Background: The sensitivity and specificity of current breath biomarkers are often inadequate for effective cancer screening, particularly in colorectal cancer (CRC). While a few exhaled biomarkers in CRC exhibit high specificity, they lack the requisite sensitivity for early-stage detection, thereby limiting improvements in patient survival rates. Methods: In this study, we developed an advanced Mass Spectrometry-based volatilomics platform, complemented by an enhanced breath sampler. The platform integrates artificial intelligence (AI)-assisted algorithms to detect multiple volatile organic compounds (VOCs) biomarkers in human breath. Subsequently, we applied this platform to analyze 364 clinical CRC and normal exhaled samples. Results: The diagnostic signatures, including 2-methyl, octane, and butyric acid, generated by the platform effectively discriminated CRC patients from normal controls with high sensitivity (89.7%), specificity (86.8%), and accuracy (AUC = 0.91). Furthermore, the metastatic signature correctly identified over 50% of metastatic patients who tested negative for carcinoembryonic antigen (CEA). Fecal validation indicated that elevated breath biomarkers correlated with an inflammatory response guided by Bacteroides fragilis in CRC. Conclusion: This study introduces a sophisticated AI-aided Mass Spectrometry-based platform capable of identifying novel and feasible breath biomarkers for early-stage CRC detection. The promising results position the platform as an efficient noninvasive screening test for clinical applications, offering potential advancements in early detection and improved survival rates for CRC patients.

Breath analysis enables rapid, noninvasive diagnosis of human health by identifying and quantifying exhaled biomarker. Here, we demonstrated an exhaled breath sensing method using the near-infrared laser spectroscopy, and sub parts-per-million (ppm) level ammonia detection inside the exhaled gas was achieved employing a distributed feedback laser centered at 1512 nm and Kalman filtering algorithm. Integration of the ammonia sensor was realized for exhaled breath analysis of kidney patients, and a dual operation mechanism with static and dynamic modes was proposed to make this method applicable for real-time and comprehensive pre-diagnosis of kidney disease.

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named \"IEsohunter\") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance.
METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC.
RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC.
CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW4-GS18-Au25) as a model, we found that although 800CW4-GS18-Au25 strongly resisted serum-protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione-mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au25 and biotransformation-generated fingerprint message of 800CW4-GS18-Au25 in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection.

Semiconductor-based photoelectrochemical (PEC) test protocols offer a viable solution for developing efficient individual health monitoring by converting light and chemical energy into electrical signals. However, slow reaction kinetics and electron-hole complexation at the interface limit their practical application. Here, we reported a triple-engineered CdS nanohierarchical structures (CdS NHs) modification scheme including morphology, defective states, and heterogeneous structure to achieve precise monitoring of the neurotransmitter dopamine (DA) in plasma and noninvasive body fluids. By precisely manipulating the Cd-S precursor, we achieved precise control over ternary CdS NHs and obtained well-defined layered self-assembled CdS NHs through a surface carbon treatment. The integration of defect states and the thin carbon layer effectively established carrier directional transfer pathways, thereby enhancing interface reaction sites and improving the conversion efficiency. The CdS NHs microelectrode fabricated demonstrated a remarkable negative response toward DA, thereby enabling the development of a miniature self-powered PEC device for precise quantification in human saliva. Additionally, the utilization of density functional theory calculations elucidated the structural characteristics of DA and the defect state of CdS, thus establishing crucial theoretical groundwork for optimizing the polymerization process of DA. The present study offers a potential engineering approach for developing high energy conversion efficiency PEC semiconductors as well as proposing a novel concept for designing sensitive testing strategies.

Accurately determining the metastatic status of sentinel lymph nodes (SLNs) through noninvasive imaging with high imaging resolution and sensitivity is crucial for cancer therapy. Herein, we report a dual-tracer-based NIR-II ratiometric fluorescence nanoplatform combining targeted and nontargeted moieties to determine the metastatic status of SLNs through the recording of ratio signals. Ratiometric fluorescence imaging revealed approximately 2-fold increases in signals in tumor-draining SLNs compared to inflamed and normal SLNs. Additionally, inflamed SLNs were diagnosed by combining the ratio value with the enlarged size outputted by NIR-II fluorescence imaging. The metastatic status diagnostic results obtained through NIR-II ratiometric fluorescence signals were further confirmed by standard H&E staining, indicating that the ratiometric fluorescence strategy could achieve distant metastases detection. Furthermore, the superior imaging quality of ratiometric probes enables visualization of the detailed change in the lymphatic network accompanying tumor growth. Compared to clinically available and state-of-the-art NIR contrast agents, our dual-tracer-based NIR-II ratiometric fluorescence probes provide significantly improved performance, allowing for the quick assessment of lymphatic function and guiding the removal of tumor-infiltrating SLNs during cancer surgery.

OBJECTIVE: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH.
METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model.
RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904).
CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

The measurement of hemoglobin is a vital index for diagnosing and monitoring diseases in clinical practice. At present, solutions need to be found for the soreness, high risk of infection, and inconvenient operation associated with invasive detection methods. This paper proposes a method for non-invasively detecting hemoglobin levels based on multi-wavelength photoplethysmography (PPG) signals. AFE4490 and TMUX1109 were used to implement the low-cost collection of an eight-LED transmissive PPG signal. We used seven regular LEDs and one broadband LED (Osram SFH4737) as light sources. Additionally, a finger clip integrating multiple sensors was designed and manufactured via 3D printing to simultaneously monitor the LED-sensor distance and the pressure from the tester\'s finger during PPG signal acquisition. We used a method to extract features from PPG signals using a sliding-window\'s variance and an evaluation metric for PPG signals based on the AdaCost classification. Data were gathered from 56 participants from the Nephrology department, including 16 anemic patients. Pearson correlation analysis was conducted on the collected data to remove any data with a weak correlation. The advantage of using a broadband LED as a light source was also demonstrated. Several non-invasive hemoglobin regression models were created by applying AdaBoost, BPNN, and Random Forest models. The study\'s results indicate that the AdaBoost model produced the best performance, with a mean absolute error (MAE) of 2.67 g/L and a correlation coefficient (R2) of 0.91 The study results show that the device we designed and manufactured can achieve effective non-invasive hemoglobin detection and represents a new methodological approach to obtaining measurements that can be applied in a clinical setting.

The advent of biosensors has tremendously increased our potential of identifying and solving important problems in various domains, ranging from food safety and environmental analysis, to healthcare and medicine. However, one of the most prominent drawbacks of these technologies, especially in the biomedical field, is to employ conventional samples, such as blood, urine, tissue extracts and other body fluids for analysis, which suffer from the drawbacks of invasiveness, discomfort, and high costs encountered in transportation and storage, thereby hindering these products to be applied for point-of-care testing that has garnered substantial attention in recent years. Therefore, through this review, we emphasize for the first time, the applications of switching over to noninvasive sampling techniques involving hair and nails that not only circumvent most of the aforementioned limitations, but also serve as interesting alternatives in understanding the human physiology involving minimal costs, equipment and human interference when combined with rapidly advancing technologies, such as microfluidics and organ-on-a-chip to achieve miniaturization on an unprecedented scale. The coalescence between these two fields has not only led to the fabrication of novel microdevices involving hair and nails, but also function as robust biosensors for the detection of biomarkers, chemicals, metabolites and nucleic acids through noninvasive sampling. Finally, we have also elucidated a plethora of futuristic innovations that could be incorporated in such devices, such as expanding their applications in nail and hair-based drug delivery, their potential in serving as next-generation wearable sensors and integrating these devices with machine-learning for enhanced automation and decentralization.

Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide 124/125I (124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with 124I-IgG and 18F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. 124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of 125I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The Kd value of 125I-anti-CD147 to CD147 protein was 6.344 nM, while that of 125I-IgG was over 100 nM. 125I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, 125I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of 124I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of 124I-anti-CD147 compared to that of 124I-IgG and 18F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUVmax) (P < 0.01). In conclusion, 124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of 124I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.