Predicting Antibiotic Tolerance in hvKP and cKP Respiratory Infections Through Biofilm Formation Analysis and Its Resistance Implications.

Introduction: Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications. Methods: We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms. Results: Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum ß-lactamases (ESBLs) and carbapenemases, differing from those of cKP. Discussion: This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.

mtTB: A Web-Based R/Shiny App for Pulmonary Tuberculosis Screening.

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global issue. However, the diagnosis of active pulmonary tuberculosis (TB) remains a challenge in the clinic. Small non-coding RNAs are potential diagnostic biomarkers for pulmonary tuberculosis. However, the current normalization methods are not stable and usually fail to reliably detect differentially expressed sncRNAs. To identify reliable biomarkers for pulmonary tuberculosis screening, we utilized the ratio-based method on the newly discovered mitochondria-derived small RNAs in human peripheral blood mononuclear cells. The prediction model of seven mtRNA biomarkers noteworthily enables the discrimination between pulmonary tuberculosis patients and controls in discovery (AUC = 0.906, 23 patients) and independent validation cohort (AUC = 0.968, 20 patients). Moreover, we present mtTB (https://tuberculosis.shinyapps.io/mtTB/), a novel R Graphical User Interface (GUI) that provides reliable biomarkers for the feasibility of blood-based screening, and produce a more accurate tool for pulmonary tuberculosis diagnosis in real clinical practice.

The Metabolome of Carbapenem-Resistant Klebsiella pneumoniae Infection in Plasma.

AIM: Carbapenem-resistant Klebsiella pneumoniae- (CR-Kp-) mediated infections represent a challenge for clinical practitioners due to their expanding prevalence in hospital environments and antibiotic resistance. However, few studies have shown metabolic changes of carbapenem-resistant Klebsiella pneumoniae and CR-Kp-negative patients, and relevant studies are urgently needed. METHODS: In this study, we comprehensively profile the metabolites of 20 CR-Kp-positive and 18 CR-Kp-negative patients in plasma by using 2D gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). RESULTS: We identified 58 metabolites that were carbapenem-resistant Klebsiella pneumoniae-associated. N-Acetyl glucosamine, butanedioic acid, and myoinositol play a significant character in CR-Kp infection. CONCLUSIONS: Our study provides valuable data to serve as potential targets for developing therapies against CR-Kp infection.

The Value of a Seven-Autoantibody Panel Combined with the Mayo Model in the Differential Diagnosis of Pulmonary Nodules.

BACKGROUND: Identifying malignant pulmonary nodules and detecting early-stage lung cancer (LC) could reduce mortality. This study investigated the clinical value of a seven-autoantibody (7-AAB) panel in combination with the Mayo model for the early detection of LC and distinguishing benign from malignant pulmonary nodules (MPNs). METHODS: The concentrations of the elements of a 7-AAB panel were quantitated by enzyme-linked immunosorbent assay (ELISA) in 806 participants. The probability of MPNs was calculated using the Mayo predictive model. The performances of the 7-AAB panel and the Mayo model were analyzed by receiver operating characteristic (ROC) analyses, and the difference between groups was evaluated by chi-square tests (χ 2). RESULTS: The combined area under the ROC curve (AUC) for all 7 AABs was higher than that of a single one. The sensitivities of the 7-AAB panel were 67.5% in the stage I-II LC patients and 60.3% in the stage III-IV patients, with a specificity of 89.6% for the healthy controls and 83.1% for benign lung disease patients. The detection rate of the 7-AAB panel in the early-stage LC patients was higher than that of traditional tumor markers. The AUC of the 7-AAB panel in combination with the Mayo model was higher than that of the 7-AAB panel alone or the Mayo model alone in distinguishing MPN from benign nodules. For early-stage MPN, the sensitivity and specificity of the combination were 93.5% and 58.0%, respectively. For advanced-stage MPN, the sensitivity and specificity of the combination were 91.4% and 72.8%, respectively. The combination of the 7-AAB panel with the Mayo model significantly improved the detection rate of MPN, but the positive predictive value (PPV) and the specificity were not improved when compared with either the 7-AAB panel alone or the Mayo model alone. CONCLUSION: Our study confirmed the clinical value of the 7-AAB panel for the early detection of lung cancer and in combination with the Mayo model could be used to distinguish benign from malignant pulmonary nodules.

LncRNA TGFB2-AS1 regulates lung adenocarcinoma progression via act as a sponge for miR-340-5p to target EDNRB expression.

Long non-coding RNA TGFB2-antisense RNA1 (TGFB2-AS1) has been reported could regulate tumorigenesis. However, the roles of TGFB2-AS1 in lung adenocarcinoma (LUAD) remain largely unknown. In this work, we aimed to explore the expression levels of TGFB2-AS1 and mechanisms in regulating LUAD progression. Expression level of TGFB2-AS1 in LUAD tissues and normal tissues was analyzed at StarBase. Moreover, its expression in LUAD cells and normal cell was analyzed with quantitative real-time polymerase chain reaction method. Gain- and loss-of-function studies were conducted to analyze the biological roles of TGFB2-AS1 in LUAD. Results indicated TGFB2-AS1 was evidently downregulated in LUAD tissues and cells. Moreover, as analyzed by cell counting kit-8 assay, wound-healing and transwell invasion assays, results revealed TGFB2-AS1 overexpression could suppress proliferation, migration and invasion abilities of LUAD cells in vitro and tumor growth in vivo. In addition, LncBase V2.0 and TargetScan prediction tools showed TGFB2-AS1 and endothelin receptor type B (EDNRB) shares binding site in microRNA-340-5p (miR-340-5p). Furthermore, luciferase activity reporter assay and RT-qPCR assay validated these prediction results. Furthermore, we showed TGFB2-AS1 functions as sponge for miR-340-5p to regulate EDNRB expression. Collectively, our results indicated TGFB2-AS1/miR-340-5p/EDNRB axis plays crucial roles in regulating LUAD progression, indicating TGFB2-AS1 may be a novel therapeutic target for LUAD.

Accurate quantification of high-purity uranium in coatings by small solid angle method.

Aiming at quantifying high-purity uranium (235U/236U/238U) in coatings, a series of experiments were carried out by a dedicated small solid angle device. The physical design of the device and the small solid angle method were here in described, focus in particular on the analysis of detection efficiency, the effect of the isotope impurity in the coatings and the correction for the non-uniform distribution of the uranium samples. The results show that the weight of 235U in the coatings is 5.2-5.6 mg, while 4.7-5.0 mg for 238U and 2.2 mg for 236U in the corresponding coatings, with relative experimental uncertainties of 1.0%--1.2%.

Lack of Efficacy of Combined Carbohydrate Antigen Markers for Lung Cancer Diagnosis.

BACKGROUND: Lung cancer (LC) is top-ranked in cancer incidence and is the leading cause of cancer death globally. Combining serum biomarkers can improve the accuracy of LC diagnosis. The identification of the best potential combination of traditional tumor markers is essential for LC diagnosis. Patients and Methods. Blood samples were collected from 132 LC cases and 118 benign lung disease (BLD) controls. The expression levels of ten serum tumor markers (CYFR21, CEA, NSE, SCC, CA15-3, CA 19-9, CA 125, CA50, CA242, and CA724) were assayed, and that the expression in the levels of tumor markers were evaluated, isolated, and combined in different patients. The performance of the biomarkers was analyzed by receiver operating characteristic (ROC) analyses, and the difference between combinations of biomarkers was compared by Chi-square (χ 2) tests. RESULTS: As single markers, CYFR21 and CEA showed good diagnostic efficacy for nonsmall cell lung cancer (NSCLC) patients, while NSE and CEA were the most sensitive in the diagnosis of small cell lung cancer (SCLC). The area under the curve (AUC) value was 0.854 for the panel of four biomarkers (CYFR21, CEA, NSE, and SCC), 0.875 for the panel of six biomarkers (CYFR21, CEA, NSE, SCC, CA125, and CA15-3), and 0.884 for the panel of ten markers (CYFR21, CEA, NSE, SCC, CA125, CA15-3, CA19-9, CA50, CA242, and CA724). With a higher sensitivity and negative predictive value (NPV), the diagnostic accuracy of the three panels was better than that of any single biomarker, but there were no statistically significant differences among them (all P values > 0.05). However, the panel of six carbohydrate antigen (CA) biomarkers (CA125, CA15-3, CA19-9, CA50, CA242, and CA724) showed a lower diagnostic value (AUC: 0.776, sensitivity: 59.8%, specificity: 73.0%, and NPV: 60.4%) than the three panels (P value < 0.05). The performance was similar even when analyzed individually by LC subtypes. CONCLUSION: The biomarkers isolated are elevated for different types of lung cancer, and the panel of CYFR21, CEA, NSE, and SCC seems to be a promising serum biomarker for the diagnosis of lung cancer, while the combination with carbohydrate antigen markers does not improve the diagnostic efficacy.

Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7).

BACKGROUND: The aim of this study was to investigate the effects and mechanisms of ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7) on lung cancer cells. METHODS: The expression characteristics of ENTPD7 and its effect on the survival of lung cancer patients were analyzed by referring to The Cancer Genome Atlas (TCGA). Streptavidin-peroxidase (SP) staining was performed to detect the ENTPD7 protein in tumor tissues and adjacent tissues. Plasmid transfection technology was also applied to silence ENTPD7 gene. Crystal violet staining and flow cytometry were performed to determine cell proliferation and apoptosis. Tumor-bearing nude mice model was established to investigate the effect of sh-ENTPD7 on tumors. RESULTS: The results showed that patients with low levels of ENTPD7 had higher survival rates. ENTPD7 was up-regulated in lung cancer tissues and cells. Down-regulation of the expression of ENTPD7 inhibited proliferation but promoted apoptosis of lung cancer cell. Silencing ENTPD7 also inhibited the expression levels of Ras and Raf proteins and the phosphorylation of mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK). Tumor-bearing nude mice experiments showed that silencing ENTPD7 had an inhibitory effect on lung cancer cells. CONCLUSIONS: ENTPD7 was overexpressed in lung cancer cells. Down-regulating ENTPD7 could inhibit lung cancer cell proliferation and promote apoptosis via inhibiting the Ras/Raf/MEK/ERK pathway.

[Preliminary study of atomic emission spectrometry of Ti (H) plasma produced by vacuum arc ion source].

In order to study the discharge process of vacuum arc ion source, make a detail description of the discharge plasma, and lay the foundation for further research on ion source, atomic emission spectrometry was used to diagnose the parameters of plasma produced by vaccum arc ion source. In the present paper, two kinds of analysis method for the emission spectra data collected by a spectrometer were developed. Those were based in the stark broadening of spectral lines and Saba-Boltzmann equation. Using those two methods, the electron temperature, electron number density and the ion temperature of the plasma can be determined. The emission spectroscopy data used in this paper was collected from the plasma produced by a vacuum are ion source whose cathode was made by Ti material (which adsorbed hydrogen during storage procedure). Both of the two methods were used to diagnose the plasma parameters and judge the thermal motion state of the plasma. Otherwise, the validity of the diagnostic results by the two methods were analyzed and compared. In addition, the affection from laboratory background radiation during the spectral acquisition process was discussed.

[Two-temperature diagnostic studies by emission spectra for nonequilibrium Ti-H plasma].

Using the T-H solid solution made by titanium absorbed hydrogen as the cathode, the Ti-H plasma produced by the pulsed vacuum are ion source was nonequilibrium: it contained both the component of titanium and hydrogen; there existed gradient in the radiaL, the horizontal and the time. As a result, it could not be described by a single temperature. The present paper assumed that the subsystem consisting of electrons and the subsystem consisting of other heavy particles reached equilibrium respectively, meaning that the Ti-H plasma was described by the two temperatures as electron temperature and heavy ion temperature, it was non-equilibrium two-temperature plasma Using Culdberg-Waage dissociation equation to describe the molecular dissociation process in the system, using Saha ionization equation to describe the atomic ionization process, combining plasma's charge quasi-neutral condition and introducing atomic emission spectroscopy as a plasma diagnostic method which would not interfere the plasma at the same time; the temperature and the particle number density of the Ti-H plasma were diagnosed. Using MATLAB as a tool, both the titanium atoms and monovalent titanium ions' ionization were considered, and the calculated results showed that with the electtron density determined by the Stark broadening of spectral lines in advance, except the heavy particle temperature and the hydrogen number density, the Ti-H plasma's parameters could be diagnosed fairly accurately; the accuracy of the electron density values had a great effect on the calculation results; if the heavy particle temperature could be determined in advance, the temperature and the particle number density of the Ti-H plasma could be accurately analyzed quantitatively.

[The effect of smoking and smoking cessation on the phosphorylation of IKK-ß in type 2 diabetic rats].

OBJECTIVE: To investigate the effect of smoking and smoking cessation on the phosphorylation of IKK-ß in type 2 diabetic rats. METHODS: Forty-two six-week-old Wistar rats were randomly divided into 4 groups: normal control (NC, n = 7), diabetes control (DC, n = 7), diabetes with smoking (DS, n = 14) and diabetes with smoking cessation (SC, n = 14). Rats in DS and SC groups were further assigned randomly into 8w and 12w subgroups. DS group was given passive smoking twice a day for 8 or 12 weeks, while SC group ceased passive smoking for 4 weeks after 8 or 12 weeks of smoking. Western blot method was used to detect the level of IKK-ß phosphorylation in skeletal muscle. RESULTS: Compared with the NC group, the phosphorylation of IKK-ß protein in DC group was increased (0.16 ± 0.05 vs 0.30 ± 0.08, P < 0.01). There was an increasing trend with the phosphorylation level of IKK-ß in the DS (8w) subgroup, but there was no statistical difference between the DC group and SC (8w) subgroup (0.40 ± 0.09 vs 0.30 ± 0.08, 0.36 ± 0.10, P > 0.05). The phosphorylation level of IKK-ß in DS (12w) group increased obviously, being significantly higher than that in the DC group and SC (12w) subgroup (0.74 ± 0.11 vs 0.30 ± 0.08, 0.35 ± 0.07, P < 0.01). CONCLUSION: With the prolongation of smoking duration, the phosphorylation of IKK-ß in type 2 diabetic rats increased. After smoking cessation, the phosphorylation of IKK-ß decreased. The phosphorylation of IKK-ß may be involved in the mechanism by which smoking causes type 2 diabetes.

[Recombinant human pigment epithelium-derived factor inhibits the proliferation of the endothelial cells from blood vessels].

OBJECTIVE: To express and purify the recombinant human pigment epithelium-derived factor (PEDF) which inhibits the proliferation of the endothelium cells from blood vessel in E.coli. METHODS: PEDF gene was inserted into the prokaryotic expression vector pGEX-4T-2. The recombinant protein PEDF was expressed in E.coli BL-21, and purified by the GST Sepharose 4B affinity column. The recombinant human PEDF protein was identified by Western blot and mass spectrum. The biological activity of the recombinant human PEDF protein was measured by using MTT. RESULTS: The 46 kDa recombinant human PEDF protein was obtained. It significantly inhibited the proliferation of the human umbilical vein cell line HUVEC. CONCLUSION: The recombinant human PEDF with anti-angiogenesis activity protein may be successfully purify through prokaryotic expression.