Synergistic promotion of microalgal growth and copper removal from synthetic wastewater by nanoscale zero-valent iron particles.

The increasing concentrations of heavy metals in livestock wastewater pose a serious threat to the environmental safety and human health, limiting its resource utilisation. In the present study, microalgae and nanoscale zero-valent iron were selected to construct a coupled system for copper-containing wastewater treatment. The addition of 50 mg·L-1 nanoscale zero-valent iron (50 nm) was the optimal value for the experiment, which could significantly increase the biomass of microalgae. In addition, nanoscale zero-valent iron stimulated microalgal secretion of extracellular polymeric substances, increasing the contents of binding sites, organic ligands, and functional groups on the microalgal surfaces and ultimately promoting the settling of microalgae and binding of heavy metals. The coupled system could quickly adapt to copper-containing wastewater of 10 mg·L-1, and the copper removal rate reached 94.99%. Adsorption and uptake by organisms, together with the contribution of zero-valent iron nanoparticles, are the major copper removal pathways. Overall, this work offers a novel technical solution for enhanced treatment of copper-containing livestock wastewater, which will help improve the efficiency and quality of wastewater treatment.

Real-world data on the first-line immune checkpoint inhibitors or in combination with chemotherapy in older patients (aged ≥ 75 years) with advanced non-small cell lung cancer.

Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

UV irradiation enhanced removal of colloidal phosphorus in agricultural runoff.

Colloidal phosphorus (P) is an important P form in agricultural runoff and can threaten water quality. However, up to date, there are few effective approaches to mitigate colloidal P pollution. This study investigated the effect of ultraviolet (UV) irradiation on medium-colloidal (MC; 220 nm-450 nm) and fine-colloidal (FC; 3 kDa-220 nm) P in agricultural runoff. Under 24 h of UV irradiation, as the most abundant colloidal P fraction, concentration of total P (TP) in FC consistently decreased by 81.0%, while TP concentration in MC first increased by 74.4% after 3 h and then decreased with irradiation time. At the same time, particulate TP (>450 nm) concentration was found to be increased from 0 to 14.7 µM. However, there were no obvious variations in TP concentrations in FC and MC fractions under dark conditions. In FC fraction, with the decrease of TP, the corresponding concentrations of iron (Fe), aluminum (Al), silicon (Si) declined synchronously, and ferric iron/ferrous iron (Fe(III)/Fe(II)) ratio and organic matter (OM) concentration were reduced as well. These results suggested that P in FC fraction was gradually transformed into particulate P during photoreduction of Fe(III) and photodegradation of OM under UV irradiation. Our study helps to understand the mechanism of the phototransformation of colloidal P, and propose an UV irradiation-based approach to remove colloidal P in agricultural runoff.

Biodegradable photo-crosslinked polycaprolactone/polydopamine elastomers with excellent light driven programmable shape memory and chemical degradation properties.

Fabrication of biodegradable shape memory polymer with remotely controllable shape actuation is of great significance in the biomedical field but remains challenging. Herein, we present a simple strategy to fabricate a monolayer-based stretchable and mechanically robust polycaprolactone/polydopamine elastomer via efficient thiol-ene click chemistry. The resultant elastomers exhibit desirable photothermal transfer efficiency and can enable rapid temperature increase over the melting temperature of polymeric matrix, and quantitative results demonstrate that the crosslinked film exhibited excellent shape memory properties with shape fixity (Rf) and shape recovery ratios (Rr) approaching 92.3 % and 95.6 %, respectively. Combined with photo stimuli, anisotropic polymer chain relaxation of the prestretched film can generate asymmetric contractions and eventually give rise to ut out-of-plane bending actuations upon photo stimulation, meanwhile, numerical simulation reveals the interaction mechanism of light with film. Beyond this, we further demonstrate that the bending angle is correlated with the parameters of prestretch strain, film thickness as well as irradiation time, and the maximum value can reach 158° with prestretch strain of 200 % and film thickness of 0.3 mm. In particular, the bent structures could be reversibly deformed into plane state via photo-directed corresponding opposite surfaces. Remarkably, the in vitro degradation properties of the elastomers on PBS-T buffer solutions demonstrated that the degradation was composed of induction stage and acceleration stage. This work will pave way for designing biodegradable light-induced shape memory materials toward biomedical device fields and so on.

Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.

The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P  = 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P  = 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P  = 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P  = 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.

Triphenylamine-Based N,O-Bidentate BF2 -Enolimine Initiator for Three-Arm Star Polymethacrylates with Dual-State Fluorescent Emission.

Three-arm star polymethacrylates with dual-phase (solution and solid-state) fluorescent emission have been synthesized via atom transfer radical polymerization (ATRP) using a triphenylamine-derived organboron complex (TAPA-BKI-3Br) as initiator. The as-synthesized three-arm star polymethacrylates exhibited bright emission in both solution and the solid states due to the highly twisted structure and intramolecular charge transfer (ICT) effect of TAPA-BKI core, as well as the steric effect and restriction of intramolecular motions from the polymer arms. And the polymer chains have an important influence on the photophysical behavior of the as-synthesized three-arm star polymethacrylates in the aggregated state.

[Analysis on Change in Soil Organic Carbon Content of Farmland in Yangtze River Economic Belt Under Different Fertilizing Measures].

The literature from a long-term fertilization experiment in the Yangtze River Economic Belt from January 1992 to May 2022 was collected, and the data of farmland soil organic carbon were extracted and integrated. Using the normalization treatment and the analysis method of relative annual variation, the overall change in soil organic carbon content in farmland in the Yangtze River Economic Belt under different long-term fertilization measures was studied, and the change differences of soil organic carbon content under three tillage modes were compared so as to judge and analyze the influence of the duration of the experiment on soil organic carbon dynamics. The results showed that under different long-term fertilization measures, the organic carbon content of farmland soil in the Yangtze River Economic Belt in China showed an overall upward trend. The NP, NPK, O, and NPKO treatments all increased the organic carbon content of agricultural soils, with that of the NPKO treatment being the largest. The sole application of inorganic nitrogen fertilizer reduced the organic carbon content of the soil. The rates of change in soil organic carbon content were 0.22 g·(kg·a)-1, 0.24 g·(kg·a)-1, and 0.16 g·(kg·a)-1for dryland, paddy, and water-dry rotation farmland, respectively. Additionally, the relatively rapid increase effect of organic carbon brought by the O and NPKO treatments could last for no more than 28 years in dryland soil but could still last for more than 28 years in paddy field and paddy-upland rotation soil. There was some variation in the rate of change of soil organic carbon content between soil types. The average rate of change of organic carbon was 0.25 g·(kg·a)-1for red soils, 0.14 g·(kg·a)-1 for brown soils, 0.19 g·(kg·a)-1 for tidal soils, and 0.15 g·(kg·a)-1 for rice soils. The trend of NPKO>O>NPK>NPK>NP>N was basically maintained for the rate of change in soil organic carbon content. The NPKO treatments were all significantly higher than the chemical fertilizer (N, NP, and NPK) treatments alone. The N treatment showed a reduction in organic carbon content in both red soil and rice soils. Considering the carbon fixation of farmland soil, the combined application of organic and inorganic fertilizers is a more suitable fertilization method in this area.

Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis.

BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. RESULTS: A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. CONCLUSION: A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD.

Eutrophication levels increase sulfur biotransformation and emissions from sediments of Lake Taihu.

Eutrophication can stimulate the emissions of volatile sulfur compounds (VSCs) accompanied by variations in environmental variables in lakes. However, the effects of eutrophication on VSC emissions from lake sediments as well as the underlying mechanisms remain unclear. In this study, depth gradient sediments at different eutrophication levels and seasons were collected from Lake Taihu to investigate the response of sulfur biotransformation in the sediments to eutrophication based on the analysis of environmental variables, microbial activity, abundance and community structure. H2S and CS2 were the main VSCs produced from the lake sediments, with the production rates of 2.3-7.9 and 1.2-3.9 ng g-1 h-1 in August, respectively, which were higher than those in March, mainly due to the increasing activity and abundance of sulfate-reducing bacteria (SRB) at high temperatures. The VSC production rates from the sediments increased with lake eutrophication level. Higher VSC production rates were detected in surface sediments in eutrophic regions but in deep sediments in oligotrophic regions. Sulfuricurvum, Thiobacillus and Sulfuricella were the main sulfur-oxidizing bacteria (SOB) in the sediments, while Desulfatiglans and Desulfobacca were the predominant SRB. Organic matter, Fe3+, NO3--N and total sulfur had significant influences on the microbial communities in the sediments. Partial least squares path modelling showed that the trophic level index could stimulate VSC emissions from lake sediments by influencing the activities and abundances of SOB and SRB. These findings indicated that sediments contributed substantially to VSC emissions from eutrophic lakes, especially surface sediments, and sediment dredging might be an effective way to mitigate VSC emissions from eutrophic lakes.

Aneuploid subtypes of circulating tumor cells and circulating tumor-derived endothelial cells predict the overall survival of advanced lung cancer.

Objective: This study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers. Methods: A total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified. Results: Based on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P<0.0001) in the four groups including triploid small cell size CTCs and multiploid small cell size CTECs, and multiploid small cell size CTCs and monoploid small cell size CTECs. Furthermore, combined detection of the specific subtypes, including triploid small CTC and monoploid small CTEC, triploid small CTC and triploid small CTEC, and multiploid small CTC and monoploid small CTEC, were associated with poor prognosis in advanced lung cancer. Conclusions: Aneuploid small CTCs are associated with the outcome of patients with advanced lung cancer. In particular, the combined detection of triploid small CTCs and monoploid small CTECs, triploid small CTCs and triploid small CTECs, and multiploid small CTCs and monoploid small CTECs has clinical significance for predicting prognosis in patients with advanced lung cancer.

Characterization of methanotrophic community and activity in landfill cover soils under dimethyl sulfide stress.

Landfill cover soil is the environmental interface between landfills and the atmosphere and plays an important role in mitigating CH4 emission from landfills. Here, stable isotope probing microcosms with CH4 or CH4 and dimethyl sulfide (DMS) were carried out to characterize activity and community structure of methanotrophs in landfill cover soils under DMS stress. The CH4 oxidation activity in the landfill cover soils was not obviously influenced at the DMS concentration of 0.05%, while it was inhibited at the DMS concentrations of 0.1% and 0.2%. DMS-S was mainly oxidized to sulfate (SO42-) in the landfill cover soils. In the landfill cover soils, DMS could inhibit the expression of bacteria and decrease the abundances of pmoA and mmoX genes, while it could prompt the expression of pmoA and mmoX genes. γ-Proteobacteria methanotrophs including Methylocaldum, Methylobacter, Crenothrix and unclassified Methylococcaceae and α-Proteobacteria methanotrophs Methylocystis dominated in assimilating CH4 in the landfill cover soils. Of them, Methylobacter and Crenothrix had strong tolerance to DMS or DMS could promote the growth and activity of Methylobacter and Crenothrix, while Methylocaldum had weak tolerance to DMS and showed an inhibitory effect. Metagenomic analyses showed that methanotrophs had the genes of methanethiol oxidation and could metabolize CH4 and methanethiol simultaneously in the landfill cover soils. These findings suggested that methanotrophs might metabolize sulfur compounds in the landfill cover soils, which may provide the potential application in engineering for co-removal of CH4 and sulfur compounds.

Bioconversion of food waste to crayfish feed using solid-state fermentation with yeast.

In order to realize the value-added utilization of food waste (FW), the preparation of crayfish (Procambarus clarkii) feed by yeast fermentation was investigated. Firstly, the suitable fermentation condition was obtained through a single factor experiment as follows: the initial moisture of the FW was adjusted to 60% with bran and inoculated with a 2% yeast mixture (Saccharomyces cerevisiae, Candida utilis, and Yarrowia lipolytica, 3:2:1) followed by aerobic solid-state fermentation for 7 days. The crude protein and acid-soluble protein contents in the fermented feed were 25.14% and 5.16%, which were increased by 8% and 140.67%, respectively. The crude fat content was 0.74%, decreased by 68.29%. The content of antioxidant glutathione (571.78 µg/g) increased 63.33%, and the activities of protease and amylase increased nearly 9 and 3 times, respectively. The maximum degradation rates of aflatoxin B1, zearalenone, and deoxynivalenol were 63.83%, 77.52%, and 80.16%, respectively. The fermented feeds were evaluated by substituting (0%, 10%, 30%, 50%, and 100%) commercial diet for crayfish (30-day culture period). When the replacement proportion was 30%, the weight gain of crayfish reached 44.87% (initial body weight 13.98 ± 0.41 g), which was significantly increased by 10.25% compared with the control (p = 0.0005). In addition, the lysozyme and SOD enzyme activities in crayfish hepatopancreas were also increased significantly. Our findings suggest that yeast-fermented feed from FW can replace 30% of crayfish's conventional diet, which may improve crayfish's antioxidant capacity and enhance non-specific immunity by providing molecules such as glutathione.

Estimation of sulfur fate and contribution to VSC emissions from lakes during algae decay.

Algae decay is an important process influencing environmental variables and emissions of volatile sulfur compounds (VSCs) in eutrophic lakes. However, effects of algae decay on VSC emissions from eutrophic lakes as well as fate of algae-derived sulfur remain poorly understood. In this study, simulated algae-sediment systems were used to explore the flow and distribution of sulfur during algae decay. VSCs including hydrogen sulfide (H2S), methanethiol (CH3SH), carbon disulfide (CS2) and dimethyl sulfide ((CH3)2S) were detected during algae decay, which increased with algae biomass and eutrophic levels in lakes. During algae decay, the highest H2S, CH3SH and (CH3)2S emission rates of 10.45, 21.82 and 43.26 µg d-1 occurred in the first 1-2 days, respectively, while the highest CS2 emission rates were observed between days 8 and 11. The maximum emissions of H2S and CS2 from algae decay were estimated at 0.51 and 0.35 mg m-2 d-1 in Lake Taihu, accounting for 1.57% and 0.69% of the total H2S and CS2 emissions of in situ, respectively. Algae decay could significantly increase the contents of total sulfur and total carbon in sediments by 2.90%-21.11% and 4.23%-45.05%, respectively. The VSC emissions during algae decay could be predicted using the multiple regression models with the contents of total carbon, total nitrogen and sulfur-containing compounds in sediments. Partial least squares path modelling demonstrated that algae decay had a low direct effect on VSC emissions with a strength of 0.06, while it had a significant influence on environmental variables with a strength of 0.63, which could affect VSC emissions with a strength of 0.85, indicating VSC emissions from eutrophic lakes were affected by the environmental variables rather than the direct influence of algae decay. These findings illustrated the mechanisms of VSC emissions during algae decay and provided insights into VSC control and mitigation for eutrophic lakes.

Second-line treatment options in advanced thymic carcinoma after failure of platinum-based chemotherapy: A multicenter retrospective study.

BACKGROUND: Currently there is no standard therapy recommended for second-line treatment for thymic carcinoma. Our study compared multidrug chemotherapy, single-agent chemotherapy, and PD-1 inhibitors in patients diagnosed with advanced thymic carcinoma who had previous platinum-based chemotherapy at the clinic. METHODS: The study included patients with thymic carcinoma who failed first-line platinum-based chemotherapy. Kaplan-Meier methods were applied in the study for estimating the progression-free survival (PFS) and overall survival (OS) curves. Pearson chi-square or Fisher's exact chi-square test was adopted to make comparisons of the objective response rate (ORR) between treatment groups. Cox regression was used for the multivariate analyses in PFS and OS. RESULTS: Among the 92 patients enrolled, multidrug chemotherapy was used in 51 (55.4%) patients for second-line therapy. Thirty-six patients (35.9%) received single-agent chemotherapy, and eight patients (8.7%) underwent PD-1 inhibitors. The multidrug chemotherapy group showed better efficacy than the other two groups, with an ORR of 35.3% (p = 0.006). The median PFS of multidrug chemotherapy, single-agent chemotherapy and PD-1 inhibitors were 5.0 months, 3.0 months, and 4.0 months, respectively (p = 0.008). Patients in the multidrug chemotherapy group also showed an advantage in OS in comparison with the other two treatment groups (p = 0.045), with a median OS of 30.4 months. Multivariate analysis showed that second-line treatment was independent factor for both PFS (p = 0.035) and OS (p = 0.037). Grade 3-4 AEs were mostly detected in patients receiving multidrug chemotherapy and were primarily hematologic. Treatment-related mortality was not found in any of the groups. CONCLUSIONS: Multidrug chemotherapy had a trend toward a more positive response rate and outcomes in longer survival time than single-agent chemotherapy and PD-1 inhibitors. Multidrug chemotherapy is a choice worth considering for second-line therapy in patients with thymic carcinoma if tolerable.

The overall survival benefit in Chinese ALK+ NSCLC patients received targeted therapies.

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement is a series of mutations of non-small cell lung cancer (NSCLC) patients. Since 2011, multiple ALK inhibitors (ALKis) have been developed and launched for targeted therapy. In this study, we sought to investigate different strategies of sequential applying the ALKis and their clinical benefits to the overall survival (OS). Methods: A total of 176 patients with advanced NSCLC (stage IIIB-IV) harboring the ALK rearrangement were included in this cohort study. They were diagnosed between February 1, 2012 and November 19, 2019 at Peking University Cancer Hospital. Clinical characters were reviewed from patients' records. Strategies of drugs, progression-free survival (PFS) and OS were collected during the follow-ups. The Kaplan-Meier method and multivariate Cox proportional-hazard analysis were used to conduct the analyses survival and to examine the relationship between the variables and OS. Results: A significantly longer OS was observed either in patients treated with crizotinib [N=106, median OS (mOS): 32.9 months] or in patients treated with a next-generation ALKi [N=34, mOS: not reached (NR)] as the initial ALKi, compared with patients treated with conventional chemotherapy but no ALKi (N=36, mOS: 10.3 months, P<0.001). After disease progression with initial crizotinib, patients who received no ALKi had shorter OS than those who received only crizotinib beyond progressive disease (CBPD) (mOS: 9.7 vs. 20.3 months; P=0.015), only subsequent next-generation ALKis (mOS: 9.7 vs. 41.1 months; P<0.001), and CBPD followed with subsequent next-generation ALKis (mOS: 9.7 months vs. NR; P<0.001). Patients treated with 2 types of ALKi had better survival than those treated with 1 ALKi (mOS: 45.8 vs. 21.3 months, P=0.003), but no such survival benefit was observed in patients treated with ≥3 ALKis (P=0.366). Conclusions: ALKis have been shown to be clinically effective in treating NSCLC patients with ALK rearrangements. In the case of disease progression with crizotinib, either of CBPD or sequential other ALKis can extend patients' OS. The sequential application of multiple ALKis was found to be better than it of single ALKi in prolonging OS. However, the question of which inhibitor to select as the initial inhibitor needs to be examined further in future studies.

Eutrophic levels and algae growth increase emissions of methane and volatile sulfur compounds from lakes.

Eutrophic lakes are hot spots of CH4 and volatile sulfur compound (VSC) emissions, especially during algal blooms and decay. However, the response of CH4 and VSC emissions to lake eutrophication and algae growth as well as the underlying mechanisms remain unclear. In this study, the emissions of CH4 and VSCs from four regions of Lake Taihu with different eutrophic levels were investigated in four months (i.e., March, May, August and December). The CH4 emissions ranged from 20.4 to 126.9 mg m-2 d-1 in the investigated sites and increased with eutrophic levels and temperature. H2S and CS2 were the dominant volatile sulfur compounds (VSCs) emitted from the lake. The CH4 oxidation potential of water ranged from 2.1 to 14.9 µg h-1 L-1, which had positive correlations with trophic level index and the environmental variables except for the NH4+-N concentration. Eutrophic levels could increase the abundances of bacteria and methanotrophs in lake water. α-Proteobacteria methanotroph Methylocystis was more abundant than γ-Proteobacteria methanotrophs in March and May, while the latter was more abundant in August and November. The relative abundance of Cyanobacteria, including Microcystis, A. granulata var. angustissima and Cyanobium had significantly positive correlations with temperature, turbidity, SO42--S, and total sulfur. Partial least squares path modelling revealed that the algal growth could promote VSC emissions, which had a positive correlation with CH4 oxidation potential, likely due to the positive correlation between the CH4 and VSC emissions from lakes. These findings indicate that water eutrophication and algae growth could increase the emissions of CH4 and VSCs from lakes. Controlling algae growth might be an effective way to mitigate the emissions of CH4 and VSCs from freshwater lakes.

Intermittent aeration reducing N2O emissions from bioreactor landfills with gas-water joint regulation.

Landfills are important emission sources of atmospheric N2O, especially bioreactor landfills with leachate recirculation. In this study, N2O emissions were characterized in four bioreactor landfills with different ventilation methods, including intermittent (2-h aeration per 12 h or 4 h/d in continuous) and continuous aeration (20 h/d), in comparison to a traditional landfill without aeration. During the experiment, the N2O emissions from the landfill reactors with intermittent aeration were 7.48 and 7.15 mg, accounting for only 20.8% and 19.9% of those with continuous aeration, respectively. Continuous aeration was more favorable for the biodegradation of organic matter than intermittent aeration in the landfilled waste and leachate. Intermittent and continuous aeration could both effectively remove total nitrogen (TN) and NH4+-N with removal efficiencies above 64% in the leachate. In the experimental landfill reactors with gas-water joint regulation, the proportion of N2O-N to TN loss ranged from 0.02% to 0.75%. Luteimonas, Pseudomonas, Thauera, Pusillimonas and Comamonas were the dominant denitrifying bacteria in the landfill reactors. The denitrifying bacterial community in the landfilled waste was closely related to its degree of stabilization and nitrogenous compound concentrations in the landfilled waste and leachate. The NO3--N and NO2--N concentrations of leachate were the most important environmental factors affecting the succession of nirS-type and nirK-type denitrifying microbial communities in the landfilled waste. These findings indicated that intermittent aeration was an economical and effective way to accelerate the stabilization of landfilled waste and reduce the pollutants in leachate and N2O emissions during landfill mining and reclamation.

CS2 increasing CH4-derived carbon emissions and active microbial diversity in lake sediments.

Lakes are important methane (CH4) sources to the atmosphere, especially eutrophic lakes with cyanobacterial blooms accompanied by volatile sulfur compound (VSC) emissions. CH4 oxidation is a key strategy to mitigate CH4 emission from lakes. In this study, we characterized the fate of CH4-derived carbon and active microbial communities in lake sediments with CS2 used as a typical VSC, based on the investigation of CH4 and VSC fluxes from Meiliang Bay in Lake Taihu. Stable isotope probing microcosm incubation showed that the efficiency of CH4-derived carbon incorporated into organic matter was 21.1% in the sediment with CS2 existence, which was lower than that without CS2 (27.3%). SO42--S was the main product of CS2 oxidation under aerobic condition, accounting for 59.3-62.7% of the input CS2-S. CS2 and CH4 coexistence led to a decrease of methanotroph and methylotroph abundances and stimulated the production of extracellular polymeric substances. CS2 and its metabolites including total sulfur, SO42- and acid volatile sulfur acted as the main drivers influencing the active microbial community structure in the sediments. Compared with α-proteobacteria methanotrophs, γ-proteobacteria methanotrophs Methylomicrobium, Methylomonas, Crenothrix and Methylosarcina were more dominant in the sediments. CH4-derived carbon mainly flowed into methylotrophs in the first stage. With CH4 consumption, more CH4-derived carbon flowed into non-methylotrophs. CS2 could prompt more CH4-derived carbon flowing into non-methanotrophs and non-methylotrophs, such as sulfur-metabolizing bacteria. These findings can help elucidate the influence of VSCs on microorganisms and provide insights to carbon fluxes from eutrophic lake systems.

Heterogeneity of humic/fulvic acids derived from composts explains the differences in accelerating soil Cd-hyperaccumulation by Sedum alfredii.

The hyperaccumulating mechanism concerning heavy metal activation or passivation and plant response triggered by fulvic acid (FA) and humic acid (HA) recruitments are investigated herein. We carefully examine the Cd activation effect by various FA and HA, tracing from pig, goat, and duck manure composts to straw compost and commercial materials (i.e., PC, GC, DC, SC, and CM), as well as their roles in plant growth promotion and Cd uptake. Our results indicate that due to the decrease of soil pH and their multiple functional groups, the contents of available Cd (AE-Cd) increased by 4.3-4.8% and 3.6-6.3% when all FA and HA sources were applied for 30 days. A 13.1-19.9% increase in AE-Cd was observed when CFA, DFA, and PFA were applied for five days, and a 9.5% increment was found when PHA was applied for 10 days. In the pot experiment, the Cd accumulation in plants increased by 2.78 and 2.17 folds with PFA and PHA applications, respectively, compared to the blank control group. This result can be attributed to the stimulative effects of the simultaneous Sedum alfredii growth and Cd phytoavailability. Notably, the Cd accumulation increased by 2.26 times with the SFA amendment due to the predominant stimulation effect to the phytoavailable Cd rather than plant growth. However, slight inhibitory effects were observed upon plant growth or Cd uptake, which led to the reduction of the Cd accumulation with DHA, SHA, and CHA employments. Consistently, the corresponding soil Cd removal efficiencies were 43.5% and 34.6% with PFA and PHA, respectively, which hold abundant O- and N-containing groups. Our research aims to gain insights into the ternary interaction in the presence of heavy metal, humic substances, and S. alfredii to simultaneously accelerate Cd activation and hyperaccumulation.

Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC.

BACKGROUND: The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. MATERIALS AND METHODS: The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. RESULTS: Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3-4 adverse events (AEs) between the two groups (p = 0.253). CONCLUSIONS: The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.