In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy.

BACKGROUND: Chemoresistance gradually develops during treatment of epithelial ovarian cancer (EOC). Metabolic alterations, especially in vivo easily detectable metabolites in paclitaxel (PTX)-resistant EOC remain unclear. METHODS: Xenograft models of the PTX-sensitive and PTX-resistant EOCs were built. Using a combination of in vivo proton-magnetic resonance spectroscopy (1H-MRS), metabolomics and proteomics, we investigated the in vivo metabolites and dysregulated metabolic pathways in the PTX-resistant EOC. Furthermore, we analyzed the RNA expression to validate the key enzymes in the dysregulated metabolic pathway. RESULTS: On in vivo 1H-MRS, the ratio of (glycerophosphocholine + phosphocholine) to (creatine + phosphocreatine) ((GPC + PC) to (Cr + PCr))(i.e. Cho/Cr) in the PTX-resistant tumors (1.64 [0.69, 4.18]) was significantly higher than that in the PTX-sensitive tumors (0.33 [0.10, 1.13]) (P = 0.04). Forty-five ex vivo metabolites were identified to be significantly different between the PTX-sensitive and PTX-resistant tumors, with the majority involved of lipids and lipid-like molecules. Spearman's correlation coefficient analysis indicated in vivo and ex vivo metabolic characteristics were highly consistent, exhibiting the highest positive correlation between in vivo GPC + PC and ex vivo GPC (r = 0.885, P < 0.001). These metabolic data suggested that abnormal choline concentrations were the results from the dysregulated glycerophospholipid metabolism, especially choline metabolism. The proteomics data indicated that the expressions of key enzymes glycerophosphocholine phosphodiesterase 1 (GPCPD1) and glycerophosphodiester phosphodiesterase 1 (GDE1) were significantly lower in the PTX-resistant tumors compared to the PTX-sensitive tumors (both P < 0.01). Decreased expressions of GPCPD1 and GDE1 in choline metabolism led to an increased GPC levels in the PTX-resistant EOCs, which was observed as an elevated total choline (tCho) on in vivo 1H-MRS. CONCLUSIONS: These findings suggested that dysregulated choline metabolism was associated with PTX-resistance in EOCs and the elevated tCho on in vivo 1H-MRS could be as an indicator for the PTX-resistance in EOCs.

Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Aliifodinibius roseus gen. nov., sp. nov., and Aliifodinibius sediminis sp. nov., two moderately halophilic bacteria isolated from salt mine samples.

Two rod-shaped, non-motile bacteria were isolated from two separate salt mines in Yunnan, south-western China. These strains, designated YIM D15(T) and YIM J21(T), were Gram-negative and moderately halophilic. The two strains required 6-10 % NaCl (w/v; optimal) for growth. The DNA G+C contents of strains YIM D15(T) and YIM J21(T) were 49.0 mol% and 48.4 mol%, respectively. The predominant isoprenoid quinone was MK-7. The polar lipid profiles of strains YIM D15(T) and YIM J21(T) were composed predominantly of diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, three unknown polar lipids and one glycolipid. Minor amounts of other lipids were also detectable. The predominant cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 1ω9c/10 methyl-C16 : 0 and C16 : 1ω7c/C16 : 1ω6c. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the two isolates formed a distinct clade with the genus Fodinibius (in the phylum Bacteroidetes) and were related to the species Fodinibius salinus, with sequence similarities of 91.9-92.4 %. Analyses of 16S rRNA gene sequences revealed that strains YIM D15(T) and YIM J21(T) were related to each other (97.3 % sequence similarity). The DNA-DNA hybridization relatedness between the two isolates was 34 %. On the basis of the phylogenetic analysis, DNA-DNA hybridization relatedness, phenotypic and chemotaxonomic characteristics, strains YIM D15(T) and YIM J21(T) should be classified as members of a novel genus and as two novel species, for which the names Aliifodinibius roseus gen. nov., sp. nov. (type strain YIM D15(T) = ACCC 10715(T) = KCTC 23442(T)) and Aliifodinibius sediminis sp. nov. (type strain YIM J21(T) = ACCC 10714(T) = DSM 21194(T)) are proposed.

Sensitivity of lysozyme crystallization to minute variations in concentration.

It is well known that the crystallization of proteins is strongly dependent on the crystallization conditions, which are sometimes very sensitive to environmental disturbances. Parameters such as the concentration of precipitants or protein, pH, temperature and many others are known to affect the probability of crystallization, and the task of crystallizing a new protein often involves a trial-and-error test using numerous combinations of crystallization conditions. These crystallization parameters, such as the concentration of either the protein or the precipitant, are important because they directly affect the driving force of crystallization: the supersaturation of the solution. Although it is common sense that the concentration can affect the crystallization process, the sensitivity of the crystallization process to variations in the concentration has seldom been addressed. Owing to the difficulty of directly preparing solutions with very small concentration variations, it is hard to carry out an investigation of their effect on the crystallization process. In this paper, a simple but novel method for studying the effect of minute concentration variations on the success rate of protein crystallization is presented. By evaporating the crystallization droplet, a fine concentration gradient could be created. With this fine-tuned concentration gradient, it was possible to observe the effects of minute variations in the concentration or supersaturation on the crystallization. A very minor change in concentration (as low as 0.13% of the initial concentration, i.e. 0.026 mg ml(-1) for lysozyme and 0.052 mg ml(-1) for NaCl in the current study) or a very minor change in supersaturation (as small as 0.018) could cause a clear difference in the crystallization success rate, indicating that the crystallization of proteins is very sensitive to the concentration level. Such sensitive behaviour may be one reason for the poor reproducibility of protein crystallization.

Rapid crystallization from acoustically levitated droplets.

This paper reports on an ultrasonic levitation system developed for crystallization from solution in a containerless condition. The system has been proven to be able to levitate droplets stably and grow crystals rapidly and freely from a levitated droplet. Crystals of four samples, including NaCl, NH(4)Cl, lysozyme, and proteinase K, were obtained successfully utilizing the system. The studies showed that the crystals obtained from the acoustically levitated droplets all exhibited higher growth rates, larger sizes, better shapes, fewer crystals, as well as fewer twins and shards, compared with the control on a vessel wall. The results indicated that containerless ultrasonic levitation could play a key role in improving the crystallization of both inorganic salts and proteins. The ultrasonic levitation system could be used as a ground-based microgravity simulation platform, which could swiftly perform crystallization and screening of crystallization conditions for space crystallization and other ground-based containerless techniques. Moreover, the approach could also be conveniently applied to researching the dynamics and mechanism of crystallization. In addition, the device could be used for the preparation of high-purity materials, analysis of minute or poisonous samples, study of living cells, environmental monitoring, and so on.

An MRI radiomics nomogram improves the accuracy in identifying eligible candidates for fertility-preserving treatment in endometrioid adenocarcinoma.

It is difficult to identify eligible candidates for fertility-preserving treatment (FPT) among endometrioid adenocarcinoma (EAC) and atypical hyperplasia (AH) patients. Therefore, new approaches for improving the accuracy of candidate selection are warranted. From December 2014 to January 2020, 236 EAC/AH patients (age <50 and premenopausal) were retrospectively reviewed and randomly divided into the primary group (n=158) and validation group 1 (n=78). From February 2020 to December 2021, 51 EAC/AH patients were prospectively enrolled and formed the validation group 2. From the primary group, 385 features were extracted using pyradiomics from multiparameter magnetic resonance imaging (MRI) (including T2-weighted imaging, diffusion-weighted imaging, apparent diffusion coefficient, and contrast enhancement sequences) and 13 radiomics features were selected using a least absolute shrinkage and selection operator. A clinical model based on clinical information (myometrial invasion on MRI and tumor grade in curettage) and a radiomics nomogram by integrating clinical information with the radiomics features was developed to identify eligible candidates of FPT. For identifying eligible candidates of FPT, the areas under the receiver operating characteristic curve (AUCs) were 0.63 (95% confidence interval [CI]: 0.53-0.73) in the primary group, and 0.62 (95% CI: 0.45-0.78) and 0.69 (95% CI: 0.53-0.86) in validation groups 1 and 2, respectively, for the clinical model; were 0.86 (95% CI: 0.80-0.93) in the primary group, and 0.82 (95% CI: 0.71-0.93) and 0.94 (95% CI: 0.87-1.0) in validation groups 1 and 2, respectively, for the radiomics nomogram. With the help of radiomics nomogram, the treatment decision determined from the clinical model was revised in 45 EAC/AH patients. The net reclassification index (NRI) was 0.80 and integrated discrimination improvement (IDI) was 0.17, indicating that the nomogram could improve the accuracy in identifying eligible EAC/AH candidates for FPT.

MRI-Based Radiomics Nomogram for Selecting Ovarian Preservation Treatment in Patients With Early-Stage Endometrial Cancer.

BACKGROUND: Ovarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT. METHODS: From February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated. RESULTS: In the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively. CONCLUSIONS: The radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.

Prediction of Platinum-based Chemotherapy Response in Advanced High-grade Serous Ovarian Cancer: ADC Histogram Analysis of Primary Tumors.

RATIONALE AND OBJECTIVES: To investigate the feasibility of apparent diffusion coefficient (ADC) histogram analysis of primary advanced high-grade serous ovarian cancer (HGSOC) to predict patient response to platinum-based chemotherapy. MATERIALS AND METHODS: A total of 70 patients with 102 advanced stage HGSOCs (International Federation of Gynecology and Obstetrics (FIGO) stages III-IV) who received standard treatment of primary debulking surgery followed by the first line of platinum-based chemotherapy were retrospectively enrolled. Patients were grouped as platinum-resistant and platinum-sensitive according to whether relapse occurred within 6 months. Clinical characteristics, including age, pretherapy CA125 level, International Federation of Gynecology and Obstetrics stage, residual tumor, and histogram parameters derived from whole tumor and solid component such as ADCmean; 10th, 20th, 25th, 30th, 40th, 50th, 60th, 70th, 75th, 80th, 90th percentiles; skewness and kurtosis, were compared between platinum-resistant and platinum-sensitive groups. RESULTS: No significantly different clinical characteristics were observed between platinum-sensitive and platinum-resistant patients. There were no significant differences in any whole-tumor histogram-derived parameters between the two groups. Significantly higher ADCmean and percentiles and significantly lower skewness and kurtosis from the solid-component histogram parameters were observed in the platinum-sensitive group when compared with the platinum-resistant group. ADCmean, skewness and kurtosis showed moderate prediction performances, with areas under the curve of 0.667, 0.733 and 0.616, respectively. Skewness was an independent risk factor for platinum resistance. CONCLUSION: Pretreatment ADC histogram analysis of primary tumors has the potential to allow prediction of response to platinum-based chemotherapy in patients with advanced HGSOC.

[Bioavailability of Dissolved Organic Carbon in Rivers for Typical Vegetation Types in the Permafrost Regions on the Qinghai-Tibet Plateau].

Samples collected from 12 rivers with typical vegetation types in the permafrost regions on the Qinghai-Tibetan Plateau were incubated in the laboratory, and the relationships among the vegetation types, river discharges, the compositions of dissolved organic carbon (DOC), permafrost areas, riverine DOC concentration, biodegradability of dissolved organic carbon (BDOC), and the biodegradation kinetics were examined. The results showed that the DOC concentrations of typical vegetation types in the basin, such as alpine meadow (AM), alpine swamp meadow-alpine meadow (ASM-AM), alpine meadow-alpine steppe (AM-AS), and alpine meadow-alpine steppe-bare soil (AM-AS-BL), were (5.17±0.21), (5.02±0.50), (3.55±0.25), and (2.79±0.41) mg ·L-1, respectively. The values for the bioavailability of river DOC of different vegetation types were (23.54±2.62)%, (23.66±3.31)%, (18.17±5.26)%, and (11.72±15.56)%, respectively. Correspondingly, the riverine DOC aromaticity increased along with the vegetation cover, while the biodegradation and degradation rates decreased gradually. During the incubation, the reaction of BDOC was in accordance with the first-order kinetics equation. Furthermore, the BDOC in continuous permafrost regions of the rivers was greater than that in the non-continuous permafrost regions. The BDOC in higher discharges were lower than those with lower discharges. Taken together, the results suggested that the vegetation types were the main controlling factors for the BDOC, and BDOC was also related to the discharge and permafrost.

Broadband spin Hall effect of light in single nanoapertures.

With properties not previously available, optical metamaterials and metasurfaces have shown their great potential in the precise control of light waves at the nanoscale. However, the use of current metamaterials and metasurfaces is limited by the collective response of the meta-atoms/molecules, which means that a single element cannot provide the functionalities required by most applications. Here, we demonstrate for the first time that a single achiral nanoaperture can be utilized as a meta-macromolecule to achieve giant angular spin Hall effect of light. By controlling the spin-related momenta, we show that these nanoapertures can enable full control of the phase gradient at a deep-subwavelength level, thus forming unique building blocks for optical metasurfaces. As a proof-of-concept demonstration, a miniaturized Bessel-like beam generator and flat lens are designed and experimentally characterized. The results presented here may open a door for the development of meta-macromolecule-based metasurfaces for integrated optical systems and nanophotonics.

Anti-cancer activity and potential mechanism of a novel aspirin derivative.

Aspirin has been used in the treatment and chemoprevention of many malignant cancers. The mechanism of its anti-cancer activity mainly involves the inhibition of cyclooxygenase-2 (COX-2). However, the application of aspirin is limited by the serious gastric mucosal damage that accompanies its usage. We have previously reported the preparation of a novel aspirin derivative that we named Ca-Asp, and showed that it causes less damage to gastric mucosa of rat and inhibits the expression of COX-2 to higher degree than Asp. However, the anti-cancer effect and mechanism of Ca-Asp was not demonstrated. In this study, the anti-cancer effect of Ca-Asp was investigated and compared with those of Asp and Hydroxyapatite (Hap) at the cell level. The results showed that treatment of SGC-7901 cells (human gastric cancer cell line) with 200-400µg/ml Ca-Asp resulted in significant reduction in cell viability, compared to treatment with either Asp or Hap, and at a higher concentration (500µg/ml). Subsequent investigation into the possible underlying mechanism showed that Ca-Asp induced apoptosis and caused cell cycle arrest at the G1 phase. Ca-Asp also up-regulated the levels of caspase-3 and p53, but down regulated the level of cyclin D1, NF-κB, COX-2 and PGE2. Furthermore, simultaneous treatment of SGC-7901 cells with Ca-Asp and exogenous PGE2 reduced the anti-proliferative effect of Ca-Asp on the cells. Taken together, the results suggested that Ca-Asp might act as a potential anti-cancer drug, and that its suppression of PGE2 production might constitute an important part of its anti-cancer activity.