Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Identification of a Hippocampus-to-Zona Incerta Projection involved in Motor Learning.

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

Propofol Protects the Blood-Brain Barrier After Traumatic Brain Injury by Stabilizing the Extracellular Matrix via Prrx1: From Neuroglioma to Neurotrauma.

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Derived from fangchinoline, LYY-35 exhibits an inhibiting effect on human NSCLC cancer A549 cells.

Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of ß-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.

Decoding heterogeneous and coordinated tissue architecture in glioblastoma using spatial transcriptomics.

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Assessment of stress levels and reproductive condition in giant pandas: insights from hair, faecal and saliva samples.

Concerted conservation efforts have brought the giant panda (Ailuropoda melanoleuca) back from the brink of extinction, but pandas continue to face anthropogenic threats in the wild and breeding success in captivity remains low. Because stress can have detrimental impacts on reproduction, monitoring stress- and sex-steroid levels would help assess the effectiveness of conservation mitigation measures in panda populations as well as monitor the welfare and reproductive health of captive animals. In this proof-of-concept study, we used faecal sex steroid and cortisol concentrations (n = 867 samples collected from five males and five females at Beijing Zoo every 4 days over the course of 12 months) as a reference to investigate if testosterone, estradiol, progesterone and cortisol can be meaningfully measured in panda hair (n = 10) using radio-immuno-assays. Additionally, we calculated the ratio of testosterone to cortisol (T:C ratio) for each male, which can provide a biomarker of stress and physical performance. Our findings revealed distinct monthly variations in faecal sex-steroid and cortisol concentrations, reflecting reproductive seasonality and visitor-related stress among individual pandas. Notably, the oldest male had a significantly lower T:C ratio than other males. Our results confirm that the level of sex steroids and cortisol can be assayed by panda hair, and the hair cortisol concentrations correlate significantly with that in faeces with one month lag behind (r = 0.68, P = 0.03). However, the concentrations of hormones detected in saliva are lower than those in faeces by two orders of magnitude, making it difficult to ensure accuracy. By assessing the applicability of hair, faecal and salivary sampling, we can infer their utility in monitoring the reproductive status and acute and chronic stress levels of giant pandas, thereby providing a means to gauge the success of ongoing habitat restoration efforts and to discuss the feasibility of sample collection from wild populations.

Non-infectious immune complexes downregulate the production of interferons and tumor necrosis factor-α in primary porcine alveolar macrophages in vitro.

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-ß, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-ß, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-ß1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/ß/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.

Recent research and applications in lipid-based food and lipid-incorporated bioink for 3D printing.

Three-dimensional (3D) printing, as an emerging digital production technology, has recently been receiving increasing attention in food processing. It is important to understand the effect of key ingredients of food materials on the printing, which makes it possible to achieve a wider range of structures using few nozzles and to provide tailored nutrition and personalization. This comprehensive review delves into the latest research on 3D-printed lipid-based foods, encompassing a variety of products such as chocolate, processed cheese, as well as meat. It also explores the development and application of food bioinks that incorporate lipids as a pivotal component, including those based on starch, protein, oleogels, bigels, and emulsions, as well as emulsion gels. Moreover, this review identifies the current challenges and presents an outlook on future research directions in the field of 3D food printing, especially the research and application of lipids in food 3D printing.

Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.

Curcumin Nanocapsules based on carbon dots for photodynamic sterilization towards Listeria monocytogenes and Staphylococcus aureus.

Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

A non-invasive osteopontin-targeted phase changeable fluorescent nanoprobe for molecular imaging of myocardial fibrosis.

Due to the elevated fatality rate of cardiovascular diseases, myocardial fibrosis emerges as a prominent pathological alteration in the majority of heart ailments and their associated pathologies, thereby augmenting the likelihood of sudden cardiac death. Consequently, the prompt and obligatory identification of myocardial fibrosis assumes paramount importance in averting malignant incidents among patients afflicted with cardiac disorders. Herein, with higher expression osteopontin (OPN) found in cardiac fibrosis tissue, we have developed a dual-modality imaging probe, namely OPN targeted nanoparticles (OPN@PFP-DiR NPs), which loaded perfluoropentane (PFP) for ultrasound (US) and 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) for near-infrared fluorescence (NIR) of molecular imaging, to investigate the molecular features of cardiac fibrosis using US and NIR imaging. Subsequently, the OPN@PFP-DiR NPs were administered intravenously to a mouse model of myocardial infarction (MI). The US and NIR molecular imaging techniques were employed to visualize the accumulation of the nanoparticles in the fibrotic myocardium. Hence, this research presents a valuable noninvasive, cost-effective, and real-time imaging method for evaluating cardiac fibrosis, with promising clinical applications.

Concurrently boosted oxygen reduction/evolution electrocatalysis over highly loaded CoNi/onion-like carbon hybrid nanosheets.

Balancing the bicatalytic activities and stabilities between oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is a critical yet challenging task for exploring advanced rechargeable Zinc-air batteries (ZABs). Herein, a hybrid nanosheet catalyst with highly dispersed and densified metallic species is developed to boost the kinetics and stabilities of both ORR and OER concurrently. Through a progressive coordination and pyrolysis approach, we directly prepared highly conductive onion-like carbon (OLC) accommodating dense ORR-active CoNC species and enveloping high-loading OER-active CoNi-synergic structures within a porous lamellar architecture. The resultant CoNi/OLC nanosheet catalyst delivers better ORR and OER activities showcasing a smaller reversible oxygen electrode index (ΔE = Ej10 - E1/2) of 0.71 V, compared to state-of-the-art Pt/C-RuO2 catalysts (0.75 V), Co/amorphous carbon polyhedrons (0.80 V), NiO nanoparticles with higher Ni loading (1.00 V), and most CoNi-based bifunctional catalysts reported so far. The rechargeable ZAB assembled with the developed catalyst achieves a remarkable peak power density of 270.3 mW cm-2 (172 % of that achieved by Pt/C + RuO2) and ultrahigh cycling stability with a negligible increase in voltage gap after 800 h (110 mV increase after 200 h for a Pt/C + RuO2-based battery), standing the top level of those ever reported.

Effects of different plasma treatments on bonding properties of zirconia.

This in vitro study was to evaluate the effect of different non-thermal atmospheric pressure plasma (NTP) on shear bond strength (SBS) between yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and self-adhesive resin cement. In this study, The Y-TZP specimens were divided into 4 groups according to the surface treatment methods as follows: Control (no surface treatment), Sb (Sandblasting), AP(argon NTP), and CP(20 % oxygen and 80 % argon combination NTP). Y-TZP specimens were randomly selected from each group to observe and test the following indexes: scanning electron microscope to observe the surface morphology; atomic force microscope to detect the surface roughness; contact angle detector to detect the surface contact angle; energy spectrometer to analyze the surface elements. Then, resin cement (Rely X-U200) was bonded to human isolated teeth with Y-TZP specimens to measure SBS. The results showed that for the SE test, the NTP group was significantly higher than the control group (p < 0.05). The results of the SBS test showed that the SBS values of the NTP group were significantly higher than those of the other groups, regardless of the plasma treatment (p < 0.05). However, there was no significant difference between groups AP and CP in a test of SBS (p > 0.05). This study shows that non-thermal atmospheric pressure plasma can improve the shear bond strength of Y-TZP by increasing the surface energy. The addition of oxygen ratio to argon is more favorable to increase the shear bond strength and is worth further investigation.

A bio-based functional separator enables dendrite-free anodes in aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have garnered considerable interest as potential solutions for large-scale energy storage systems, owing to their cost-effectiveness and high safety. Nonetheless, the development of AZIBs is hindered by significant challenges associated with dendrite growth and side reactions on Zn anodes. Here, a bio-based separator derived from cellulose was developed for the dendrite-free anode in AZIBs. In addition, the separator is notable for its ultra-low cost and biodegradability in contrast to the commonly used commercial glass fiber (GF) separators. The mechanical strength of the separator is enhanced by the cross-linking of hydrogen bonds, effectively inhibiting dendrite growth. The zinc-philic groups facilitate better binding to Zn2+, resulting in uniform nucleation and deposition. The hydrophilic groups aid in trapping water molecules, thereby preventing side reactions of the electrolyte. The Zn||Zn symmetric cell with this separator can sustain a long cycle life for over 800 h, indicating stable Zn2 + plating and stripping with suppressed dendrite growth. Concurrently, the assembled Zn||VO2 full batteries exhibited a capacity retention rate of 61.87% after 1,000 cycles at 1 A g-1 with an initial capacity of 140 mAh g-1. This work highlights a stable, economical, and eco-friendly approach to the design of bio-based separators in AZIBs for sustainable energy storage systems.

TurboID-mediated proximity labeling technologies to identify virus co-receptors.

Virus receptors determine the tissue tropism of viruses and have a certain relationship with the clinical outcomes caused by viral infection, which is of great importance for the identification of virus receptors to understand the infection mechanism of viruses and to develop entry inhibitor. Proximity labeling (PL) is a new technique for studying protein-protein interactions, but it has not yet been applied to the identification of virus receptors or co-receptors. Here, we attempt to identify co-receptor of SARS-CoV-2 by employing TurboID-catalyzed PL. The membrane protein angiotensin-converting enzyme 2 (ACE2) was employed as a bait and conjugated to TurboID, and a A549 cell line with stable expression of ACE2-TurboID was constructed. SARS-CoV-2 pseudovirus were incubated with ACE2-TurboID stably expressed cell lines in the presence of biotin and ATP, which could initiate the catalytic activity of TurboID and tag adjacent endogenous proteins with biotin. Subsequently, the biotinylated proteins were harvested and identified by mass spectrometry. We identified a membrane protein, AXL, that has been functionally shown to mediate SARS-CoV-2 entry into host cells. Our data suggest that PL could be used to identify co-receptors for virus entry.

Ferroptosis: a novel mechanism of cell death in ophthalmic conditions.

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation and differs from programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is associated with a variety of physiological and pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence and development of diseases by targeting metabolic pathways and signaling pathways in tumors, ischemic organ damage, and other degenerative diseases related to lipid peroxidation. Increasing evidence suggests that ferroptosis is closely linked to the onset and progression of various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, and retinoblastoma. Our review of the current research on ferroptosis in ophthalmic diseases reveals significant advancements in our understanding of the pathogenesis, aetiology, and treatment of these conditions.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.