A data-adaptive methods in detecting exogenous methyltransferase accessible chromatin in human genome using nanopore sequencing.

MOTIVATION: Identifying chromatin accessibility is one of the key steps in studying the regulation of eukaryotic genomes. The combination of exogenous methyltransferase and nanopore sequencing provides an strategy to identify open chromatin over long genomic ranges at the single-molecule scale. However, endogenous methylation, non-open-chromatin-specific exogenous methylation and base-calling errors limit the accuracy and hinders its application to complex genomes. RESULTS: We systematically evaluated the impact of these three influence factors, and developed a model-based computational method, methyltransferase accessible genome region finder (MAGNIFIER), to address the issues. By incorporating control data, MAGNIFIER attenuates the three influence factors with data-adaptive comparison strategy. We demonstrate that MAGNIFIER is not only sensitive to identify the open chromatin with much improved accuracy, but also able to detect the chromatin accessibility of repetitive regions that are missed by NGS-based methods. By incorporating long-read RNA-seq data, we revealed the association between the accessible Alu elements and non-classic gene isoforms. AVAILABILITY AND IMPLEMENTATION: Freely available on web at https://github.com/Goatofmountain/MAGNIFIER.

Ultrahigh-Flux Water Nanopumps Generated by Asymmetric Terahertz Absorption.

Controlling active transport of water through membrane channels is essential for advanced nanofluidic devices. Despite advancements in water nanopump design using techniques like short-range invasion and subnanometer-level control, challenges remain facilely and remotely realizing massive waters active transport. Herein, using molecular dynamic simulations, we propose an ultrahigh-flux nanopump, powered by frequency-specific terahertz stimulation, capable of unidirectionally transporting massive water through asymmetric-wettability membrane channels at room temperature without any external pressure. The key physics behind this terahertz-powered water nanopump is revealed to be the energy flow resulting from the asymmetric optical absorption of water.

Enhanced water permeation through the terahertz-induced phase and diffusion transition in metal-organic framework membranes.

Freshwater scarcity is a pressing global concern, and water desalination has emerged as a promising solution. Metal-organic framework (MOF) membranes have demonstrated exceptional potential in this regard. However, previous efforts to improve the permeability of MOFs have primarily focused on chemical modifications and synthesis rather than exploring physical methods. Using molecular dynamics simulations, we propose that the use of terahertz waves at a specific frequency of 7.5 ± 1.0 THz significantly enhances water permeability across MOF membranes, up to 27-fold, while maintaining effective ion rejection capabilities throughout the process. The mechanism behind this enhancement involves the resonance between the terahertz wave and the hydrogen bond vibrations of water within the MOF. This resonance amplifies the rotational kinetic energy of water molecules, disrupting the hydrogen bonds and causing a phase transition from quasi 1D square ice to a gas-like phase. Additionally, the diffusion behavior shifts from Fickian diffusion to sub-diffusion, resulting in improved water permeation across the MOF membrane. This study highlights the potential of terahertz waves as a physical tool to enhance the permeability of MOFs in water desalination, providing new avenues for efficient water treatment and resource sustainability.

Biomechanical impact of different isthmus positions in mandibular first molar root canals: a finite element analysis.

OBJECTIVE: This study used image-based finite element analysis (FEA) to assess the biomechanical changes in mandibular first molars resulting from alterations in the position of the root canal isthmus. METHODS: A healthy mandibular first molar, characterized by two intact root canals and a cavity-free surface, was selected as the subject. A three-dimensional model for the molar was established using scanned images of the patient's mandibular teeth. Subsequently, four distinct finite element models were created, each representing varied root canal morphologies: non-isthmus (Group A), isthmus located at the upper 1/3 of the root (Group B), middle 1/3 of the root (Group C), and lower 1/3 of the root (Group D). A static load of 200 N was applied along the tooth's longitudinal axis on the occlusal surface to simulate regular chewing forces. The biomechanical assessment was conducted regarding the mechanical stress profile within the root dentin. The equivalent stress (Von Mises stress) was used to assess the biomechanical features of mandibular teeth under mechanical loading. RESULTS: In Group A (without an isthmus), the maximum stress was 22.2 MPa, while experimental groups with an isthmus exhibited higher stresses, reaching up to 29.4 MPa. All maximum stresses were concentrated near the apical foramen. The presence of the isthmus modified the stress distribution in the dentin wall of the tooth canal. Notably, dentin stresses at specific locations demonstrated differences: at 8 mm from the root tip, Group B: 13.6 MPa vs. Group A: 11.4 MPa; at 3 mm from the root tip, Group C: 14.2 MPa vs. Group A: 4.5 MPa; at 1 mm from the root tip, Group D: 25.1 MPa vs. Group A: 10.3 MPa. The maximum stress in the root canal dentin within the isthmus region was located either at the top or bottom of the isthmus. CONCLUSION: A root canal isthmus modifies the stress profile within the dentin. The maximum stress occurs near the apical foramen and significantly increases when the isthmus is located closer to the apical foramina.

Microwell Confined Electro-Coalescence for Rapid Formation of High-Throughput Droplet Array.

Droplet array is widely applied in single cell analysis, drug screening, protein crystallization, etc. This work proposes and validates a method for rapid formation of uniform droplet array based on microwell confined droplets electro-coalescence of screen-printed emulsion droplets, namely electro-coalescence droplet array (ECDA). The electro-coalescence of droplets is according to the polarization induced electrostatic and dielectrophoretic forces, and the dielectrowetting effect. The photolithographically fabricated microwells are highly regular and reproducible, ensuring identical volume and physical confinement to achieve uniform droplet array, and meanwhile the microwell isolation protects the paired water droplets from further fusion and broadens its feasibility to different fluidic systems. Under optimized conditions, a droplet array with an average diameter of 85 µm and a throughput of 106 in a 10 cm × 10 cm chip can be achieved within 5 s at 120 Vpp and 50 kHz. This ECDA chip is validated for various microwell geometries and functional materials. The optimized ECDA are successfully applied for digital viable bacteria counting, showing comparable results to the plate culture counting. Such an ECDA chip, as a digitizable and high-throughput platform, presents excellent potential for high-throughput screening, analysis, absolute quantification, etc.

Transcriptomic data recover a new superfamily-level phylogeny of Cucujiformia (Coleoptera, Polyphaga).

Cucujiformia, the largest taxon in the order Coleoptera, exhibits extraordinary morphological, ecological, and behavioral diversity. This infraorder is currently divided into seven superfamilies, but considerably incongruent relationships among superfamilies have been reported by recent phylogenomic studies. Here, we combined the 21 newly sequenced transcriptomes representing six superfamilies with nine previously published cucujiform genomes/transcriptomes to elucidate the phylogeny and evolution of Cucujiformia. The monophyly of each of five superfamilies were consistently supported by all phylogenetic analyses based on the twelve datasets (matrix occupancy, amino acid and nucleotide data) and the two analytical methods (maximum likelihood method and Bayesian inference). Both the amino acid datasets and the RY recoded nucleotide datasets recovered the monophyly of Cucujoidea. Topology test results statistically supported the following robust superfamily-level phylogeny in Cucujiformia: (Coccinelloidea, (Cleroidea, (Tenebrionoidea, (Cucujoidea, (Chrysomeloidea, Curculionoidea))))). Our divergence time analyses recovered a Permian origin of Cucujiformia and a Jurassic-Cretaceous origin of most superfamilies. The diversification of phytophagous beetles that occurred in the Cretaceous can be attributed to its co-evolution with angiosperms, supporting the hypothesis of a Cretaceous Terrestrial Revolution.

A real-world disproportionality analysis of Rucaparib: Post-marketing Pharmacovigilance Data.

BACKGROUND: Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database. METHODS: Disproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed. RESULTS: A total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1-62 days), and had early failure types. CONCLUSION: Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.

Design and characteristic analysis of flexible CNT film patch for potential application in ultrasonic therapy.

Ultrasonic therapy has drawn increasing attention due to its noninvasiveness, great sensitivity and strong penetration capabilities. However, most of traditional rigid ultrasonic probes cannot achieve a solid interfacial contact with irregular nonplanar surfaces, which leads to unstable therapeutic effects and limitations of widespread use in practical applications. In this paper, a new flexible ultrasonic patch based on carbon nanotube (CNT) films is designed and fabricated to achieve a potential application in ultrasonic therapy. This patch is composed of a CNT film, a thermal protective layer and a heat sinking layer, and has the advantages of simple structure, soft, ultrathin and completely conforming to the treatment area. Theoretical and experimental studies are performed to investigate the acoustic and temperature fields before and after deformation. Effects of key design parameters of the patch on acoustic performances and temperature distributions are revealed. Numerical results indicate that the CNT film patch can produce ultrasounds over a wide frequency range and temperatures under the threshold of burn injury whether it is bent or not. Furthermore, it is also noted that the sound waves emitted from the bending patch are focused at the center of the bending patch, which demonstrates that the target treatment area can be controlled.

Low-rank fusion convolutional neural network for prediction of remission after stereotactic radiosurgery in patients with acromegaly: a proof-of-concept study.

Artificial intelligence approaches to analyze pathological images (pathomic) for outcome prediction have not been sufficiently considered in the field of pituitary research. A total of 5,504 hematoxylin & eosin-stained pathology image tiles from 58 acromegalic patients with a good or poor outcome were integrated with other clinical and genetic information to train a low-rank fusion convolutional neural network (LFCNN). The model was externally validated in 1,536 patches from an external cohort. The primary outcome was the time to the first endocrine remission after stereotactic radiosurgery (SRS). The median time of initial endocrine remission was 43 months (interquartile range [IQR]: 13-60 months) after SRS, and the 24-month initial cumulative remission rate was 57.9% (IQR: 46.4-72.3%). The patient-wise accuracy of the LFCNN model in predicting the primary outcome was 92.9% in the internal test dataset, and the sensitivity and specificity were 87.5 and 100.0%, respectively. The LFCNN model was a strong predictor of initial cumulative remission in the training cohort (hazard ratio [HR] 9.58, 95% confidence interval [CI] 3.89-23.59; p < 0.001) and was higher than that of established prognostic markers. The predictive value of the LFCNN model was further validated in an external cohort (HR 9.06, 95% CI 1.14-72.25; p = 0.012). In this proof-of-concept study, clinically and genetically useful prognostic markers were integrated with digital images to predict endocrine outcomes after SRS in patients with active acromegaly. The model considerably outperformed established prognostic markers and can potentially be used by clinicians to improve decision-making regarding adjuvant treatment choices. © 2022 The Pathological Society of Great Britain and Ireland.

The association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services: 2008 ~ 2018.

BACKGROUND: The changes in demographic and family structures have weakened the traditional norms of filial piety and intergenerational relationships dramatically. This study aims to examine the dynamic association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services. METHODS: Data was derived from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), which is a longitudinal survey of a nationally representative sample of individuals aged 60 and over. Random effects model was used to assess the association between financial support and informal care provision of adult children to their parents. RESULTS: It was found that financial support showed an upward trend while informal care provision showed a download trend from 2008 to 2018. The result indicated a significant and negative association between financial support and informal care provision of adult children to their parents (B = -0.500, 95% confidence interval (CI) = -0.761 to -0.239). And the association was significant among elderly people who were from urban areas (B = -0.628, 95% CI = -0.970 to -0.287), co-resided with adult children (B = -0.596, 95% CI = -0.939 to -0.253), and had community-based services (B = -0.659, 95% CI = -1.004 to -0.315). CONCLUSION: Financial support was negatively associated with informal care provision of adult children to their parents in China, and the association has differences in household registration, residence arrangement and community-based care services. It is suggested that policymakers should prioritize planning interventions for elderly care services and establish a family caregiver support system.

Accurate single-cell genotyping utilizing information from the local genome territory.

Single-nucleotide variant (SNV) detection in the genome of single cells is affected by DNA amplification artefacts, including imbalanced alleles and early PCR errors. Existing single-cell genotyper accuracy often depends on the quality and coordination of both the target single-cell and external data, such as heterozygous profiles determined by bulk data. In most single-cell studies, information from different sources is not perfectly matched. High-accuracy SNV detection with a limited single data source remains a challenge. We developed a new variant detection method, SCOUT (Single Cell Genotyper Utilizing Information from Local Genome Territory), the greatest advantage of which is not requiring external data while base calling. By leveraging base count information from the adjacent genomic region, SCOUT classifies all candidate SNVs into homozygous, heterozygous, intermediate and low major allele SNVs according to the highest likelihood score. Compared with other genotypers, SCOUT improves the variant detection performance by 2.0-77.5% in real and simulated single-cell datasets. Furthermore, the running time of SCOUT increases linearly with sequence length; as a result, it shows 400% average acceleration in operating efficiency compared with other methods.

Vision-Based Automated Recognition and 3D Localization Framework for Tower Cranes Using Far-Field Cameras.

Tower cranes can cover most of the area of a construction site, which brings significant safety risks, including potential collisions with other entities. To address these issues, it is necessary to obtain accurate and real-time information on the orientation and location of tower cranes and hooks. As a non-invasive sensing method, computer vision-based (CVB) technology is widely applied on construction sites for object detection and three-dimensional (3D) localization. However, most existing methods mainly address the localization on the construction ground plane or rely on specific viewpoints and positions. To address these issues, this study proposes a framework for the real-time recognition and localization of tower cranes and hooks using monocular far-field cameras. The framework consists of four steps: far-field camera autocalibration using feature matching and horizon-line detection, deep learning-based segmentation of tower cranes, geometric feature reconstruction of tower cranes, and 3D localization estimation. The pose estimation of tower cranes using monocular far-field cameras with arbitrary views is the main contribution of this paper. To evaluate the proposed framework, a series of comprehensive experiments were conducted on construction sites in different scenarios and compared with ground-truth data obtained by sensors. The experimental results show that the proposed framework achieves high precision in both crane jib orientation estimation and hook position estimation, thereby contributing to the development of safety management and productivity analysis.

circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1.

Circular RNA (circRNA) participates in a variety of pathophysiological processes, including the development of gastric cancer (GC). However, the role of circ_0006089 in GC progression and its underlying molecular mechanism need to be further revealed. Quantitative real-time PCR was utilized for detecting circ_0006089, microRNA (miR)-361-3p and transforming growth factor-ß1 (TGFB1) expression. The interaction between miR-361-3p and circ_0006089 or TGFB1 was confirmed using a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. Cell proliferation, metastasis, apoptosis, and angiogenesis were determined using colony formation assay, EdU assay, transwell assay, flow cytometry, and tube formation assay. Cell glycolysis was evaluated by detecting glucose consumption, lactate production, and ATP levels. In addition, western blot (WB) analysis was used to measure protein expression. Xenograft tumor models were used to assess the effect of circ_0006089 knockdown on GC tumorigenesis. circ_0006089 had been found to be upregulated in GC tissues and cells, and it could act as an miR-361-3p sponge. circ_0006089 knockdown suppressed GC proliferation, metastasis, glycolysis, angiogenesis, and increased apoptosis, while this effect could be revoked by miR-361-3p inhibitor. TGFB1 was targeted by miR-361-3p, and its overexpression reversed the effects of miR-361-3p on GC cell function. Also, circ_0006089 promoted TGFB1 expression via sponging miR-361-3p. Animal experiments showed that silenced circ_0006089 inhibited GC tumorigenesis through the miR-361-3p/TGFB1 pathway. Our results revealed that the circ_0006089/miR-361-3p/TGFB1 axis contributed to GC progression, confirming that circ_0006089 might be a potential therapeutic target for GC.

Predictive Model of Chemotherapy-Induced Myelosuppression for Patients with Esophageal Cancer.

BACKGROUND: The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to develop a model for prediction of incidence of myelosuppression during chemotherapy among patients with esophageal cancer. METHODS: In this retrospective study, a total of 1446 patients with esophageal cancer who underwent five different chemotherapy regimens between 2013 and 2020 at our institute were randomly assigned in a 7:3 ratio to training and validation data sets. Clinical and drug-related variables were used to develop the prediction model from the training data set by the machine learning method of random forest. Finally, this model were tested in the validation data set. RESULTS: The prediction model were established with 16 indispensable variables selected from 46 variables. The model obtained an area under the receiver-operating characteristic curve of .883 and accompanied by prediction accuracy of 80.0%, sensitivity of 77.8% and specificity of 81.8%. CONCLUSION: This new prediction model showed excellent predictive ability of incidence of myelosuppression in turn providing preventative measures for patients with esophageal cancer during chemotherapy.

Serum NFL discriminates Parkinson disease from essential tremor and reflect motor and cognition severity.

OBJECTIVE: To investigate the diagnostic value of serum neurofilament light chain (NFL) for discriminating Parkinson disease (PD) from Essential tremor (ET) and healthy controls, and to evaluate its correlation with some clinical features of PD patients. METHODS: This cross-sectional study measured NFL levels with electrochemiluminescence immunoassay in serum of 146 PD patients, 82 ET patients and 60 age-matched healthy controls. We used multivariate regression analyses to examine whether NFL contributes to PD biomarkers. Disease severity were assessed by Unified Parkinson's Disease Rating Scale part III (UPDRS III), Hoehn & Yahr (H-Y) stage and Mini-Mental State Examination (MMSE). RESULTS: Serum NFL levels were significantly higher in PD than in ET and healthy controls (16.6 ± 3.5, 12.2 ± 2.4 and 11.8 ± 2.4 pg/mL, respectively, p < 0.001). In patients with PD, serum NFL were markedly increased in patients with advanced H-Y stage and patients with dementia (both p < 0.001). The correlation analysis revealed that serum NFL was positively associated with UPDRS III score (r = 0.79, p < 0.001) and H-Y stage (r = 0.86, p < 0.001), and negatively correlated with MMSE scores (r = - 0.70, p < 0.001). Further multivariate regression analyses showed that serum NFL was an independent contributor to motor symptom and cognition severity in PD patients (all p < 0.01). CONCLUSIONS: Serum NFL levels were markedly elevated may be a useful clinical biomarker for discriminating PD patients from ET and controls. Serum NFL may serve as a potential blood biomarker for motor and cognition severity of PD.

Hsa_circ_0001550 facilitates colorectal cancer progression through mediating microRNA-4262/nuclear casein kinase and cyclin-dependent kinase substrate 1 cascade.

BACKGROUND: Circular RNAs (circRNAs) play important roles in various malignancies, such as colorectal cancer (CRC). However, the function of hsa_circ_0001550 in CRC remains to be elucidated. METHODS: The expression levels of hsa_circ_0001550, microRNA (miR)-4262, and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were determined by real-time qPCR. Cell biological behaviors were evaluated via colony formation assay, transwell assay, flow cytometry, and sphere formation assays. The target relationship was validated via dual-luciferase reporter and RNA pull-down assays. Protein expression was analyzed by western blot. Xenograft tumor model was adopted to evaluate hsa_circ_0001550 function in vivo. RESULTS: Hsa_circ_0001550 enrichment was enhanced in CRC tissue specimens and cell lines. Hsa_circ_0001550 absence hindered CRC cell proliferation, metastasis, stemness, and caused apoptosis. Hsa_circ_0001550 targeted miR-4262, and hsa_circ_0001550 absence-caused impacts were diminished by anti-miR-4262. MiR-4262 targeted NUCKS1. Hsa_circ_0001550 had positive regulation on NUCKS1 expression. NUCKS1 overexpression overturned the influences of hsa_circ_0001550 silencingon CRC cell progression. Hsa_circ_0001550 interference notably blocked in vivo xenograft tumor growth. CONCLUSION: Hsa_circ_0001550 facilitated CRC progression by binding to miR-4262 to positively regulate NUCKS1 abundance.

Antibacterial activity and action target of phenyllactic acid against Staphylococcus aureus and its application in skim milk and cheese.

Phenyllactic acid (PLA) has been demonstrated to possess antibacterial activity and capacity to prolong food shelf life. However, studies on the performance of PLA in inhibiting Staphylococcus aureus and its effectiveness when applied to dairy products are largely lacking. Here, antibacterial activity (planktonic and biofilm states) of PLA against S. aureus CICC10145 (S. aureus_45) were investigated. The results showed that PLA inhibited growth of S. aureus_45 and formation of S. aureus_45 biofilm. Next, the antibacterial action target of PLA was uncovered from both physiological and phenotypic perspectives. The results showed that PLA decreased cell metabolic activity and cell viability, damaged cell membrane integrity, triggered leakage of intracellular contents (DNA, proteins, and ATP), and caused oxidative stress damage and morphological deformation of S. aureus_45. In practical application, the antibacterial activity of PLA against S. aureus_45 cells was further confirmed in skim milk and cheese as dairy food models, and the antibacterial effects can be adequately maintained during storage for 21 d, at least at 4°C. These findings suggested that PLA could be a potential candidate for controlling S. aureus outgrowth in dairy foods.

A novel bacteriocin against Staphylococcus aureus from Lactobacillus paracasei isolated from Yunnan traditional fermented yogurt: Purification, antibacterial characterization, and antibiofilm activity.

Staphylococcus aureus and its biofilm have emerged as a significant threat to the safety of dairy products. In recent years, lactic acid bacteria (LAB) bacteriocins have been widely acknowledged as the potential natural antibacterial substance in food biopreservation due to their excellent antibacterial effects. However, few LAB bacteriocins with antibacterial and antibiofilm activity against S. aureus have been reported in dairy products. In the present study, a novel bacteriocin LSX01 of Lactobacillus paracasei LS-6 isolated from a traditional fermented yogurt produced in Yunnan, China, was purified and characterized extensively. The LSX01 possessed a molecular weight of 967.49 Da and an AA sequence of LDQAGISYT. The minimum inhibitory concentration of LSX01 against S. aureus_45 was 16.90 µg/mL, which was close to or lower than the previously reported bacteriocins. The LSX01 exhibited an extensive antimicrobial spectrum against both gram-positive and gram-negative bacteria. Moreover, LSX01 exhibited excellent tolerance to heat and acid-base treatments, and sensitivity to the proteolytic enzymes, such as pepsin and proteinase K. Furthermore, the treatment of S. aureus_45 planktonic cells with LSX01 significantly reduced their metabolic activity and disrupted the cell membrane integrity. Scan electron microscopy results demonstrated that LSX01 induced cytoplasmic content leakage and cell deformation. Additionally, biofilm formation of S. aureus_45 was also significantly inhibited by LSX01. Overall, the results suggested that the novel LAB bacteriocin LSX01 possessed antibacterial activity and antibiofilm activity against S. aureus and, hence, could have potential for improving safety of dairy products.

Precise pathological classification of non-small cell lung adenocarcinoma and squamous carcinoma based on an integrated platform of targeted metabolome and lipidome.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear. METHODS: Totally, 128 plasma samples of NSCLC patients were collected before initial treatments, followed by determination of LC-ESI-Q TRAP-MS/MS. Differentially expressed metabolites were screened based on a strict standard. RESULTS: Based on the integrated platform of targeted metabolome and lipidome, a total of 1141 endogenous metabolites (including 809 lipids) were finally detected in the plasma of NSCLC patients, including 16 increased and 3 decreased endogenous compounds in LUAD group when compared with LUSC group. Thereafter, a logistic regression model integrating four differential metabolites [2-(Methylthio) ethanol, Cortisol, D-Glyceric Acid, and N-Acetylhistamine] was established and could accurately differentiate LUAD and LUSC with an area under the ROC curve of 0.946 (95% CI 0.886-1.000). The cut-off value showed a satisfactory efficacy with 92.0% sensitivity and 92.9% specificity. KEGG functional enrichment analysis showed these differentially expressed metabolites could be further enriched in riboflavin metabolism, steroid hormone biosynthesis, prostate cancer, etc. The endogenous metabolites identified in this study have the potential to be used as novel biomarkers to distinguish LUAD from LUSC. CONCLUSIONS: Our research might provide more evidence for exploring the pathogenesis and differentiation of NSCLC. This research could promote a deeper understanding and precise treatment of lung cancer.

Elevated serum ferritin level effectively discriminates severity illness and liver injury of coronavirus disease 2019 pneumonia.

AIM: Ferritin is a hepatic protein that plays vital roles in diagnosing and predicting diseases, but its potential in coronavirus disease 2019 (COVID-19) remains unknown. METHOD: We collected clinical records from 79 COVID-19 patients at Wuhan Union hospital (China). Spearman's correlation analysis, receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves were employed. RESULTS: Patients with elevated ferritin levels had a higher incidence of severity illness (50.0 vs 2.9%) and liver injury (52.3 vs 20.0%) when compared with patients with normal ferritin levels (p < 0.05). Ferritin could effectively identify the severity of illness (ROC area 0.873) and liver injury (ROC area 0.752). The elevated ferritin group showed longer viral clearance time (median 16 vs 6 days, p < 0.001) and in-hospital length (median 18 vs 10 days, p < 0.001). CONCLUSIONS: It suggests that ferritin could act as an easy-to-use tool to identify liver injury and severity illness and predict the prognosis of COVID-19 patients. Intensive surveillance is necessary for patients with abnormal ferritin levels.