Environmentally responsive hydrogel promotes vascular normalization to enhance STING anti-tumor immunity.

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

OBJECTIVES: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. METHODS: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. RESULTS: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. CONCLUSION: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. CLINICAL RELEVANCE STATEMENT: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. KEY POINTS: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

Predicting High-risk Capsular Features in Pleomorphic Adenoma of the Parotid Gland Through a Nomogram Model Based on ADC Imaging.

RATIONALE AND OBJECTIVES: Based on Apparent Diffusion Coefficient (ADC) images, a nomogram model is established to accurately predict the high-risk capsular characteristics associated with pleomorphic adenoma of the parotid gland (PAP) recurrence. MATERIALS AND METHODS: This retrospective study analyzed 190 patients with PAPs. Significant clinical radiological factors were identified through univariate difference analysis and multivariate regression analysis. The optimal threshold was determined by analyzing the average ADC value of the entire tumor, using the best Youden index and sensitivity analysis, and tumor subregions were delineated accordingly. Three radiomic models were constructed for the whole tumor and for high/low ADC areas, with the best model determined through statistical analysis. Ultimately, a nomogram model was constructed by combining the independent predictive factor of high-risk capsular features with the optimal radiomic predictive score. Model performance was comprehensively assessed by the area under the receiver operating characteristic curve (ROC AUC), accuracy, sensitivity, and specificity. RESULTS: The best ADC division threshold as 1.25 × 10-3 mm2/s. Multivariate analysis identified High-ADC Zone Volume Percentage as an independent predictor for PAPs with high-risk capsular characteristics. The radiomic model based on the low ADC tumor subregion was optimal (AUC 0.899). The nomogram model, combining independent predictors and optimal imaging studies predictive score, demonstrated high performance (AUC 0.909). Decision curve analysis confirmed the nomogram's clinical applicability. CONCLUSION: The nomogram model constructed from ADC quantitative imaging can predict PAPs patients with high-risk capsular features. These patients require intraoperative preventive measures to avoid tumor spillage and residuals, as well as extended postoperative follow-up.

Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging.

OBJECTIVES: Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. METHODS: Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. RESULTS: On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). CONCLUSIONS: Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

Quantitative evaluation of meniscus injury using synthetic magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) can diagnose meniscal lesions anatomically, while quantitative MRI can reflect the changes of meniscal histology and biochemical structure. Our study aims to explore the association between the measurement values obtained from synthetic magnetic resonance imaging (SyMRI) and Stoller grades. Additionally, we aim to assess the diagnostic accuracy of SyMRI in determining the extent of meniscus injury. This potential accuracy could contribute to minimizing unnecessary invasive examinations and providing guidance for clinical treatment. METHODS: Total of 60 (n=60) patients requiring knee arthroscopic surgery and 20 (n=20) healthy subjects were collected from July 2022 to November 2022. All subjects underwent conventional MRI and SyMRI. Manual measurements of the T1, T2 and proton density (PD) values were conducted for both normal menisci and the most severely affected position of injured menisci. These measurements corresponded to the Stoller grade of meniscus injuries observed in the conventional MRI. All patients and healthy subjects were divided into normal group, degeneration group and torn group according to the Stoller grade on conventional MRI. One-way analysis of variance (ANOVA) was employed to compare the T1, T2 and PD values of the meniscus among 3 groups. The accuracy of SyMRI in diagnosing meniscus injury was assessed by comparing the findings with arthroscopic observations. The diagnostic efficiency of meniscus degeneration and tear between conventional MRI and SyMRI were analyzed using McNemar test. Furthermore, a receiver operating characteristic curve (ROC curve) was constructed and the area under the curve (AUC) was utilized for evaluation. RESULTS: According to the measurements of SyMRI, there was no statistical difference of T1 value or PD value measured by SyMRI among the normal group, degeneration group and torn group, while the difference of T2 value was statistically significant among 3 groups (P=0.001). The arthroscopic findings showed that 11 patients were meniscal degeneration and 49 patients were meniscal tears. The arthroscopic findings were used as the gold standard, and the difference of T1 and PD values among the 3 groups was not statistically significant, while the difference of T2 values (32.81±2.51 of normal group, 44.85±3.98 of degeneration group and 54.42±3.82 of torn group) was statistically significant (P=0.001). When the threshold of T2 value was 51.67 (ms), the maximum Yoden index was 0.787 and the AUC value was 0.934. CONCLUSIONS: The measurement values derived from SyMRI could reflect the Stoller grade, illustrating that SyMRI has good consistency with conventional MRI. Moreover, the notable consistency observed between SyMRI and arthroscopy suggests a potential role for SyMRI in guiding clinical diagnoses.

Development and validation of a nomogram to predict leptomeningeal metastases in lung adenocarcinoma: Cervical lymph node metastasis is an important association factor.

BACKGROUND: The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs. METHODS: Two hundred and seventy-three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer-Lemeshow test were used for internal validation of the nomogram. RESULTS: Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912-0.979) for the training cohort and 0.861 (95% CI 0.761-0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes. CONCLUSIONS: We created a user-friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Distinguishing EGFR mutation molecular subtypes based on MRI radiomics features of lung adenocarcinoma brain metastases.

OBJECTIVE: To explore the feasibility of identifying epidermal growth factor receptor (EGFR) mutation molecular subtypes in primary lesions based on the radiomics features of lung adenocarcinoma brain metastases using magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed clinical, imaging, and genetic testing data of patients with lung adenocarcinoma with EGFR gene mutations who had brain metastases. Three-dimensional radiomics features were extracted from contrast-enhanced T1-weighted images. The volume of interest was delineated and normalized using Z-score, dimensionality reduction was performed using principal component analysis, feature selection using Relief, and radiomics model construction using adaptive boosting as a classifier. Data were randomly divided into training and testing datasets at an 8:2 ratio. Five-fold cross-validation was conducted in the training set to select the optimal radiomics features and establish a predictive model for distinguishing between exon 19 deletion (19Del) and exon 21 L858R point mutation (21L858R), the two most common EGFR gene mutations. The testing set was used for external validation of the models. Model performance was evaluated using receiver operating characteristic curve and decision curve analyses. RESULTS: Overall, 86 patients with 228 brain metastases were included. Patient age was identified as an independent predictor for distinguishing between 19Del and 21L858R. The area under the curve (AUC) values of the radiomics model in the training and testing datasets were 0.895 (95% confidence interval [CI]: 0.850-0.939) and 0.759 (95% CI: 0.0.614-0.903), respectively. The AUC for diagnosis of all cases using a combined model of age and radiomics was 0.888 (95% CI: 0.846-0.930), slightly higher than that of the radiomics model alone (0.866, 95% CI: 0.820-0.913), but without statistical significance (p=0.1626). In the decision curve analysis, both models demonstrated clinical net benefits. CONCLUSIONS: The radiomics model based on MRI of lung adenocarcinoma brain metastases could distinguish between EGFR 19Del and 21L858R mutations in the primary lesion.

Drug-loaded lipid nanoparticles improve the removal rates of the Staphylococcus aureus biofilm.

Biofilms of the foodborne pathogen Staphylococcus aureus show improved resistance to antibiotics and are difficult to eliminate. To enhance antibacteria and biofilm dispersion via extracellular matrix diffusion, a new lipid nanoparticle was prepared, which employed a mixture of phospholipids and a 0.8% surfactin shell. In the lipid nanoparticle, 31.56 µg mL-1 of erythromycin was encapsulated. The lipid nanoparticle size was approximately 52 nm and the zeta-potential was -67 mV, which was measured using a Marvin laser particle size analyzer. In addition, lipid nanoparticles significantly dispersed the biofilms of S. aureus W1, CICC22942, and CICC 10788 on the surface of stainless steel, reducing the total viable count of bacteria in the biofilms by 103 CFU mL-1 . In addition, the lipid nanoparticle can remove polysaccharides and protein components from the biofilm matrix. The results of laser confocal microscopy showed that the lipid nanoparticles effectively killed residual bacteria in the biofilms. Thus, to thoroughly eliminate biofilms on material surfaces in food factories to avoid repeated contamination, drug-lipid nanoparticles present a suitable method to achieve this.

Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Clinical and imaging predictors for hemorrhagic transformation of acute ischemic stroke after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a common complication of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS). Our study aims to investigate the clinical and imaging predictors of HT and symptomatic intracranial hemorrhage (sICH) in patients who underwent EVT. METHODS: A retrospective analysis of 118 patients undergoing EVT for acute anterior circulation stroke was performed. Potential clinical and imaging predictors of all patients were collected and multivariate logistic regression was performed. The risk prediction system was constructed according to the multivariate logistic regression results. RESULTS: The incidence of HT and sICH after EVT were 46.6% and 15.3%, respectively. The multivariate logistic regression results showed that Alberta Stroke Program Early CT Score (ASPECTS) (p = .001, odds ratio [OR] = 0.367, 95% [confidence interval] CI, 0.201-0.670), collateral status (p<.001, OR = 0.117, 95% CI, 0.042-0.325), relative cerebral blood flow (CBF) ratio (p = .025, OR = 0.943, 95% CI, 0.895-0.993), and blood glucose on admission (p = .012, OR = 1.258, 95% CI, 1.053-1.504) were associated with HT. While for sICH, collateral circulation (p = .007, OR = 0.148, 95% CI, 0.037-0.589), ASPECTS (p = .033, OR = 0.510, 95% CI, 0.274-0.946), and blood glucose (p = .005, OR = 1.304, 95% CI, 1.082-1.573) were independent factors. The predictive model for HT after EVT was established, and the sensitivity and specificity of it were 90.9% and 79.4%, respectively, with the area under the curve of 90.0% (84.5%-95.4%). CONCLUSION: Collateral status, ASPECTS, relative CBF ratio, and blood glucose on admission were predictors for HT in AIS patients, while collateral status, ASPECTS, and blood glucose on admission were also predictors for sICH. In addition, the established predictive model showed good diagnostic value for prediction of HT after EVT.

A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.

Background: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations' antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib. Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds. Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI). Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.

Case report: Intensive statin and PCSK-9 inhibitor combo reduces plaque volume and stenosis in ischemic stroke patient.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

Assessment of left ventricular structure and function in preeclampsia subtypes by multimodal echocardiography.

AIM: To explore left ventricular structural/functional abnormalities in preeclampsia patients by using multimodal echocardiography and to analyze the cardiac impact in preeclampsia subtypes. METHODS: A total of 103 individuals, including 64 preeclampsia patients and 39 healthy pregnant women were recruited for this study from 2019 to 2021. There were 34 patients with preeclampsia with severe features (SPE) patients and 30 with preeclampsia with nonsevere features (NSPE), including 9 with early-onset NSPE (EO-NSPE) patients, 27 early-onset SPE (EO-SPE) patients, 21 later-onset NSPE (LO-NSPE), and 7 with later-onset SPE (LO-SPE). All patients underwent multimodal echocardiography before treatment, including two-dimensional, Doppler, and speckle-tracking echocardiography, to evaluate left ventricular structure/function. Analysis of variance was used to determine statistical significance across groups. RESULTS: EO-SPE patients showed decreased left ventricular ejection fractions, peak longitudinal systolic strain at apical four-chambers, peak circumferential, and radial systolic strain at the apical and mitral annular plane systolic excursion (MAPSE), and increased mitral regurgitation compared to other preeclampsia patients. Compared to LO-NSPE and EO-SPE patients, LO-SPE patients showed increased left ventricular mass indexed to height2.7 and early diastolic left ventricular diastolic filling/mitral annular velocity, and decreased MAPSE and early/late diastolic mitral annular velocity. CONCLUSION: EO-SPE patients were characterized by left ventricular injury and systolic function reduced. LO-SPE patients were characterized by left ventricular hypertrophy and reduced diastolic function. Multimodal echocardiography can detect myocardial injury in PE patients at an early stage.

Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.

Atypical primary central nervous system lymphoma and glioblastoma: multiparametric differentiation based on non-enhancing volume, apparent diffusion coefficient, and arterial spin labeling.

OBJECTIVES: To evaluate the multiparametric diagnostic performance with non-enhancing tumor volume, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) to differentiate between atypical primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). METHODS: One hundred and fifty-eight patients with pathologically confirmed typical PCNSL (n = 59), atypical PCNSL (hemorrhage, necrosis, or heterogeneous contrast enhancement, n = 29), and GBM (n = 70) were selected. Relative minimum ADC (rADCmin), mean (rADCmean), maximum (rADCmax), and rADCmax-min (rADCdif) were obtained by standardization of the contralateral white matter. Maximum cerebral blood flow (CBFmax) was obtained according to the ASL-CBF map. The regions of interests (ROIs) were manually delineated on the inner side of the tumor to further generate a 3D-ROI and obtain the non-enhancing tumor (nET) volume. The area under the curve (AUC) was used to evaluate the diagnostic performance. RESULTS: Atypical PCNSLs showed significantly lower rADCmax, rADCmean, and rADCdif than that of GBMs. GBMs showed significantly higher CBFmax and nET volume ratios than that of atypical PCNSLs. Combined three-variable models with rADCmean, CBFmax, and nET volume ratio were superior to one- and two-variable models. The AUC of the three-variable model was 0.96, and the sensitivity and specificity were 90% and 96.55%, respectively. CONCLUSION: The combined evaluation of rADCmean, CBFmax, and nET volume allowed for reliable differentiation between atypical PCNSL and GBM. KEY POINTS: • Atypical PCNSL is easily misdiagnosed as glioblastoma, which leads to unnecessary surgical resection. • The nET volume, ADC, and ASL-derived parameter (CBF) were lower for atypical PCNSL than that for glioblastoma. • The combination of multiple parameters performed well (AUC = 0.96) in the discrimination between atypical PCNSL and glioblastoma.

The global regulator SpoVG regulates Listeria monocytogenes biofilm formation.

Biofilms provide a suitable environment for L. monocytogenes and are the cause of enormous risks in the food industry. SpoVG is a global regulatory factor that plays a vital role in physiological activity of L. monocytogenes. We constructed spoVG mutant strains to investigate the effects of these mutants on L. monocytogenes biofilms. The results show that L. monocytogenes biofilm formation was decreased by 40%. Furthermore, we measured biofilm related phenotypes to study the regulation of SpoVG. The motility capacity of L. monocytogenes was found to decrease after the deletion of spoVG. The cell surface properties changed in the spoVG mutant strains, with an increase in both the cell surface hydrophobicity and the auto-aggregation capacity after spoVG deletion. SpoVG mutant strains were found to be more sensitive to antibiotics, and had a reduced tolerance to inappropriate pH, salt stress and low temperature. The RT-qPCR results showed that SpoVG effectively regulated the expression of genes related to quorum sensing, flagella, virulence and stress factors. These findings suggest that spoVG has potential as a target to decrease biofilm formation and control L. monocytogenes contamination in the food industry.

Noninvasive Prediction of Histological Grading in Pediatric Low-Grade Gliomas Using Preoperative T2-FLAIR Radiomics Features.

OBJECTIVE: To investigate the clinical application value of radiomics based on magnetic resonance T2-fluid attenuated inversion recovery (FLAIR) sequence images to distinguish pediatric low-grade gliomas of histological grades 1 and 2. METHODS: A retrospective study of pediatric low-grade gliomas treated in our institution from April 2017 to July 2021. The histological grading follows the 2021 WHO (World Health Organization) classification of tumors of the central nervous system and contains the necessary molecular phenotype information. The 3D slicer (https://slicer.org/) is used to outline volume of interest based on T2-FLAIR sequence and extract three-dimensional imaging features. All enrolled cases are randomly assigned to training set and test set according to 7:3; SMOTE (Synthetic Minority Oversampling Technique) method was used to balance the data of the training set, and then min-max normalization was used to normalize the data of the radiomics features. Dimension reduction and screening were carried out through Pearson correlation coefficients, analysis of variance (ANOVA), and least absolute shrinkage and selection operator (LASSO) algorithms for the radiomics features. The best binary logistic regression model is established by using the best subset regression, and the receiver operating characteristic curve, calibration curve and decision curve are used to analyze and evaluate the model. RESULTS: A total of 113 patients were enrolled, 79 in the training set and 34 in the test set. There was no significant difference in sex and age between WHO grade 1 and 2 pediatric low-grade gliomas. A total of 1643 radiomics features were extracted from T2-FLAIR images, and finally 9 features were selected to construct a binary logistic regression model. The areas under the curve were 0.902 (95% confidence interval, 0.814-0.967) and 0.831 (95% confidence interval, 0.613-0.975) for the training and test sets, with sensitivities of 86.70% and 85.7% and specificities of 81.3% and 59.3%, respectively. For model calibration, the mean absolute errors were 0.054 and 0.058 for the training and test sets, respectively. The decision curve analysis showed clinical gains for using the model in both the training and testing sets. CONCLUSIONS: The T2-FLAIR radiomics model can be used for preoperative identification of grade 1 and grade 2 pediatric low-grade gliomas.