Nano-titanium dioxide exacerbates the harmful effects of perfluorooctanoic acid on the health of mussels.

Exposing marine organisms to contemporary contaminants, such as perfluorooctanoic acid (PFOA) and nano-titanium dioxide (nano-TiO2), can induce multifaceted physiological consequences. Our investigation centered on the responses of the mussel, Mytilus coruscus, to these agents. We discerned pronounced disruptions in gill filament connections, pivotal structures for aquatic respiration, suggesting compromised oxygen uptake capabilities. Concurrently, the respiratory rate exhibited a marked decline, indicating a respiratory distress. Furthermore, the mussels' clearance rate, a metric of their filtration efficacy, diminished, suggesting the potential for bioaccumulation of deleterious substances. Notably, the co-exposure of PFOA and nano-TiO2 exhibits interactive effects on the physiological performance of the mussels. The mussels' digestive performance waned in the face of heightened PFOA and nano-TiO2 concentrations, possibly hampering nutrient assimilation and energy accrual. This was mirrored in the noticeable contraction of their energy budget, suggesting long-term growth repercussions. Additionally, the dysregulation of the gut microbiota and the reduction in its diversity further confirm alterations in intestinal homeostasis, subsequently impacting its physiological functions and health. Collectively, these findings underscore the perils posed by escalated PFOA and nano-TiO2 levels to marine mussels, accentuating the need for a deeper understanding of nanoparticle-pollutant synergies in marine ecosystems.

A case report of typical well-differentiated papillary mesothelial tumor diagnosed by internal thoracoscopy and literature review.

We report a case of well-differentiated papillary mesothelial tumor (WDPMT) diagnosed using internal thoracoscopic biopsy in a patient who has suffered from recurrent pleural effusions for over 35 years together with a history of elevated CA125. We hope to provide a case for the diagnosis of this rare benign and preinvasive pleural tumor and recommend that internal thoracoscopy may be a good choice in these recurrent pleural effusion patients especially for those minimal lesions not easily detected using CT scan.

The effects of sucrose/NaCl combined pickling on the textural characteristics, moisture distribution, and protein aggregation behavior of egg yolk.

Salted egg yolks have a tender, loose, gritty, and oily texture and are commonly employed as fillings in baked goods. This study investigated the formation mechanism of egg yolk gels using three different pickling methods: NaCl, sucrose, and mixed groups. The results revealed that of these pickling methods, egg yolks pickled with the mixture had the lowest moisture content (11.59% at 25°C and 10.21% at 45°C), almost no free water content, and the highest hardness (19.11 N at 25°C and 31.01 N at 45°C). Intermolecular force measurements indicated that pickling with the mixture mitigated the surface hardening effect of sucrose and facilitated protein cross-linking. Moreover, confocal laser scanning microscopy of the egg yolk gels pickled with the mixture displayed macromolecular aggregates and oil exudation, suggesting that this method partially disrupted the lipoprotein structure and notably promoted yolk protein aggregation and lipid release. Overall, egg yolks formed a dense gel via the mixed pickling method owing to the ionic concentration and dehydration effects. These findings show the impact of NaCl and sucrose in pickling egg yolks, providing a crucial foundation for developing innovative and desirable egg yolk products. PRACTICAL APPLICATION: This study introduces a novel pickling strategy that combines sucrose and NaCl for egg yolk processing. The egg yolk pickled using this method exhibited improved quality according to the evaluated textural characteristics, moisture distribution, and protein aggregation behavior. The findings may broaden the use of sucrose as a pickling agent for egg yolk processing and provide new ideas for developing and producing pickled eggs and other food products.

Surgical evidence-based comparison of [68Ga]Ga-FAPI-04 PET and MRI-DWI for assisting debulking surgery in ovarian cancer patients.

PURPOSE: Imaging assessment of abdominopelvic tumor burden is crucial for debulking surgery decision in ovarian cancer patients. This study aims to compare the efficiency of [68Ga]Ga-FAPI-04 FAPI PET and MRI-DWI in the preoperative evaluation and its potential impact to debulking surgery decision. METHODS: Thirty-six patients with suspected/confirmed ovarian cancer were enrolled and underwent integrated [68Ga]Ga-FAPI-04 PET/MRI. Nineteen patients (15 stage III-IV and 4 I-II stage) who underwent debulking surgery were involved in the diagnostic efficiency analysis. The images of [68Ga]Ga-FAPI-04 PET and MRI-DWI were visually analyzed respectively. Immunohistochemistry on FAP was performed in metastatic lesions to investigate the radiological missing of [68Ga]Ga-FAPI-04 PET as well as its different performance in primary debulking surgery (PDS) and interval debulking surgery (IDS) patients. Potential imaging impact on management was also studied in 35 confirmed ovarian cancer patients. RESULTS: [68Ga]Ga-FAPI-04 PET displayed higher sensitivity (76.8% vs.59.9%), higher accuracy (84.9% vs. 80.7%), and lower missing rate (23.2% vs. 40.1%) than MRI-DWI in detecting abdominopelvic metastasis. The diagnostic superiority of [68Ga]Ga-FAPI-04 PET is more obvious in PDS patients but diminished in IDS patients. [68Ga]Ga-FAPI-04 PET outperformed MRI-DWI in 70.8% abdominopelvic regions (17/24), which contained seven key regions that impact the resectability and surgical complexity. MRI-DWI hold advantage in the peritoneal surface of the bladder and the central tendon of the diaphragm. Of the contradictory judgments between the two modalities (14.9%), [68Ga]Ga-FAPI-04 PET correctly identified more lesions, particularly in PDS patients (73.8%). In addition, FAP expression was independent of lesion size and decreased in IDS patients. [68Ga]Ga-FAPI-04 PET changed 42% of surgical planning that was previously based on MRI-DWI. CONCLUSION: [68Ga]Ga-FAPI-04 PET is more efficient in assisting debulking surgery in ovarian cancer patients than MRI-DWI. Integrated [68Ga]Ga-FAPI-04 PET/MR imaging is a potential method for planning debulking surgery in ovarian cancer patients.

How variable progenitor clones construct a largely invariant neocortex.

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors (RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

Ginseng Saponin Rb1 Attenuates Cigarette Smoke Exposure-Induced Inflammation, Apoptosis and Oxidative Stress via Activating Nrf2 and Inhibiting NF-κB Signaling Pathways.

Objective: Cigarette smoke exposure is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Ginseng saponin Rb1 (Rb1) is a natural extract from ginseng root with anti-inflammatory and anti-oxidant effects. However, the underlying mechanism of the Rb1 in COPD remains unknown. Therefore, we sought to explore the role of Rb1 in cigarette smoke-induced damage and to reveal the potential mechanism. Methods: The cell viability and lactose dehydrogenase (LDH) activity were analyzed using cell counting kit-8 (CCK-8) and LDH release assays. We further investigated the inflammation, apoptosis and oxidative stress markers and analyzed the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf2) pathways in BEAS-2B cells and COPD rat model following cigarette smoke extract (CSE) exposure. Results: Our results showed that CSE promoted inflammation, apoptosis and oxidative stress in BEAS-2B cells. Rb1 suppressed the inflammatory response by inhibiting expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß and inhibiting the NF-κB signaling pathway. Rb1 possessed the ability to hinder cell apoptosis induced by CSE. In addition, Rb1 concurrently reduced CSE-induced oxidative reactions and promoted Nrf2 translocation to nucleus. For in vivo study, Rb1 treatment alleviated CSE-induced lung injury, apoptosis, reactive oxygen species (ROS) release and inflammatory reactions. Also, Rb1 treatment activated Nrf2 signaling and inactivated NF-κB signaling in COPD rats. Conclusion: Rb1 attenuates CSE-induced inflammation, apoptosis and oxidative stress by suppressing NF-κB and activating Nrf2 signaling pathways, which provides novel insights into the mechanism underlying CSE-induced COPD.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

OBJECTIVE: To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. PATIENTS AND METHODS: A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. RESULTS: The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. CONCLUSION: ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Underlying mechanisms of egg white thinning in hot spring eggs during storage: Weak gel properties and quantitative proteome analysis.

As a weakly gelling protein, hot spring egg white underwent thinning during storage. This study explored the mechanism of thinning in hot spring egg white from the perspective of "gel structure and protein composition" using quantitative proteomics, SEM, SDS-PAGE, and other techniques. Quantitative proteomics analysis showed that there were 81 (44 up-regulated and 21 down-regulated) key proteins related to thinning of hot spring egg white. The changes in the relative abundance of proteins such as ovalbumin-related Y, mucin-6, lysozyme, ovomucoid, and ovotransferrin might be important reasons for thinning in hot spring egg white. SEM results indicated that the gel network gradually became regular and uniform, with large pores appearing on the cross-section and being pierced. Along with the decrease in intermolecular electrostatic repulsion, protein molecules gradually aggregated. The particle size gradually increased from 139.1 nm to 422.5 nm. Meanwhile, the surface hydrophobicity, and disulfide bond content gradually increased. These changes might be the reasons for thinning in hot spring egg white during storage. It can provide a new perspective for studying the thinning mechanism of weakly gelling egg whites.

Effects of caffeic acid phenethyl ester against multi-species cariogenic biofilms.

Dental caries is a biofilm-related disease, widely perceived to be caused by oral ecological imbalance when cariogenic/aciduric bacteria obtain an ecological advantage. Compared with planktonic bacteria, dental plaques are difficult to remove under extracellular polymeric substance protection. In this study, the effect of caffeic acid phenethyl ester (CAPE) on a preformed cariogenic multi-species biofilm was evaluated, which was comprised of cariogenic bacteria (Streptococcus mutans), commensal bacteria (Streptococcus gordonii), and a pioneer colonizer (Actinomyces naeslundii). Our result revealed that treatment with 0.08 mg/mL CAPE reduced live S. mutans in the preformed multi-species biofilm while not significantly changing the quantification of live S. gordonii. CAPE significantly reduced the production of lactic acid, extracellular polysaccharide, and extracellular DNA and made the biofilm looser. Moreover, CAPE could promote the H2O2 production of S. gordonii and inhibit the expression of SMU.150 encoding mutacin to modulate the interaction among species in biofilms. Overall, our results suggested that CAPE could inhibit the cariogenic properties and change the microbial composition of the multi-species biofilms, indicating its application potential in dental caries prevention and management.

Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer.

BACKGROUND: The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS: In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS: Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION: Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.

LMNB1 deletion in ovarian cancer inhibits the proliferation and metastasis of tumor cells through PI3K/Akt pathway.

Ovarian cancer (OC) is a common malignant tumor in gynecology. LMNB1 is an important component of the nuclear skeleton. The expression of LMNB1 in ovarian cancer is significantly higher than that in normal tissues, but its role in tumor still needs comprehensive investigation. In this study, we overexpressed and knocked down LMNB1 in ovarian cancer cells and explore the effect of LMNB1 on the cell proliferation, migration and the underlying mechanism. We analyzed the expression levels of LMNB1 in ovarian cancer and their clinical relevance by using bioinformatics methods, qRT-PCR, Western blot and immunohistochemistry. To state the effect and mechanism of LMNB1 on OC in vitro and in vivo, we performed mouse xenograft studies, CCK8, cloning formation, Edu incorporation, wound healing, transwell and flow cytometry assay in stable LMNB1 knockdown OC cells, following by RNA-seq. Overexpression of LMNB1 indicates the progression of OC. LMNB1 knockdown inhibited the proliferation and migration of OC cells by suppressing the FGF1-mediated PI3K-Akt signaling pathway. Our study shows LMNB1 as a novel prognostic factor and therapeutic target in OC.

A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients.

BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS: The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS: In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS: EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.

Chitin and chitin-based biomaterials: A review of advances in processing and food applications.

Chitin is the most abundant natural amino polysaccharide, showing various practical applications owing to its functional properties. However, there are barriers in the development due to the difficulty of chitin extraction and purification, regarding its high crystallinity and low solubility. In recent years, some novel technologies such as microbial fermentation, ionic liquid, electrochemical extraction have emerged for the green extraction of chitin from new sources. Furthermore, nanotechnology, dissolution systems and chemical modification were applied to develop a variety of chitin-based biomaterials. Remarkably, chitin was used in delivering active ingredients and developing functional foods for weight loss, lipid reduction, gastrointestinal health, and anti-aging. Moreover, the application of chitin-based materials was expanded into medicine, energy and the environment. This review outlined the emerging extraction methods and processing routes of different chitin sources and advances in applying chitin-based materials. We aimed to provide some direction for the multi-disciplinary production and application of chitin.

Developmental neuronal origin regulates neocortical map formation.

Sensory neurons in the neocortex exhibit distinct functional selectivity to constitute the neural map. While neocortical map of the visual cortex in higher mammals is clustered, it displays a striking "salt-and-pepper" pattern in rodents. However, little is known about the origin and basis of the interspersed neocortical map. Here we report that the intricate excitatory neuronal kinship-dependent synaptic connectivity influences precise functional map organization in the mouse primary visual cortex. While sister neurons originating from the same neurogenic radial glial progenitors (RGPs) preferentially develop synapses, cousin neurons derived from amplifying RGPs selectively antagonize horizontal synapse formation. Accordantly, cousin neurons in similar layers exhibit clear functional selectivity differences, contributing to a salt-and-pepper architecture. Removal of clustered protocadherins (cPCDHs), the largest subgroup of the diverse cadherin superfamily, eliminates functional selectivity differences between cousin neurons and alters neocortical map organization. These results suggest that developmental neuronal origin regulates neocortical map formation via cPCDHs.

Patterned cPCDH expression regulates the fine organization of the neocortex.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2-6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)-the largest subgroup of the cadherin superfamily of cell-adhesion molecules7-regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain.

A novel amelogenesis-inspired hydrogel composite for the remineralization of enamel non-cavitated lesions.

Enamel non-cavitated lesions (NCLs) are subsurface enamel porosity from carious demineralization. The developed enamel cannot repair itself once NCLs occurs. The regeneration of mineral crystals in a biomimetic environment is an effective way to repair enamel subsurface defects. Previously, an amelogenin-derived peptide named QP5 was proven to repair demineralized enamel. In this work, inspired by amelogenesis, a novel biomimetic hydrogel composite containing the QP5 peptide and bioactive glass (BG) was designed, in which QP5 could promote enamel remineralization by guiding the calcium and phosphorus ions provided by BG. Also, BG could adjust the mineralization micro-environment to alkalinity, simulating the pH regulation of ameloblasts during enamel maturity. The BQ hydrogel composite showed biosafety and possessed capacity for enamel binding, ion release and pH buffering. Enamel NCLs treated with the BQ hydrogel composite showed a higher reduction in lesion depth and mineral loss both in vitro and in vivo. Moreover, compared to the hydrogels containing only BG or QP5, groups treated with the BQ hydrogel composite attained more surface microhardness recovery and color recovery, exhibiting resistance to erosion and abrasion of the remineralization layer. We envision that the BQ hydrogel composite can provide a biomimetic micro-environment to favor enamel remineralization, thus reducing the lesion depth and increasing the mineral content as a promising biomimetic material for enamel NCLs.

Roll to roll in situ preparation of recyclable, washable, antibacterial Ag loaded nonwoven fabric.

Functional fabrics with antibacterial performance are more welcome nowadays. However, the fabrication of functional fabrics with durable, steady performance via a cost-effective way remains a challenge. Polypropylene (denoted as PP) nonwoven fabric was modified by polyvinyl alcohol (denoted as PVA), followed by the in-situ deposition of silver nanoparticles (denoted as Ag NPs) to afford PVA-modified and Ag NPs-loaded PP (denoted as Ag/PVA/PP) fabric. The encapsulation of PP fiber by PVA coating contributes to greatly enhancing the adhesion of the loaded Ag NPs to the PP fiber, and the Ag/PVA/PP nonwoven fabrics exhibit significantly improved mechanical properties as well as excellent antibacterial activity against Escherichia coli (coded as E. coli). Typically, the Ag/PVA/PP nonwoven fabric obtained at a silver ammonia concentration of 30 mM has the best mechanical properties and the antibacterial rate reaches 99.99% against E. coli. The fabric retains excellent antibacterial activity even after washing for 40 cycles, showing prospects in reuse. Moreover, the Ag/PVA/PP nonwoven fabric could find promising application in industry, thanks to its desired air-permeability and moisture-permeability. In addition, we developed a roll-to-roll production process and conducted preliminary exploration to verify the feasibility of this method.

EIF5A2 Is Involved in the Biological Process of Cervical Cancer Cells through AGR2.

INTRODUCTION: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer. METHODS: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined. RESULTS: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells. CONCLUSION: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

A Novel Four Genes of Prognostic Signature for Uveal Melanoma.

Autophagy and immunity play critical roles in various cancers, but the prognostic impact of autophagy and immunity for uveal melanoma (UM) remains lacking. Therefore, the RNA sequencing of data in the TCGA-UVM dataset was downloaded from UCSC Xena database. The prognostic autophagy- and immunity-related genes (AIRGs) were selected via univariate Cox regression. Next, we applied LASSO method to construct four genes of signature in the TCGA-UVM and verified in another two GEO datasets (GSE84976 and GSE22138). This signature intimately associated with overall survival (OS) time and metastasis-free survival (MFS) time of UM, which could be considered as a prognostic indicator. Besides, by applying risk assessment, the patients of UM can be divided into two subgroups (high/low risk) with different survival time, distinct clinical outcomes, and immune microenvironments. Gene set enrichment analysis (GSEA) manifested that cancer hallmark epithelial-mesenchymal transition and KRAS pathways were positively activated in the high-risk group. Moreover, the high-risk group could be more sensitive to chemotherapies than the low-risk group. Thus, our finding suggested that the four genes of signature closely linked with UM risk and survival can afford more accurate survival prediction and potential therapeutic targets for clinical application.

Landscape of Infiltrated Immune Cell Characterization in Uveal Melanoma to Improve Immune Checkpoint Blockade Therapy.

Background: Numerous studies indicated that tumor-infiltrated immune cells (TIC) in the microenvironment are substantially linked to immunotherapy response and cancer prognosis. However, systematic studies of infiltrated immune cell characterization in uveal melanoma (UM) for prognosis and immune checkpoint blockade therapy are lacking. Methods: UM datasets were extracted from open access resources (TCGA and GEO databases). The tumor-infiltrated immune cells in the microenvironment were decoded by using the CIBERSORT algorithm, which was further applied to classify UM patients into subgroups using an unsupervised clustering method. The Boruta algorithm and principal component analysis were used to calculate the TIC scores for UM patients. Kaplan-Meier curves were plotted to prove the prognostic value of TIC scores. Besides, the correlations of the TIC score with clinical features, mutated characteristics, and the immune therapeutic response were subsequently investigated. Results: As a result, we defined three subtypes among 171 UM patients according to the TIC profiles and then calculated the TIC score to characterize the immune patterns for all patients. We discovered that high-TIC score patients with low BAP1 and high EIF1AX mutations have a better prognosis than low-TIC score patients. Activation of immune inflammatory response and increase in immune checkpoint-related genes in high-TIC score patients may account for good prognosis and immunotherapy response. Three melanoma cohorts received immunotherapy, proving that high-TIC score patients have substantial clinical and immune therapeutic improvements. Besides, several potential therapeutic agents were identified in the low-TIC score group. Conclusion: Our study afforded a comprehensive view of infiltrated immune cell characterization to elucidate different immune patterns of UM. We also established a robust TIC-score signature, which may work as a prognostic biomarker and immune therapeutic predictor.