The clinical, molecular, and therapeutic implications of time from primary diagnosis to brain metastasis in lung and breast cancer patients.

PURPOSE: Lung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM. METHODS: We retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan-Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively. RESULTS: The median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple-negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM. CONCLUSIONS: This single-institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

New insights into the kinetics of bacterial growth and decay in pig manure-wheat straw aerobic composting based on an optimized PMA-qPCR method.

Aerobic composting is a bacteria-driven process to degrade and recycle wastes. This study quantified the kinetics of bacterial growth and decay during pig manure-wheat straw composting, which may provide insights into microbial reaction mechanisms and composting operations. First, a propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) method was developed to quantify the viable bacteria concentration of composting samples. The optimal PMA concentration and light exposure time were 100 µM and 8 min respectively. Subsequently, the concentrations of total and decayed bacteria were quantified. Viable and decayed bacteria coexisted during the entire composting period (experiments A and B), and the proportion of viable bacteria finally fell to only 35.1%. At the beginning, bacteria grew logarithmically and decayed rapidly. Later, the bacterial growth in experiment A remained stable, while that of experiment B was stable at first and then decomposed. The duration of the stable stage was positively related to the soluble sugar content of composting materials. The logarithmic growth and rapid decay of bacteria followed Monod equations with a specific growth (0.0317 ± 0.0033 h-1 ) and decay rate (0.0019 ± 0.0000 h-1 ). The findings better identified the bacterial growth stages and might enable better prediction of composting temperatures and the degree of maturation.

Degradation of tetra- and trichloroethylene under iron reducing conditions by Acidimicrobiaceae sp. A6.

The degradation of trichloroethylene (TCE) and tetrachloroethylene (PCE), in incubations where ammonium was oxidized while iron was being reduced indicates that these compounds can be degraded during the Feammox process by Acidimicrobiaceae sp. A6 (ATCC, PTA-122488). None of these compounds were degraded in incubations to which no ammonium was added, indicating that they were degraded during the oxidation of ammonium. Degradation of TCE and PCE (ranging between 32% and 55%) was observed in incubations with a pure Acidimicrobiaceae sp. A6 culture as well as an Acidimicrobiaceae sp. A6 enrichment culture over a 2-week period. In addition to these batch studies, a column study, with a 5-h hydraulic residence time, was conducted contrasting the degradation of TCE in iron-rich soil columns that were either seeded with a pure or an enrichment culture of Acidimicrobiaceae sp. A6 to achieve ammonium oxidation under iron reduction, and a control column that was initially not seeded and later seeded with Geobacter metallireducens. While there was ∼22% TCE removal in the columns seeded with Acidimicrobiaceae sp. A6, there was no removal in the unseeded column or the column seeded with G. metallireducens which was being operated under iron reducing conditions. Feammox is an anoxic process that requires acidic conditions. Hence, these results indicate that this process might be harnessed where other bioremediation strategies are difficult, since many require neutral or alkaline conditions, and supplying ammonium to an anoxic aquifer is relatively easy, since there are not many processes that will oxidize ammonium in the absence of dissolved oxygen.

Multivariate and Multiscale Approaches for Interpreting the Mechanisms of Nitrous Oxide Emission during Pig Manure-Wheat Straw Aerobic Composting.

Nitrous oxide (N2O) emission during composting causes nitrogen loss and air pollution. The interpretation of N2O emission mechanisms will help to customize composting strategies that mitigate climate change. At pile and particle scales, this study characterized N2O emission-related variables (gases, ions, and microbes) and their correlations during pig manure-wheat straw aerobic composting. Pile-scale results showed that N2O emission mainly occurred in mesophilic, thermophilic, and cooling phases; the nitrification by ammonia-oxidizing bacteria ( AOB) and nitrite-oxidizing bacteria ( NOB) coexisted with the denitrification by denitrificans ( DEN); the major NOB and DEN were Nitrobacter ( NOB_Nba) and Thiobacillus denitrificans ( DEN_Tb), respectively. The mechanisms of nitrification, nitrifier denitrification, and anaerobic denitrification in composting particles were initially visualized by confocal laser scanning microscopy: Betaproteobacteria ( AOB_ Beta) sporadically distributed on the outer area of the particles, NOB_Nba internally attached to AOB_ Beta, and Nitrosomonas europea/ Nitrosomonas eutropha ( AOB_eu) and DEN_Tb concentrated in the interior. Correlation analysis of the variables showed that the distribution area of AOB_eu was proportional to N2O emission ( R2 = 0.84); AOB not only participated in nitrification but also nitrifier denitrification, and N2O formation was mainly from nitrifier denitrification by AOB_eu during the mesophilic-thermophilic phase and from denitrification by AOB_eu and DEN during the cooling phase.

Modelling for reactor-style aerobic composting based on coupling theory of mass-heat-momentum transport and Contois equation.

This study establishes an optimal mathematical modelling to rationally describe the dynamic changes and spatial distribution of temperature and oxygen concentration in the aerobic composting process using coupling mass-heat-momentum transfer based on the microbial mechanism. Two different conditional composting experiments, namely continuous aeration and intermittent aeration, were performed to verify the proposed model. The results show that the model accurately predicted the dynamic changes in temperature (case I: R2 = 0.93, RMSE = 1.95 K; case II: R2 = 0.86, RMSE = 4.69 K) and oxygen concentration (case I: R2 = 0.90, RMSE = 1.26%; case II: R2 = 0.75, RMSE = 2.93%) in the central point of compost substrates. It also systematically simulated fluctuations in oxygen concentration caused by boundary conditions and the spatial distribution of the actual temperature and oxygen concentration. The proposed model exhibits good applicability in simulating the actual working conditions of aerobic composting process.

Particle-scale visualization of the evolution of methanogens and methanotrophs and its correlation with CH4 emissions during manure aerobic composting.

Methane (CH4) emissions are a major environmental concern in composting facilities. Therefore, this study initially visualized the dynamic distribution and quantity of methanogens and methanotrophs in composting particles during manure aerobic composting using fluorescence in situ hybridization-confocal laser scanning microscopy (FISH-CLSM) and quantified their correlation with CH4 emissions. The visualization results showed that methanogens existed inside the particles, while methanotrophs clustered in the outer layer; a facultative anaerobic zone existed in between. The quantification results of integral optical density of methanogens and methanotrophs per unit particle area (Ugen and Uoxi, respectively) indicated that, in the cooling phase, CH4 generation and oxidation could still be high and could strike a balance if the initial organic matter content of composting materials is high, while both could be extremely low if the content is low. A strong linearity between Ugen obtained by FISH-CLSM and methyl-coenzyme M reductase copy number obtained by quantitative polymerase chain reaction analysis (R2 = 0.88) was observed, which justified the effectiveness of the FISH-CLSM method and demonstrated that macro-scale CH4 emissions were essentially an accumulation of particle-scale CH4 emissions. CH4 emissions were equal to 3.3297 × 107Ugen - 3.1814 × 106Uoxi - 3902.9900 (R2 = 0.98). Overall, the results showed that methanogens exerted more influence on CH4 emissions than methanotrophs. Combining these results with CH4-generation and -oxidation kinetics may help illustrate CH4-emission mechanisms, improve particle-scale CH4-emission models, and thereby provide theoretical guidance for operation optimization and emission reduction in composting processes.

Effect of aeration interval on oxygen consumption and GHG emission during pig manure composting.

To verify the optimal aeration interval for oxygen supply and consumption and investigate the effect of aeration interval on GHG emission, reactor-scale composting was conducted with different aeration intervals (0, 10, 30 and 50 min). Although O2 was sufficiently supplied during aeration period, it could be consumed to <10 vol% only when the aeration interval was 50 min, indicating that an aeration interval more than 50 min would be inadvisable. Compared to continuous aeration, reductions of the total CH4 and N2O emissions as well as the total GHG emission equivalent by 22.26-61.36%, 8.24-49.80% and 12.36-53.20%, respectively, was achieved through intermittent aeration. Specifically, both the total CH4 and N2O emissions as well as the total GHG emission equivalent were inversely proportional to the duration of aeration interval (R2 > 0.902), suggesting that lengthening the duration of aeration interval to some extent could effectively reduce GHG emission.

Particle-Scale Modeling of Methane Emission during Pig Manure/Wheat Straw Aerobic Composting.

Inefficient aerobic composting techniques significantly contribute to the atmospheric methane (CH4) levels. Macro-scale models assuming completely aerobic conditions cannot be used to analyze CH4 generation in strictly anaerobic environments. This study presents a particle-scale model for aerobic pig manure/wheat straw composting that incorporates CH4 generation and oxidation kinetics. Parameter estimation revealed that pig manure is characterized by high CH4 yield coefficient (0.6414 mol CH4 mol(-1) Cman) and maximum CH4 oxidation rate (0.0205 mol CH4 kg(-1) VS(aero) h(-1)). The model accurately predicted CH4 emissions (R(2) = 0.94, RMSE = 2888 ppmv, peak time deviation = 0 h), particularly in the self-heating and cooling phases. During mesophilic and thermophilic stages, a rapid increase of CH4 generation (0.0130 mol CH4 kg(-1) VS h(-1)) and methanotroph inactivation were simulated, implying that additional measures should be performed during these phases to mitigate CH4 emissions. Furthermore, CH4 oxidation efficiency was related to oxygen permeation through the composting particles. Reducing the ambient temperature and extending the aeration duration can decrease CH4 emission, but the threshold temperature is required to trigger the self-heating phase. These findings provide insights into CH4 emission during composting and may inform responsible strategies to counteract climate change.

Mechanism and kinetics of organic matter degradation based on particle structure variation during pig manure aerobic composting.

Characterization of the dynamic structure of composting particles may facilitate our understanding of the mechanisms of organic matter degradation during pig manure-wheat straw aerobic composting. In this study, changes in the size, shape, pores, chemical compositions, and crystal structures of pig manure particles during composting were investigated. The results showed that the median diameter (D50) decreased exponentially, while the particle aspect ratio and sphericity were unchanged, suggesting that particles were degraded uniformly along different radial directions. Pores had a mean diameter of 15-30 µm and were elliptical. The particle porosity increased linearly mainly because of hemicellulose degradation. Furthermore, the influence of particle structure variation on the first order rate constant (k) of organic matter degradation was corrected, which may facilitate the optimization of operation conditions. The k value was proportional to the reciprocal of D50 according to the specific surface area of particles, and it decreased with increased porosity due to the stabilized chemical compositions and crystal structures of particles. However, the applicability of these data to other composting materials should be verified.

Characterization of the dynamic thickness of the aerobic layer during pig manure aerobic composting by Fourier transform infrared microspectroscopy.

A new method for characterizing the aerobic layer thickness in pig manure based on Fourier transform infrared microspectroscopy (FTIRM) is presented to improve the anaerobic/aerobic co-process mechanism, to ensure adequate oxygen supply and, thus, minimize methane emissions during aerobic composting. Freeze-dried manure particles were microtomed into 10 µm thick sections; the spectral range, spectral resolution, and pixel dimensions in the transmission spectra were 4000-650 cm(-1), 16 cm(-1), and 6.25 × 6.25 µm, respectively. A mean spectrum of 16 scans was used for the second-derivative analysis with nine smoothing points. This is the first attempt at determining the oxidation profile of composting particles according to the radial variations in second-derivative spectra at 2856 and 1568 cm(-1), which are attributed to the reactants and products of the oxidation, respectively. In addition, an intermediate area is detected between the aerobic layer and anaerobic core. The experimental values of the aerobic layer thickness are consistent with the estimates, and an exponential increase is observed, which is influenced by multiple dynamic factors. However, the contribution of each factor to dynamic variations in the aerobic layer thickness should be investigated using available methods.