Identification and characterization of a phosphinothricin N-acetyltransferase from Enterobacter LSJC7.

Phosphinothricin (PPT) is a widely used and non-selective herbicide. PPT-resistance genes, especially PPT N-acetyltransferase genes, have been used in the development of transgenic PPT-resistant crops. However, there are only a limited number of available PPT-resistance genes for use in plant biotechnology. In this study, we found that Enterobacter LSJC7 is highly resistant to PPT and can acetylate PPT to N-acetyl phosphinothricin (Ac-PPT). Furthermore, a novel PPT N-acetyltransferase gene, named LsarsN, was identified from LSJC7. When LsarsN was expressed in E. coli AW3110, it confered resistance to PPT. Ac-PPT was detected in both the culture medium and cells of AW3110 expressing the LsarsN-pET22b plasmid. The purified LsArsN protein also showed strong N-acetylation ability in vitro, and its enzymatic kinetic curve was fitted with the Michaelis-Mentan equation. Compared with wild-type LsArsN, both R72A and R74A mutants showed significantly lower PPT N-acetylation ability. In summary, our results systematically characterized LsArsN with strong ability for PPT N-acetylation, which lays the groundwork for future research into the use of this novel gene, LsarsN, to create PPT-resistant crops.

Occurrence, distribution, and characteristics of microplastics in agricultural soil around a solid waste treatment center in southeast China.

Purpose: In recent years, microplastic (MP) contamination has raised enormous concern. However, data on the influence of solid waste treatment systems on MP pollution around agricultural soil are lacking. This study investigated the distribution and characteristics of MPs in agricultural soil surrounding a solid waste treatment center in southeastern China. Materials and methods: Fifty-seven agricultural topsoil samples around the solid waste treatment center were collected. The samples were pretreated by drying, flotation separation using NaCl solution, and digestion by H2O2. The abundance and morphological characteristics of MPs were determined by a microscope, followed by Raman spectroscopy analysis identified polymer types and SEM-EDS analysis observed surface morphology and the type of metals accumulated on the MPs. Results and discussion: Soil MPs' abundance ranged from 280 to 2360 items/kg, while a higher abundance of MPs was distributed in the downwind area. The < 1-mm MPs were dominant, and white fragment MPs were widely found. Polyethylene (52.86%) and polypropylene (27.14%) were the most common. Moreover, SEM-EDS images illustrated that MPs were significantly weathered and showed the uneven distribution of metal(loid) elements on the surface, implying that MPs may migrate as heavy metal vectors to threaten agroecosystem safety. Conclusions: This study reveals the distribution and characteristics of MPs in agricultural soil surrounding a solid waste treatment center in southeastern China, as well as the potential source of soil MPs, and provides systematic data for further research on MP pollution in agricultural soil. Supplementary Information: The online version contains supplementary material available at 10.1007/s11368-022-03341-6.

Reutilization of waste oyster shell as filler for filter for drinking water pretreatment: Feasibility and implication.

Oyster shell (OS) is a kind of reusable resource that can serve as carbon source, biofilms carrier and basifying agent, suggesting it is an attractive filler option for biofiltration, but studies on its application in drinking water treatment are limited. In this study, one pilot-scale up-flow filter filled with OS media were designed to pretreat surface source water. Filter performance and biological functions were investigated to determine its application scope. The results showed that effluent pH increased and was stable around 7.5 due to the alkalinity provided by OS and its buffering capacity. High and stable removal efficiencies of turbidity (mostly >60%) were achieved. The removal efficiencies of NH4+-N changed in a wide range (mostly <30%). TOC and UV254 removal rate was low (<10%). The biofilms formation period took about 45 days. During this period, this filter mainly removed pollutants through adsorption by OS. High-throughput sequencing results showed that functional taxa did not play a key role after adsorption saturation in early operation period. Functional microbial taxa formed on the OS surface after long-term operation and NH4+-N removal rate increased to some extent. Our results suggested that unburned OS filter can be used as rough filter for turbidity removal instead of coagulation and sedimentation process. Preoxidation, calcination of OS, mixed with other filler and are recommended to improve the performance if it would be used for biofiltration. This study provides an insight for the reuse of OS in drinking water treatment.

Incorporating bioaccessibility and source apportionment into human health risk assessment of heavy metals in urban dust of Xiamen, China.

Heavy metals in urban dust could pose noticeable human health risks, but there are few studies focusing on comprehensive human health risk assessment with the incorporation of both bioaccessibility and source apportionment in urban dust. Thus, fifty-eight urban dust samples were collected from kindergartens in Xiamen to analyze the bioaccessibility-based, source-specific health risk of heavy metals (V, Co, Ni, As, Mo, Cr, Mn, Cu, Zn, and Pb). Most heavy metals, except for V and Mn, were significantly enriched in urban dust based on their values of geoaccumulation index (Igeo) and may be influenced by human activities. The oral bioaccessibility values of heavy metals, which were estimated by the Solubility/Bioaccessibility Research Consortium (SBRC) in vitro model, ranged from 1.563% to 76.51%. The source apportionment determined by applying the absolute principal component analysis-multiple linear regression (APCS-MLR) model indicated five main potential sources, coal combustion, traffic and industrial, natural, construction and furniture sources, and unidentified sources, with contributions of 34.09%, 20.72%, 18.72%, 7.597% and 18.87%, respectively, to the accumulation of heavy metals in urban dust. After incorporating bioaccessibility adjustments, lower non-carcinogenic and carcinogenic risks of heavy metals were observed than those based on total metal content, with the mean hazard index (HI) values being less than the threshold value (1) and the mean total carcinogenic risk (TCR) values exceeding the precautionary criterion (10-6) for both adults and children. By combining bioaccessibility-based health risk assessment and source apportionment, traffic and industrial emissions and coal combustion dominated the noncarcinogenic and carcinogenic risks induced by heavy metals in urban dust, respectively. This study is expected to promote the systematic integration of source apportionment and bioaccessibility into health risk estimation for heavy metal contamination in urban dust, thus providing useful implications for better human health protection.

Potential exposure to metals and health risks of metal intake from Tieguanyin tea production in Anxi, China.

The metal content of Tieguanyin tea from Anxi, Southeast China, was studied. Leaching experiments were designed based on the local tea-drinking habits, and tea infusions were prepared using three types of water and two methods of soaking tea. Twelve metals (Cd, As, Cr, Pb, Se, Sb, Ag, Tl, Cu, Zn, Be, and Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS), and a human health risk assessment was performed. The results showed that the quality of water used for steeping tea has a direct effect on the leaching concentrations of metals in the tea infusion and this effect can be reduced by using pure water or commercially available drinking water. Further, the two tea-soaking methods used by local residents can reduce the metal intake. The health risk assessment determined that the carcinogenic risk values of Cr, As, and Pb (Cr > Pb > As) were within an acceptable range (10-7-10-4); therefore, the concentrations of these metals in tea infusions do not pose substantial carcinogenic risk to tea drinkers. The results also indicate that the high concentrations of Tl in the tea infusions pose a substantial noncarcinogenic risk and may result from the dissolution characteristics of Tl and the water quality.

Systemic platelet inhibition with localized chemotherapy by an injectable ROS-scavenging gel against postsurgical breast cancer recurrence and metastasis.

Early solid tumors benefit from surgical resection, but residual stubborn microtumors, pro-inflammatory microenvironment and activated platelets at the postoperative wound site are prone to recurrence and metastasis, resulting in poor prognosis. Here, we developed a dual-pronged strategy consisting of (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs at the postoperative wound site to improve the tumor microenvironment and inhibit the recurrence of residual microtumors after orthotopic surgery, and (ii) systemic administration of clopidegrol via albumin nanoparticles for inhibiting activated platelets in the circulation thus inhibiting tumor remote migration. In a mouse model of postoperative recurrence and metastasis of orthotopic 4T1 breast cancer, the dual-pronged strategy greatly inhibited postoperative orthotopic tumor recurrence and reduced lung metastasis. This work provides an effective strategy for the postoperative intervention and treatment of solid tumors to inhibit postoperative tumor recurrence and metastasis, which has the potential to improve the prognosis and survival of patients with postoperative solid tumors. STATEMENT OF SIGNIFICANCE: Early-stage solid tumors benefit from surgical resection. However, the presence of residual microtumors, pro-inflammatory tumor microenvironment, and activated platelets at the postoperative wound site lead to recurrence and metastasis, ultimately resulting in poor prognosis. Here, we have devised a dual-pronged approach that includes (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs (TM@Gel) at the wound site after surgery to enhance the tumor microenvironment (TME) and hinder the reappearance of residual microtumors, and (ii) systemic administration of clopidegrol through albumin nanoparticles (HHP) for inhibiting activated platelets in the circulation thus impeding tumor distant migration. This work provides a viable option for postoperative intervention and treatment of solid tumors to suppress postoperative tumor recurrence and metastasis.

Ascertaining appropriate measuring methods to determine tire wear particle pollution on driving school grounds in China.

Tire wear particles (TWPs) are garnering increasing attention due to their potential adverse environmental impacts. However, precisely ascertaining TWPs content is challenging due to the complexity and variability of the tire components used in the environment, indicating that more reliable methods to accurately determine TWPs are necessary. In this study, driving school grounds were used as a case study to ascertain an appropriate and reliable method to determine TWPs levels based on a comprehensive comparison between different analytical results using styrene butadiene rubber (SBR), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and zinc (Zn) as analytical markers. Thermogravimetric analysis-Gas chromatography mass spectrometry (TGA-GC-MS) method reliability using SBR was verified and applied to measure TWPs levels on driving school grounds. By reliably converting SBR content to TWPs content, the average TWPs content on driving school grounds was measured at 190.13 ± 101.89 mg/g. The highest TWPs content was 281.83 ± 171.44 mg/g under the reverse stall parking driving programs, while the slope start and stop driving programs was lower at 208.36 ± 124.11 mg/g. Our findings highlight the importance of accurately determining TWPs content within specific environments while comprehensively exploring associated patterns of change to better understand the environmental risks of TWPs.

Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

Tire wear particles: Trends from bibliometric analysis, environmental distribution with meta-analysis, and implications.

Tire wear particles (TWPs), as one of pristine microplastics and non-exhaust emission pollutants, have received extensive attention from scholars worldwide in recent years. In the context of the increasing number of related research results, this study evaluated the current status of TWPs research based on bibliometric analysis and meta-analysis and then discussed in-depth the environmental implications involving transport, transformation of released additives in potential and combined pollution with other microplastics in TWPs researches. Results showed that the regional layout of TWPs research was mainly concentrated in Europe and North America, but with specific countries of the United States, Germany, China, the United Kingdom, and Sweden. Thus, Asia and Africa should timely carry out related research on TWPs considering their large vehicle ownerships. In addition, keyword co-occurrence analysis based on CiteSpace showed that biotoxicity, environmental distribution and human health risks are the current research hotspots. Furthermore, the content of TWPs varied greatly by country and environmental media according to the meta-analysis. It is warranted to be urgently investigated on the distribution, quantitative analysis, migration, additives transformation with toxic effects and control measures of TWPs under the influence of various complex factors such as energy innovation and smart driving. The obtained findings can help understand the developing status of TWPs and then promoting their related investigations in future.

Source apportionment and transfer characteristics of Pb in a soil-rice-human system, Jiulong River Basin, southeast China.

The source apportionment and transfer of Pb in a paddy soil-rice-human system within the Jiulong River Basin in southeast China was investigated by analyzing (1) the chemical fractionation of Pb in paddy soils using a modified BCR four-step sequential extraction procedure, and (2) the bioaccessibility of Pb in both paddy soils and rice grains using a Simple Bioaccessibility Extraction Test method. In addition, a qualitative Pb isotopic model was used in combination with IsoSource software to quantify the contribution of potential Pb sources. The results show the enrichment of Pb in agro-ecosystems in the Jiulong River Basin. Contaminant Pb in paddy soils was mainly present in the reducible (42.9%) and the residual fractions (27.1%). The average bioaccessibility of Pb in rice grains was significantly higher than that in paddy soil, with values of 77.85% and 37.44%, respectively. Lead in paddy soils was primarily derived from agricultural (35.3%), natural (25.5%), industrial (24.5%) and coal combustion sources (14.7%), while Pb in rice grains was primarily derived from coal combustion (54.1%), agricultural (35.1%), industrial (6.0%) and natural sources (4.8%). The bioaccessible Pb was mainly derived from anthropogenic sources [agricultural (42.3% for soil and 25.3% for grain) and coal combustion sources (25.3% for soil and 59.3% for grain)]. Lead isotopic ratios are an effective tracer of Pb transfer from potential sources to rice plants and within the rice plants. Rice plants absorb Pb from the soil and the atmosphere through the roots and leaves, respectively. Most of the Pb was accumulated in roots. The integrated use of chemical fractionation, bioaccessibility and Pb isotopic data provides an effective method to study the source apportionment and transfer characteristics of Pb in paddy soil-rice-human systems.

Oyster shell for drinking water filtration compared with granular activated carbon: advantages and limitations.

Deliberate media selection can be conducted to achieve targeted objective in filters. In this study, three biofilters (BFs) packed with calcinated oyster shell (COS), granular activated carbon (GAC), and COS + GAC (Mix) were set up in parallel following a rough filter packed with natural oyster shell to compare the performance for treating micro-polluted source water. Different media showed selective removal effects for different pollutants. GAC outperformed COS in terms of TOC and UV254. COS achieved higher reduction in turbidity than GAC. Due to the removal of total bacteria, the absolute and relative abundance of antibiotic resistance genes (ARGs) both decreased much in rough filter treated water (1.16 × 1014 to 1.40 × 1013 copies L-1 and 81.6 to 36.9%, respectively). The highest diverse and rich bacterial community was found in the biofilms on the COS filler, so microbial leakage gave rise to high bacterial content, leading to the highest absolute abundance of ARGs in COS BF effluent (2.11 × 1013 copies L-1). The highest relative abundance of ARGs (41.2%) was found in GAC BF effluent. SourceTracker and biomarker analysis both suggested that treatment process played a more important role in shaping the bacterial community structure in Mix BF effluent than single media BFs, which contributed to the lowest absolute (8.69 × 1012 copies L-1) and relative abundance (25.2%) of ARGs in Mix BF effluent among the three BFs. Our results suggested that mix COS + GAC can not only give full play to their respective advantages for traditional pollutants, but also achieve highest reduction in ARGs.

TLR4 Blockade Using Docosahexaenoic Acid Restores Vulnerability of Drug-Tolerant Tumor Cells and Prevents Breast Cancer Metastasis and Postsurgical Relapse.

Nonmutational mechanisms were recently discovered leading to reversible drug tolerance. Despite the rapid elimination of a majority of tumor cells, a small subpopulation of "'drug-tolerant"' cells remain viable with lethal drug exposure, which may further lead to resistance or tumor relapse. Several signaling pathways are involved in the local or systemic inflammatory responses contributing to drug-induced phenotypic switch. Here, we report that Toll-like receptor 4 (TLR4)-interacting lipid docosahexaenoic acid (DHA) restores the cytotoxic effect of doxorubicin (DOX) in the lipopolysaccharide-treated breast tumor cell line 4T1, preventing the phenotypic switch to drug-tolerant cells, which significantly reduces primary tumor growth and lung metastasis in both 4T1 orthotopic and experimental metastasis models. Importantly, DHA in combination with DOX delays and inhibits tumor recurrence following surgical removal of the primary tumor. Furthermore, the coencapsulation of DHA and DOX in a nanoemulsion significantly prolongs the survival of mice in the postsurgical 4T1 tumor relapse model with significantly reduced systemic toxicity. The synergistic antitumor, antimetastasis, and antirecurrence effects of DHA + DOX combination are likely mediated by attenuating TLR4 activation, thus sensitizing tumor cells to standard chemotherapy.

Machine learning application in forecasting tire wear particles emission in China under different potential socioeconomic and climate scenarios with tire microplastics context.

Little information is available on different contribution of TMPs from tire wear particles (TWPs), recycled tire crumbs (RTCs) and tire repair-polished Debris (TRDs) in the environment at national scale and their potential tendency. In this study, the TWPs were predicted using machine learning method of CNN (Convolutional Neural Networks) algorithms under different potential socioeconomic and climate scenarios based on the estimation of TMPs in China. Results showed that TWPs emission exhibited the most important part of TMPs, followed by RTCs and TRDs in China. The three mentioned tire microplastics largely distributed in Chinese coastal provinces. After machine learning applied in CNN using the dataset of estimated emission of TWPs from 2008 to 2018, the express delivery volume and education funding at the current increased rate would not have significant impacts on TWPs emissions; Additionally, TWPs emissions were also sensitive to changes of economic and transportation development; Low temperature conditions would further promote TWPs emissions. Accordingly, the rational development of logistics and green economy, the equilibrium improvement of education quality, and the increase of public traffic with new energy would be helpful to mitigate TWPs emissions. The obtained findings can enhance the understanding TMPs emission at particular scale and their corresponding precise management.

Inhibitory effect of polyethylene microplastics on roxarsone degradation in soils.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox(V)), an extensively used organoarsenical feed additive, enters soils through the application of Rox(V)-containing manure and further degrades to highly toxic arsenicals. Microplastics, as emerging contaminants, are also frequently detected in soils. However, the effects of microplastics on soil Rox(V) degradation are unknown. A microcosm experiment was conducted to investigate soil Rox(V) degradation responses to polyethylene (PE) microplastics and the underlying mechanisms. PE microplastics inhibited soil Rox(V) degradation, with the main products being 3-amino-4-hydroxyphenylarsonic acid [3-AHPAA(V)], N-acetyl-4-hydroxy-m-arsanilic acid [N-AHPAA(V)], arsenate [As(V)], and arsenite [As(III)]. This inhibition was likely driven by the decline in soil pH by PE microplastic addition, which may directly enhance Rox(V) sorption in soils. The decreased soil pH further suppressed the nfnB gene related to nitroreduction of Rox(V) to 3-AHPAA(V) and nhoA gene associated with acetylation of 3-AHPAA(V) to N-AHPAA(V), accompanied by a decrease in the relative abundance of possible Rox(V)-degrading bacteria (e.g., Pseudomonadales), although the diversity, composition, network complexity, and assembly of soil bacterial communities were largely influenced by Rox(V) rather than PE microplastics. Our study emphasizes microplastic-induced inhibition of Rox(V) degradation in soils and the need to consider the role of microplastics in better risk assessment and remediation of Rox(V)-contaminated soils.

Roxarsone biotransformation by a nitroreductase and an acetyltransferase in Pseudomonas chlororaphis, a bacterium isolated from soil.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox), a widely used organoarsenical feed additive, can enter soils and be further biotransformed into various arsenic species that pose human health and ecological risks. However, the pathway and molecular mechanism of Rox biotransformation by soil microbes are not well studied. Therefore, in this study, we isolated a Rox-transforming bacterium from manure-fertilized soil and identified it as Pseudomonas chlororaphis through morphological analysis and 16S rRNA gene sequencing. Pseudomonas chlororaphis was able to biotransform Rox to 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), N-acetyl-4-hydroxy-m-arsanilic acid (N-AHPAA), arsenate [As(V)], arsenite [As(III)], and dimethylarsenate [DMAs(V)]. The complete genome of Pseudomonas chlororaphis was sequenced. PcmdaB, encoding a nitroreductase, and PcnhoA, encoding an acetyltransferase, were identified in the genome of Pseudomonas chlororaphis. Expression of PcmdaB and PcnhoA in E. coli Rosetta was shown to confer Rox(III) and 3-AHPAA(III) resistance through Rox nitroreduction and 3-AHPAA acetylation, respectively. The PcMdaB and PcNhoA enzymes were further purified and functionally characterized in vitro. The kinetic data of both PcMdaB and PcNhoA were well fit to the Michaelis-Menten equation, and nitroreduction catalyzed by PcMdaB is the rate-limiting step for Rox transformation. Our results provide new insights into the environmental risk assessment and bioremediation of Rox(V)-contaminated soils.

Characteristics and provenances of rare earth elements and Nd isotopes in surface sediments of mangrove wetlands in the Jiulong River Estuary, China.

Rare earth elements (REEs) and Nd isotopes are frequently employed to determine provenance, although their characteristics and provenances in the surface sediments of mangrove wetlands are rarely analyzed. In this study, a thorough analysis of the characteristics and provenances of REEs and Nd isotopes in the surface sediments of mangrove wetland in the Jiulong River Estuary was carried out. According to the results, the mean concentration of REEs in the surface sediments was 290.9 mg·kg-1, which was greater than the background value. Unpolluted to moderately polluted for La and Ce, as well as a moderate ecological risk for Lu, were indicated by the geoaccumulation index (Igeo) and potential ecological risk of individual factors ([Formula: see text]), respectively. The surface sediments showed substantial negative Eu anomalies but no significant Ce anomalies. The enrichments in LREE and flat HREE patterns are visible in the chondrite-normalized REE patterns. REEs in the surface sediments might be attributed to both natural sources (granite and magmatic rocks) and anthropogenic activities, including coal combustion, vehicle exhaust, steel smelting, and fertilizer, based on the (La/Yb)N-∑REE and ternary (La/Yb)N-(La/Sm)N-(Gd/Yb)N plots. The three-dimensional ∑LREE/∑HREE-Eu/Eu*-εNd(0) plot, when combined with the Nd isotope, further demonstrated that the REEs in the surface sediments appeared to have come from additional nonlocal potential sources.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

Mining, metallurgy and the historical origin of mercury pollution in lakes and watercourses in Central Sweden.

In Central Sweden an estimated 80% of the lakes contain fish exceeding health guidelines for mercury. This area overlaps extensively with the Bergslagen ore region, where intensive mining of iron ores and massive sulfide ores occurred over the past millennium. Although only a few mines still operate today, thousands of mineral occurrences and mining sites are documented in the region. Here, we present data on long-term mercury pollution in 16 sediment records from 15 lakes, which indicate that direct release of mercury to lakes and watercourses was already significant prior to industrialization (

Quantifying the source and formation of nitrate in PM2.5 using dual isotopes combined with Bayesian mixing model: A case study in an inland city of southeast China.

Atmospheric nitrate has been attracting increasing attention because it is one of the important components of PM2.5. Understanding the sources and formation mechanism of nitrate in PM2.5 is essential to take effective measures to prevent and control the emission of nitrogen oxides in the atmosphere and reduce the formation of haze. In this study, PM2.5 samples were collected from Ganzhou, an inland city in southeast China, during summer and winter. The concentrations of PM2.5 and NO3- were determined, and the isotopic compositions of NO3- (δ15N-NO3- and δ18O-NO3-) were analyzed in order to quantify the relative contributions of different emission sources and formation pathways of nitrate in PM2.5. The results showed that PM2.5 and NO3- concentrations were lower in summer (39.80 ± 11.10 µg·m-3 and 1.79 ± 0.70 µg·m-3) while higher in winter (69.85 ± 29.58 µg·m-3 and 10.83 ± 9.89 µg·m-3). The values of δ18O-NO3- and δ15N-NO3- ranged from 42.84‰ to 56.80‰ and from -11.17‰ to -2.08‰ in summer, while from 55.86‰ to 78.66‰ and from -10.63‰ to -1.88‰ in winter, respectively. The results of δ15N-NO3- combined with Bayesian isotope mixing model showed that the relative contributions of vehicle exhaust, soil microbial activity, biomass combustion and coal fired power plants were 59.3%, 28.5%, 8.7% and 3.4% in summer, while 65.1%, 20.1%, 10.6% and 4.1% in winter, respectively. The results of δ18O-NO3- combined with Bayesian isotope mixing model showed that the possible relative contributions of pathway 1 (P1) (NO2 + ·OH), pathway 2 (P2) (NO3 + HC) and pathway 3 (P3) (N2O5 + H2O) were 73.5%, 12.4% and 14.1% in summer, while 41.6%, 28.9% and 29.5% in winter, respectively. Moreover, P2 and P3 contributed more when NO3- concentrations were higher, suggesting that P2 and P3 were of significance to the formation of nitrate in PM2.5, especially during winter.