Method of adaptive wide dynamic range gas concentration detection based on optimized direct absorption spectroscopy.

For wide dynamic range gas concentration detection based on tunable diode laser absorption spectroscopy (TDLAS), direct absorption spectroscopy (DAS) and wavelength modulation spectroscopy (WMS) are usually used in combination. However, in some application scenarios such as high-speed flow field detection, natural gas leakage, or industrial production, the requirements of wide-range, fast response and calibration-free must be met. Taking applicability and cost of TDALS-based sensor into consideration, a method of optimized direct absorption spectroscopy (ODAS) based on signal correlation and spectral reconstruction is developed in this paper. This method can achieve adaptive selection of the optimal benchmark spectrum for spectral reconstruction. Moreover, methane (CH4) is taken as an example to carry out the experimental verification. Experimental results proved that the method satisfies wide dynamic range detection of more than 4 orders of magnitude. It is worth noting that when measuring large absorbance with concentration of 75 × 104 ppm with DAS and ODAS method, respectively, the maximum value of residual is reduced from 3.43 to 0.07. Furthermore, whether measuring gas of small or large absorbance with different concentrations, which vary from 100 ppm to 75 × 104 ppm, the correlation coefficient between standard concentrations and inverted concentrations is 0.997, showing the linear consistency of the method in wide dynamic range. In addition, the absolute error is 1.81 × 104 ppm when measuring large absorbance of 75 × 104 ppm. It greatly improves the accuracy and reliability with the new method. In summary, the ODAS method can not only fulfill the measurement of gas concentration in wide range, but also further expand the application prospects of TDLAS.

Comparison of Diagnostic Performance of Spread Through Airspaces of Lung Adenocarcinoma Based on Morphological Analysis and Perinodular and Intranodular Radiomic Features on Chest CT Images.

OBJECT: STAS is associated with poor differentiation, KRAS mutation and poor recurrence-free survival. The aims of this study are to evaluate the ability of intra- and perinodular radiomic features to distinguish STAS at non-contrast CT. PATIENTS AND METHODS: This retrospective study included 216 patients with pathologically confirmed lung adenocarcinoma (STAS+, n = 56; STAS-, n = 160). Texture-based features were extracted from intra- and perinodular regions of 2, 4, 6, 8, 10, and 20 mm distances from the tumor edge using an erosion and expansion algorithm. Traditional radiologic features were also analyzed including size, consolidation tumor ratio (CTR), density, shape, vascular change, cystic airspaces, tumor-lung interface, lobulation, spiculation, and satellite sign. Nine radiomic models were established by using the eight separate models and a total of the eight VOIs (eight-VOI model). Then the prediction efficiencies of the nine radiomic models were compared to predict STAS of lung adenocarcinomas. RESULTS: Among the traditional radiologic features, CTR, unclear tumor-lung interface, and satellite sign were found to be associated with STAS significantly, and the AUCs were 0.796, 0.677, and 0.606, respectively. Radiomic model of combined tumor bodies and all the distances of perinodular areas (eight-VOI model) had better predictive efficiency for predicting STAS+ lung adenocarcinoma. The AUCs of the eight-VOI model in the training and verification sets were 0.907 (95%CI, 0.862-0.947) in the training set, and 0.897 (95%CI, 0.784-0.985) in the testing set, and 0.909 (95%CI, 0.863-0.949) in the external validation set, and the diagnostic accuracy in the external validation set was 0.849. CONCLUSION: Radiomic features from intra- and perinodular regions of nodules can best distinguish STAS of lung adenocarcinoma.

Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway limitation accompanied with infiltration of inflammatory cells. Mucosal associated invariant T (MAIT) cells can recognize bacteria and play an important role in controlling host immune responses by producing cytokines. In this study, we characterized the function and the ability of MAIT cells to secrete cytokines measured by flow cytometry. In COPD patients, MAIT cells have the ability to produce more IL-17 and less IFN-γ compared to healthy individuals. We found that HLA-DR expression levels reflected the degree of inflammation and the proportion of IL-17 was significantly correlated with lung function in peripheral blood. In addition, we found that MAIT cells were highly expressed in the lung, and the increased expression of CXCR2, CXCL1 indicated that MAIT cells had the potential to migrate to inflammatory tissues. This evidence implies that MAIT cells may play a potential role in COPD immunopathology.

Predictors of CT Morphologic Features to Identify Spread Through Air Spaces Preoperatively in Small-Sized Lung Adenocarcinoma.

OBJECTIVES: This study aimed to explore the predictive CT features of spread through air spaces (STAS) in patients with small-sized lung adenocarcinoma. METHODS: From January 2017 to May 2019, patients with confirmed pathology of small-sized lung adenocarcinoma (less than or equal to 2 cm) and who underwent surgery were retrospectively analyzed. The clinical, pathological, and surgical information and CT features were analyzed. RESULTS: A total of 47 patients with STAS (males, 61.7%; mean age, 56 ± 8years) and 143 patients without STAS (males, 58%; mean age, 53 ± 11 years) were included. Pathologically, papillary, micropapillary, solid predominant subtypes, and vascular and pleural invasion were most commonly observed features in the STAS group. Radiologically, higher consolidation tumor ratio (CTR), presence of spiculation, satellites, ground glass ribbon sign, pleural attachment, and unclear tumor-lung interface were more commonly observed features in the STAS group. CTR, presence of ground glass ribbons and pleural connection, and absence of cystic airspaces were considered as stable predictors of STAS in multivariate logistic models. The receiver operating characteristic curve (ROC) analysis for predicting STAS demonstrated higher area under the curve (AUC) in the model that used CTR (0.760, 95% confidence interval, 0.69-0.83) for predicting STAS than in the model that used long diameter of entire lesion (0.640). CONCLUSIONS: CTR is the best CT sign for predicting STAS in small-sized lung adenocarcinoma. The ground glass ribbon is a newly found indicator and has the potential for predicting STAS.

Improving the activity of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

Nattokinase (NK), a bacterial serine protease from Bacillus subtilis var. natto, is a potential cardiovascular drug exhibiting strong fibrinolytic activity. To broaden its commercial and medical applications, we constructed a single-mutant (I31L) and two double-mutants (M222A/I31L and T220S/I31L) by site-directed mutagenesis. Active enzymes were expressed in Escherichia coli with periplasmic secretion and were purified to homogeneity. The kinetic parameters of enzymes were examined by spectroscopy assay and isothermal titration calorimetry (ITC), and their fibrinolytic activities were determined by fibrin plate method. The substitution of Leu(31) for Ile(31) resulted in about 2-fold enhancement of catalytic efficiency (Kcat/KM) compared with wild-type NK. The specific activities of both double-mutants (M222A/I31L and T220S/I31L) were significantly increased when compared with the single-mutants (M222A and T220S) and the oxidative stability of M222A/I31L mutant was enhanced with respect to wild-type NK. This study demonstrates the feasibility of improving activity of NK by site-directed mutagenesis and shows successful protein engineering cases to improve the activity of NK as a potent therapeutic agent.

NF-κB, JNK and p53 pathways are involved in tubeimoside-1-induced apoptosis in HepG2 cells with oxidative stress and G2/M cell cycle arrest.

Tubeimoside-1 is a triterpenoid saponin extracted from the traditional Chinese herb Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). We investigated the cytotoxic effect and apoptosis mechanism of tubeimoside-1. Tubeimoside-1 was cytotoxic in seven human cancer cell lines, with HepG2 the most sensitive. Tubeimoside-1 induced apoptosis of HepG2 cells dose and time dependently. Both the extrinsic and intrinsic pathways were triggered by tubeimoside-1. Caspase-3, -8 and -9 were activated and the expression of Fas, Fas ligand, Bcl-2, Bak and Bax was regulated. Moreover, tubeimoside-1 induced accumulation of reactive oxygen species and arrested cell cycle at the G(2)/M phase, thus contributing to apoptosis, through signaling regulation by tumor necrosis factor α, nuclear factor κB (NF-κB), Jun N-terminal kinase (JNK) and p53. We provide further insight into the tubeimoside-1 cytotoxic effect for antitumor chemotherapeutic treatment.

Functional analysis of propeptide as an intramolecular chaperone for in vivo folding of subtilisin nattokinase.

Here, we show that during in vivo folding of the precursor, the propeptide of subtilisin nattokinase functions as an intramolecular chaperone (IMC) that organises the in vivo folding of the subtilisin domain. Two residues belonging to ß-strands formed by conserved regions of the IMC are crucial for the folding of the subtilisin domain through direct interactions. An identical protease can fold into different conformations in vivo due to the action of a mutated IMC, resulting in different kinetic parameters. Some interfacial changes involving conserved regions, even those induced by the subtilisin domain, blocked subtilisin folding and altered its conformation. Insight into the interaction between the subtilisin and IMC domains is provided by a three-dimensional structural model.

Enhancement of oxidative stability of the subtilisin nattokinase by site-directed mutagenesis expressed in Escherichia coli.

Nattokinase (subtilisin NAT, NK) is a bacterial serine protease with strong fibrinolytic activity and it is a potent cardiovascular drug. In medical and commercial applications, however, it is susceptible to chemical oxidation, and subsequent inactivation or denaturation. Here we show that the oxidative stability of NK was substantially increased by optimizing the amino acid residues Thr(220) and Met(222), which were in the vicinity of the catalytic residue Ser(221) of the enzyme. Two nonoxidative amino acids (Ser and Ala) were introduced at these sites using site-directed mutagenesis. Active enzymes were successfully expressed in Escherichia coli with periplasmic secretion and enzymes were purified to homogeneity. The purified enzymes were analyzed with respect to oxidative stability, kinetic parameters, fibrinolytic activity and thermal stability. M222A mutant was found to have a greatly increased oxidative stability compared with wild-type enzyme and it was resistant to inactivation by more than 1 M H(2)O(2), whereas the wild-type enzyme was inactivated by 0.1 M H(2)O(2) (t(1/2) approximately 11.6 min). The other mutant (T220S) also showed an obvious increase in antioxidative ability. Molecular dynamic simulations on wild-type and T220S mutant proteins suggested that a hydrogen bond was formed between Ser(220) and Asn(155), and the spatial structure of Met(222) was changed compared with the wild-type. The present study demonstrates the feasibility of improving oxidative stability of NK by site-directed mutagenesis and shows successful protein engineering cases to improve stability of NK as a potent therapeutic agent.

[Progress in regulatory T cells research].

Regulatory T cells (Treg) are functionally mature T cell subpopulations which are key players of maintaining the balance of immunological defense system. Treg can proliferate in vivo or in vitro by antigen specific way or non-antigen specific way, and actively control the properties of other immune cells by suppressing their functional activity and their proliferation as well.