Fully automated hybrid approach on conventional MRI for triaging clinically significant liver fibrosis: A multi-center cohort study.

Establishing reliable noninvasive tools to precisely diagnose clinically significant liver fibrosis (SF, ≥F2) remains an unmet need. We aimed to build a combined radiomics-clinic (CoRC) model for triaging SF and explore the additive value of the CoRC model to transient elastography-based liver stiffness measurement (FibroScan, TE-LSM). This retrospective study recruited 595 patients with biopsy-proven liver fibrosis at two centers between January 2015 and December 2021. At Center 1, the patients before December 2018 were randomly split into training (276) and internal test (118) sets, the remaining were time-independent as a temporal test set (96). Another data set (105) from Center 2 was collected for external testing. Radiomics scores were built with selected features from Deep learning-based (ResUNet) automated whole liver segmentations on MRI (T2FS and delayed enhanced-T1WI). The CoRC model incorporated radiomics scores and relevant clinical variables with logistic regression, comparing routine approaches. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC). The additive value of the CoRC model to TE-LSM was investigated, considering necroinflammation. The CoRC model achieved AUCs of 0.79 (0.70, 0.86), 0.82 (0.73, 0.89), and 0.81 (0.72-0.91), outperformed FIB-4, APRI (all p < 0.05) in the internal, temporal, and external test sets and maintained the discriminatory power in G0-1 subgroups (AUCs range, 0.85-0.86; all p < 0.05). The AUCs of joint CoRC-LSM model were 0.86 (0.79-0.94), and 0.81 (0.72-0.90) in the internal and temporal sets (p = 0.01). The CoRC model was useful for triaging SF, and may add value to TE-LSM.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI.

OBJECTIVES: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). METHODS: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. CONCLUSIONS: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. CLINICAL RELEVANCE STATEMENT: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. KEY POINTS: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.

Myocardial tissue remodeling in early adult obesity and its association with regional adipose tissue distribution and ectopic fat deposits: a prospective study.

OBJECTIVES: To evaluate the left ventricular (LV) myocardial tissue characteristics in early adult obesity and its association with regional adipose tissue and ectopic fat deposition. METHODS: Forty-nine obese adults (mean body mass index: 29.9 ± 2.0 kg/m2) and 44 healthy controls were prospectively studied. LV native and post-contrast T1 values, extracellular volume fraction (ECV), regional adipose tissue (epicardial, visceral, and subcutaneous adipose tissue (EAT, VAT, and SAT)), and ectopic fat deposition (hepatic and pancreatic proton density fat fractions (H-PDFF and P-PDFF)) based on magnetic resonance imaging were compared. The association was assessed by multivariable linear regression. RESULTS: The obese participants showed reduced global ECV compared to the healthy controls (p < 0.05), but there was no significant difference in global native or post-contrast T1 values between the two groups. Additionally, the obese individuals exhibited higher EAT, VAT, SAT, H-PDFF, and P-PDFF than the controls (p < 0.05). ECV was associated with insulin resistance, dyslipidemia, and systolic blood pressure (SBP) (p < 0.05). Multiple linear regression demonstrated that H-PDFF and SAT were independently associated with ECV in entire population (ß = - 0.123 and - 0.012; p < 0.05). CONCLUSIONS: Reduced myocardial ECV in patients with mild-to-moderate obesity and its relationship to SBP may indicate that cardiomyocyte hypertrophy, rather than extracellular matrix expansion, is primarily responsible for myocardial tissue remodeling in early adult obesity. Our findings further imply that H-PDFF and SAT are linked with LV myocardial tissue remodeling in this cohort beyond the growth difference and cardiovascular risk factors. CLINICAL TRIALS REGISTRATION: Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476). CLINICAL RELEVANCE STATEMENT: Myocardial fibrosis in severe obesity predicts poor prognosis. We showed that cardiomyocyte hypertrophy, not myocardial fibrosis, is the main myocardial tissue characteristic of early obesity. This finding raises the possibility that medical interventions, like weight loss, may prevent cardiac fibrosis. KEY POINTS: • Myocardial tissue characteristics in early adult obesity are unclear. • Myocardial extracellular volume fraction (ECV) can be quantitatively evaluated using T1 mapping based on cardiac magnetic resonance imaging (MRI). • Cardiac MRI-derived ECV may noninvasively evaluate myocardial tissue remodeling in early adult obesity.

Deep learning-based 3D quantitative total tumor burden predicts early recurrence of BCLC A and B HCC after resection.

OBJECTIVES: This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm3) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses. RESULTS: A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC An stage; whilst the BCLC B high-TTB patients remained in a BCLC Bn stage. The 2-year ER rate was 30.5% for BCLC An patients vs. 58.1% for BCLC Bn patients (HR = 2.8; p < 0.001). CONCLUSIONS: TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B. CLINICAL RELEVANCE STATEMENT: Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy. KEY POINTS: Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients.

MRI-based prediction of the need for wide resection margins in patients with single hepatocellular carcinoma.

OBJECTIVES: To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins. MATERIALS AND METHODS: This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN"). Survival outcomes were compared between wide and narrow resection margins in a propensity-score matched cohort for the score-stratified low- and high-risk groups, respectively. RESULTS: Four hundred nineteen patients (median age, 54 years; 361 men) were included, 282 (67.3%) undergoing narrow resection margins. In patients with narrow resection margins, age, alpha-fetoprotein (AFP) > 400 ng/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) > 200 mAU/mL, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS (p values, 0.002-0.04) and formed the MARGIN score with a testing dataset C-index of 0.75 (95% CI: 0.65-0.84). In the matched cohort, wide resection margin was associated with improved early RFS rate for the high-risk group (MARGIN score ≥ - 1.3; 71.1% vs 41.0%; p = 0.02), but not for the low-risk group (MARGIN score < - 1.3; 79.7% vs 76.1%; p = 0.36). CONCLUSION: In patients with single BCLC 0/A HCC, the MARGIN score may serve as promising decision-making to indicate the need for wide resection margins. CLINICAL RELEVANCE STATEMENT: The MARGIN score has the potential to identify patients who would benefit more from wide resection margins than narrow resection margins, improving the postoperative survival of patients with single BCLC 0/A hepatocellular carcinoma (HCC). KEY POINTS: Age, AFP, PIVKA-II, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS and formed the MARGIN score. The MARGIN score achieved a testing dataset C-index of 0.75. Wide resection margins were associated with improved early RFS for the high-risk group, but not for the low-risk group.

Ferric Oxide Nanomaterials and Plant-Rhizobacteria Symbionts Cogenerate Iron Plaque for Removing Highly Chlorinated Contaminants in Dryland Soils.

Rhizosphere iron plaques derived from Fe-based nanomaterials (NMs) are a promising tool for sustainable agriculture. However, the requirement for flooded conditions to generate iron plaque limits the scope of the NM application. In this study, we achieved in situ Fenton oxidation of a highly chlorinated persistent organic pollutant (2,2',4,5,5'-pentachlorobiphenyl, PCB101) through iron plaque mediated by the interaction between α-Fe2O3 NMs and plant-rhizobacteria symbionts under dryland conditions. Mechanistically, the coexistence of α-Fe2O3 NMs and Pseudomonas chlororaphis JD37 stimulated alfalfa roots to secrete acidic and reductive agents as well as H2O2, which together mediated the rhizosphere Fenton reaction and converted α-Fe2O3 NMs into iron plaque rich in Fe(II)-silicate. Further verifications reproduced the Fenton reaction in vitro using α-Fe2O3 NMs and rhizosphere compounds, confirming the critical role of •OH in the oxidative degradation of PCB101. Significant reductions in PCB101 content by 18.6%, 42.9%, and 23.2% were respectively found in stem, leaf, and soil after a 120-d treatment, proving the effectiveness of this NMs-plant-rhizobacteria technique for simultaneously safe crop production and soil remediation. These findings can help expand the potential applications of nanobio interaction and its mediated iron plaque generation for both agricultural practice and soil remediation.

Association of abdominal adiposity, hepatic shear stiffness with subclinical left-ventricular remodeling evaluated by magnetic resonance in adults free of overt cardiovascular diseases: a prospective study.

BACKGROUND: Abdominal ectopic fat deposition and excess visceral fat depots in obesity may be related to cardiovascular disease (CVD) as both are involved in the metabolic syndrome (MetS). The awareness of the link between abdominal adiposity and subclinical cardiac remodeling would help improve treatment and outcome. Besides, liver fibrosis has also shown a potential relationship with cardiac dysfunction. Thus, we aimed to investigate the associations of magnetic resonance (MR)-based abdominal adiposity and hepatic shear stiffness with subclinical left ventricular (LV) remodeling while taking account of MetS-related confounders in adults free of overt CVD. METHODS: This was an exploratory, prospective study of 88 adults (46 subjects with obesity, 42 healthy controls) who underwent 3 T cardiac and body MR exams. Measures of abdominal MR included hepatic and pancreatic proton density fat fraction (H-PDFF and P-PDFF), hepatic shear stiffness by MR elastography, and subcutaneous and visceral adipose tissue (SAT and VAT). Cardiac measures included epicardial adipose tissue (EAT) and parameters of LV geometry and function. Associations were assessed using Pearson correlation and multivariable linear regression analyses, in which age, sex, and MetS-related confounders were adjusted for. RESULTS: The LV ejection fractions of all participants were within the normal range. Higher H-PDFF, P-PDFF, SAT and VAT were independently associated with lower LV global myocardial strain parameters (radial, circumferential and longitudinal peak strain [PS], longitudinal peak systolic strain rate and diastolic strain rate) (ß = - 0.001 to - 0.41, p < 0.05), and P-PDFF, SAT and VAT were independently and positively associated with LV end-diastolic volume and stroke volume (ß = 0.09 to 3.08, p ≤ 0.02) in the over-all cohort. In the obesity subgroup, higher P-PDFF and VAT were independently associated with lower circumferential and longitudinal PS, respectively (ß = - 0.29 to - 0.05, p ≤ 0.01). No independent correlation between hepatic shear stiffness and EAT or LV remodeling was found (all p ≥ 0.05). CONCLUSIONS: Ectopic fat depositions in the liver and pancreas, and excess abdominal adipose tissue pose a risk of subclinical LV remodeling beyond MetS-related CVD risk factors in adults without overt CVD. VAT may play a more considerable role as a risk factor for subclinical LV dysfunction than does SAT in individuals with obesity. The underlying mechanisms of these associations and their longitudinal clinical implications need further investigation.

Prognostic MRI features to predict postresection survivals for very early to intermediate stage hepatocellular carcinoma.

OBJECTIVES: Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS). MATERIALS AND METHODS: Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS. RESULTS: This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS. CONCLUSION: Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs. CLINICAL RELEVANCE STATEMENT: The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models. KEY POINTS: • Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival. • Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival. • Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years.

Fe-Based Nanomaterials and Plant Growth Promoting Rhizobacteria Synergistically Degrade Polychlorinated Biphenyls by Producing Extracellular Reactive Oxygen Species.

Plant growth promoting rhizobacteria (PGPR) produce extracellular reactive oxygen species (ROS) to protect plants from external stresses. Fe-based nanomaterials can potentially interact with PGPR and synergistically degrade organic pollutants, yet they have received no study. Here, we studied how the interaction between a typical PGPR (Pseudomonas chlororaphis, JD37) and Fe-based nanomaterials facilitated the degradation of 2,4,4'-trichlorobiphenyl (PCB28), by comparing the zerovalent iron of 20 nm (nZVI20), 100 nm (nZVI100), and 5 µm; iron oxide nanomaterials (α-Fe2O3, γ-Fe2O3, and Fe3O4) of ca. 20 nm; and ferrous and ferric salts. Although all Fe materials (0.1 g L-1) alone could not degrade aqueous PCB28 (0.1 mg L-1) under dark or aerobic conditions, nZVI20, nZVI100, α-Fe2O3, and Fe2+ promoted PCB28 degradation by JD37, with the half-life of PCB28 shortened from 16.5 h by JD37 alone to 8.1 h with nZVI100 cotreatment. Mechanistically, the nanomaterials stimulated JD37 to secrete phenazine-1-carboxylic acid and accelerated the NADH/NAD+ conversion, promoting O2*- generation; JD37 increased Fe(II) dissolution from the nanomaterials, facilitating *OH generation; and the ROS gradually degraded PCB28 into benzoic acid through dihydroxy substitution, oxidation to quinone, and Michael addition. These findings provide a new strategy of nanoenabled biodegradation of organic pollutants by applying Fe-based nanomaterials and PGPR.

Comparison of a preoperative MR-based recurrence risk score versus the postoperative score and four clinical staging systems in hepatocellular carcinoma: a retrospective cohort study.

OBJECTIVES: To establish a risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical parameters to predict recurrence after hepatectomy for patients with hepatocellular carcinoma (HCC) and to compare its performance with that of a postoperative score and four clinical staging systems. METHODS: Consecutive patients with surgically confirmed HCC who underwent preoperative EOB-MRI between July 2015 and November 2020 were retrospectively included. Two recurrence risk scores, one incorporating only preoperative variables and the other incorporating all preoperative and postoperative variables, were constructed via Cox regression models. RESULTS: A total of 214 patients (derivation set, n = 150; test set, n = 64) were included. Six preoperative variables, namely tumor number, infiltrative appearance, corona enhancement, alpha-fetoprotein (AFP) level, aspartate aminotransferase (AST) level, and sex, were independently associated with recurrence. After adding postoperative features, microvascular invasion and tumor differentiation were additional significant variables in lieu of corona enhancement and AFP level. Using the above variables, the preoperative score achieved a C-index of 0.741 on the test set, which was comparable with that of the postoperative score (0.729; p = 0.235). The preoperative score yielded a larger time-dependent area under the receiver operating characteristic curve at 1 year (0.844) than three existing systems (0.734-0.742; p < 0.05 for all). Furthermore, the preoperative score stratified patients into two prognostically distinct risk strata with low and high risks of recurrence (p < 0.001). CONCLUSION: The preoperative score integrating EOB-MRI features, AFP and AST levels, and sex improves recurrence risk estimation in HCC. KEY POINTS: • The preoperative risk score incorporating three EOB-MRI findings, AFP and AST levels, and sex achieved comparable performance with that of the postoperative score for predicting recurrence after hepatectomy in patients with HCC. • Two risk strata with low and high risks of recurrence were obtained based on the preoperative score. • The preoperative score may help tailor pretreatment decision-making and facilitate candidate selection for adjuvant clinical trials.

LI-RADS category 5 hepatocellular carcinoma: preoperative gadoxetic acid-enhanced MRI for early recurrence risk stratification after curative resection.

OBJECTIVES: To explore the role of preoperative gadoxetic acid-enhanced MRI in stratifying the risk of early recurrence in patients with LR-5 hepatocellular carcinoma (HCC) by LI-RADS v2018 after curative resection. METHODS: Between July 2015 and August 2018, this study evaluated consecutive treatment-naïve at-risk LR-5 HCC patients who underwent gadoxetic acid-enhanced MRI examination within 2 weeks before curative resection. The Cox regression analysis was performed to identify potential predictors of early recurrence. Disease-free survival (DFS) rates were analyzed and compared by using the Kaplan-Meier method and log-rank tests. RESULTS: Fifty-three of 103 (51.5%) patients experienced early recurrence. Three MRI findings were significantly associated with early recurrence: corona enhancement (hazard ratio [HR]: 2.116; p = 0.013), peritumoral hypointensity on hepatobiliary phase (HBP) (HR: 2.262; p = 0.007), and satellite nodule (HR: 2.777; p = 0.005). An additional risk factor was AFP level > 400 ng/mL (HR: 1.975; p = 0.016). Based on the number of MRI predictors, LR-5 HCC patients were stratified into three subgroups: LR-5a (60/103; no predictor), LR-5b (26/103; one predictor), and LR-5c (17/103; two or three predictors), with low, medium, and high risk of early recurrence, respectively. The 2-year DFS rate of LR-5a, LR-5b, and LR-5c patients was 65.0%, 38.5%, and 5.9%, respectively, while the corresponding median DFS was undefined, 17.1 months, and 5.1 months, respectively (p < 0.001). CONCLUSIONS: In at-risk LR-5 HCC patients, corona enhancement, peritumoral hypointensity on HBP, and satellite nodule could be used to preoperatively stratify the risk of early recurrence after hepatectomy. KEY POINTS: • Corona enhancement, peritumoral hypointensity on HBP, satellite nodule, and serum AFP level > 400 ng/mL were significant predictors of early recurrence in patients with LR-5 HCC after hepatectomy. • Based on the number of predictive MRI findings, LR-5 HCC patients could be preoperatively stratified into three subgroups: LR-5a, LR-5b, and LR-5c, with significantly different risk of early recurrence and disease-free survival. • Preoperative risk stratification is essential for the identification of patients at increased risk of postoperative early recurrence, which may contribute to risk-based personalized management for LR-5 HCC patients.

Application of a Multi-Metal Stable-Isotope-Enriched Bioassay to Assess Changes to Metal Bioavailability in Suspended Sediments.

The direct measurement of particulate contaminant bioavailability is a challenging aspect for the environmental risk assessment of contaminated sites. Here, we demonstrated a multi-metal stable-isotope-enriched bioassay to simultaneously measure the bioavailability of Cd, Cu, and Zn in naturally contaminated sediments following differing periods of resuspension treatment. Freshwater filter-feeding clams were pre-labeled with the isotopes 114Cd, 65Cu, and 68Zn to elevate isotope abundances in their tissues and then exposed to metal-contaminated suspended sediments. The assimilation of sediment-associated metals by clams would decrease the isotope ratios (Cd114/111, Cu65/63, and Zn68/64) in tissues, providing a direct measurement of metal bioavailability. For the sediments tested here, the method revealed bioavailable cadmium and non-bioavailable copper in sediments but was inconclusive for zinc. With a longer resuspension time, the bioavailability of particulate cadmium increased, but that of copper was unaffected. Metal bioavailability predicted using traditional wet-chemical extraction methods was inconsistent with these findings. The study indicated that multi-metal stable-isotope-enriched bioassay provides a new tool for directly assessing metal bioavailability in sediments, and this method is amenable for use in in situ assessments.

Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis.

BACKGROUND: N-cadherin is an important molecular in epithelial-mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N-cadherin in solid malignancies remains controversially. MATERIALS AND METHODS: The Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role. RESULTS: Involving 36 studies with 5705 patients were performed to investigate relationships between N-cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N-cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N-cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N-cadherin was correlated with poor prognosis of 3-year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5-year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test). CONCLUSIONS: Taken together, upregulation of N-cadherin is associated with more aggressive behaviours of epithelial-derived solid malignancies and can be regarded as a predictor of poor survival.

Imaging evaluation of sorafenib for treatment of advanced hepatocellular carcinoma.

Sorafenib, which is a novel targeted agent, plays an important role in treating advanced hepatocellular carcinoma (HCC) through its antiangiogenic and antiproliferative effects. However, conventional morphology-based radiographic evaluation systems may underestimate the efficacy of sorafenib in HCC due to a lack of apparent tumor shrinkage or altered tumor morphology in many cases. This calls for the development of more accurate imaging methods for evaluating sorafenib. The introduction of tumor burden measurements based on viability and other evolving imaging approaches for assessing therapeutic effects are promising for overcoming some of the limitations of the morphology-based criteria. In this review, we summarize various imaging methods that are used to assess treatment responses of advanced HCC to sorafenib. Imaging markers predictive of prognosis in advanced HCC after treatment with sorafenib are also included and discussed.

Nanoplastics increase algal absorption and toxicity of Cd through alterations in cell wall structure and composition.

Nanoplastics (NPs) may act as carriers of heavy metals and cause complex toxicity to aquatic organisms, while the exact role of NPs in the joint toxicity remains unclear. Here, we investigated the joint toxicity of polystyrene NPs (PS-NPs) and Cd to freshwater algae (Chlorella vulgaris). It was found that PS-NPs (1 mg L-1) could hardly enter algal cells and slightly inhibit algal growth (p < 0.01). The effect of PS-NPs as carriers on the joint toxicity of PS-NPs and heavy metals could be neglected because of the limited adsorption of Cd by PS-NPs, while the PS-NPs altered the cell wall structure and composition, which resulted in the increased algal absorption and toxicity of Cd. Compared to the low dose Cd (0.4 mg L-1) treatment alone, the extracellular and intracellular Cd contents in the cotreatment were significantly increased by 27.3 % and 18.0 %, respectively, due to the increased contents of cell wall polysaccharides (pectin and hemicellulose in particular) by the PS-NPs. Furthermore, after the high dose Cd (2 mg L-1) exposure, the inhibited polysaccharide biosynthesis and the loosen cell wall structure weakened the tolerance of cell wall to abiotic stress, facilitating the entry of PS-NPs into the algal cells and inducing the higher toxicity. These results elucidate the mechanism by which NPs enhance heavy metal toxicity to algae, providing a novel insight into environmental risks of NPs.

Nanoplastics inhibit carbon fixation in algae: The effect of aging.

Despite the considerable efforts devoted to the toxicological assessment of nanoplastics, the effect of UV-irradiation induced aging, a realistic environmental process, on the toxicity of nanoplastics toward microalgae and its underlying mechanisms remain largely unknown. Herein, this study comparatively investigated the toxicities of polystyrene nanoplastics (nano-PS) and the UV-aged nano-PS on the eukaryotic alga Chlorella vulgaris, focusing on evaluating their inhibitory effects on carbon fixation. Exposure to environmentally relevant concentrations (0.1-10 mg/L) of nano-PS caused severe damage to chloroplast, inhibited the photosynthetic efficiency and electron transport, and suppressed the activities of carbon fixation related enzymes. Multi-omics results revealed that nano-PS interfered with energy supply by disrupting light reactions and TCA cycle and hindered the Calvin cycle, thereby inhibiting the photosynthetic carbon fixation of algae. The above alterations partially recovered after a recovery period. The aged nano-PS were less toxic than the pristine ones as evidenced by the mitigated inhibitory effect on algal growth and carbon fixation. The aging process introduced oxygen-containing functional groups on the surface of nano-PS, increased the hydrophilicity of nano-PS, limited their attachment on algal cells, and thus reduced the toxicity. The findings of this work highlight the potential threat of nanoplastics to the global carbon cycle.

Noninvasive diagnosis of liver cirrhosis: qualitative and quantitative imaging biomarkers.

A diagnosis of cirrhosis initiates a shift in the management of chronic liver disease and affects the diagnostic workflow and treatment decision of primary liver cancer. Liver biopsy remains the gold standard for cirrhosis diagnosis, but it is invasive and susceptible to sampling bias and observer variability. Various qualitative and quantitative imaging biomarkers based on ultrasound, CT and MRI have been proposed for noninvasive diagnosis of cirrhosis. Qualitative imaging features are easy to apply but have moderate diagnostic sensitivity. Elastography techniques allow quantitative assessment of liver stiffness and are highly accurate for cirrhosis diagnosis. Ultrasound elastography are widely used in clinical practice, while MR elastography has narrower availability. Although not applicable in clinical practice yet, other quantitative imaging features, including liver surface nodularity, linear and volumetric measurement, extracellular volume fraction, liver enhancement on hepatobiliary phase, and parameters derived from diffusion-weighted imaging, can provide additional information of liver morphology, perfusion, and function, thus may increase diagnosis performance. The introduction of radiomics and deep learning has further improved diagnostic accuracy while reducing subjectivity. Several imaging features may also help to assess liver function and outcomes in patients with cirrhosis. In this review, we summarize the qualitative and quantitative imaging biomarkers for noninvasive cirrhosis diagnosis, and the assessment of liver function and outcomes, and discuss the challenges and future directions in this field.

MRI radiomics based on deep learning automated segmentation to predict early recurrence of hepatocellular carcinoma.

OBJECTIVES: To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). METHODS: This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. RESULTS: Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with 5 mm tumor border extension and liver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor "capsule," a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). CONCLUSION: A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor "capsule" accurately predicted early postsurgical recurrence of a single HCC. CRITICAL RELEVANCE STATEMENT: The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor "capsule" hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. KEY POINTS: A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS.

CT and MR imaging of primary biliary cholangitis: a pictorial review.

Primary biliary cholangitis (PBC) is a rare chronic autoimmune-mediated cholestatic liver disease involving medium and small bile ducts that can lead to liver fibrosis and cirrhosis. To date, the pathogenesis of PBC remains elusive, and there is currently no curative medical treatment. Computed tomography (CT) and magnetic resonance (MR) imaging, as common technical tools that allow non-invasive monitoring of liver tissue in vivo, play crucial roles in the diagnosis, staging, and prognosis prediction in PBC by enabling assessment of abnormalities in liver morphology and parenchyma, irregular configuration of bile ducts, lymphadenopathy, portal hypertension, and complications of cirrhosis. Moreover, CT and MRI can be used to monitor the disease progression after treatment of PBC (e.g. the onset of cirrhotic decompensation or HCC) to guide the clinical decisions for liver transplantation. With the optimization of imaging technology, magnetic resonance elastography (MRE) offers additional information on liver stiffness, allows for the identification of early cirrhosis in PBC and provides a basis for predicting prognosis. Gadoxetic acid-enhanced MRI enables the assessment of liver function in patients with PBC. The purpose of this review is to detail and illustrate the definition, pathological basis, and clinical importance of CT and MRI features of PBC to help radiologists and clinicians enhance their understanding of PBC.Critical Relevance StatementCharacteristic CT and MR imaging manifestations of primary biliary cholangitis may reflect the course of the disease and provide information associated with histological grading and altered cellular function.Key points• Imaging has become highly useful for differentiating PBC from other diseases.• Key pathological alterations of PBC can be captured by CT and MRI.• Characteristic manifestations provide information associated with histological grade and cellular function.• Despite this, the CT or MRI features of PBC are not specific.