Hybrid and enhanced electrokinetic system for soil remediation from heavy metals and organic matter.

The electrokinetic (EK) process has been proposed for soil decontamination from heavy metals and organic matter. The advantages of the EK process include the low operating energy, suitability for fine-grained soil decontamination, and no need for excavation. During the last three decades, enhanced and hybrid EK systems were developed and tested for improving the efficiency of contaminants removal from soils. Chemically enhanced-EK processes exhibited excellent efficiency in removing contaminants by controlling the soil pH or the chemical reaction of contaminants. EK hybrid systems were tested to overcome environmental hurdles or technical drawbacks of decontamination technologies. Hybridization of the EK process with phytoremediation, bioremediation, or reactive filter media (RFM) improved the remediation process performance by capturing contaminants or facilitating biological agents' movement in the soil. Also, EK process coupling with solar energy was proposed to treat off-grid contaminated soils or reduce the EK energy requirements. This study reviews recent advancements in the enhancement and hybrid EK systems for soil remediation and the type of contaminants targeted by the process. The study also covered the impact of operating parameters, imperfect pollution separation, and differences in the physicochemical characteristics and microstructure of soil/sediment on the EK performance. Finally, a comparison between various remediation processes was presented to highlight the pros and cons of these technologies.

Current status of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms.

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

Endoscopic detection and diagnosis of gastric cancer using image-enhanced endoscopy: A systematic review and meta-analysis.

Objectives: We aimed to conduct a systematic review and meta-analysis to assess the value of image-enhanced endoscopy including blue laser imaging (BLI), linked color imaging, narrow-band imaging (NBI), and texture and color enhancement imaging to detect and diagnose gastric cancer (GC) compared to that of white-light imaging (WLI). Methods: Studies meeting the inclusion criteria were identified through PubMed, Cochrane Library, and Japan Medical Abstracts Society databases searches. The pooled risk ratio for dichotomous variables was calculated using the random-effects model to assess the GC detection between WLI and image-enhanced endoscopy. A random-effects model was used to calculate the overall diagnostic performance of WLI and magnifying image-enhanced endoscopy for GC. Results: Sixteen studies met the inclusion criteria. The detection rate of GC was significantly improved in linked color imaging compared with that in WLI (risk ratio, 2.20; 95% confidence interval [CI], 1.39-3.25; p < 0.01) with mild heterogeneity. Magnifying endoscopy with NBI (ME-NBI) obtained a pooled sensitivity, specificity, and area under the summary receiver operating curve of 0.84 (95 % CI, 0.80-0.88), 0.96 (95 % CI, 0.94-0.97), and 0.92, respectively. Similarly, ME-BLI showed a pooled sensitivity, specificity, and area under the curve of 0.81 (95 % CI, 0.77-0.85), 0.85 (95 % CI, 0.82-0.88), and 0.95, respectively. The diagnostic efficacy of ME-NBI/BLI for GC was evidently high compared to that of WLI, However, significant heterogeneity among the NBI studies still existed. Conclusions: Our meta-analysis showed a high detection rate for linked color imaging and a high diagnostic performance of ME-NBI/BLI for GC compared to that with WLI.

Recent advancements in image-enhanced endoscopy in the pancreatobiliary field.

Image-enhanced endoscopy (IEE) has advanced gastrointestinal disease diagnosis and treatment. Traditional white-light imaging has limitations in detecting all gastrointestinal diseases, prompting the development of IEE. In this review, we explore the utility of IEE, including texture and color enhancement imaging and red dichromatic imaging, in pancreatobiliary (PB) diseases. IEE includes methods such as chromoendoscopy, optical-digital, and digital methods. Chromoendoscopy, using dyes such as indigo carmine, aids in delineating lesions and structures, including pancreato-/cholangio-jejunal anastomoses. Optical-digital methods such as narrow-band imaging enhance mucosal details and vessel patterns, aiding in ampullary tumor evaluation and peroral cholangioscopy. Moreover, red dichromatic imaging with its specific color allocation, improves the visibility of thick blood vessels in deeper tissues and enhances bleeding points with different colors and see-through effects, proving beneficial in managing bleeding complications post-endoscopic sphincterotomy. Color enhancement imaging, a novel digital method, enhances tissue texture, brightness, and color, improving visualization of PB structures, such as PB orifices, anastomotic sites, ampullary tumors, and intraductal PB lesions. Advancements in IEE hold substantial potential in improving the accuracy of PB disease diagnosis and treatment. These innovative techniques offer advantages paving the way for enhanced clinical management of PB diseases. Further research is warranted to establish their standard clinical utility and explore new frontiers in PB disease management.

Contrast-Enhanced Ultrasonography Findings Within 3 Days Postoperatively Are Associated With 1-Month Graft Failure After Split Liver Transplantation.

RATIONALE AND OBJECTIVES: This study aimed to evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) within 3 days postoperative can identify 1-month graft failure after split liver transplantation (SLT). MATERIALS AND METHODS: A total of 58 consecutive patients who underwent SLT between February 2022 and September 2023 were included. The DUS and CEUS images and parameters within 3 days postoperatively were analyzed and recorded. The DUS parameters included peak systolic velocity (PSV), resistive index, and systolic acceleration time for the hepatic artery and PSV for the portal vein and hepatic vein. The CEUS qualitative analysis variables included the liver parenchyma enhancement pattern and the posterior enhancement attenuation. Logistic regression and Cox proportional hazard regression were used to evaluate the relationship between DUS/CEUS findings and 1-month graft failure. RESULTS: Seven of the 58 liver grafts failed within 1 month. Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was observed in five of seven patients (71.4%) of graft failure, whereas good contrast enhancement (pattern Ⅰ) was found in 47 of the 51 patients (92.1%) in the successful group on postoperative day 3. Multivariate logistic regression analysis revealed that 1-month graft failure was independently predicted by operative time (odds ratio [OR] = 3.79, 95% confidence interval [CI]: 1.27-11.29, p = .017) and CEUS enhancement pattern on postoperative day 3 (OR = 90.88, 95% CI: 2.77-2979.56, p = .011). Cox proportional hazard regression showed that operative time (hazard ratio [HR] = 1.6, 95% CI: 1.15-2.22, p = .005) and CEUS enhancement pattern on postoperative day 3 (HR = 11.947, 95% CI: 2.04-69.98, p = .006) were independent predictors for graft failure. CONCLUSION: Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was associated with 1-month graft failure in SLT recipients. CEUS may serve as a noninvasive, valuable prognostic tool to predict clinical outcomes early after SLT.

Dual Oxygen-Supply Immunosuppression-Inhibiting Nanomedicine to Avoid the Intratumoral Recruitment of Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft.

Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells.

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

[Application Values of New Ultrasound Technologies in the Diagnosis of Hepatic Sinusoidal Obstruction Syndrome].

Hepatic sinusoidal obstruction syndrome (HSOS),a toxic liver injury,can lead to multiple organ failure in severe cases and is even fatal.Early diagnosis is of great significance for the selection of treatment regimens and prognosis.Currently,ultrasound,as the preferred diagnostic method for liver diseases,has been recommended in expert consensus and criteria for the diagnosis of HSOS.However,there are no definitive imaging diagnostic standards.This paper summarizes the sonographic features of ultrasound and new ultrasound technologies in HSOS research.Analyzing the characteristic sonographic images from gray-scale ultrasonography,Doppler ultrasonography,ultrasound elastography,and contrast-enhanced ultrasonography at different stages of the disease enables the establishment and refining of the corresponding imaging diagnostic standards and provides effective auxiliary examination methods for the early diagnosis and differential diagnosis of HSOS.

Metallo-Supramolecular Helicates as Surface-Enhanced Raman Scattering (SERS) Substrates with High Tailorability.

The exploration of novel functionalized supramolecular coordination complexes (SCCs) can enable new applications in domains that include purification and sensing. In this study, employing a coordination-driven self-assembly strategy, we designed and prepared a series of benzochalcogenodiazole-based metallohelicates as high-efficiency charge transfer surface-enhanced Raman scattering (SERS) substrates, expanding the range of applications for these metallohelicates. Through structural modifications, including the substitution of single heteroatoms on ligands, replacement of coordinating metals, and alteration of ligand framework linkages, the Raman performance of these metallohelicates as substrates were systematically optimized. Notably, the SERS enhancement factors (EFs) of the metallohelicate-based SERS substrates were significantly enhanced to levels as high as 1.03 × 107, which rivals the EFs of noble metals devoid of "hot spots". Additionally, the underlying Raman enhancement mechanisms of these metallohelicates have been investigated through a combination of control experiments and theoretical calculations. This study not only demonstrates the utility of metallohelicates as SERS substrates but also offers insights and materials for the development of high-efficiency new charge transfer SERS substrates.

Monitoring Hot Holes in Plasmonic Catalysis on Silver Nanoparticles by Using an Ion Label.

Energetic carriers generated by localized surface plasmon resonance (LSPR) provide an efficient way to drive chemical reactions. However, their dynamics and impact on surface reactions remain unknown due to the challenge in observing hot holes. This makes it difficult to correlate the reduction and oxidation half-reactions involving hot electrons and holes, respectively. Here we detect hot holes in their chemical form, Ag(I), on a Ag surface using surface-enhanced Raman scattering (SERS) of SO32- as a hole-specific label. It allows us to determine the dynamic correlations of hot electrons and holes. We find that the equilibrium of holes is the key factor of the surface chemistry, and the wavelength-dependent plasmonic chemical anode refilling (PCAR) effect plays an important role, in addition to the LSPR, in promoting the electron transfer. This method paves the way for visualizing hot holes with nanoscale spatial resolution toward the rational design of a plasmonic catalytic platform.

Polypropylene Blends with Durable Hydrophobicity and Enhanced Mechanical Properties Based on POSS and Alkane Modified Polypentafluorophenyl Methacrylate.

Durable functionalization on polypropylene (PP) surfaces is always a key problem to besolved. Coatings with low surface energy peel off easily especially under extreme conditions, owing to their weak adhesion. In this paper, side groups of both polyhedral oligomeric silsesquioxane (POSS) and alkane are grafted to polypentafluorophenyl methacrylate (PFP), and then PP blends with these side-group modified PFP are obtained through a melt-blending process. It is found that POSS can result in surface segregation and provide hydrophobicity in blends. Microfibers are formed because of the orientation effect during the tensile testing, which furtherly promotes mechanical strength. Significantly, alkaneside-groups can be entangled with PP segments, which brings about cross linking. Therefore, with crosslinking and synchronous orientation of POSS, the elongation at the break of blends is greatly increased up to 974%. The final blend demonstrates quite durable hydrophobicity under many extreme conditions, such as repeated tape peeling, ultrasonic washing, strong friction, and soaking in strong acid (pH = 1), strong alkali (pH = 14) and alcohol. The heat and UV resistance of the blend are also obviously improved. This study will develop anovel and facile strategy to endow PP with durable hydrophobicity as well as greatly enhanced mechanical properties.

Impact of frequency of spaced retrieval using repeat testing on asthma pharmacotherapy knowledge retention.

OBJECTIVE: "Test-enhanced learning" is a strategy utilized to impact knowledge retention. This study aimed to assess the effect of the frequency of spaced retrieval using repeat testing on knowledge depreciation in a Doctor of Pharmacy (PharmD) Program. METHODS: The study randomly assigned second-year pharmacy students to one of three retrieval practice groups: (1) two retrieval practice assessments (2 and 4 months after the course), (2) one retrieval practice assessment (4 months after the course), or (3) no retrieval practice. A final assessment was administered to all participants 6 months after the course. The retrieval assessments and final assessment consisted of five multiple-choice questions on asthma pharmacotherapy. RESULTS: In total, 94 participants were included in the study, with 32 in Group 1 and 31 in both Groups 2 and 3. All three groups performed similarly on the final assessment regardless of the frequency of spaced retrieval. While Group 1 scored numerically higher than Group 2 on the 4-month retrieval practice assessment and did not impact performance on the final assessment. In Group 1, final assessment scores were decreased compared to the two previous retrieval assessments. CONCLUSION: Regardless of the frequency of spaced retrieval following the academic course where asthma pharmacotherapy was initially learned, retrieval practice using multiple choice assessments, with the gap times of this study, did not impact asthma pharmacotherapy knowledge depreciation among second-year student pharmacists.

Exploring the impact of fulvic acid on electrochemical hydrogen-driven autotrophic denitrification system: Performance, microbial characteristics and mechanism.

In this study, the effect of modulating fulvic acid (FA) concentrations (0, 25 and 50 mg/L) on nitrogen removal in a bioelectrochemical hydrogen autotrophic denitrification system (BHDS) was investigated. Results showed that FA increased the nitrate (NO3--N) removal rate of the BHDSs from 37.8 to 46.2 and 45.2 mg N/L·d with a current intensity of 40 mA. The metagenomic analysis revealed that R2 (25 mg/L) was predominantly populated by autotrophic denitrifying microorganisms, which enhanced denitrification performance by facilitating electron transfer. Conversely, R3 (50 mg/L) exhibited an increase in genes related to the heterotrophic process, which improved the denitrification performance through the collaborative action of both autotrophic and heterotrophic denitrification pathways. Besides, the study also identified a potential for nitrogen removal in Serpentinimonas, which have been rarely studied. The interesting set of findings provide valuable reference for optimizing BHDS for nitrogen removal and promoting specific denitrifying genera within the system.

Characterization of Indeterminate Breast Lesions Based on Pressure Estimates by Noninvasive 3D Contrast-Enhanced Ultrasound.

OBJECTIVE: To assess the ability of the pressure gradient between breast lesions and adjacent normal tissue estimated by 3D subharmonic-aided pressure estimation (SHAPE) to characterize indeterminate breast lesions. METHODS: This prospective study enrolled patients scheduled for ultrasound-guided needle biopsies of a breast lesion. Before the biopsy, 3D SHAPE data were collected from the breast lesion during the infusion of an ultrasound contrast agent (Definity) as well as after clearance of the agent. Direct, invasive pressure measurements in the lesion and adjacent normal tissue were then obtained using an intracompartmental pressure monitoring system (C2DX) before tissue sampling as part of the biopsy procedure. The mean SHAPE gradient and invasive measurement gradient between the lesion and adjacent normal tissue were compared to the biopsy results. The SHAPE gradients were also compared to the invasive pressure gradients. RESULTS: There were 8 malignant and 13 benign lesions studied. The SHAPE gradients and invasive pressure gradients were significantly different between the benign and malignant lesions (2.86 ± 3.24 vs. -0.03 ± 1.72 a.u.; p = 0.03 and 9.9 ± 8.5 vs. 20.9 ± 8.0 mmHg; p = 0.008, respectively). The area under the curves, specificities, and sensitivities for detecting malignancy by SHAPE gradients and invasive pressure gradients were 0.79 and 0.88, 77% and 92%, and 88% and 50%, respectively. A weak negative correlation was found between the SHAPE and invasive pressure gradients (r = -0.2). CONCLUSION: The pressure gradient between a breast lesion and adjacent normal tissue estimated by 3D SHAPE shows potential for characterizing indeterminate breast lesions.

Contrast-enhanced magnetic resonance neurography for diagnosing brachial plexopathy: improved visualization and additional imaging features.

Contrast-enhanced magnetic resonance neurography (CE-MRN) holds promise for diagnosing brachial plexopathy by enhancing nerve visualization and revealing additional imaging features in various lesions. This study aims to validate CE-MRN's efficacy in improving brachial plexus (BP) imaging across different patient cohorts. Seventy-one subjects, including 19 volunteers and 52 patients with BP compression/entrapment, injury, and neoplasms, underwent both CE-MRN and plain MRN. Two radiologists assessed nerve visibility, with inter-reader agreement evaluated. Quantitative parameters such as signal intensity (SI), contrast-to-noise ratio (CNR), and contrast ratio (CR) of the C7 nerve were measured. Both qualitative scoring and quantitative metrics were compared between CE-MRN and plain MRN within each patient group. Patient classification followed the Neuropathy Score Reporting and Data System (NS-RADS), summarizing additional imaging features for each brachial plexopathy type. Inter-reader agreement for qualitative assessment was strong. CE-MRN significantly enhanced BP visualization and nerve-tissue contrast across all cohorts, particularly in volunteers and patients with injuries. It also uncovered additional imaging features such as hypointense signals in ganglia, compressed nerve sites, and neoplastic enhancements. CE-MRN effectively mitigated muscle edema and vascular contamination, enabling precise classification of BP injuries. Overall, CE-MRN consistently enhances BP visualization and provides valuable imaging features for accurate diagnosis.

Antegrade persufflation of porcine kidneys improves renal function after warm ischemia.

Introduction: Transplantation of kidneys from expanded criteria donors (ECD), including after circulatory death (DCD), is associated with a higher risk of adverse events compared to kidneys from standard criteria donors. In previous studies, improvements in renal transplant outcomes have been seen when kidneys were perfused with gaseous oxygen during preservation (persufflation, PSF). In the present study, we assessed ex-vivo renal function from a Diffusion Contrast Enhanced (DCE)-MRI estimation of glomerular filtration rate (eGFR); and metabolic sufficiency from whole-organ oxygen consumption (WOOCR) and lactate production rates. Methods: Using a porcine model of DCD, we assigned one kidney to antegrade PSF, and the contralateral kidney to static cold storage (SCS), both maintained for 24 h at 4°C. Post-preservation organ quality assessments, including eGFR, WOOCR and lactate production, were measured under cold perfusion conditions, and biopsies were subsequently taken for histopathological analysis. Results: A significantly higher eGFR (36.6 ± 12.1 vs. 11.8 ± 4.3 ml/min, p < 0.05), WOOCR (182 ± 33 vs. 132 ± 21 nmol/min*g, p < 0.05), and lower rates of lactate production were observed in persufflated kidneys. No overt morphological differences were observed between the two preservation methods. Conclusion: These data suggest that antegrade PSF is more effective in preserving renal function than conventional SCS. Further studies in large animal models of transplantation are required to investigate whether integration with PSF of WOOCR, eGFR or lactate production measurements before transplantation are predictive of post-transplantation renal function and clinical outcomes.

Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE.

Small-molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures. Moreover, designing selective drugs often benefits from the targeting of diverse metastable conformations. Therefore, direct application of AlphaFold2 models in virtual screening and drug discovery remains tentative. Here, we demonstrate an AlphaFold2-based framework combined with all-atom enhanced sampling molecular dynamics and Induced Fit docking, named AF2RAVE-Glide, to conduct computational model-based small-molecule binding of metastable protein kinase conformations, initiated from protein sequences. We demonstrate the AF2RAVE-Glide workflow on three different mammalian protein kinases and their type I and II inhibitors, with special emphasis on binding of known type II kinase inhibitors which target the metastable classical DFG-out state. These states are not easy to sample from AlphaFold2. Here, we demonstrate how with AF2RAVE these metastable conformations can be sampled for different kinases with high enough accuracy to enable subsequent docking of known type II kinase inhibitors with more than 50% success rates across docking calculations. We believe the protocol should be deployable for other kinases and more proteins generally.

The value of contrast-enhanced ultrasound in cervical cancer assessed in comparison with magnetic resonance imaging.

Introduction: Currently, magnetic resonance imaging (MRI) is the most commonly used imaging method in the assessment of the loco-regional extension in cervical cancer. Contrast-enhanced ultrasound (abbreviated CEUS) is being investigated as an alternative or complement to the MRI investigation. Objectives: To evaluate the performance of CEUS in identifying loco-regional invasion of cervical cancer compared to MRI, considered the accepted reference standard. Methods: Sixty-one patients with histopathologically confirmed cervical cancer were investigated as part of the pre-treatment workup by CEUS and MRI. We calculated the accuracy and concordance of CEUS versus MRI for tumor invasion in the vagina, bladder, rectum, parametrium, and uterus. For the time-intensity curve associated parameters analyzed (TTPK, AUC, peak intensity, wash in and wash out gradient) we calculated sensitivity, specificity and threshold value of positivity, for tumor invasion at the above-mentioned sites, with graphical representation of the ROC (receiver operating characteristic) curve. Results: CEUS was highly accurate in detecting bladder (93.4%, 95% CI: 87.2-99.6) and uterine invasion (88.5%, 95% CI: 80.5-96.5). Substantial agreement between CEUS and MRI was observed for invasion in the uterine body (k=0.77, 95% CI: 0.56-0.98) and bladder (k=0.56, 95% CI: 0.35-0.77). ROC curve analysis for loco-regional invasions showed that the wash in gradient at a cut-off value of 2.23 had a sensitivity of 76% and a specificity of 67% in predicting uterine invasion. Conclusions: Our results demonstrate high accuracy and good agreement between CEUS and MRI regarding especially uterine and bladder invasion. This imaging method could help select patients in early stages for fertility sparing surgery, and also be of use in cases in which early bladder invasion is suspected.

Molecular-Sieving Label-Free Surface-Enhanced Raman Spectroscopy for Sensitive Detection of Trace Small-Molecule Biomarkers in Clinical Samples.

Small-molecule biomarkers are ubiquitous in biological fluids with pathological implications, but major challenges persist in their quantitative analysis directly in complex clinical samples. Herein, a molecular-sieving label-free surface-enhanced Raman spectroscopy (SERS) biosensor is reported for selective quantitative analysis of trace small-molecule trimetazidine (TMZ) in clinical samples. Our biosensor is fabricated by decorating a superhydrophobic monolayer of microporous metal-organic frameworks (MOF) shell-coated Au nanostar nanoparticles on a silicon substrate. The design strategy principally combines the hydrophobic surface-enabled physical confinement and preconcentration, MOF-assisted molecular enrichment and sieving of small molecules, and sensitive SERS detection. Our biosensor utilizes such a "molecular confinement-and-sieving" strategy to achieve a five orders-of-magnitude dynamic detection range and a limit of detection of ≈0.5 nM for TMZ detection in either urine or whole blood. We further demonstrate the applicability of our biosensing platform for longitudinal label-free SERS detection of the TMZ level directly in clinical samples in a mouse model.

A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.

Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated ß-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H2O2. Overall, a novel SlipChip-SERS system is developed for single-cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing-related diseases.