Correlation of LLT-1 and NLRC4 inflammasome and its effect on glioblastoma prognosis.

PURPOSE: LLT-1 is a well-known ligand for the natural killer (NK) cell inhibitory receptor NKRP1A. Here, we examined NLRC4 inflammasome components and LLT-1 expression in glioblastoma (GBM) tissues to elucidate potential associations and interactions between these factors. METHODS: GBM tissues were collected for RNA sequencing (RNA-seq) and Immunofluorescent experiments. Colocalization of LLT-1 and other proteins was assessed by immunofluorescence. Computational analyses utilized RNA-seq data from 296 to 52 patients from the Chinese Glioma Genome Atlas and CHA medical records, respectively. These data were subjected to survival, non-negative matrix factorization clustering, Gene Ontology enrichment, and protein-protein interaction analyses. Receptor-ligand interactions between tumor and immune cells were confirmed by single-cell RNA-seq analysis. RESULTS: In GBM tissues, LLT-1 was predominantly colocalized with glial fibrillary acidic protein (GFAP)-expressing astrocytes, but not with microglial markers like Iba-1. Additionally, LLT-1 and activated NLRC4 inflammasomes were mainly co-expressed in intratumoral astrocytes, suggesting an association between LLT-1, NLRC4, and glioma malignancy. High LLT-1 expression correlates with poor prognosis, particularly in the mesenchymal subtype, and is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. At the single-cell level, mesenchymal-like malignant cells showed high NF, NLR, and IL-1 signaling pathway enrichment compared to other malignant cell types. CONCLUSION: We revealed an association between NLRC4 inflammasome activity and LLT-1 expression, suggesting a novel regulatory pathway involving TNF, inflammasomes, and IL-1, potentially offering new NK-cell-mediated anti-glioma approaches.

Qualitative Analysis of Nitrogen and Sulfur Compounds in Vacuum Gas Oils via Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry.

Analysis of the heavy fractions in crude oil has been important in petroleum industries. It is well known that heavy fractions such as vacuum gas oils (VGOs) include heteroatoms, of which sulfur and nitrogen are often characterized in many cases. We conducted research regarding the molecular species analysis of VGOs. Further refine processes using VGOs are becoming important when considering carbon recycling. In this work, we attempted to classify compounds within VGOs provided by Kuwait Institute for Scientific Research. Two VGOs were priorly distillated from Kuwait Export crude and Lower Fars crude. Quantitative analysis was performed mainly using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOFMS). MALDI-TOF-MS has been developed for analyzing high-molecular-weight compounds such as polymer and biopolymers. As matrix selection is one of the most important aspects in MALDI-TOFMS, the careful selection of a matrix was firstly evaluated, followed by analysis using a Kendrick plot with nominal mass series (z*). The objective was to evaluate if this work could provide an effective classification of VGOs compounds. The Kendrick plot is a well-known method for processing mass data. The difference in the Kendrick mass defect (KMD) between CnH2n-14S and CnH2n-20O is only 0.0005 mass units, which makes it difficult in general to distinguish these compounds. However, since the z* value showed effective differences during the classification of these compounds, qualitative analysis could be possible. The analysis using nominal mass series showed the potential to be used as an effective method in analyzing heavy fractions.

Comparison of pain relief in soft tissue tumor excision: anesthetic injection using an automatic digital injector versus conventional injection.

BACKGROUND: The pain caused by local anesthetic injection can lead to patient anxiety prior to surgery, potentially necessitating sedation or general anesthesia during the excision procedure. In this study, we aim to compare the pain relief efficacy and safety of using a digital automatic anesthetic injector for local anesthesia. METHODS: Thirty-three patients undergoing excision of a benign soft tissue tumor under local anesthesia were prospectively enrolled from September 2021 to February 2022. A single-blind, randomized controlled study was conducted. Patients were divided into two groups by randomization: the experimental group with digital automatic anesthetic injector method (I-JECT group) and the control group with conventional injection method. Before surgery, the Amsterdam preoperative anxiety information scale was used to measure the patients' anxiety. After local anesthetic was administered, the Numeric Pain Rating Scale was used to measure the pain. The amount of anesthetic used was divided by the surface area of the lesion was recorded. RESULTS: Seventeen were assigned to the conventional group and 16 to the I-JECT group. The mean Numeric Pain Rating Scale was 1.75 in the I-JECT group and 3.82 in conventional group. The injection pain was lower in the I-JECT group (p< 0.01). The mean Amsterdam preoperative anxiety information scale was 11.00 in the I-JECT group and 9.65 in conventional group. Patient's anxiety did not correlate to injection pain regardless of the method of injection (p= 0.47). The amount of local anesthetic used per 1 cm 2 of tumor surface area was 0.74 mL/cm2 in the I-JECT group and 2.31 mL/cm2 in the conventional group. The normalization amount of local anesthetic was less in the I-JECT group (p< 0.01). There was no difference in the incidence of complications. CONCLUSION: The use of a digital automatic anesthetic injector has shown to reduce pain and the amount of local anesthetics without complication.

Magnetically Stimulated Integrin Binding Alters Cell Polarity and Affects Epithelial-Mesenchymal Plasticity in Metastatic Cancer Cells.

Inorganic nanoparticles (NPs) have been widely recognized for their stability and biocompatibility, leading to their widespread use in biomedical applications. Our study introduces a novel approach that harnesses inorganic magnetic nanoparticles (MNPs) to stimulate apical-basal polarity and induce epithelial traits in cancer cells, targeting the hybrid epithelial/mesenchymal (E/M) state often linked to metastasis. We employed mesocrystalline iron oxide MNPs to apply an external magnetic field, disrupting normal cell polarity and simulating an artificial cellular environment. These led to noticeable changes in the cell shape and function, signaling a shift toward the hybrid E/M state. Our research suggests that apical-basal stimulation in cells through MNPs can effectively modulate key cellular markers associated with both epithelial and mesenchymal states without compromising the structural properties typical of mesenchymal cells. These insights advance our understanding of how cells respond to physical cues and pave the way for novel cancer treatment strategies. We anticipate that further research and validation will be instrumental in exploring the full potential of these findings in clinical applications, ensuring their safety and efficacy.

Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

Amino acid deprivation induces TXNIP expression by NRF2 downregulation.

Thioredoxin-interacting protein (TXNIP) is sensitive to oxidative stress and is involved in the pathogenesis of various metabolic, cardiovascular, and neurodegenerative disorders. Therefore, several studies have suggested that TXNIP is a promising therapeutic target for several diseases, particularly cancer and diabetes. However, the regulation of TXNIP expression under amino acid (AA)-restricted conditions is not well understood. In the present study, we demonstrated that TXNIP expression was promoted by the deprivation of AAs, especially arginine, glutamine, lysine, and methionine, in non-small cell lung cancer (NSCLC) cells. Interestingly, we determined that increased TXNIP expression induced by AA deprivation was associated with nuclear factor erythroid 2-related factor 2 (NRF2) downregulation, but not with activating transcription factor 4 (ATF4) activation. Furthermore, N-acetyl-l-cysteine (NAC), a scavenger of reactive oxygen species (ROS), suppressed TXNIP expression in NSCLC cells deprived of AA. Collectively, the induction of TXNIP expression by AA deprivation was mediated by ROS production, potentially through NRF2 downregulation. Our findings suggest that TXNIP expression may be associated with the redox homeostasis of AA metabolism and provide a possible rationale for a therapeutic strategy to treat cancer with AA restriction.

Development and validation of an artificial intelligence algorithm for detecting vocal cords in video laryngoscopy.

Airway procedures in life-threatening situations are vital for saving lives. Video laryngoscopy (VL) is commonly performed during endotracheal intubation (ETI) in the emergency department. Artificial intelligence (AI) is widely used in the medical field, particularly to detect anatomical structures. This study aimed to develop an AI algorithm that detects vocal cords from VL images acquired during emergent situations. This retrospective study used VL images acquired in the emergency department to facilitate the ETI. The vocal cord image was labeled with a ground-truth bounding box. The dataset was divided into training and validation datasets. The algorithm was developed from a training dataset using the YOLOv4 model. The performance of the algorithm was evaluated using a test set. The test set was further divided into specific environments during the ETI for clinical subgroup analysis. In total, 20,161 images from 84 patients were used in this study. A total of 10,287, 5766, and 4108 images were used for the model training, validation, and test sets, respectively. The developed algorithm achieved F1 score 0.906, sensitivity 0.963, and specificity 0.842 in the validation set. The performance in the test set was F1 score 0.808, sensitivity 0.823, and specificity 0.804. We developed and validated an AI algorithm to detect vocal cords in VL. This algorithm demonstrated a high performance. The algorithm can be used to determine the vocal cord to ensure safe ETI.

The significance of split-face studies and electromyography in forehead rejuvenation.

BACKGROUND: Botulinum toxin is a neurotoxic substance with a wide range of uses, from the treatment of musculoskeletal spasms to antiaging regimens by improving wrinkles. Split-face studies in which drugs are injected in the right and left sides of the faces have been actively conducted in botulinum toxin studies. In this study, we aimed to investigate the reliability of a split-face study for determining the effectiveness of botulinum toxin based on eyebrow height and movement, and electromyography results. METHODS: Thirty-one women aged 35 to 55 years were included in the study. Eyebrow height was measured as the distance from the eyebrows to the upper eyelid margin on the primary gaze, and eyebrow movement was measured as the distance when the forehead was wrinkled for 5 seconds. A noninvasive method was used for electromyography of the frontalis muscles. RESULTS: No statistically significant differences in right and left eyebrow heights and movements, and electromyography findings (p= 0.256, p= 1.000, and p= 0.978, respectively) were found. Pearson correlation analysis showed that electromyography muscle activity is positively associated with eyebrow movement, respectively (p< 0.001). CONCLUSION: We advocate the reliability of split-face study and the usefulness of electromyography of frontalis muscle in forehead rejuvenation research.

Brain magnetic resonance imaging (MRI) findings in central precocious puberty patients: is routine MRI necessary for newly diagnosed patients?

PURPOSE: The overall incidence of central precocious puberty (CPP) has increased in recent decades, and brain magnetic resonance imaging (MRI) evaluations are recommended in cases of suspected brain lesions. This study aimed to investigate the prevalence of MRI abnormalities and to evaluate the need for routine brain MRI in patients with newly diagnosed CPP. METHODS: This retrospective study reviewed the data of patients newly diagnosed with CPP who underwent routine pituitary MRI at Korea University Anam Hospital from March 2020 to September 2021. A total of 199 girls and 24 boys was enrolled in this study. Positive MRI findings were categorized as abnormal pituitary, nonpituitary incidental, and pathological. In addition, we investigated the incidence of MRI abnormalities and evaluated their associations with clinical and biochemical factors. RESULTS: Positive brain MRI findings were observed in 84 patients (37.7%). Pituitary abnormalities were found in 54 patients (24.2%), with Rathke cleft cysts being the most common (16.1%). Incidental nonpituitary findings were observed in 29 patients (13.0%), while a pathological brain lesion (diagnosed as hypothalamic hamartoma) was observed in only 1 female patient (0.4%). No significant differences in sex or age were found in incidence of pituitary abnormalities or nonpituitary incidental findings. Compared with headache controls, significant associations were observed between abnormal pituitary findings on MRI and CPP (unadjusted odds ratio, 3.979; 95% confidence interval, 1.726-9.173). CONCLUSION: True pathological findings were rare, even though the prevalence of abnormalities on pituitary MRI in patients with CPP was relatively high. Considering its cost-effectiveness, MRI screenings should be carefully considered in patients with CPP.

Comparing the Expression of Canonical and Non-Canonical Inflammasomes Across Glioma Grades: Evaluating Their Potential as an Aggressiveness Marker.

BACKGROUND: Inflammasomes are key in the initiation of inflammatory responses and serve to defend the organism. However, when the immune system is imbalanced, these complexes contribute to tumor progression. The purpose of this study was to investigate the effect of non-canonical inflammasomes on glioma malignancy. METHODS: We performed bioinformatics analysis to confirm the expression of canonical and non-canonical inflammasome-related molecules according to the degree of malignancy through immunohistochemical examination of glioma tissues obtained with patient consent from our institution. RESULTS: Bioinformatics analysis confirmed that the expression levels of non-canonical inflammasome-related molecules were significantly higher in tumor tissues than in normal tissues, and they also increased according to malignancy, which adversely affected the survival rate. Furthermore, in gliomas, positive correlations were found between N-form gasdermin-D, a key molecule associated with the non-canonical inflammasome, and other related molecules, including NLRP3, caspase-1, caspase-4, and caspase-5. These results were verified by immunohistochemical examination of glioma tissues, and the expression levels of these molecules also increased significantly with increasing grade. In addition, the features of pyroptosis were confirmed. CONCLUSION: This study identified the potential of non-canonical inflammasomes as aggressiveness markers for gliomas and presented a perspective for improving glioma treatment.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance. METHODS: Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival. RESULTS: Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. CONCLUSIONS: We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Molecular Characteristics of Catalytic Nitrogen Removal from Coal Tar Pitch over γ-Alumina-Supported NiMo and CoMo Catalysts.

The removal of nitrogen from coal tar pitch (CTP) through the hydrodenitrogenation (HDN) of CTP and its molecular behavior were evaluated in the presence of NiMo/γ-alumina and CoMo/γ-alumina catalysts. Fourier transform ion cyclotron resonance mass spectrometry with atmospheric pressure photoionization was used to analyze the complicated chemical classes and species of CTP and the treated products at the molecular level. Nitrogen species were qualitatively analyzed before and after hydrotreatment. A single-stage hydrotreatment with an HDN catalyst resulted in a high sulfur removal performance (85.6-94.7%) but a low nitrogen removal performance (26.8-29.2%). Based on relative abundance analyses of nitrogen and binary nitrogen species, CcHh-NnSs was the most challenging species to remove during HDN treatment. Furthermore, prior hydrodesulfurization was combined with HDN treatment, and the dual hydrotreatments yielded a significantly improved nitrogen removal performance (46.4-48.7%).

Imaging of Umbilical Venous Catheter-Related Hepatic Complications in Neonates.

An umbilical venous catheter (UVC) is commonly placed for central venous access in preterm or critically ill full-term neonates to provide total parenteral nutrition (TPN) and medication. However, UVCs can result in complications, including infection, portal vein thrombosis, and hepatic tissue injury. The inadvertent administration of hypertonic fluid through a malpositioned UVC can also cause hepatic parenchymal damage with mass-like fluid collection that simulates a tumorous condition during imaging. Ultrasonography and radiographic examinations play an essential role in detecting UVC-related complications. This pictorial essay aims to present the imaging findings of UVC-related hepatic complications in neonates.

Selective attachment of prokaryotes and emergence of potentially pathogenic prokaryotes on four plastic surfaces: Adhesion study in a natural marine environment.

This study employed 16S rRNA metabarcoding to establish the diversity of prokaryotic communities and specific characteristics of potentially pathogenic prokaryotic primary colonizers of four plastic materials (EPS, expanded polystyrene; PE, polyethylene; PP, polypropylene; and PET, polyethylene terephthalate). Bacteria inhabiting plastic and seawater differ; thus, distinct changes in the attached prokaryotic community were observed over an exposure time of 21 days, specifically on Days 3, 6, 9, and 12-21. Frist colonizers were Gammaproteobacteria and Alphaproteobacteria; Bacilli and Clostridia represented secondary colonizers. On Day 3, Pseudoalteromonas had a relative abundance >80 %; whereas, the prevalence of Vibrio spp. (potentially pathogenic prokaryotes) increased rapidly on Days 6 and 9. However, after Day 12, the prevalence of other potential pathogens, namely, Clostridium spp., steadily increased. Despite the diversity of the plastic surfaces, attached prokaryotes changed over time instead of showing similar adherent diversity in all plastic materials.

The effect of low-intensity cold atmospheric plasma jet on photoaging-induced hyperpigmentation in mouse model.

BACKGROUND: Cold atmospheric plasma (CAP) produces reactive oxygen/nitrogen species (RONS) in the target and can induce cytoprotective effects by activating hormesis-related pathways when its intensity is in the low range. OBJECTIVES: The aim of this study is to evaluate the effect of low-intensified CAP (LICAP) on skin with photoaging-induced hyperpigmentation in an animal model. METHODS: Changes in cell viability and RONS production following LICAP treatment were measured. For the in vivo study, 30 hairless mice underwent antecedent photoaging induction followed by the allocated therapy (i.e., LICAP, topical ascorbic acid (AA), or both). During the first 4 weeks of the treatment period (8 weeks), ultraviolet (UV)-B irradiation was concurrently administered. Visual inspection and measurement of the melanin index (MI) were performed to assess the change in skin pigmentation at Weeks 0, 2, 4, 6, and 8. RESULTS: RONS production increased linearly until the saturation point. Cell viability was not significantly affected by LICAP treatment. At Week 8, MI was significantly decreased in every treatment group compared with the values at Week 0 and Week 4. The treatment effect of the concurrent therapy group was superior to that of the LICAP and AA groups. CONCLUSION: LICAP appears to be a novel modality for photoprotection and pigment reduction in photodamaged skin. LICAP treatment and topical AA application seem to exert a synergistic effect.

Rice pollen-specific OsRALF17 and OsRALF19 are essential for pollen tube growth.

Pollen tube growth is essential for successful double fertilization, which is critical for grain yield in crop plants. Rapid alkalinization factors (RALFs) function as ligands for signal transduction during fertilization. However, functional studies on RALF in monocot plants are lacking. Herein, we functionally characterized two pollen-specific RALFs in rice (Oryza sativa) using multiple clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9-induced loss-of-function mutants, peptide treatment, expression analyses, and tag reporter lines. Among the 41 RALF members in rice, OsRALF17 was specifically expressed at the highest level in pollen and pollen tubes. Exogenously applied OsRALF17 or OsRALF19 peptide inhibited pollen tube germination and elongation at high concentrations but enhanced tube elongation at low concentrations, indicating growth regulation. Double mutants of OsRALF17 and OsRALF19 (ralf17/19) exhibited almost full male sterility with defects in pollen hydration, germination, and tube elongation, which was partially recovered by exogenous treatment with OsRALF17 peptide. This study revealed that two partially functionally redundant OsRALF17 and OsRALF19 bind to Oryza sativa male-gene transfer defective 2 (OsMTD2) and transmit reactive oxygen species signals for pollen tube germination and integrity maintenance in rice. Transcriptomic analysis confirmed their common downstream genes, in osmtd2 and ralf17/19. This study provides new insights into the role of RALF, expanding our knowledge of the biological role of RALF in regulating rice fertilization.

Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors.

BACKGROUND/AIM: The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. MATERIALS AND METHODS: Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. RESULTS: Nebivolol, a third generation ß1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. CONCLUSION: Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

Suppressing cancer by damaging cancer cell DNA using LED irradiation.

BACKGROUND: High-energy irradiation eliminates cancer cells by destroying their genetic components. However, there are several side effects from doing this, such as fatigue, dermatitis, and hair loss, which remain obstacles to this treatment. Here, we propose a moderate method that uses low-energy white light from a light-emitting diode (LED) to selectively inhibit cancer cell proliferation without affecting normal cells. METHODS: The association between LED irradiation and cancer cell growth arrest was evaluated based on cell proliferation, viability, and apoptotic activity. Immunofluorescence, polymerase chain reaction, and western blotting were performed in vitro and in vivo to identify the metabolism related to the inhibition of HeLa cell proliferation. RESULTS: LED irradiation aggravated the defective p53 signaling pathway and induced cell growth arrest in cancer cells. Consequently, cancer cell apoptosis was induced by the increased DNA damage. Additionally, LED irradiation inhibited the proliferation of cancer cells by suppressing the MAPK pathway. Furthermore, the suppression of cancer growth by the regulation of p53 and MAPK was observed in cancer-bearing mice irradiated with LED. CONCLUSIONS: Our findings suggest that LED irradiation can suppress cancer cell activity and may contribute to preventing the proliferation of cancer cells after medical surgery without causing side effects.

Mitochondria in reproduction.

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine.

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy.

BACKGROUND: The present study was designed to explore the pathological role of non-canonical NLRC4 inflammasome in glioma. METHODS: This retrospective study included bioinformatical analysis, including survival, gene ontology, ssGSEA, cox regression, IPA and drug repositioning with TCGA and DepMap database. Experimental validations were conducted in glioma patient's sample and evaluated with histological or cellular functional analysis. RESULT: Clinical dataset analysis revealed that non-canonical NLRC4 inflammasomes significantly contribute to glioma progression and poor survival rates. Experimental validation was revealed that the expression of non-canonical NLRC4 inflammasomes were co-localized with astrocytes in malignant gliomas, with a sustained clinical correlation observed between astrocytes and inflammasome signatures. Indeed, the formation of an inflammatory microenvironment increased in malignant gliomas, leading to pyroptosis, known as inflammatory cell death. Molecular interaction analysis revealed that NF-κB pathways potentially serve as the connecting point between the canonical and noncanonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis of non-canonical NLRC4 inflammasome-associated molecules revealed that MK-5108, PF4981517, and CTEP may represent effective options for glioma therapy. CONCLUSION: The findings of this study suggest that non-canonical NLRC4 inflammasomes contribute to poor prognosis in patients with glioma and induce an inflammatory microenvironment. We propose the pathological phenomenon of non-canonical NLRC4 inflammasomes and several therapeutic strategies based on the modulation of the inflammatory tumor microenvironment.