Reaction Templates: Bridging Synthesis Knowledge and Artificial Intelligence.

ConspectusThe field of chemical research boasts a long history of developing software to automate synthesis planning and reaction prediction. Early software relied heavily on expert systems, requiring significant effort to encode vast amounts of synthesis knowledge into a computer-readable format. However, recent advancements in deep learning have shifted the focus toward AI models, offering improved prediction capabilities. Despite these advancements, current AI models often lack the integration of known synthesis rules and intuitions, creating a gap that hinders interpretability and future development of the models. To bridge them, our research group has been actively working on incorporating reaction templates into deep learning models, achieving promising results across various applications.In this Account, we present our latest works to incorporate the known synthesis knowledge into the deep learning models through the utilization of reaction templates. We begin by highlighting the limitations of early computer programs heavily reliant on hand-coded rules. These programs, while providing a foundation for the field, presented limitations in scalability and adaptability. We then introduce SMARTS (SMILES arbitrary target specification), a popular Python-readable format for representing chemical reactions. This format of reaction encoding facilitates the quick integration of synthesis knowledge into AI models built using the Python language. With the SMARTS-based reaction templates, we introduce our recent efforts of developing an AI model for reaction-based molecule optimization. Subsequently, we discuss the recent efforts to automate the extraction of reaction templates from vast chemical reaction databases. This approach eliminates the previously required manual effort of encoding knowledge, a process that could be time-consuming and prone to error when dealing with large data sets. By customizing the automated extraction algorithm, we have developed powerful AI models for specific tasks such as retrosynthesis (LocalRetro), reaction outcome prediction (LocalTransform), and atom-to-atom mapping (LocalMapper). These models, aligned with the intuition of chemists, demonstrate the effectiveness of incorporating reaction templates into deep learning frameworks.Looking toward the future, we believe that utilizing reaction templates to connect known chemical knowledge and AI models holds immense potential for various applications. Not only can this approach significantly benefit future AI models focused on challenging tasks like reaction mechanism labeling and prediction, but we anticipate it can also extend its reach to the realm of inorganic synthesis. By integrating synthesis knowledge, we can not only achieve improved performance but also enhance the interpretability of AI models, paving the way for further advancements in AI-powered chemical synthesis.

Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-ß1-Induced PDL Fibroblastic Differentiation.

Human periodontal ligament cells (hPDLCs) cultured from periodontal ligament (PDL) tissue contain postnatal stem cells that can be differentiated into PDL fibroblasts. We obtained PDL fibroblasts from hPDLCs by treatment with low concentrations of TGF-ß1. Since the extracellular matrix and cell surface molecules play an important role in differentiation, we had previously developed a series of monoclonal antibodies against PDL fibroblast-specific cell surface molecules. One of these, the anti-PDL51 antibody, recognized a protein that was significantly upregulated in TGF-ß1-induced PDL fibroblasts and highly accumulated in the PDL region of the tooth root. Mass spectrometry revealed that the antigen recognized by the anti-PDL51 antibody was leucine-rich repeat containing 15 (LRRC15), and this antibody specifically recognized the extracellular glycosylated moiety of LRRC15. Experiments presented here show that as fibroblastic differentiation progresses, increased amounts of LRRC15 localized at the cell surface and membrane. Inhibition of LRRC15 by siRNA-mediated depletion and by antibody blocking resulted in downregulation of the representative PDL fibroblastic markers. Moreover, following LRRC15 inhibition, the directed and elongated cell phenotypes disappeared, and the long processes of the end of the cell body were no longer found. Through a specific interaction between integrin ß1 and LRRC15, the focal adhesion kinase signaling pathway was activated in PDL fibroblasts. Furthermore, it was shown that increased LRRC15 was important for the activation of the integrin-mediated cell adhesion signal pathway for regulation of cellular functions, including fibroblastic differentiation, proliferation, and cell migration arising from the expression of PDL-related genes in TGF-ß1-induced PDL fibroblastic differentiation.

Heat Shock Protein 90's Mechanistic Role in Contact Hypersensitivity.

Despite the known dangers of contact allergens and their long-lasting use as models in immunology, their molecular mode of action largely remains unknown. In this study, we report that a contact allergen, 1-chloro-2,4-dinitrobenzene (DNCB), elicits contact hypersensitivity through binding the protein we identify. Starting from an unbiased sampling of proteomics, we found nine candidate proteins with unique DNCB-modified peptide fragments. More than half of these fragments belonged to heat shock protein 90 (HSP90), a common stress-response protein and a damage-associated molecular pattern, and showed the highest probability of incidence. Inhibition and short hairpin RNA knockdown of HSP90 in human monocyte cell line THP-1 suppressed the potency of DNCB by >80%. Next, we successfully reduced DNCB-induced contact hypersensitivity in HSP90-knockout mice, which confirmed our findings. Finally, we hypothesized that DNCB-modified HSP90 activates the immune cells through HSP90's receptor, CD91. Pretreatment of CD91 in THP-1 cell lines and BALB/c mice attenuated the potency of DNCB, consistent with the result of HSP90-knockout mice. Altogether, our data show that DNCB-HSP90 binding plays a role in mediating DNCB-induced contact hypersensitivity, and the activation of CD91 by DNCB-modified HSP90 proteins could mediate this process.

On the Analysis of Inter-Relationship between Auto-Scaling Policy and QoS of FaaS Workloads.

A recent development in cloud computing has introduced serverless technology, enabling the convenient and flexible management of cloud-native applications. Typically, the Function-as-a-Service (FaaS) solutions rely on serverless backend solutions, such as Kubernetes (K8s) and Knative, to leverage the advantages of resource management for underlying containerized contexts, including auto-scaling and pod scheduling. To take the advantages, recent cloud service providers also deploy self-hosted serverless services by facilitating their on-premise hosted FaaS platforms rather than relying on commercial public cloud offerings. However, the lack of standardized guidelines on K8s abstraction to fairly schedule and allocate resources on auto-scaling configuration options for such on-premise hosting environment in serverless computing poses challenges in meeting the service level objectives (SLOs) of diverse workloads. This study fills this gap by exploring the relationship between auto-scaling behavior and the performance of FaaS workloads depending on scaling-related configurations in K8s. Based on comprehensive measurement studies, we derived the logic as to which workload should be applied and with what type of scaling configurations, such as base metric, threshold to maximize the difference in latency SLO, and number of responses. Additionally, we propose a methodology to assess the scaling efficiency of the related K8s configurations regarding the quality of service (QoS) of FaaS workloads.

Automated Cephalometric Landmark Detection Using Deep Reinforcement Learning.

Accurate cephalometric landmark detection leads to accurate analysis, diagnosis, and surgical planning. Many studies on automated landmark detection have been conducted, however reinforcement learning-based networks have not yet been applied. This is the first study to apply deep Q-network (DQN) and double deep Q-network (DDQN) to automated cephalometric landmark detection to the best of our knowledge. The performance of the DQN-based network for cephalometric landmark detection was evaluated using the IEEE International Symposium of Biomedical Imaging (ISBI) 2015 Challenge data set and compared with the previously proposed methods. Furthermore, the clinical applicability of DQN-based automated cephalometric landmark detection was confirmed by testing the DQN-based and DDQN-based network using 500-patient data collected in a clinic. The DQN-based network demonstrated that the average mean radius error of 19 landmarks was smaller than 2 mm, that is, the clinically accepted level, without data augmentation and additional preprocessing. Our DQN-based and DDQN-based approaches tested with the 500-patient data set showed the average success detection rate of 67.33% and 66.04% accuracy within 2 mm, respectively, indicating the feasibility and potential of clinical application.

Development of Real-Time Monitoring System Based on IoT Technology for Curing Compound Application Process during Cement Concrete Pavement Construction.

Among the construction processes of Portland cement concrete pavement (PCCP), the curing compound spraying process is one of the most important processes. If the curing compound spraying amount does not meet the standard or if the curing compound is not applied evenly, distresses occur at the early age of construction, ultimately causing deterioration in concrete pavement performance. The purpose of this study is to develop a real-time monitoring system for a curing compound spraying process based on the Internet of Things (IoT) and sensing technologies to improve the construction quality of concrete pavement. To achieve the goal of this research, we conducted various laboratory and field experiments. The curing compound spraying amount and sprayed status were measured and analyzed using flowmeters, image acquisition sensors, and an image processing program, and the data were provided to workers in real time and simultaneously transmitted to the IoT cloud to form a database. From this study, it is confirmed that the IoT-technology-based curing compound spraying amount and sprayed status monitoring systems can be successfully established to manage construction quality related to the curing of concrete pavement.

BRD4 Inhibition Enhances the Antitumor Effects of Radiation Therapy in a Murine Breast Cancer Model.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured, and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor, indicating that it may induce systemic immune responses. The expression of HIF-1α and PD-L1 in the tumor was significantly downregulated by the BRD4 inhibitor. The proportion of M1 tumor-associated macrophages (TAMs) increased, and the proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations in the tumor microenvironment. Additionally, splenic monocytic myeloid derived suppressor cells, which were increased by RT, were reduced upon the addition of BRD4 inhibitor. Therefore, the addition of BRD4 inhibitor significantly enhanced the systemic antitumor responses of local RT.

Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

A Rare Case Report of Successful Laparoscopy-Guided Reduction of Non-Puerperal Uterine Inversion.

Non-puerperal uterine inversion is an extremely rare and potentially dangerous condition. Cases are poorly described in the literature, and their actual incidence is unknown. A 34-year-old nulliparous female patient visited the emergency department following a loss of consciousness. She had experienced continuous vaginal bleeding over the preceding two months, with a two-day history of worsening symptoms. The patient showed signs of hypovolemic shock secondary to unceasing vaginal bleeding. Ultrasound and computed tomography revealed an inverted uterus and a large hematoma inside the patient's vaginal cavity. An emergency explorative laparoscopy was performed, which confirmed uterine inversion. Initially, Johnson's maneuver was attempted under laparoscopic visualization, but this failed to achieve uterine reduction. Following the unsuccessful performance of Huntington's maneuver, a re-trial of the manual reduction allowed the uterus to recover to its normal anatomy. The patient's vaginal bleeding was dramatically reduced after successful uterine reduction. The pathologic report conducted confirmed endometrioid adenocarcinoma. Laparoscopic visualization is a feasible and safe procedure for achieving uterine reduction in cases of non-puerperal uterine inversion with an unconfirmed pathology. Uterine malignancies should be considered in patients with non-puerperal uterine inversion.

A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement.

This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations (p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups (p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

Tomato ARPC1 regulates trichome morphology and density and terpene biosynthesis.

MAIN CONCLUSION: Based on transcriptomic analysis of wild-type and mutant tomato plants, ARPC1 was found to be important for trichome formation and development and it plays a key role in terpene synthesis. Trichomes are protruding epidermal cells in plant species. They function as the first defense layer against biotic and abiotic stresses. Despite the essential role of tomato trichomes in defense against herbivores, the understanding of their development is still incomplete. Therefore, the aim of this study was to identify genes involved in trichome formation and morphology and terpene synthesis, using transcriptomic techniques. To achieve this, we examined leaf morphology and compared the expression levels of some putative genes involved in trichome formation between wild-type (WT) and hairless-3 (hl-3) tomato mutant. The hl-3 plants displayed swollen and distorted trichomes and reduced trichome density (type I and IV) and terpene synthesis compared with that of the WT plants. Gene expression analysis showed that Actin-Related Protein Component1 (ARPC1) was expressed more highly in the WT than in the hl-3 mutant, indicating its critical role in trichome morphology and density. Additionally, the expression of MYC1 and several terpene synthase genes (TPS9, 12, 20), which are involved in type VI trichome initiation and terpene synthesis, was lower in the hl-3 mutant than in the WT plants. Moreover, transformation of the hl-3 mutant with WT ARPC1 restored normal trichome structure and density, and terpene synthesis. Structural and amino acid sequence analysis showed that there was a missplicing mutation in the hl-3 mutant, which was responsible for the abnormal trichome structure and density, and impaired terpene synthesis. Overall, the findings of this study demonstrated that ARPC1 is involved in regulating trichome structure and terpene synthesis in tomato.

Live isolation of naïve ESCs via distinct glucose metabolism and stored glycogen.

Naïve and primed pluripotent stem cells recapitulate the peri- and post-implantation development, respectively. Thus, investigation of distinct traits between each pluripotent stem cell type would shed light on early embryonic processes. Herein, by screening a fluorescent probe library, we found that intracellular glycogen led to specific reactivity to CDg4, a glycogen fluorescence sensor, in both human and mouse naïve embryonic stem cells (ESCs). The requirement of constant inhibition of Gsk3ß as well as high oxidative phosphorylation (OxPHOS) in naïve compared to primed ESCs was closely associated to high level of intracellular glycogen in naïve ESCs. Both capacity of OxPHOS and stored glycogen, rescued naïve ESCs by transient inhibition of glycolysis, which selectively eliminated primed ESCs. Additionally, naïve ESCs with active OxPHOS were enriched from a mixture with primed ESCs by high reactivity to ATP-Red1, a mitochondrial ATP fluorescence probe. These results indicate the active OxPHOS and high intracellular glycogen as a novel "biomarker" delineating metabolic remodeling during the transition of naïve pluripotency.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

Tenebrionicola larvae gen. nov., sp. nov., isolated from larvae of mealworm Tenebrio molitor L., and a proposal to transfer Erwinia teleogrylli Liu et al. 2016 to a new genus Entomohabitans as Entomohabitans teleogrylli comb. nov.

Two enterobacterial strains, designated YMB-R21T and YMB-R22, were isolated from larvae of mealworm Tenebrio molitor L. and examined for their taxonomic characteristics. A 16S rRNA gene-based neighbour-joining tree showed that the two isolates formed two distinct sublineages within the family Enterobacteriaceae and were separated from other genera of the family. The isolates showed 16S rRNA gene sequence similarity of 98.9 % to each other and ≤96.5 % to members of the order Enterobacteriales. The phylogenomic analysis based on 92 singly-copy core genes showed that the two isolates belonged to the family Enterobacteriaceae and formed a distinct sublineage at a position located remotely from the genera of the family. The loosely associated members were the type strain of Erwinia teleogrylli and members of the genus Shimwellia. Average nucleotide identity and digital DNA-DNA hybridization values showed that the isolates represented members of a novel species in the family Enterobacteriaceae. The values of amino acid identity between the two isolates and the closest relatives were 74.5-75.0 % with the type strain of E. teleogrylli and 74.5-74.8 % with the type strains of two Shimwellia species, while E. teleogrylli showed the amino acid identity values of 76.3-76.5 % with two Shimwellia species. Based on the results obtained here, we propose a new genus Tenebrionicola with the description of Tenebrionicola larvae sp. nov. (type strain YMB-R21T=KCTC 82597T=CCM 9152T and strain YMB-R22=KCTC 82598=CCM 9153), with the transfer of Erwinia teleogrylli Liu et al. 2016 to a new genus Entomohabitans as Entomohabitans teleogrylli comb. nov. (type strain SCU-B244T=CGMCC 1.12772T=DSM 28222T=KCTC 42022T).

Females with impaired ovarian function could be vulnerable to environmental pollutants: identification via next-generation sequencing of the vaginal microbiome.

The vaginal microbiome has been widely investigated. However, its relationship with impaired ovarian function has not been evaluated. We conducted a next-generation sequencing (NGS) study of the vaginal microbiome in females with normal and decreased ovarian function and analysed its sensitivity to environmental pollutants. Vaginal swabs were collected from 92 individuals (22 with impaired ovarian function). The 16S rDNA sequences were assembled by FLASH and clustered in OTUs. Diversity analysis was performed using QIIME. The impaired function group showed lower AMH (p < .01) and higher FSH (p = .04). Only two species showed significant differences: Propionibacterium acnes and Prevotella copri. Moreover, more environmental pollutants were related to changes in the vaginal microbiome in the impaired ovarian function group than in the normal group. Vaginal microbiomes in young women with decreased ovarian function tended to be more sensitive to environmental pollutants, especially volatile organic compounds.Impact StatementWhat is already known on this subject? In this study, the possible influence of environmental pollutants, especially volatile organic compounds to ovarian function were identified via next-generation sequencing.What do the results of this study add? This is the first study that shows vaginal microbiomes in young women with decreased ovarian function to be more sensitive to environmental pollutants.What are the implications of these findings for clinical practice and/or further research? The association between impaired ovarian function and environmental pollutants from this study could be helpful when counselling patients with POI.

SlHair2 Regulates the Initiation and Elongation of Type I Trichomes on Tomato Leaves and Stems.

Trichomes are hair-like structures that are essential for abiotic and biotic stress responses. Tomato Hair (H), encoding a C2H2 zinc finger protein, was found to regulate the multicellular trichomes on stems. Here, we characterized Solyc10g078990 (hereafter Hair2, H2), its closest homolog, to examine whether it was involved in trichome development. The H2 gene was highly expressed in the leaves, and its protein contained a single C2H2 domain and was localized to the nucleus. The number and length of type I trichomes on the leaves and stems of knock-out h2 plants were reduced when compared to the wild-type, while overexpression increased their number and length. An auto-activation test with various truncated forms of H2 using yeast two-hybrid (Y2H) suggested that H2 acts as a transcriptional regulator or co-activator and that its N-terminal region is important for auto-activation. Y2H and pull-down analyses showed that H2 interacts with Woolly (Wo), which regulates the development of type I trichomes in tomato. Luciferase complementation imaging assays confirmed that they had direct interactions, implying that H2 and Wo function together to regulate the development of trichomes. These results suggest that H2 has a role in the initiation and elongation of type I trichomes in tomato.

Superionic Halogen-Rich Li-Argyrodites Using In Situ Nanocrystal Nucleation and Rapid Crystal Growth.

Although several crystalline materials have been developed as Li-ion conductors for use as solid electrolytes in all-solid-state batteries (ASSBs), producing materials with high Li-ion conductivities is time-consuming and cost-intensive. Herein, we introduce a superionic halogen-rich Li-argyrodite (HRLA) and demonstrate its innovative synthesis using ultimate-energy mechanical alloying (UMA) and rapid thermal annealing (RTA). UMA with a 49 G-force milling energy provides a one-pot process that includes mixing, glassification, and crystallization, to produce as-milled HRLA powder that is ∼70% crystallized; subsequent RTA using an infrared lamp increases this crystallinity to ∼82% within 25 min. Surprisingly, this HRLA exhibits the highest Li-ion conductivity among Li-argyrodites (10.2 mS cm-1 at 25 °C, cold-pressed powder compact) reported so far. Furthermore, we confirm that this superionic HRLA works well as a promising solid electrolyte without a decreased intrinsic electrochemical window in various electrode configurations and delivers impressive cell performance (114.2 mAh g-1 at 0.5 C).

Role of Stem Cells in the Ovarian Tissue Cryopreservation and Transplantation for Fertility Preservation.

Although the cancer survival rate has increased, cancer treatments, including chemotherapy and radiotherapy, can cause ovarian failure and infertility in women of reproductive age. Preserving fertility throughout cancer treatment is critical for maintaining quality of life. Fertility experts should propose individualized fertility preservation methods based on the patient's marital status, pubertal status, partner status, and the urgency of treatment. Widely practiced fertility preservation methods, including ovarian transposition and embryo and oocyte cryopreservation, are inappropriate for prepubertal girls or those needing urgent initiation of cancer treatment. Ovarian tissue cryopreservation and transplantation, an emerging new technology, may be a solution for these cancer patients. The use of stem cells in ovarian tissue cryopreservation and transplantation increases oxygenation, angiogenesis, and follicle survival rates. This review discusses the recent advances in ovarian tissue cryopreservation and transplantation with special focus on the use of stem cells to improve fertilization techniques.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells.

Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of biological activities like antioxidant, antitumor, and antiproliferative effects. In the present study, we have investigated the antitumor potential of iridin in AGS gastric cancer cells. Iridin treatment decreases AGS cell growth and promotes G2/M phase cell cycle arrest by attenuating the expression of Cdc25C, CDK1, and Cyclin B1 proteins. Iridin-treatment also triggered apoptotic cell death in AGS cells, which was verified by cleaved Caspase-3 (Cl- Caspase-3) and poly ADP-ribose polymerase (PARP) protein expression. Further apoptotic cell death was confirmed by increased apoptotic cell death fraction shown in allophycocyanin (APC)/Annexin V and propidium iodide staining. Iridin also increased the expression of extrinsic apoptotic pathway proteins like Fas, FasL, and cleaved Caspase-8 in AGS cells. On the contrary, iridin-treated AGS cells did not show variations in proteins related to an intrinsic apoptotic pathway such as Bax and Bcl-xL. Besides, Iridin showed inhibition of PI3K/AKT signaling pathways by downregulation of (p-PI3K, p-AKT) proteins in AGS cells. In conclusion, these data suggest that iridin has anticancer potential by inhibiting PI3K/AKT pathway. It could be a basis for further drug design in gastric cancer treatment.