further explore the mechanisms underlying the secondary injury. The current article reviews the structure and gating mechanisms of Piezo1, its roles in the physiology/pathophysiology of neurons, astrocytes, microglia, and bone-marrow-derived macrophages, and especially its roles in erythrocytic turnover and iron metabolism, revealing a potential interplay between the biomechanics and biochemistry of hematoma in ICH. Collectively, these advances provide deeper insights into the secondary injury of ICH and lay the foundations for future research.

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both in vitro and in vivo studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from Swertia chirayita, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

Despite achieving a high cure rate with the direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response. By the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis levels, and the improvement in fibrosis was analyzed in both short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.0% and 67.6% of the patients during the short-term and long-term follow-up, respectively. Short-term improvement was associated with factors including ribavirin usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index, while long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, which will provide crucial insights for enhancing patient care in hepatitis C management.

Reliable molecular biomarkers to predict fertility remain scarce. The current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm quality. Using reverse transcription-PCR and real-time reverse transcription-PCR assays, we identified seven circular RNAs from the human BOULE gene in human sperm. We observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia, while the expression levels of both circEx2-6 and circEx2-7 were decreased in teratozoospermia, compared with the controls. Furthermore, we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm DNA fragmentation index, and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive technologies. Further functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male fertility. Collectively, our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA quality. Therefore, clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, their roles in mammalian female meiosis, which accounts for over 80% of gamete-originated human reproductive diseases, remain unexplored. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced the chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. We demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, significantly eliminated KL2 expression from chromosomes. Additionally, KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase, and they competed for chromosome binding. Phosphorylated KL2 was also localized at spindle poles, with its phosphorylation regulated by extracellular signal-regulated kinase 1/2. In summary, the current study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The adequate knowledge of RPE pathology is hindered by a lack of the patients' RPE datasets, especially at the single-cell resolution. In the current study, we delved into a large-scale single-cell resource of AMD donors, in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2), was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.

Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities. It is the most common form of short-limbed skeletal dysplasia. A morbidly obese pregnant patient warrants specific anatomical and physiological considerations, such as a difficult airway with potential hypoxia, full stomach precautions, and a reduced functional residual capacity. Achondroplasia increases the risks of maternal and fetal complications. Although neuraxial techniques are generally preferred for cesarean sections, there is no consensus among patients with achondroplasia. We aimed to discuss the anesthetic challenges in an achondroplastic patient and report our regional anesthesia approach for an elective cesarean section.