Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) promotes stress granule formation via YBX1 phosphorylation in ovarian cancer.

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.

Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy.

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.

POLM variant G312R promotes ovarian tumorigenesis through genomic instability and COL11A1-NF-κB axis.

In ovarian cancer (OC), identifying key molecular players in disease escalation and chemoresistance remains critical. Our investigation elucidates the role of the DNA Polymerase Mu (POLM) , especially G312R mutation, in propelling oncogenesis through dual pathways. POLMG312R markedly augments the ribonucleotide insertion capability of POLM, precipitating genomic instability. Additionally, our research reveals that POLMG312R perturbs Collagen alpha-1 (XI) chain (COL11A1) expression-a gene plays a key role in oncogenesis-and modulates the NF-κB signaling pathway, alters the secretion of downstream inflammatory cytokines, and promotes tumor-macrophage interactions. We illustrate a bidirectional regulatory interaction between POLM, particularly its G312R variant, and COL11A1. This interaction regulates NF-κB signaling, culminating in heightened malignancy and resistance to chemotherapy in OC cells. These insights position the POLM as a potential molecular target for OC therapy, shedding light on the intricate pathways underpinning POLM variant disease progression.

The proteomics and metabolomics studies of GZU001 on promoting the Merisis of maize (Zea mays L.) roots.

BACKGROUND: Plant growth regulators are chemicals that regulate plant growth and development, which can regulate hormonal balance and affect plant growth, thereby increasing crop yield and improving crop quality. Our studies have revealed a new compound, GZU001, which could be used as a plant growth regulator. This compound has been observed to affect root elongation in maize significantly. However, the exact mechanism of this phenomenon is still being investigated. RESULTS: Metabolomics and proteomics were used in unison in this study to explore the response pathway and regulation mechanism of GZU001 in promoting maize root elongation. From the appearance, we can see that both roots and plants of maize treated with GZU001 are significantly improved. Maize root metabolism revealed 101 differentially abundant proteins and 79 differentially expressed metabolites. The current study identified altered proteins and metabolites associated with physiological and biochemical processes. GZU001 treatment has been demonstrated to promote primary metabolism, essential for carbohydrates, amino acids, energy, and secondary metabolism. The result suggests that the stimulation of primary metabolism is beneficial for the growth and development of maize and plays a significant role in sustaining metabolism and growth. CONCLUSIONS: This study recorded the changes of related proteins and metabolites in maize roots after GZU001 treatment and provided evidence for this compound's action mode and mechanism in plants.

Exposure to Butylparaben Induces Craniofacial Bone Developmental Toxicity in Zebrafish (Danio rerio) Embryos.

Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.

Genome Analysis of a Novel Polysaccharide-Degrading Bacterium Paenibacillus algicola and Determination of Alginate Lyases.

Carbohydrate-active enzymes (CAZymes) are an important characteristic of bacteria in marine systems. We herein describe the CAZymes of Paenibacillus algicola HB172198T, a novel type species isolated from brown algae in Qishui Bay, Hainan, China. The genome of strain HB172198T is a 4,475,055 bp circular chromosome with an average GC content of 51.2%. Analysis of the nucleotide sequences of the predicted genes shows that strain HB172198T encodes 191 CAZymes. Abundant putative enzymes involved in the degradation of polysaccharides were identified, such as alginate lyase, agarase, carrageenase, xanthanase, xylanase, amylases, cellulase, chitinase, fucosidase and glucanase. Four of the putative polysaccharide lyases from families 7, 15 and 38 were involved in alginate degradation. The alginate lyases of strain HB172198T exhibited the maximum activity 152 U/mL at 50 °C and pH 8.0, and were relatively stable at pH 7.0 and temperatures lower than 40 °C. The average degree of polymerization (DP) of the sodium alginate oligosaccharide (AOS) degraded by the partially purified alginate lyases remained around 14.2, and the thin layer chromatography (TCL) analysis indicated that it contained DP2-DP8 oligosaccharides. The complete genome sequence of P. algicola HB172198T will enrich our knowledge of the mechanism of polysaccharide lyase production and provide insights into its potential applications in the degradation of polysaccharides such as alginate.

O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.

Protein synthesis is essential for cell growth, proliferation, and survival. Protein synthesis is a tightly regulated process that involves multiple mechanisms. Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer. Here we show that the dynamic modification of proteins by O-linked ß-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively. Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G. In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation. In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA. Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation. The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis. Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.

Oxyfluorfen induces hepatotoxicity through lipo-sugar accumulation and inflammation in zebrafish (Danio rerio).

Oxyfluorfen (OXY) is widely used in agriculture as a herbicide, resulting in its continuous accumulation in the environment. The presence of OXY can be detected in soil and rivers. However, until now, the potential toxicity of OXY to aquatic organisms has not been evaluated. In this study, zebrafish was used as a model animal to evaluate OXY-induced liver toxicity. The study found that 0.25, 0.5, and 1 mg/L of OXY affected the early development of zebrafish and severely damaged the lipid and sugar metabolism in the liver of zebrafish larvae. Furthermore, a metabolic function disorder caused liver damage. OXY also caused inflammation by upregulating the inflammatory factors IL-6, IL-8, and TNF-α, and activated the apoptotic pathway to inhibit hepatocyte proliferation, resulting in zebrafish liver toxicity. Our research showed that OXY had certain toxic effects on zebrafish development and liver and could cause potential harm to other aquatic organisms and humans.

Computational Optimization of Spectral Library Size Improves DIA-MS Proteome Coverage and Applications to 15 Tumors.

Efficient peptide and protein identifications from data-independent acquisition mass spectrometric (DIA-MS) data typically rely on a project-specific spectral library with a suitable size. Here, we describe subLib, a computational strategy for optimizing the spectral library for a specific DIA data set based on a comprehensive spectral library, requiring the preliminary analysis of the DIA data set. Compared with the pan-human library strategy, subLib achieved a 41.2% increase in peptide precursor identifications and a 35.6% increase in protein group identifications in a test data set of six colorectal tumor samples. We also applied this strategy to 389 carcinoma samples from 15 tumor data sets: up to a 39.2% increase in peptide precursor identifications and a 19.0% increase in protein group identifications were observed. Our strategy for spectral library size optimization thus successfully proved to deepen the proteome coverages of DIA-MS data.

Synthesis of trans- methyl ferulate bearing an oxadiazole ether as potential activators for controlling plant virus.

A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans-ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a, 6b, 6e, 6f and 6h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV.

Paenibacillus algicola sp. nov., a novel alginate lyase-producing marine bacterium.

A Gram-stain-variable, facultatively anaerobic, endospore-forming, rod-shaped bacterium, designated HB172198T, was isolated from brown alga collected at Qishui Bay, Hainan, PR China. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain HB172198T belonged to the genus Paenibacillus, and the closest phylogenetically related species was Paenibacillus lemnae NBRC 109972T (97.6% similarity). The other 16S rRNA gene sequence similarities were under 97.0%. The whole genome average nucleotide identity value between strain HB172198T and the closest type strain was 75.3% and the in silico DNA-DNA hybridization value was 20.2%. The predominant isoprenoid quinone was menaquinone 7 and the major fatty acids were anteiso-C15:0, C16:0, anteiso-C17:0, iso C16:0 and C16:1 ω11c. The combined phylogenetic relatedness, phenotypic and genotypic features supported the conclusion that strain HB172198T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus algicola sp. nov. is proposed. The type strain is HB172198T (=CGMCC 1.13583T=JCM 32683T).

ZFP403, a novel tumor suppressor, inhibits the proliferation and metastasis in ovarian cancer.

OBJECTIVE: Zinc finger protein 403 (ZFP403) is located on human chromosome 17q12-21, the most common loss of heterozygosity regions for some oncogenes. However, the biological function of ZFP403 on tumor is controversial and its role in ovarian cancer remains unknown. This study aimed to investigate its biological function in ovarian cancer. METHODS: qRT-PCR and western blotting were first performed to detect the expression level of ZFP403 in ovarian cancer tissues and cells, respectively. The effect of ZFP403 on cell proliferation was determined by colony formation assays. Its effects on cell cycle were analyzed by flow cytometry and western blotting. Wound healing, Boyden chamber, western blotting and gelatin zymography assays were utilized to assess migration and invasion abilities of cells overexpressed with ZFP403. The xenograft model in nude mice was used to elucidate the role of ZFP403 on tumorigenesis in vivo. RESULTS: Compared with normal ovarian tissues and cells, significantly lower expression levels of ZFP403 were observed in ovarian cancer tissues and cells. Ectopic overexpression of ZFP403 in ovarian cancer cells dramatically suppressed cell proliferation by inducing cell cycle arrest at G2/M phase. Moreover, overexpression of ZFP403 in SK-OV3 cells inhibited cell migration and invasion. Xenograft study also demonstrated that overexpression of ZFP403 suppressed the tumor growth in vivo. CONCLUSION: The effects of ZFP403 on cell proliferation and metastasis suggest that it may serve as a tumor suppressor in ovarian cancer.

Modified filter-aided sample preparation (FASP) method increases peptide and protein identifications for shotgun proteomics.

RATIONALE: Mass spectrometry (MS)-based protein identification depends mainly on protein extraction and digestion. Although sodium dodecyl sulfate (SDS) can preclude enzymatic digestion and interfere with MS analysis, it is still the most widely used surfactant in these steps. To overcome these disadvantages, a SDS-compatible proteomic technique for SDS removal prior to MS-based analyses was developed, namely filter-aided sample preparation (FASP). METHODS: Herein, based on the effectiveness of sodium deoxycholate and a detergent removal spin column, we developed a modified FASP (mFASP) method and compared its overall performance, total number of peptides and proteins identified for shotgun proteomic experiments with that of the FASP method. RESULTS: Identification of 4570 ± 392 and 9139 ± 317 peptides and description of 862 ± 46 and 1377 ± 33 protein groups with two or more peptides from the ovarian cancer cell line A2780 was accomplished by FASP and mFASP methods, respectively. The mFASP method (21.2 ± 0.2%) had higher average peptide to protein coverage than FASP method (13.2 ± 0.5%). More hydrophobic peptides were identified by mFASP than by FASP, as indicated by the GRAVY score distribution. CONCLUSIONS: The reported method enables reliable and efficient identification of proteins and peptides in whole-cell extracts containing SDS. The new approach allows for higher throughput (the simultaneous identification of more proteins), a more comprehensive investigation of proteins, and potentially the discovery of new biomarkers. Copyright © 2016 John Wiley & Sons, Ltd.

Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats.

BACKGROUND Wound healing in chronic diabetic mellitus is mainly associated with the management of angiogenesis. The angiogenic mechanism of vascular endothelial growth factor (VEGF) has been widely studied in the context of diabetic ulcers. The aim of this study was to investigate the wound-healing potential of curcumol in streptozotocin-induced diabetic rats. MATERIAL AND METHODS Sixty male SD (Sprague Dawley) rats were purchased and randomly assigned into four groups: a control group and a model group treated with blank ointment, a high-dose curcumol group, and a low-dose curcumol group. The number of animals in each group was 15. Diabetes was induced by an intraperitoneal injection of streptozotocin. Two cutaneous wounds were incised at the dorsal region of all the experimental animals. Wound healing was assessed for all animal groups by observing the rate of wound closure. The expression of VEGF at the wound sites was studied by immunohistochemical staining to evaluate the vascular endothelial cell reaction. VEGF protein and related mRNA levels were analyzed by Western blotting and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS Curcumol treatment significantly increased the rates of wound closure in treated animals, and hence wound healing was drastically enhanced for treatment groups compared to control groups. Histological observations and related mRNA and protein levels showed a higher VEGF expression in the treatment groups. CONCLUSIONS Our analyses clearly suggested that the observed enhancement in wound healing as a result of curcumol administration was attributable to VEGF-mediated angiogenesis.

Down-regulation of Ras-related protein Rab 5C-dependent endocytosis and glycolysis in cisplatin-resistant ovarian cancer cell lines.

Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared with A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes, and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and Western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes pyruvate kinase, glucose-6-phosphate isomerase, fructose-bisphosphate aldolase, lactate dehydrogenase, and phosphoglycerate kinase 1 were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, whereas vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes, and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step toward a comprehensive understanding of drug resistance in ovarian cancer.

Evaluation of N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine as an irreversible inhibitor of mammalian thioredoxin reductase1.

CONTEXT: Thioredoxin reductase (TrxR) is up-regulated in a number of human malignant cells and becomes a promising target for anticancer drug development. OBJECTIVE: To evaluate N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine (NACC), a potent anticancer agent against melanoma, as an inhibitor of mammalian TrxR1. MATERIAL AND METHODS: The mechanism of inhibition against TrxR1 was investigated using substrate protection, dialysis and liquid chromatography-tandem mass spectrometry. RESULTS: NACC inhibits TrxR1 in a time and concentration dependent manner. The K(I) and k(inact) of NACC against TrxR1 were determined to be 80 µM and 0.178 min(-1), respectively. The inhibition occurred only in the presence of NADPH and persisted after extensive dialysis. The tandem mass spectrometric analysis demonstrated that the selenocysteine rather than cysteine residue at the active site was p-chlorophenyl carbamoylated by NACC. Inhibition of intracellular TrxR by NACC in cultured melanoma cells was observed. DISCUSSION AND CONCLUSION: NACC which irreversibly inhibits TrxR1 by forming a covalent bond with selenocysteine can be an effective tool in the study of TrxR1.

Establishment and Characterization of a CD20-Positive NK/T-Cell Lymphoma Cell Line.

BACKGROUND: CD20 positive NK/T-cell lymphoma is extremely rare and difficult for clinical treatment. Due to the lack of an established cell model for this disease, less is known about its biological characterization and potential therapeutic options. METHODS: A cell line of NK/T-cell lymphoma, which was enriched by magnetic sorting with proper cell surface markers (CD56) from peripheral blood mononuclear cells (PBMCs) drawn from a 21-year-old male patient with nasal angiocentric NK/T-cell lymphoma, was designated as ZQNK-29. Immunophenotypic analysis of ZQNK-29 was performed by flow cytometric and immunohistochemical analysis. Comparative genomic hybridization (CGH) analysis was used for cytogenetic analysis of ZQNK-29. Potential rearrangements of the immunoglobulin gene and Epstein-Barr virus (EBV) infection were examined by PCR and RT-PCR, respectively. RESULTS: ZQNK-29 cells express the phenotypic T-cell marker (CD3), T cell activation markers (HLA-DR), markers for both NK and cytotoxic T lymphocytes (TIA-1), and B-lineage marker CD20; however, expression of CD56 was not detected in expanded ZQNK-29 cells although this NK cell surface marker was used as one of selective cell surface markers for the initial isolation of NK/T cells. RT-PCR analysis showed that the pattern of gene expressions for infected EBV was latency type III, with the expressions of LMP1, EBNA-1, and EBNA-2; no rearrangements were found in the heavy-chain of the immunoglobulin gene or in the y chain of the T cell receptors (TCRs) gene. CGH analysis demonstrated that ZQNK-29 possessed an abnormal karyotype, 46XY, 1p (dist)+, 4p (dist)+, 4q (mid)-, 5q (mid)-, 9q (dist)+, 16p (dist)+, 16q (dist)+, 17p+, 17q (dist)+, 19q (dist)+, 20p+, 20q+, 21q+, and 22q+. Of these, 1p (dist)+, which has been confirmed to be mitochondrial DNA amplification, is believed to be mainly caused by EBV infection. CONCLUSIONS: ZQNK-29 is a well characterized premature human NK/T-cell lymphoma cell line with expression of the B-cell marker CD20 and will provide a useful pre-clinic model for characterization and potential therapeutic studies of the aggressive NK/T-cell lymphoma.

Candidate prognostic biomarkers and prediction models for high-grade serous ovarian cancer from urinary proteomics.

High-grade serous ovarian cancer (HGSOC) is one of the most common histologic types of ovarian cancer. The purpose of this study was to identify potential prognostic biomarkers in urine specimens from patients with HGSOC. First, 56 urine samples with information on relapse-free survival (RFS) months were collected and classified into good prognosis (RFS ≥ 12 months) and poor prognosis (RFS < 12 months) groups. Next, data-independent acquisition (DIA)-based mass spectrometry (MS) analysis was combined with MSFragger-DIA workflow to identify potential prognostic biomarkers in a discovery set (n = 31). With the aid of parallel reaction monitoring (PRM) analysis, four candidate biomarkers (ANXA1, G6PI, SPB3, and SPRR3) were finally validated in both the discovery set and an independent validation set (n = 25). Subsequent RFS and Cox regression analyses confirmed the utility of these candidate biomarkers as independent prognostic factors affecting RFS in patients with HGSOC. Regression models were constructed to predict the 12-month RFS rate, with area under the receiver operating characteristic curve (AUC) values ranging from 0.847 to 0.905. Overall, candidate prognostic biomarkers were identified in urine specimens from patients with HGSOC and prediction models for the 12-month RFS rate constructed. SIGNIFICANCE: OC is one of the leading causes of death due to gynecological malignancies. HGSOC constitutes one of the most common histologic types of OC with aggressive characteristics, accounting for the majority of advanced cases. In cases where patients with advanced HGSOC potentially face high risk of unfavorable prognosis or disease advancement within a 12-month period, intensive medical monitoring is necessary. In the era of precision cancer medicine, accurate prediction of prognosis or 12-month RFS rate is critical for distinguishing patient groups requiring heightened surveillance. Patients could significantly benefit from timely modifications to treatment regimens based on the outcomes of clinical monitoring. Urine is an ideal resource for disease surveillance purposes due to its easy accessibility. Furthermore, molecules excreted in urine are less complex and more stable than those in other liquid samples. In the current study, we identified candidate prognostic biomarkers in urine specimens from patients with HGSOC and constructed prediction models for the 12-month RFS rate.

NHC-Catalyzed Chemo- and Enantioselective Reaction between Aldehydes and Enals for Access to Axially Chiral Arylaldehydes.

A chiral carbene-catalyzed chemo- and enantioselective reaction with racemic biaryl aldehydes and α-bromoenals is developed for access to axially chiral 2-arylbenzaldehydes through atroposelective dynamic kinetic resolution (DKR) processes. This atroposelective DKR strategy can tolerate a broad scope of substrates with diverse functionalities. The axially chiral 2-aryl benzaldehyde products generally afford moderate to good yields and enantioselectivities. The axially chiral molecules afforded from the current approach are variable through simple transformations to afford axially chiral functional molecules with excellent optical purities.

Diagnosing and tracking depression based on eye movement in response to virtual reality.

Introduction: Depression is a prevalent mental illness that is primarily diagnosed using psychological and behavioral assessments. However, these assessments lack objective and quantitative indices, making rapid and objective detection challenging. In this study, we propose a novel method for depression detection based on eye movement data captured in response to virtual reality (VR). Methods: Eye movement data was collected and used to establish high-performance classification and prediction models. Four machine learning algorithms, namely eXtreme Gradient Boosting (XGBoost), multilayer perceptron (MLP), Support Vector Machine (SVM), and Random Forest, were employed. The models were evaluated using five-fold cross-validation, and performance metrics including accuracy, precision, recall, area under the curve (AUC), and F1-score were assessed. The predicted error for the Patient Health Questionnaire-9 (PHQ-9) score was also determined. Results: The XGBoost model achieved a mean accuracy of 76%, precision of 94%, recall of 73%, and AUC of 82%, with an F1-score of 78%. The MLP model achieved a classification accuracy of 86%, precision of 96%, recall of 91%, and AUC of 86%, with an F1-score of 92%. The predicted error for the PHQ-9 score ranged from -0.6 to 0.6.To investigate the role of computerized cognitive behavioral therapy (CCBT) in treating depression, participants were divided into intervention and control groups. The intervention group received CCBT, while the control group received no treatment. After five CCBT sessions, significant changes were observed in the eye movement indices of fixation and saccade, as well as in the PHQ-9 scores. These two indices played significant roles in the predictive model, indicating their potential as biomarkers for detecting depression symptoms. Discussion: The results suggest that eye movement indices obtained using a VR eye tracker can serve as useful biomarkers for detecting depression symptoms. Specifically, the fixation and saccade indices showed promise in predicting depression. Furthermore, CCBT demonstrated effectiveness in treating depression, as evidenced by the observed changes in eye movement indices and PHQ-9 scores. In conclusion, this study presents a novel approach for depression detection using eye movement data captured in VR. The findings highlight the potential of eye movement indices as biomarkers and underscore the effectiveness of CCBT in treating depression.