Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization.

Background: Investigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient. Methods: The performance of mNGS in distinguishing Aspergillus infection from colonization, along with the differences in patients' characteristics, antibiotic adjustment, and lung microbiota, were analyzed. Results: The abundance of Aspergillus significantly differed between patients with Aspergillus infection (n=36) and colonization (n=32) (P < 0.0001). Receiver operating characteristic (ROC) curve result for bronchoalveolar lavage fluid (BALF) mNGS indicated an area under the curve of 0.894 (95%CI: 0.811-0.976), with an optimal threshold value of 23 for discriminating between Aspergillus infection and colonization. The infection group exhibited a higher proportion of antibiotic adjustments in comparison to the colonization group (50% vs. 12.5%, P = 0.001), with antibiotic escalation being more dominant. Age, length of hospital stay, hemoglobin, cough and chest distress were significantly positively correlated with Aspergillus infection. The abundance of A. fumigatus and Epstein-Barr virus (EBV) significantly increased in the infection group, whereas the colonization group exhibited higher abundance of A. niger. Conclusion: BALF mNGS is a valuable tool for differentiating between colonization and infection of Aspergillus. Variations in patients' age, length of hospital stay, hemoglobin, cough and chest distress are observable between patients with Aspergillus infection and colonization.

Development of an impedimetric sensor for susceptible detection of melatonin at picomolar concentrations in diverse pharmaceutical and human specimens.

Our investigation aimed to create and manufacture an electrochemical impedance sensor with the purpose of improving the detection efficiency of melatonin (ME). To achieve this objective, we employed gold nanoparticles coated on polydopamine formed in glassy carbon electrodes (AuNPs/PDA/GCE) as a means to enhance the sensor's capabilities. A novel approach employing the signal-off strategy and electrochemical impedance spectroscopy (EIS) technique was utilized to determine ME. When the AuNPs/PDA/GCE electrode was immersed in a buffered solution containing ME, and the oxidation current of AuNPs was recorded, it was observed that the oxidation current of AuNPs decreased upon the introduction of ME molecules. The decrease in electrical current can be ascribed to the inhibitory impact of ME molecule adsorption on the electrode surface with applying -0.2 V for 150 s in acetate buffer solution (ABS) (pH, 5) through various mechanisms, which hinders the electron transfer process crucial for AuNPs oxidation. Consequently, by utilizing EIS, various concentrations of ME were quantified spanning from 1 to 18 pM. Moreover, the ME sensor achieved an impressive detection limit of 0.32 pM, indicating its remarkable sensitivity in detecting low concentrations of ME. Importantly, these novel sensors demonstrated exceptional attributes in terms of sensitivity, specificity, stability, and repeatability. The outstanding performance of these sensors, coupled with their desirable attributes, establishes their considerable potential for a wide range of practical applications. These applications encompass various fields such as clinical diagnostics, pharmaceutical analysis, environmental monitoring, and industrial quality control, where accurate and sensitive detection of ME is of utmost importance.

Evaluation of thallium ion as an effective ion in human health using an electrochemical sensor.

Exposure to thallium (Tl), a noxious heavy metal, poses significant health risks to both humans and animals upon ingestion. Therefore, monitoring Tl levels in the environment is crucial to prevent human exposure and reduce the risk of developing severe health problems. This paper presents the development of a highly sensitive Tl ions sensor through surface modification of a glassy carbon electrode with a nanocomposite comprising MnO2 magnetic sepiolite and multi-walled carbon nanotubes (MnO2@Fe3O4/Sep/MWCNT/GCE). Multiple methodologies were employed to assess the performance of the newly developed sensor. By employing square wave anodic stripping voltammetry (SWASV) to optimize the measurement conditions, notable enhancements were observed in the stripping peak currents of Tl (I) on the MnO2@Fe3O4/Sep/MWCNT/GCE surface. The effectiveness of the nanocomposite in facilitating electron transfer between the Tl (I) ions (guest) and the electrode (host) was demonstrated from the enhanced signals observed at the different modified electrode surfaces under optimal conditions. The developed sensor displayed a wide linear range of 0.1-1500 ppb for Tl (I) and a low detection limit of 0.03 ppb for Tl (I). It was found to be selective for Tl (I) ions while remaining unaffected by interfering non-target ions in the presence of the target ions. Despite its simple preparation procedure, the modified electrode exhibited high stability and excellent reproducibility for measuring Tl (I). The outstanding electroanalytical performances of the MnO2@Fe3O4/Sep/MWCNT/GCE electrode enabled its successful use as an ultrasensitive sensor for determining trace amounts of Tl in environmental samples.

Inhibition of pulmonary artery smooth muscle cells via the delivery of curcuminoid WZ35 by Cu-based metal organic frameworks.

Hypoxic pulmonary hypertension (HPH) is a life-threatening disease that occurs due to a lack of oxygen in the lungs, leading to an increase in pulmonary vascular resistance, right ventricular failure, and ultimately death. HPH is a multifactorial disorder that involves multiple molecular pathways, making it a challenge for clinicians to identify effective therapies. Pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPH pathogenesis by proliferating, resisting apoptosis, and promoting vascular remodelling. Curcumin, a natural polyphenolic compound, has shown potential as a therapeutic agent for HPH by reducing pulmonary vascular resistance, inhibiting vascular remodelling, and promoting apoptosis of PASMCs. Regulation of PASMCs could significantly inhibits HPH. However, curcumin has the disadvantages of poor solubility and low bioavailability, and its derivative WZ35 has better biosafety. Here, Cu-based metal organic frameworks (MOFCu ) was fabricated to encapsulate the curcumin analogue WZ35 (MOFCu @WZ35) for the inhibition of PASMCs proliferation. The authors found that the MOFCu @WZ35 could promote the death of PASMCs. Furthermore, the authors believed that this drug delivery system will effectively alleviate the HPH.

Supplementary benefits of CT-guided transthoracic lung aspiration biopsy for core needle biopsy.

Objective: This study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection. Materials and methods: We retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy. Results: The pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90). Conclusion: CT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

UBE2V2 Positively Correlates With PD-L1 Expression and Confers Poor Patient Survival in Lung Adenocarcinoma.

This research aims to explore the diagnostic and prognostic value of ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2) in lung adenocarcinoma (LUAD). The expression of UBE2V2 in clinical specimens was evaluated by bioinformatics analyses and immunohistochemistry. Bioinformatics analyses relying on the The Cancer Genome Atlas (TCGA) database suggested the elevated UBE2V2 mRNA levels in LUAD in comparison to adjacent normal tissues. Gene set enrichment analyses and gene ontology term enrichment analyses further showed the involvement of UBE2V2 in the modulation of cell cycle and immune associated signaling. The correlation analyses in TCGA LUAD data set revealed the positive correlation between UBE2V2 and CCNE1, CCNE2, CCNA2, CCNB1, CCNB2, cyclin-dependent kinase (CDK)2, CDK4, and CDK1 at the mRNA level. Moreover, UBE2V2 mRNA levels were positively correlated with PD-L1 mRNA levels, the T classification, and poor survival of LUAD patients, and were negatively correlated with type II interferon response. Consistent with the results obtained from TCGA data mining, immunohistochemistry demonstrated that UBE2V2 protein levels were upregulated in LUAD in comparison to normal tissues and were positively associated with T classification. Intriguingly, a positive correlation between UBE2V2 protein levels and PD-L1 expression was also elucidated in clinical samples. Besides, UBE2V2 expression indicated a poor prognosis in LUAD patients. Our study found that UBE2V2 was identified as an independent prognostic indicator for LUAD and might serve as an alternative target for LUAD treatment.

Development of a bead-based suspension array for the detection of pathogens in acute respiratory tract infections.

We developed a high-throughput bead-based suspension array for simultaneous detection of 20 respiratory tract pathogens in clinical specimens. Pathogen-specific genes were amplified and hybridized to probes coupled to carboxyl-encoded microspheres. Fluorescence intensities generated via the binding of phycoerythrin-conjugated streptavidin with biotin-labeled targets were measured by the Luminex 100 bead-based suspension array system. The bead-based suspension array detected bacteria in a significantly higher number of samples compared to the conventional culture. There was no significant difference in the detection rate of atypical pathogensatypical pathogens or viruses between the bead-based suspension array and real-time PCR. This technology can play a significant role in screening patients with pneumonia.

Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer.

Livin, an inhibitor of apoptosis protein (IAP), is overexpressed in various cancers and decreases tumor sensitivity to chemotherapy and radiotherapy. However, the effect of Livin on lung adenocarcinoma metastasis and the specific mechanism involved remain unclear. RNAi technology was used to stably silence Livin in A549 cells in the present study. The effect of Livin on tumor growth and invasion was investigated in lung cancer cells in vitro and animal models were established to determine the anti-metastasis ability of Livin silencing in vivo. The results indicated that Livin knock-down suppressed cell proliferation and inhibited cell invasion, accompanied by downregulation of VEGF and MMP-2/-9. Silencing of Livin resulted in the prevention of xenograft tumor formation. Seventy-five immunodeficient male BALB/C nude mice were randomly divided into three groups, the relative ratio of the areas with pulmonary nodules in the experimental group decreased from 46.71±7.27% to 11.07±2.94% compared with the negative control group (P<0.001), indicating the interaction between Livin, VEGF and MMPs. The xenograft tumor model of intravenous injection of tumor cells were successfully established and applied for the analysis of lung cancer tumorigenesis and metastasis in a time-dependent manner for the first time. Based on the reliable and reproducible animal model, our findings indicate that knock-down of Livin inhibits cell growth and invasion through blockade of the VEGF and MMPs pathways in lung cancer cells in vitro, and inhibits tumorigenesis and metastasis of lung cancer in vivo, suggesting that Livin is a promising antitumor target.