A modified diffusion-weighted magnetic resonance imaging-based model from the radiologist's perspective: improved performance in determining the surgical resectability of advanced high-grade serous ovarian cancer.

BACKGROUND: Complete resection of all visible lesions during primary debulking surgery is associated with the most favorable prognosis in patients with advanced high-grade serous ovarian cancer. An accurate preoperative assessment of resectability is pivotal for tailored management. OBJECTIVE: This study aimed to assess the potential value of a modified model that integrates the original 8 radiologic criteria of the Memorial Sloan Kettering Cancer Center model with imaging features of the subcapsular or diaphragm and mesenteric lesions depicted on diffusion-weighted magnetic resonance imaging and growth patterns of all lesions for predicting the resectability of advanced high-grade serous ovarian cancer. STUDY DESIGN: This study included 184 patients with high-grade serous ovarian cancer who underwent preoperative diffusion-weighted magnetic resonance imaging between December 2018 and May 2023 at 2 medical centers. The patient cohort was divided into 3 subsets, namely a study cohort (n=100), an internal validation cohort (n=46), and an external validation cohort (n=38). Preoperative radiologic evaluations were independently conducted by 2 radiologists using both the Memorial Sloan Kettering Cancer Center model and the modified diffusion-weighted magnetic resonance imaging-based model. The morphologic characteristics of the ovarian tumors depicted on magnetic resonance imaging were assessed as either mass-like or infiltrative, and transcriptomic analysis of the primary tumor samples was performed. Univariate and multivariate statistical analyses were performed. RESULTS: In the study cohort, both the scores derived using the Memorial Sloan Kettering Cancer Center (intraclass correlation coefficients of 0.980 and 0.959, respectively; both P<.001) and modified diffusion-weighted magnetic resonance imaging-based models (intraclass correlation coefficients of 0.962 and 0.940, respectively; both P<.001) demonstrated excellent intra- and interobserver agreement. The Memorial Sloan Kettering Cancer Center model (odds ratio, 1.825; 95% confidence interval, 1.390-2.395; P<.001) and the modified diffusion-weighted magnetic resonance imaging-based model (odds ratio, 1.776; 95% confidence interval, 1.410-2.238; P<.001) independently predicted surgical resectability. The modified diffusion-weighted magnetic resonance imaging-based model demonstrated improved predictive performance with an area under the curve of 0.867 in the study cohort and 0.806 and 0.913 in the internal and external validation cohorts, respectively. Using the modified diffusion-weighted magnetic resonance imaging-based model, patients with scores of 0 to 2, 3 to 4, 5 to 6, 7 to 10, and ≥11 achieved complete tumor debulking rates of 90.3%, 66.7%, 53.3%, 11.8%, and 0%, respectively. Most patients with incomplete tumor debulking had infiltrative tumors, and both the Memorial Sloan Kettering Cancer Center and the modified diffusion-weighted magnetic resonance imaging-based models yielded higher scores. The molecular differences between the 2 morphologic subtypes were identified. CONCLUSION: When compared with the Memorial Sloan Kettering Cancer Center model, the modified diffusion-weighted magnetic resonance imaging-based model demonstrated enhanced accuracy in the preoperative prediction of resectability for advanced high-grade serous ovarian cancer. Patients with scores of 0 to 6 were eligible for primary debulking surgery.

Development, characterization and functional properties of sodium alginate-based films incorporated with Schisandra chinensis extract-natamycin complex.

Because of the impact of petroleum-based polymers on environmental deterioration and the need for safe, efficient, and functional packaging films, a sodium alginate (SA)-based film incorporating a Schisandra chinensis extract (SCE)-natamycin (NA) complex was developed for the desired physical and functional properties. The incorporation of SCE-NA into SA-based films decreased the water vapor transmission rate (WVTR), moisture content (MC), and hydrophilicity of the films and improved their opacity, elongation at break (EAB), and thermal stability. Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray Diffraction (XRD) analyses showed that SA, SCE, and NA had positive interactions and compatibility. In addition, the antimicrobial activity analysis indicated that the SA-SCE-NA film-forming solutions had satisfactory antimicrobial activity against Staphylococcus aureus, Escherichia coli, Saccharomyces cerevisiae, and Aspergillus niger. SA-based composite films have been used to coat cucumbers and blueberries to extend their shelf life. Compared to the neat SA film, the shelf life of cucumbers treated with the SA-SCE-NA film increased by 6 days compared to that in the untreated group at 28 °C, and the shelf life of blueberries increased by 5 days at 4 °C, revealing its potential utilization in food packaging.

Whole-tumor ADC histogram analysis for differentiating endometriosis-related tumors: seromucinous borderline tumor, clear cell carcinoma and endometrioid carcinoma.

PURPOSE: To investigate the feasibility of whole-tumor apparent diffusion coefficient (ADC) histogram analysis for improving the differentiation of endometriosis-related tumors: seromucinous borderline tumor (SMBT), clear cell carcinoma (CCC) and endometrioid carcinoma (EC). METHODS: Clinical features, solid component ADC (ADCSC) and whole-tumor ADC histogram-derived parameters (volume, the ADCmean, 10th, 50th and 90th percentile ADCs, inhomogeneity, skewness, kurtosis and entropy) were compared among 22 SMBTs, 42 CCCs and 21 ECs. Statistical analyses were performed using chi-square test, one-way ANOVA or Kruskal-Wallis test, and receiver operating characteristic curves. RESULTS: A significantly higher ADCSC and smaller volume were associated with SMBT than with CCC/EC. The ADCmean was significantly higher in CCC than in EC. The 10th percentile ADC was significantly lower in EC than in SMBT/CCC. The 50th and 90th percentile ADCs were significantly higher in CCC than in SMBT/EC. For differentiating SMBT from CCC, AUCs of the ADCSC, volume, and 50th and 90th percentile ADCs were 0.97, 0.86, 0.72 and 0.81, respectively. For differentiating SMBT from EC, AUCs of the ADCSC, volume and 10th percentile ADC were 0.97, 0.71 and 0.72, respectively. For differentiating CCC from EC, AUCs of the ADCmean and 10th, 50th and 90th percentile ADCs were 0.79, 0.72, 0.81 and 0.85, respectively. CONCLUSION: Whole-tumor ADC histogram analysis was valuable for differentiating endometriosis-related tumors, and the 90th percentile ADC was optimal in differentiating CCC from EC.

Double-wing switch nanodevice-mediated primer exchange reaction for the activity analysis of cancer biomarker FEN1.

DNA damage repair is one of the foremost factors leading to changes in tumor drug resistance. The analysis of Flap endonuclease 1 (FEN1), a kind of pivotal enzyme in various DNA metabolic pathways, has been of great support to tumor research and the development of chemotherapeutics. Nevertheless, few analytical techniques can achieve quantitative and simplified FEN1 measurement. Here, we constructed a double-wing switch nanodevice (DWSN)-mediated primer exchange technique for rapid and label-free quantification of FEN1 activity. Target FEN1 triggered the generation of numerous telomeric repeat fragments in different lengths through recognizing the three-base mismatched sites on the DWSN to release the 5'-Flaps. Further binding to the fluorescent dye ThT resulted in significantly enhanced fluorescence. This study broke the limitation of traditional single-site identification and demonstrated good sensitivity and specificity with detection limits up to 0.55 mU. Besides, the extraordinary analytical performance allowed the method to be utilized to monitor FEN1 extracted from cells and clinical serum samples and to compare the effect of targeted FEN1 inhibitors.

Diffusion-Weighted Magnetic Resonance Imaging and Morphological Characteristics Evaluation for Outcome Prediction of Primary Debulking Surgery for Advanced High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Preoperative assessment of whether a successful primary debulking surgery (PDS) can be performed in patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains a challenge. A reliable model to precisely predict resectability is highly demanded. PURPOSE: To investigate the value of diffusion-weighted MRI (DW-MRI) combined with morphological characteristics to predict the PDS outcome in advanced HGSOC patients. STUDY TYPE: Prospective. SUBJECTS: A total of 95 consecutive patients with histopathologically confirmed advanced HGSOC (ranged from 39 to 77 years). FIELDS STRENGTH/SEQUENCE: A 3.0 T, readout-segmented echo-planar DWI. ASSESSMENT: The MRI morphological characteristics of the primary ovarian tumor, a peritoneal carcinomatosis index (PCI) derived from DWI (DWI-PCI) and histogram analysis of the primary ovarian tumor and the largest peritoneal carcinomatosis were assessed by three radiologists. Three different models were developed to predict the resectability, including a clinicoradiologic model combing MRI morphological characteristic with ascites and CA125 level; DWI-PCI alone; and a fusion model combining the clinical-morphological information and DWI-PCI. STATISTICAL TESTS: Multivariate logistic regression analyses, receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used. A P < 0.05 was considered to be statistically significant. RESULTS: Sixty-seven cases appeared as a definite mass, whereas 28 cases as an infiltrative mass. The morphological characteristics and DWI-PCI were independent factors for predicting the resectability, with an AUC of 0.724 and 0.824, respectively. The multivariable predictive model consisted of morphological characteristics, CA-125, and the amount of ascites, with an incremental AUC of 0.818. Combining the application of a clinicoradiologic model and DWI-PCI showed significantly higher AUC of 0.863 than the ones of each of them implemented alone, with a positive NRI and IDI. DATA CONCLUSIONS: The combination of two clinical factors, MRI morphological characteristics and DWI-PCI provide a reliable and valuable paradigm for the noninvasive prediction of the outcome of PDS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Magnetic resonance imaging findings of intravascular leiomyomatosis of the uterus: a case report.

Background: Intravascular leiomyomatosis (IVL) is often a non-malignant condition that grows inside the blood vessels and does not invade surrounding tissues. However, its presence within the blood vessels can lead to obstructions. The majority of IVL cases manifest symptoms related to blockage. Case presentation: We present a case of a 50-year-old female patient who was referred to our institution due to the presence of a common non-cancerous tumor in the uterus, known as a benign uterine leiomyoma. The tumor was identified during an ultrasound examination during a routine physical examination. Postoperative pathology established the existence of intrapelvic IVL. Conclusion: Intrapelvic IVL often not present with complications when it is confined to the pelvic cavity. Furthermore, the imaging features of intrapelvic IVL resemble those of typical benign uterine leiomyomas. This can often result in the clinical misdiagnosis of the tumor as a typical benign uterine leiomyoma.

The Prevalence, Progress and Risk Factor Control of Chronic Kidney Disease in Chinese Adults With Type 2 Diabetes Mellitus in Primary Care.

Objective: This study aimed to evaluate the prevalence of chronic kidney disease (CKD) in Chinese adults with T2DM in primary care, and the association of HbA1c, blood pressure (BP) and triglycerides (TG), i.e. ABC control at follow up (FU) with the progress and regression of CKD. Methods: A total of 5123 patients with ≥3 measurements of estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), HbA1c, BP, LDL-C and TG, and FU ≥ 12 months were included into final analysis. The presence of CKD was defined as the presence of albuminuria (UACR ≥ 30 mg/g), impaired eGFR (eGFR < 60 ml/min/1.73 m2) or both, and was categorised as low, moderate and high/very high risk. The change of CKD risk for outcome was categorised as stable (no change), progress (risk increase) and regress (risk decrease) from baseline to the last visits (LV). Results: The prevalence of CKD, impaired eGFR and albuminuria was 29.6%, 5.8% and 27.1% at baseline, with 70.4%, 20.3%, 7.0% and 2.3% of patients distributed in low, moderate, high and very high risk group. There were 3457 (67.5%), 1120 (21.8%) and 546 (10.7%) patients had CKD outcome risk stable, progressed and regressed respectively. The proportion of patients reaching targets of BP ≤ 130/80 mmHg, HbA1c<7.5%, LDL-C<2.60 mmol/L increased from baseline to FU and LV, together with increased usage of insulin, RAS inhibitors and lipid lowering medications. After multivariable adjustment, the HbA1c<7.5% (OR: 0.66, 95%CI 0.56-0.78), TG< 1.7 mmol/L (OR: 0.81, 95%CI 0.68-0.96) at FU and BP ≤ 130/80 mmHg at LV (OR: 0.82, 95%CI 0.70-0.95) was negatively associated with CKD outcome risk progress. Conclusion: The prevalence of CKD was high with 21.8% of patients progressing to higher CKD outcome risk at FU, attention should be paid on long term and better ABC control.

The fluorescence amplification strategy based on 3D DNA walker and CRISPR/Cas12a for the rapid detection of BRAF V600E.

Circulating tumor DNA (ctDNA) is a fragment of single- or double-stranded DNA originating from tumor or circulating tumor cells and provides accurate information regarding the molecular characteristics of tumors. Therefore, sensitive detection of ctDNA is of great significance to mutation analysis and clinical diagnosis. Among various ctDNAs, the BRAF V600E is related to aggressive behavior, disease recurrence, and disease-specific mortality in papillary thyroid carcinoma. Herein, we selected the BRAF V600E gene sequence as an in vitro biomarker, and established a fluorescence detection strategy combined 3D DNA walker with CRISPR/Cas12a. In the presence of the target ctDNA, 3D DNA walker could identify and bind it, and thus released a large amount of output DNAs through cyclic cleavage with the assistance of specific endonuclease (Nb.BbvCI). The output DNAs were specifically bound to crRNA and activated the non-specific trans-cleavage activity of Cas12a. Finally, the fluorescence signal was significantly enhanced. Notably, this method can detect the BRAF V600E in a range of 1 fM ~ 20 nM with a detection limit of 0.37 fM without DNA polymerase. Due to the powerful amplification capability of 3D DNA walker and high specificity and programmability of CRISPR/Cas12a, the entire process took only a maximum of 70 min. Furthermore, it can be potentially used for the detection of ctDNA in human serum. In summary, this method not only provides a platform for the rapid detection of ctDNA, but also shows good potential for early clinical diagnosis and biomedical research.

A novel fluorescence amplification strategy combining cascade primer exchange reaction with CRISPR/Cas12a system for ultrasensitive detection of RNase H activity.

Ribonuclease H (RNase H), which plays a vital role in various cellular processes, is to be closely related to the emergence of many diseases. As an essential therapeutic target, it shows great prospects in the development of associated drugs. Herein, a DNA-RNA chimeric hairpin (DR HP) was designed to introduce a new signal amplification strategy based on cascade primer exchange reaction (cPER) and CRISPR/Cas12a system for sensitive and specific analysis of RNase H activity. In the presence of RNase H, the RNA fragment of DR HP was specifically degraded and the blocked primer DNA was released. The process of enzymatic hydrolysis of substrate hairpin and cyclic signal amplification was completed in a one-step method under isothermal conditions, enriching many activator strands to initiate trans-cleavage of CRISPR/Cas system, thereby restoring the fluorescence signal. Under optimized conditions, the developed strategy exhibited a good linear relationship ranging from 0.005 to 0.1U/mL and offered a detection limit of 0.00061U/mL. Moreover, this method was used for RNase H activity assay in complicated human serum and real cell lysates with good stability and repeatability, and was also demonstrated to apply for RNase H inhibitors screening and inhibitory capability assessment. Therefore, the proposed system is a promising platform not only for determination of RNase H activity, but open up new thoughts for the biological enzyme research and inhibitor screening.

Latitudinal Distribution of Gaseous Elemental Mercury in Tropical Western Pacific: The Role of the Doldrums and the ITCZ.

The role of the tropical western Pacific in the latitudinal distribution of atmospheric mercury is still unclear. In this study, we conducted continuous measurements of gaseous elemental mercury (GEM) in the marine boundary layer (MBL) along a large latitudinal transect (∼60° S to ∼30° N) of the western Pacific, accompanied by measurements of dissolved gaseous mercury (DGM) in the surface seawater. We found that the GEM latitudinal gradient is the most significant in the tropical western Pacific, which to some extent might be attributed to the impact of the doldrums and the Intertropical Convergence Zone (ITCZ) in this area. For the doldrums, calm weather may delay the transport of GEM, facilitating its accumulation in the tropical western Pacific. Furthermore, the regional transport, and low O3 and sea-salt aerosol levels in this area which would not favor the oxidation of GEM in the MBL, would intensify the accumulation of GEM in the tropical western Pacific. For the ITCZ, the vast wet deposition of Hg would drive elevated DGM in the surface seawater, which can increase the evasion flux and may further influence the spatial distribution of GEM. This study provides insight into the role of the tropical western Pacific in the regional atmospheric mercury cycle.

MRI-Based Radiomics Analysis for Intraoperative Risk Assessment in Gravid Patients at High Risk with Placenta Accreta Spectrum.

BACKGROUND: Gravid patients at high risk with placenta accreta spectrum (PAS) face life-threatening risk at delivery. Intraoperative risk assessment for patients is currently insufficient. We aimed to develop an assessment system of intraoperative risks through MRI-based radiomics. METHODS: A total of 131 patients enrolled were randomly grouped according to a ratio of 7:3. Clinical data were analyzed retrospectively. Radiomic features were extracted from sagittal Fast Imaging Employing State-sate Acquisition images. Univariate and multivariate regression analyses were performed to build models using R software. A receiver operating characteristic curve and decision curve analysis (DCA) were performed to determine the predictive performance of models. RESULTS: Six radiomic features and two clinical variables were used to construct the combined model for selection of removal protocols of the placenta, with an area under the curve (AUC) of 0.90 and 0.91 in the training and test cohorts, respectively. Nine radiomic features and two clinical variables were obtained to establish the combined model for prediction of intraoperative blood loss, with an AUC of 0.90 and 0.88 in the both cohorts, respectively. The DCA confirmed the clinical utility of the combined model. CONCLUSION: The analysis of combined MRI-based radiomics with clinics could be clinically beneficial for patients.

Dry-deposition of inorganic and organic nitrogen aerosols in Xiamen Bay: Fluxes, sources, and biogeochemical significance.

Increased dry deposition of nitrogen aerosols (aerosol-N) as a result of anthropogenic emissions has caused large negative impacts on marine ecosystems. We monitored the number concentrations and sizes of inorganic nitrogen aerosols (aerosol-IN: NH4+ and NO3-) and organic nitrogen aerosols (aerosol-ON: methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, and triethylamine) by single-particle aerosol mass spectrometry (SPAMS) during the warm season (WS) and cold season (CS) of 2013 and 2015 in Xiamen Bay. The mean hourly number concentration of aerosol-IN (874/h) overwhelmed that of aerosol-ON (103/h), accounting for 83.9 ± 16.1% of aerosol-N. More than 90% of aerosol-N was concentrated in the condensation mode (0.1-0.5 µm) and droplet mode (0.5-2.0 µm). Aerosol-IN was the main contributor (80.1-94.2%) to aerosol-N deposition. New production potentially supported by the ocean's external nitrogen supply provided aerosol-N input of 11.51-11.96 g C m-2 yr-1, which contributed 17.5-18.2% of total new production in the southern East China Sea. Four potential sources of aerosol-N were identified based on the results of positive matrix factorization analysis, including secondary formation (F1), biogenic source (F2), sea spray, soil dust, biomass burning (F3), and anthropogenic sources (F4). Aerosol-N concentrations in Xiamen Bay were mainly affected by the ocean air masses during the WS and inland air masses during the CS. The percentages of aerosol-N at each backward trajectory cluster showed that the inland air masses brought more aerosol-IN emitted from biomass burning, soil dust, and secondary formation sources, whereas the ocean air masses brought more aerosol-ON emitted from a marine biogenic source into Xiamen Bay. This study provides an example of determining the number concentrations and sizes of IN and ON in aerosols by SPAMS, and helps us further understand the dry deposition and sources of IN and ON in aerosols in Xiamen Bay.

MRI-Based Multiple Instance Convolutional Neural Network for Increased Accuracy in the Differentiation of Borderline and Malignant Epithelial Ovarian Tumors.

BACKGROUND: Preoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT vs. MEOT) is challenging and can significantly impact surgical management. PURPOSE: To develop a multiple instance convolutional neural network (MICNN) that can differentiate BEOT from MEOT, and to compare its diagnostic performance with that of radiologists. STUDY TYPE: Retrospective study of eight clinical centers. SUBJECTS: Between January 2010 and June 2018, a total of 501 women (mean age, 48.93 ± 14.05 years) with histopathologically confirmed BEOT (N = 165) or MEOT (N = 336) were divided into the training (N = 342) and validation cohorts (N = 159). FIELD STRENGTH/SEQUENCE: Three axial sequences from 1.5 or 3 T scanner were used: fast spin echo T2-weighted imaging with fat saturation (T2WI FS), echo planar diffusion-weighted imaging, and 2D volumetric interpolated breath-hold examination of contrast-enhanced T1-weighted imaging (CE-T1WI) with FS. ASSESSMENT: Three monoparametric MICNN models were built based on T2WI FS, apparent diffusion coefficient map, and CE-T1WI. Based on these monoparametric models, we constructed an early multiparametric (EMP) model and a late multiparametric (LMP) model using early and late information fusion methods, respectively. The diagnostic performance of the models was evaluated using the receiver operating characteristic (ROC) curve and compared to the performance of six radiologists with varying levels of experience. STATISTICAL TESTS: We used DeLong test, chi-square test, Mann-Whitney U-test, and t-test, with significance level of 0.05. RESULTS: Both EMP and LMP models differentiated BEOT from MEOT, with an area under the ROC curve (AUC) of 0.855 (95% CI, 0.795-0.915) and 0.884 (95% CI, 0.831-0.938), respectively. The AUC of the LMP model was significantly higher than the radiologists' pooled AUC (0.884 vs. 0.797). DATA CONCLUSION: The developed MICNN models can effectively differentiate BEOT from MEOT and the diagnostic performances (AUCs) were more superior than that of the radiologists' assessments. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Ultra-sensitive detection of DNA N6-adenine methyltransferase based on a 3D tetrahedral fluorescence scaffold assisted by symmetrical double-ring dumbbells.

DNA methylation is an epigenetic modification that plays a vital role in X chromosome inactivation, genome imprinting, and gene expression. DNA methyltransferase establishes and maintains a stable methylation state in genomic DNA. Efficient and specific DNA methyltransferase testing is essential for the early diagnosis and treatment of cancer. In this study, we designed an ultra-sensitive fluorescent biosensor, based on a 3D tetrahedral fluorescent scaffold assisted by symmetrical double-ring dumbbells, for the detection of DNA-[N 6-adenine]-methyltransferase (Dam MTase). Double-stranded DNA was methylated by Dam MTase and then digested by DpnI to form two identical dumbbell rings. The 3D tetrahedral fluorescent scaffold was synthesized from four oligonucleotide chains containing hairpins. When the sheared dumbbells reacted with the 3D tetrahedral fluorescent scaffold, the hairpins opened and a fluorescence signal could be detected. The strategy was successful over a wide detection range, from 0.002 to 100 U mL-1 Dam MTase, and the lowest detection limit was 0.00036 U mL-1. Control experiments with M.SssI methyltransferase and HpaII methylation restriction endonuclease confirmed the specificity of the method. Experiments with spiked human serum and the 5-fluorouracil inhibitor proved the suitability of the method for early cancer diagnosis.

Non-ignorable contribution of anthropogenic source to aerosols in Arctic Ocean.

Arctic Ocean (AO) atmospheric aerosols, which are a factor influencing regional and global climate, have been greatly influenced by an increase in anthropogenic sources. To identify the impact of anthropogenic sources on regional aerosols in the AO and middle and low latitudes (MLO), a single-particle aerosol mass spectrometer was used to count and size aerosols with diameters less than 2.5 µm (PM2.5) and determine their chemical composition. The mean hourly count of PM2.5 aerosols was 1639/h in the AO, which was 57.1% lower than that in the MLO. Na_MSA, sulfate, and Na_rich were three major components, which accounted for 74.3% of PM2.5 aerosols in the AO. The size distribution of PM2.5 aerosols was unimodal, peaking between 0.42 µm and 1.64 µm. A source apportionment method for single aerosol particles in the Arctic was established using positive matrix factorization (PMF) combined with backward air mass trajectory and principal component analysis (PCA). Three potential sources of aerosols were identified: marine sources; anthropogenic sources; and secondary formation. The largest contribution to aerosols in the AO was from marine sources, accounting for 50.6%. This source was 20.4% higher in the AO than that in the MLO. Secondary formation contributed 19.8% and 36.5% to aerosols in the AO and MLO, respectively. However, the contribution of anthropogenic sources to aerosols was 29.6% in the AO, and this was 3.7% lower than that in the MLO. Our study provides a useful method for identifying sources of aerosols in the Arctic, and the results showed that although marine sources were the largest contributors to aerosols in the AO, the contribution of anthropogenic sources could not be ignored.

Reduced O-GlcNAcylation of SNAP-23 promotes cisplatin resistance by inducing exosome secretion in ovarian cancer.

Exosomes have been associated with chemoresistance in various cancers, but such a role in ovarian cancer is not yet clear. Here, using in vitro cell-based and in vivo mouse model experiments, we show that downregulation of O-GlcNAcylation, a key post-translational protein modification, promotes exosome secretion. This increases exosome-mediated efflux of cisplatin from cancer cells resulting in chemoresistance. Mechanistically, our data indicate that downregulation of O-GlcNAclation transferase (OGT) reduces O-GlcNAclation of SNAP-23. Notably, O-GlcNAcylation of SNAP-23 is vital for regulating exosome release in ovarian cancer cells. Reduced O-GlcNAclation of SNAP-23 subsequently promotes the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of SNAP-23, VAMP8, and Stx4 proteins. This enhances exosome release causing chemoresistance by increasing the efflux of intracellular cisplatin.

Screening and Identification of a Specific Binding Peptide to Ovarian Cancer Cells from a Phage-Displayed Peptide Library.

To select specific binding peptides for imaging and detection of human ovarian cancer. The phage 12-mer peptide library was used to select specific phage clones to ovarian cancer cells. After four rounds of biopanning, the binding specificity of randomly selected phage clones to ovarian cancer cells was determined by enzyme-linked immunosorbent assay (ELISA). DNA sequencing and homology analysis were performed on specifically bound phages. The binding ability of the selected peptides to SKOV3 cells was confirmed by fluorescence microscopy and flow cytometry. After four rounds of optimized biological panning, phage recovery was 34-fold higher than that of the first round, and the specific phage clones bound to SKOV3 cells were significantly enriched. A total of 32 positive phage clones were preliminarily identified by ELISA from 54 randomly selected clones, and the positive rate was 59.3%. S36 was identified as the clone with best affinity to SKOV3 cells via fluorescence microscopy and flow cytometry. A representative clone of OSP2, S36 is expected to be an effective probe for diagnosis and treatment of ovarian cancer.

Noninvasive prediction of residual disease for advanced high-grade serous ovarian carcinoma by MRI-based radiomic-clinical nomogram.

OBJECTIVES: To develop a preoperative MRI-based radiomic-clinical nomogram for prediction of residual disease (RD) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). METHODS: In total, 217 patients with advanced HGSOC were enrolled from January 2014 to June 2019 and randomly divided into a training set (n = 160) and a validation set (n = 57). Finally, 841 radiomic features were extracted from each tumor on T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) sequence, respectively. We used two fusion methods, the maximal volume of interest (MV) and the maximal feature value (MF), to fuse the radiomic features of bilateral tumors, so that patients with bilateral tumors have the same kind of radiomic features as patients with unilateral tumors. The radiomic signatures were constructed by using mRMR method and LASSO classifier. Multivariable logistic regression analysis was used to develop a radiomic-clinical nomogram incorporating radiomic signature and conventional clinico-radiological features. The performance of the nomogram was evaluated on the validation set. RESULTS: In total, 342 tumors from 217 patients were analyzed in this study. The MF-based radiomic signature showed significantly better prediction performance than the MV-based radiomic signature (AUC = 0.744 vs. 0.650, p = 0.047). By incorporating clinico-radiological features and MF-based radiomic signature, radiomic-clinical nomogram showed favorable prediction ability with an AUC of 0.803 in the validation set, which was significantly higher than that of clinico-radiological signature and MF-based radiomic signature (AUC = 0.623, 0.744, respectively). CONCLUSIONS: The proposed MRI-based radiomic-clinical nomogram provides a promising way to noninvasively predict the RD status. KEY POINTS: • MRI-based radiomic-clinical nomogram is feasible to noninvasively predict residual disease in patients with advanced HGSOC. • The radiomic signature based on MF showed significantly better prediction performance than that based on MV. • The radiomic-clinical nomogram showed a favorable prediction ability with an AUC of 0.803.

Growth differentiation factor-15 promotes immune escape of ovarian cancer via targeting CD44 in dendritic cells.

Immune escape is the main cause of the low response rate to immunotherapy for cancer, including ovarian cancer. Growth differentiation factor-15 (GDF-15) inhibits immune cell function. However, only few reports described the mechanism. Therefore, the aim of this study was to investigate the mechanism of immune escape regulated by GDF-15 in ovarian cancer. Ovarian cancer patients and healthy women were enrolled in this study. Immunohistochemistry and ELISA were performed to measure GDF-15 expression. Immunoprecipitation combined with mass spectrometry, surface plasmon resonance, and co-immunoprecipitation assay were used to evaluate the interaction between GDF-15 and the surface molecules of DCs. Immunofluorescence analysis, flow cytometry and transwell assay were used to evaluate additional effects of GDF-15 on DCs. The results showed that GDF-15 expression was higher in the ovarian cancer patients compared to that in the healthy women. The TIMER algorithm revealed that highly GDF-15 expression is associated with immune DC infiltration in immunoreactive high-grade serous carcinoma. A further study showed that GDF-15 suppressed DCs maturation, as well as IL-12p40 and TNF-α secretion, the length and number of protrusions and the migration. More importantly, CD44 in the surface of DCs interacted with GDF-15. The overexpression of CD44 in DCs resulted in the suppression of the inhibitory effect of GDF-15 on the length and number of DC synapses. In DCs overexpressing CD44 the inhibition of GDF-15 on the expression of CD11c, CD83 and CD86 was decreased, while in DCs with a knockdown of CD44 the inhibition was further enhanced. Knockdown of CD44 in DCs enhanced the inhibitory effect of GDF-15 on DC migration, while the overexpression of CD44 inhibited the inhibitory effect of GDF-15 on DC migration. In conclusion, the present study suggested that GDF-15 might facilitate ovarian cancer immune escape by interacting with CD44 in DCs to inhibit their function.

Multifunctional electrochemical biosensor with "tetrahedral tripods" assisted multiple tandem hairpins assembly for ultra-sensitive detection of target DNA.

Nucleic acids are genetic materials in the human body that play important roles in storing, copying, and transmitting genetic information. Abnormal nucleic acid sequences, base mutations, and genetic changes often lead to cancer and other diseases. Meanwhile, methylated DNA is one of the main epigenetic modifications, which is considered to be an excellent biomarker in the early detection, prognosis, and treatment of cancers. Therefore, a multifunctional electrochemical biosensor was constructed with sturdy tetrahedral tripods, which assisted multiple tandem hairpins through base complementary pairing and effective ultra-sensitive detection of targets (DNA, microRNA, and methylated DNA). In the experiments, experimental conditions were optimized, and different DNA concentrations in serum were detected to verify the sensitivity of the biosensor and the feasibility of this protocol. In addition, microRNA and DNA methylation were detected through different designs of tetrahedral tripods (TTs) that capture probes to prove the superiority of this scheme. A sturdy pyramid structure of TTs extremely enhanced the capture efficiency of targets. The targets triggered the one-step isothermal multi-tandem amplification reaction by incubating multiple hairpin assemblies. To our knowledge, a combination of two parts, which greatly reduced background interference and decreased non-specific substance interference, has appeared for the first time in this paper. Moreover, the load area of electrochemical substances was significantly increased than that in previous studies. This greatly increased the detection range and detection limit of targets. The electrochemical signal responses were generated in freely diffusing hexaammineruthenium(iii) chloride (RuHex). RuHex could adhere to the DNA phosphate backbone by a powerful electrostatic attraction, causing increased current responses.