Investigation of the non-small cell lung cancer patients with bronchus involvements: A population-based study.

BACKGROUND: We aimed to explore the prognostic differences among T1-4N0-2M0 non-small cell lung cancer (NSCLC) patients with bronchus involvements and to validate the T category of these patients in an external cohort. METHODS: Univariable and multivariable Cox analysis was performed to determine the prognostic factors. Kaplan-Meier method with a log-rank test was used to compare overall survival differences between groups. Propensity score matching method was used to minimize the bias caused by the imbalanced covariates between groups. RESULTS: A total of 169 390 eligible T1-4N0-2M0 NSCLC cases were included. There were 2354, 3367, 1638, 75, 87 585, 42 056, 19 246, and 13 069 cases in the group of superficial tumors of any size with invasive component limited to bronchial wall (T1-bronchus), tumors involving main stem bronchus ≥2 cm from carina (T2-main bronchus [≥2 cm]), tumors involving main stem bronchus <2 cm from carina (T2-main bronchus [<2 cm]), tumors with carina invasion (T4-carina), T1, T2, T3, and T4, respectively. Multivariable Cox analysis indicated that T1-bronchus patients had the best prognosis; T2-main bronchus (≥2 cm) and T2-main bronchus (<2 cm) patients had similar prognosis both in the entire cohort and in several subgroups. Survival curves showed that T1-bronchus and T1 patients had similar survival rates; the survivals of T2-main bronchus patients regardless of the distance from carina were comparable to those of T2 patients, and the survivals of T4-carina patients were also similar to those of T4 patients. CONCLUSIONS: Our results validated and supported the current T category for the patients with bronchus involvements, which might provide certain reference value for the revisions of T category in the next version of the tumor-node-metastasis stage classification.

Structure and Adsorption Performance of Cationic Entermorpha prolifera Polysaccharide-Based Hydrogel for Typical Pollutants: Methylene Blue, Cefuroxime, and Cr (VI)

Hydrogels with polysaccharides as high polymer substrates have surprising advantages in wastewater treatment with complex components. Therefore, in this study, polysaccharides named EPS were extracted from Enteromorpha prolifera, a coastal pollutant with a wide range of sources, and cationic modification was performed to obtain CAEPS, the hydrogel with a double network structure was prepared based on EPS and CAEPS. Meanwhile, the structural characteristic of EPS and CAEPS-based hydrogel were identified by HPLC, AFM, FT-IR, TGA, SEM-EDS, Pore size distribution, and WCA, which showed that the porosity, apparent (skeletal) density, and hydrophilicity of CAEPS-hydrogels. We used nonlinear isotherms to uncover the adsorption mechanism of hydrogel applied to the water environment containing three typical pollutants (Methylene blue, Cefuroxime, and Cr (VI)). The results showed that the adsorption isotherm of the two hydrogels fit the Langmuir isotherm model, which indicated the monolayer adsorption of the pollution factor onto EPS- and CAEPS-hydrogels. The maximum adsorption capacities of CAEPS-hydrogels were higher than EPS-hydrogels, which indicated the microstructure and adsorption performance of the CAEPS-hydrogel are strengthened.

Degradation of Rhodococcus erythropolis SY095 modified with functional magnetic Fe3O4 nanoparticles.

Alkali-surfactant-polymer flooding technology is widely employed to extract crude oil to enhance its production. The bacterial strain Rhodococcus erythropolis SY095 has shown high degradation activity of alkane of crude oil. In the past, many treatment strategies have been implemented to reduce oil concentration in wastewater. Previous studies mainly focused on the extracellular products of Erythrococcus rather than its degradation properties. In the current study, we designed an immobilization method to modify the surface of R. erythropolis SY095 with functional Fe3O4 nanoparticles (NPs) for biodegradation of crude oil and separation of the immobilized bacteria after degradation. We characterize the synthesized NPs through various methods, including scanning electron microscope energy-dispersive spectrometer, Fourier transform infrared spectroscopy, X-ray diffraction (XRD) and a vibrating sample magnetometer. We found that the size of the synthesized NPs was approximately 100 nm. Our results showed that R. erythropolis SY095 was successfully coated with functional magnetic NPs (MNPs) that could be easily separated from the solution via the application of an external magnetic field. The coated cells had a high tolerance for heavy metals. Our findings demonstrated that the immobilization of MNPs to bacterial surfaces is a promising approach for the degradation of crude oil.

Evaluation of degradation behavior over tetracycline hydrochloride by microbial electrochemical technology: Performance, kinetics, and microbial communities.

Tetracycline hydrochloride (TCH), as a typical antibiotic-pollutant, is desired to enhance its removal from public environment, due to its toxicity and persistence. Microbial electrochemical technology (MET) is a series complex microorganisms-driven processes with characteristics of simultaneous wastewater treatment and electricity generation. The study was presented to evaluate the TCH removal behavior and power generation performance through the co-metabolism under constant glucose with different TCH concentrations using MET. It was found that the TCH removal efficiency arrived at 40% during the first 6 h, when TCH concentrations ranged from 1 to 50 mg/L. It was interesting that TCH degradation rate increased to a maximum of 4.15 × 10-2 h-1 with its concentrations varying from 1 to 20 mg/L, however, the further increase to 50 mg/L in TCH concentration resulted in a reverse 66% reduction. In the meantime, the generated bioelectricity declared a similar fluctuation trend with a maximum power density of 600 mW/m2 under the condition of 20 mg/L TCH co-degradation with glucose. What's more, the TCH inhibition effect fitted well with Haldane's model, indicating that the microbial electrochemical system had a better potency toward TCH toxicity than that reported (EC50 = 2.2 mg/L). Thauera as mainly functional aromatics-degrading bacteria and Bdellovibrio against bacterial pathogens, only existed in the mixed cultures with TCH and glucose, indicating extremely remarkable changes in bacterial community with TCH addition. In summary, a new approach for the anaerobic biodegradation of TCH was explored through co-metabolism with glucose using MET. The results should be useful for antibiotics wastewater disposal of containing TCH.

Basified Human Lysozyme: A Potent Inhibitor against Amyloid ß-Protein Fibrillogenesis.

The aggregation of amyloid ß-proteins (Aß) has been recognized as a key process in the pathogenesis of Alzheimer's disease (AD), so inhibiting Aß aggregation is an important strategy to prevent the onset and treatment of AD. Our recent work indicated that decreasing the positive charges (or introducing negative charges) on human lysozyme (hLys) was unfavorable in keeping the inhibiting capability of hLys on Aß aggregation. Therefore, we have herein proposed to basify hLys by conversion of the carboxyl groups into amino groups by modification with ethylene diamine. Basified hLys (Lys-B) preparations of three modification degrees (MDs), denoted as hLys-B1 (MD, 1.5), hLys-B2 (MD, 3.3), and hLys-B3 (MD, 4.4), were synthesized for modulating Aß fibrillogenesis. The hLys-B preparations kept the stability and biocompatibility as native hLys did, whereas the inhibitory potency of hLys-B on Aß fibrillogenesis increased with increasing MD. Cytotoxicity analysis showed that cell viability with 2.5 µM hLys-B3 increased from 62.5% (with 25 µM Aß only) to 76.1%, similar to the case with 12.5 µM hLys (75.5%); cell viability with 6.25 µM hLys-B3 increased to 82.0%, similar to the case with 25 µM hLys (80.9%). The results indicate about four- to fivefold increase in the inhibition efficiency of hLys by the amino modification. Mechanistic analysis suggests that such a superior inhibitory capability of hLys-B was attributed to its more widely distributed positive charges, which promoted broad electrostatic interactions between Aß and hLys-B. Thus, hLys-B suppressed the conformational transition of Aß to ß-sheet structures at low concentrations (e.g., 2.5 µM hLys-B3), leading to changes in the aggregation pathway and the formation of Aß species with less cytotoxicity. The findings provided new insights into the development of more potent protein-based inhibitors against Aß fibrillogenesis.

Bifunctionality of Iminodiacetic Acid-Modified Lysozyme on Inhibiting Zn2+-Mediated Amyloid ß-Protein Aggregation.

Aggregation of amyloid ß-proteins (Aß) mediated by metal ions such as Zn2+ has been suggested to be implicated in the progression of Alzheimer's disease (AD). Hence, development of bifunctional agents capable of inhibiting Aß aggregation and modulating metal-Aß species is an effective strategy for the treatment of AD. In this work, we modified iminodiacetic acid (IDA) onto human lysozyme (hLys) surface to create an inhibitor of Zn2+-mediated Aß aggregation and cytotoxicity. The IDA-modified hLys (IDA-hLys) retained the stability and biocompatibility of native hLys. Extensive biophysical and biological analyses indicated that IDA-hLys significantly attenuated Zn2+-mediated Aß aggregation and cytotoxicity due to its strong binding affinity for Zn2+, whereas native hLys showed little effect. Stopped-flow fluorescence spectroscopy showed that IDA-hLys could protect Aß from Zn2+-induced aggregation and rapidly depolymerize Zn2+-Aß aggregates. The research indicates that IDA-hLys is a bifunctional agent capable of inhibiting Aß fibrillization and modulating Zn2+-mediated Aß aggregation and cytotoxicity as a strong Zn2+ chelator.

The Anti-Inflammatory Effect and Structure of EPCP1-2 from Crypthecodinium cohnii via Modulation of TLR4-NF-κB Pathways in LPS-Induced RAW 264.7 Cells.

Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and its anti-inflammatory effect was evaluated on protein expression of toll-like receptor 4 and nuclear factor κB pathways in macrophages. The structural characteristics of EPCP1-2 were characterized by GC (gas chromatography) and GC-MS (gas Chromatography-Mass Spectrometer) analyses. The molecular weight was about 82.5 kDa. The main chain of EPCP1-2 consisted of (1→6)-linked mannopyranosyl, (1→6)-linked glucopyranosyl, branched-chain consisted of (1→3,6)-linked galactopyranosyl and terminal consisted of t-l-Rhapyranosyl. The in vitro anti-inflammatory activity was representated through assay of proliferation rate, pro-inflammatory factor (NO) and expressions of proteins on RAW 264.7, the macrophage cell line. The results revealed that EPCP1-2 exhibited significant anti-inflammatory activity by regulating the expression of toll-like receptor 4, mitogen-activated protein kinases, and Nuclear Factor-κB protein.

Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against Metal-Associated Amyloid ß-Protein Aggregation and Cytotoxicity.

Metal-induced amyloid ß-protein (Aß) aggregation plays a key role in the pathogenesis of Alzheimer's disease. Although several agents have been recognized to block metal-associated Aß aggregation, their therapeutic potential is marred due to the high-concentration metal ions in the amyloid plaques. To overcome this problem, we have herein developed iminodiacetic acid-modified human serum albumin (I-HSA) to fight against the aggregation. The multifunctional nature of I-HSA was extensively characterized in inhibiting the Aß42 aggregation associated with Zn2+ and Cu2+. The results revealed the following: (1) I-HSA significantly inhibited Aß42 aggregation and alleviated its cytotoxicity. (2) I-HSA possessed a metal-chelate capacity as high as 31.2 mol/mol, and 25 µM I-HSA could effectively inhibit the influence of 250 µM Zn2+ on Aß42 aggregation. (3) Equimolar I-HSA remarkably attenuated the reactive oxygen species damage caused by the Aß42 and Cu2+-Aß42 species. (4) I-HSA could remodel metal-Aß42 fibrils into unstructured aggregates with less neurotoxicity. The cytotoxicity of mature Cu2+-Aß42 aggregates was mitigated from 64.8% to 25.4% under the functioning of I-HSA. In conclusion, I-HSA showed prominent advantages for the high metal-chelate capacity. To our knowledge, I-HSA is the first multifunctional macromolecule for inhibiting high-concentration metal-induced Aß42 aggregation and remodeling mature metal-induced Aß42 species.

Modulation effect of acidulated human serum albumin on Cu2+-mediated amyloid ß-protein aggregation and cytotoxicity under a mildly acidic condition.

Aggregation of amyloid ß-proteins (Aß) induced by Cu2+ is a crucial element in the pathogenesis of Alzheimer's disease (AD), and cerebral acidosis is a common complication of AD. Under mildly acidic conditions, Cu2+-Aß species have higher tendency to generate neurotoxic aggregates. Hence it is of significance to develop potent agents that inhibit Cu2+-mediated Aß aggregation under a mildly acidic condition. Herein we synthesized acidulated human serum albumin (A-HSA) to mitigate Cu2+-mediated Aß42 aggregation and cytotoxicity at pH6.6. Extensive experiments showed that A-HSA altered the pathway of Cu2+-mediated Aß42 aggregation and protected SH-SY5Y cells from cytotoxicity and oxidative damage induced by Cu2+-Aß42 species. Equimolar A-HSA increased cell viability from 52% to 91% as compared to Cu2+-Aß42-treated group. Stopped-flow fluorescence analysis revealed that A-HSA changed the Cu2+-Aß42 coordination mode from component I to II on the second timescale at pH6.6, which avoided the formation of aggregation-prone Cu2+-Aß42 aggregates. The findings revealed that the more negative charges on A-HSA surface could stabilize the protonated form of the adjacent histidine residues of Aß42. Hence, component I, which is necessary to form toxic aggregates, became unstable in the presence of A-HSA. On the other hand, hydrophobic binding and electrostatic repulsion could work simultaneously on the bound Aß42 on A-HSA surface. The two opposite forces stretched Aß42 conformations, which inhibited the formation of toxic Cu2+-Aß42 aggregates. Thus, A-HSA worked as a bifunctional inhibitor against Cu2+-mediated Aß42 aggregation and cytotoxicity under a mildly acidic condition.

Multifunctionality of Acidulated Serum Albumin on Inhibiting Zn²âº-Mediated Amyloid ß-Protein Fibrillogenesis and Cytotoxicity.

Fibrillogenesis of amyloid ß-proteins (Aß) mediated by transition-metal ions such as Zn(2+) in neuronal cells plays a causative role in Alzheimer's disease. Hence, it is highly desired to design multifunctional agents capable of inhibiting Aß aggregation and modulating metal-Aß species. In this study, we fabricated acidulated human serum albumin (A-HSA) as a multifunctional agent for binding Zn(2+) and modulating Zn(2+)-mediated Aß fibrillogenesis and cytotoxicity. On average, 19.5 diglycolic anhydrides were modified onto the surface of human serum albumin (HSA). It was confirmed that A-HSA kept the stability and biocompatibility of native HSA. Moreover, it could inhibit Aß42 fibrillogenesis and change the pathway of Zn(2+)-mediated Aß42 aggregation, as demonstrated by extensive biophysical assays. In addition, upon incubation with A-HSA, the cytotoxicity presented by Zn(2+)-Aß42 aggregates was significantly mitigated in living cells. The results showed that A-HSA had much stronger inhibitory effect on Zn(2+)-mediated Aß42 fibrillogenesis and cytotoxicity than equimolar HSA. Isothermal titration calorimetry and stopped-flow fluorescence measurements were then performed to investigate the working mechanism of A-HSA. The studies showed that the A-HSA surface, with more negative charges, not only had stronger affinity for Zn(2+) but also might decrease the binding affinity of Aß42 for Zn(2+). Moreover, hydrophobic binding and electrostatic repulsion could work simultaneously on the bound Aß42 on the A-HSA surface. As a result, Aß42 conformations could be stretched, which avoided the formation of toxic Zn(2+)-Aß42 aggregates. The research thus revealed that A-HSA is a multifunctional agent capable of altering the pathway of Zn(2+)-mediated Aß42 aggregation and greatly mitigating the amyloid cytotoxicity.

Insight into the inhibition effect of acidulated serum albumin on amyloid ß-protein fibrillogenesis and cytotoxicity.

Alzheimer's disease (AD) is the most prevalent form of dementia, and aggregation of amyloid ß-proteins (Aß) into soluble oligomers and fibrils has been implicated in the pathogenesis of AD. Herein we developed acidulated serum albumin for the inhibition of Aß42 fibrillogenesis. Bovine serum albumin (BSA) was modified with diglycolic anhydride, leading to the coupling of 14.5 more negative charges (carboxyl groups) on average on each protein surface. The acidulated BSA (A-BSA) was characterized and confirmed to keep the tertiary structure and stability of BSA. Extensive biophysical and biological analyses showed that A-BSA significantly inhibited Aß42 fibrillogenesis and mitigated amyloid cytotoxicity. As compared to the Aß42-treated group (cell viability, 50%), the cell viability increased to 88% by the addition of equimolar A-BSA. The inhibitory effect was remarkably higher than that of BSA at the same concentration. On the basis of the experimental findings, a mechanistic model was proposed. The model considers that Aß42 is bound to the A-BSA surface by hydrophobic interactions, but the widely distributed negative charges on the A-BSA surface give rise to electrostatic repulsions to the bound Aß42 that is also negatively charged. The two well-balanced opposite forces make Aß42 adopt extended conformations instead of the ß-sheet structure that is necessary for the on-pathway fibrillogenesis, even when the protein is released off the surface. Thus, A-BSA greatly slows down the fibrillation and changes the fibrillogenesis pathway, leading to the formation of less toxic aggregates. The findings and the mechanistic model offer new insights into the development of more potent inhibitors of Aß fibrillogenesis and cytotoxicity.