Advancing Breathomics through Accurate Discrimination of Endogenous from Exogenous Volatiles in Breath.

Breathomics, a growing field in exposure monitoring and clinical diagnostics, has faced accuracy challenges due to unclear contributing factors. This study aims to enhance the potential of breathomics in various frontiers by categorizing exhaled volatile organic compounds (VOCs) as endogenous or exogenous. Analyzing ambient air and breath samples from 271 volunteers via TD-GC × GC-TOF MS/FID, we identify and quantify 50 common VOCs in exhaled breath. Advanced quantitative structure-property relationships and compartment models are employed to obtain VOCs kinetic parameters. This in-depth approach allows us to accurately determine the alveolar concentration of VOCs and further discern their origins, facilitating personalized application of breathomics in exposure assessment and disease diagnosis. Our findings demonstrate that prolonged external exposure turns humans into secondary pollutant sources. Analysis of endogenous VOCs reveals that internal exposure poses more significant health risks than external. Moreover, by correcting environmental backgrounds, we improve the accuracy of gastrointestinal disease diagnostic models by 15-25%. This advancement in identifying VOC origins via compartmental models promises to elevate the clinical relevance of breathomics, marking a leap forward in exposure assessment and precision medicine.

GPAT1 Deficiency in Mice Modulates NASH Progression in a Model-Dependent Manner.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), and its more severe form, nonalcoholic steatohepatitis (NASH), is the leading cause for liver failure and liver cancer. Although the etiology is likely multifactorial, genes involved in regulating lipid metabolism are enriched in human NAFLD genome-wide association studies (GWAS), pointing to dysregulated lipid metabolism as a major pathogenic factor. Glycerol-3-phosphate acyltransferase 1 (GPAT1), encoded by GPAM, converts acyl-CoAs and glycerol-3-phosphate into lysophosphatidic acid and has been shown to regulate lipid accumulation in the liver. However, its role in mediating the progression from NAFLD to NASH has not been explored. METHODS: GPAT1-deficient mice were generated and challenged with diets inducing hepatic steatosis and NASH. Effects of GPAT1 deficiency on lipid and systemic metabolic end points were evaluated. RESULTS: Ablating GPAT1 globally or specifically in mouse hepatocytes reduced hepatic steatosis in the context of diet-induced or genetic obesity. Interestingly, blunting of progression from NAFLD to NASH in global GPAT1 knockout (KO) mice was model dependent. GPAT1 KO mice were protected from choline deficient, amino acid defined high-fat diet-induced NASH development, but not from the high fat, high carbohydrate, and high cholesterol diet-induced NASH. CONCLUSIONS: Our preclinical data support the notion that lipid metabolism pathways regulated by GPAT1 in hepatocytes play an essential role in NASH progression, albeit in a model-dependent manner.

Visible-Light-Promoted Intermolecular ß-Acyl Difunctionalization of Alkenes via Oxidative Radical-Polar Crossover.

A visible-light-induced ß-acyl difunctionalization of alkenes with acyl oxime esters and various nucleophiles was developed to achieve molecular complexity from readily available raw materials via oxidative radical-polar crossover. A variety of nucleophiles, including NH-sulfoximines, indoles, indazole, and trimethoxybenzene, were all effectively applicable to the sustainable reaction system. The novel synthetic strategy features mild reaction conditions, a broad substrate scope (39 examples), easy scale-up, and excellent regioselectivity.

Accurate real-time obstacle detection of coal mine driverless electric locomotive based on ODEL-YOLOv5s.

The accurate identification and real-time detection of obstacles have been considered the premise to ensure the safe operation of coal mine driverless electric locomotives. The harsh coal mine roadway environment leads to low detection accuracy of obstacles based on traditional detection methods such as LiDAR and machine learning, and these traditional obstacle detection methods lead to slower detection speeds due to excessive computational reasoning. To address the above-mentioned problems, we propose a deep learning-based ODEL-YOLOv5s detection model based on the conventional YOLOv5s. In this work, several data augmentation methods are introduced to increase the diversity of obstacle features in the dataset images. An attention mechanism is introduced to the neck of the model to improve the focus of the model on obstacle features. The three-scale prediction of the model is increased to a four-scale prediction to improve the detection ability of the model for small obstacles. We also optimize the localization loss function and non-maximum suppression method of the model to improve the regression accuracy and reduce the redundancy of the prediction boxes. The experimental results show that the mean average precision (mAP) of the proposed ODEL-YOLOv5s model is increased from 95.2 to 98.9% compared to the conventional YOLOv5s, the average precision of small obstacle rock is increased from 89.2 to 97.9%, the detection speed of the model is 60.2 FPS, and it has better detection performance compared with other detection models, which can provide technical support for obstacle identification and real-time detection of coal mine driverless electric locomotives.

Metabolic switch from glycogen to lipid in the liver maintains glucose homeostasis in neonatal mice.

Neonates strive to acquire energy when the continuous transplacental nutrient supply ceases at birth, whereas milk consumption takes hours to start. Using murine models, we report the metabolic switches in the first days of life, with an unexpected discovery of glucose as the universal fuel essential for neonatal life. Blood glucose quickly drops as soon as birth, but immediately rebounds even before suckling and maintains stable afterward. Meanwhile, neonatal liver undergoes drastic metabolic changes, from extensive glycogenolysis before suckling to dramatically induced fatty acid oxidation (FAO) and gluconeogenesis after milk suckling. Unexpectedly, blocking hepatic glycogenolysis only caused a transient hypoglycemia before milk suckling without causing lethality. Limiting lipid supply in milk (low-fat milk, [LFM]) using Cidea-/- mice, however, led to a chronic and severe hypoglycemia and consequently claimed neonatal lives. While fat replenishment rescued LFM-caused neonatal lethality, the rescue effects were abolished by blocking FAO or gluconeogenesis, pointing to a funneling of lipids and downstream metabolites into glucose as the essential fuel. Finally, glucose administration also rescued LFM-caused neonatal lethality, independent on FAO or gluconeogenesis. Therefore, our results show that the liver works as an energy conversion center to maintain blood glucose homeostasis in neonates, providing theoretical basis for managing infant hypoglycemia.

Adversarial Defense Method Based on Latent Representation Guidance for Remote Sensing Image Scene Classification.

Deep neural networks have made great achievements in remote sensing image analyses; however, previous studies have shown that deep neural networks exhibit incredible vulnerability to adversarial examples, which raises concerns about regional safety and production safety. In this paper, we propose an adversarial denoising method based on latent representation guidance for remote sensing image scene classification. In the training phase, we train a variational autoencoder to reconstruct the data using only the clean dataset. At test time, we first calculate the normalized mutual information between the reconstructed image using the variational autoencoder and the reference image as denoised by a discrete cosine transform. The reconstructed image is selectively utilized according to the result of the image quality assessment. Then, the latent representation of the current image is iteratively updated according to the reconstruction loss so as to gradually eliminate the influence of adversarial noise. Because the training of the denoiser only involves clean data, the proposed method is more robust against unknown adversarial noise. Experimental results on the scene classification dataset show the effectiveness of the proposed method. Furthermore, the method achieves better robust accuracy compared with state-of-the-art adversarial defense methods in image classification tasks.

Application of low molecular weight heparins in umbilical artery thrombosis: A case series and review of the literature.

RATIONALE: Low molecular weight heparins are widely used in various thrombotic diseases and exert a preventive effect on thrombosis in high-risk patients. Umbilical artery thrombosis (UAT) is a rare occurrence that is difficult to detect during routine prenatal visits but can lead to adverse perinatal outcomes. PATIENT CONCERNS: The aim of this study was to elucidate the therapeutic effect of low molecular weight heparins on UAT and to provide a new treatment option for the timing of delivery timing. DIAGNOSES AND INTERVENTIONS: A retrospective study was conducted on cases involving thrombosis of the umbilical cord enrolled from July 2017 to July 2022. Data were acquired and analyzed from medical records and the final diagnosis was confirmed by histopathology. All included patients received LWMHs therapy after initial diagnosis of UAT. OUTCOMES: The mean age of the 10 pregnant women recruited into this study was 27.9 ± 4.0 year-of-age; 1 (10%) was elderly. The gestational age at diagnosis was 29.9 ± 3.7 weeks, the gestational age at termination was 36.3 ± 2.5 weeks and the mean gestational age of extension was 6.4 ± 4.2 weeks. Low molecular weight heparin sodium was administered after umbilical artery embolism was detected on ultrasound. The LWMHs treatment received by the included patients in this study was subcutaneous injection. The specific usage varies due to the types of LWMHs. Of the 10 cases, 5 (50%) had fetal distress but all fetuses were born alive without neonatal asphyxia. With regards to delivery mode, 9 pregnancies were terminated by cesarean section. LESSON: Early anticoagulant treatment with LWMHs may improve pregnancy outcomes. The timing and mode of termination of pregnancy should be determined according to the condition of the mother and the fetus along with the gestational age.

Hyaluronic Acid-Guided Cerasome Nano-Agents for Simultaneous Imaging and Treatment of Advanced Atherosclerosis.

Early noninvasive screening and regression therapy for vulnerable atherosclerotic plaques remain challenging. In this study, it is aimed to develop a new approach for the active targeting of atherosclerotic plaques with nano-agents to aid imaging and treatment. Biocompatible hyaluronic acid (HA)-guided cerasomes are generated to selectively target CD44-positive cells within the plaque in in vitro studies and in vivo testing in Apoe-/- mice. Rosuvastatin (RST) is encapsulated in the HA-guided cerasome nano-formulation to produce HA-CC-RST, which results in significant plaque regression as compared to treatment with the free drug. Moreover, gadodiamide-loaded HA-CC enhances magnetic resonance images of vulnerable plaques, thereby attaining the goal of improved simultaneous treatment and imaging. Transcriptomic analysis confirms plaque regression with HA-CC-RST treatment, which potentially benefits from the anti-inflammatory effect of RST. In summary, a safe and efficient nano-formulation for the targeted delivery of active agents to atherosclerotic plaques is developed and may be applicable to other diagnostic and therapeutic agents for atherosclerosis treatment.

Inhibition of myeloid-derived suppressive cell function with all-trans retinoic acid enhanced anti-PD-L1 efficacy in cervical cancer.

PD-1/PD-L1 inhibitor treatments are relatively inefficacious in advanced cervical cancer patients. The presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment may be one significant barrier to efficacy. It has been shown that all-trans retinoic acid (ATRA) can differentiate MDSCs into mature myeloid cells. However, whether ATRA suppression of MDSCs function could enhance PD-L1 blockade-mediated tumor immunotherapy remains unknown. Here, the frequency of tumor-infiltrating MDSCs in cervical cancer patients was measured. ATRA was used to target MDSCs both in vitro and in tumor-bearing mice. The impact of ATRA on the human cell line HeLa was also investigated. The frequency of MDSCs and T cells was determined by flow cytometry. The expression of immunosuppressive genes was measured with quantitative real time-PCR and infiltration of immune cells was assessed by immunohistochemical examination. We found that tumor-infiltrating PD-L1+ MDSCs were more prevalent in cervical cancer patients. Blockade of PD-L1 expression in MDSCs with anti-PD-L1 antibody cannot relieve the suppressive activity of MDSCs induced by HeLa cells, while ATRA efficiently abrogated the suppressive activity of MDSCs. Furthermore, ATRA had no effect on PD-L1 expression in HeLa cells in vitro. In in vivo treatment, ATRA decreased MDSCs accumulation and increased the frequency of CD8+ T cells in BALB/C mice with U14 cervical tumors. Importantly, a combination treatment of ATRA and anti-PD-L1 antibody further delayed U14 tumor growth and increased the proportion of CD62L-CD8+ T cells, CD62L-CD4+ T cells, CD107a+CD8+ T cells as well as IFN-γ and TNF-α levels in tumors. Our results provide a rationale for the use of ATRA to suppress MDSCs and enhance anti-PD-L1 cancer immunotherapy in cervical cancer.

Development of a single capacitor-voltage-divider flux-loop for field-reversed theta-pinch plasmas.

As one of the most important diagnostics of field reversed plasma, the single-flux loop around the vacuum chamber is usually used to measure the magnetic flux to deduce the plasma size. In the theta-pinch process, the power supply will drive a large current through the coil in a short time to generate a high magnetic field, which will cause the magnetic flux in the vacuum chamber to rise sharply. Therefore, the induced voltage on the single-flux loop may be very strong and have high-frequency components. A voltage divider must be used to reduce the induced voltage to the range that the transmission line can withstand. According to the high-frequency characteristics of the measured signal, this paper designs a capacitor voltage divider single-flux loop with reference to the capacitive voltage divider in the industry. After theoretical derivation of parameter selection and then in the preliminary experimental test with and without plasma, the effectiveness of the distributed capacitor flux loop is verified.