A combined amendment (CF) consisting of 90% calcium sulfate (CaSO
4
) and 10% ferric oxide (Fe
2
O
3
) was used to investigate the feasibility, active principles, and possible mechanisms of the ...immobilization of heavy metals in paddy soil. A soil incubation experiment, two consecutive pot trials, and a field experiment were conducted to evaluate the effectiveness and persistence of CF on metal(loid) immobilization. Soil incubation experiment results indicated that the application of CF significantly decreased the concentrations of cadmium (Cd), lead (Pb), and arsenic (As) in soil solution. CF treatments simultaneously reduced the accumulation of Cd, Pb, and As in two consecutive pot trials. The total Cd, Pb, and As concentrations in the rice grains were respectively 0.02, 2.08, and 0.62 mg kg
−1
in the control treatment in the second year, which exceeded the safety limits of contaminants in food products in China. However, a high amount of CF amendment (CF-H, 0.3%) effectively decreased Cd, Pb, and As by 75.0%, 75.5%, and 46.8%, respectively. Further, with the CF amendment, the bioavailable Cd and Pb in the soil and the accumulation of Cd, Pb, and As in rice grain in the field experiment were also significantly decreased. The concentrations of Cd, Pb, and As in grains were respectively 0.02, 0.03, and 0.39 mg kg
−1
in the control treatment in the field experiment, which decreased to 0.01, 0.01, and 0.22 mg kg
−1
with CF addition, suggesting that grains produced in the field could pose less health risk. In conclusion, these results implied that CF was an effective and persistent combined amendment to immobilize heavy metals in soil and thereby can reduce the exposure risk of metal(loid)s associated with rice consumption.
Genealogical patterns in different genomic regions may be different due to the joint influence of gene flow and selection. The existence of two subspecies of cultivated rice provides a unique ...opportunity for analyzing these effects during domestication. We chose 66 accessions from the three rice taxa (about 22 each from Oryza sativa indica, O. sativa japonica, and O. rufipogon) for whole-genome sequencing. In the search for the signature of selection, we focus on low diversity regions (LDRs) shared by both cultivars. We found that the genealogical histories of these overlapping LDRs are distinct from the genomic background. While indica and japonica genomes generally appear to be of independent origin, many overlapping LDRs may have originated only once, as a result of selection and subsequent introgression. Interestingly, many such LDRs contain only one candidate gene of rice domestication, and several known domestication genes have indeed been "rediscovered" by this approach. In summary, we identified 13 additional candidate genes of domestication.
This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE).
A search was conducted on PubMed, ...EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction.
In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel.
This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.
Spatially resolved transcriptomics involves a set of emerging technologies that enable the transcriptomic profiling of tissues with the physical location of expressions. Although a variety of methods ...have been developed for data integration, most of them are for single-cell RNA-seq datasets without consideration of spatial information. Thus, methods that can integrate spatial transcriptomics data from multiple tissue slides, possibly from multiple individuals, are needed. Here, we present PRECAST, a data integration method for multiple spatial transcriptomics datasets with complex batch effects and/or biological effects between slides. PRECAST unifies spatial factor analysis simultaneously with spatial clustering and embedding alignment, while requiring only partially shared cell/domain clusters across datasets. Using both simulated and four real datasets, we show improved cell/domain detection with outstanding visualization, and the estimated aligned embeddings and cell/domain labels facilitate many downstream analyses. We demonstrate that PRECAST is computationally scalable and applicable to spatial transcriptomics datasets from different platforms.
•The species and biotransformation genes of As in the sludge during anaerobic digestion was explored.•As(III) and As(V) were the predominant forms in the influent sludge, whereas MMA increased ...significantly after digestion.•As biotransformation genes were highly abundant in the sludge, and arsM gene was the predominant.•The abundance and diversity of the arsM-like sequences increased significantly after digestion.•Co-occurrence network analysis indicated a strong correlation between the microbial communities and As.
Arsenic (As) is a potential contaminant in sewage sludge that may affect waste treatment and limit the use of these waste materials as soil amendments. Anaerobic digestion (AD) is an important and effective process for the treatment of sewage sludge and the chemical speciation of As is particularly important in sludge AD. However, the biotransformation genes of As in sludge during AD has not been fully explored. In this study, the influent and effluent sludge of anaerobic digester in a wastewater treatment plant (WWTP) was collected to investigate the species transformations of As, the abundance and diversity of As biotransformation genes was explored by real-time PCR (qPCR) and metagenomic sequencing, separately. The results showed that arsenite As(III) and arsenate As(V) were predominant in the influent sludge, whereas the relative abundance of monomethylarsenic acid (MMA) increased by 25.7% after digestion. As biotransformation genes were highly abundant, and the As(III) S-adenosylmethionine methyltransferase (arsM) gene was the predominant which significantly increased after AD by qPCR analysis. Metagenomic analysis indicated that the diversity of the arsM-like sequences also increased significantly after AD. Most of the arsM-like sequences in all the influent and effluent sludge samples were related to Bacteroidetes and Alphaproteobacteria. Furthermore, co-occurrence network analysis indicated a strong correlation between the microbial communities and As. This study provides a direct and reliable reference on As biotransformation genes and microbial community in the AD of sludge.
EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of ...79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.
Mesenchymal epithelial transition factor ( MET) activation has been implicated as an oncogenic driver in epidermal growth factor receptor ( EGFR)-mutant non-small-cell lung cancer (NSCLC) and can ...mediate primary and secondary resistance to EGFR tyrosine kinase inhibitors (TKI). High copy number thresholds have been suggested to enrich for response to MET inhibitors. We examined the clinical relevance of MET copy number gain (CNG) in the setting of treatment-naive metastatic EGFR-mutant-positive NSCLC.
MET fluorescence in situ hybridization was performed in 200 consecutive patients identified as metastatic treatment-naïve EGFR-mutant-positive. We defined MET-high as CNG greater than or equal to 5, with an additional criterion of MET/centromeric portion of chromosome 7 ratiο greater than or equal to 2 for amplification. Time-to-treatment failure (TTF) to EGFR TKI in patients identified as MET-high and -low was estimated by Kaplan-Meier method and compared using log-rank test. Multiregion single-nucleotide polymorphism array analysis was performed on 13 early-stage resected EGFR-mutant-positive NSCLC across 59 sectors to investigate intratumoral heterogeneity of MET CNG.
Fifty-two (26%) of 200 patients in the metastatic cohort were MET-high at diagnosis; 46 (23%) had polysomy and six (3%) had amplification. Median TTF was 12.2 months (95% CI, 5.7 to 22.6 months) versus 13.1 months (95% CI, 10.6 to 15.0 months) for MET-high and -low, respectively ( P = .566), with no significant difference in response rate regardless of copy number thresholds. Loss of MET was observed in three of six patients identified as MET-high who underwent postprogression biopsies, which is consistent with marked intratumoral heterogeneity in MET CNG observed in early-stage tumors. Suboptimal response (TTF, 1.0 to 6.4 months) to EGFR TKI was observed in patients with coexisting MET amplification (five 3.2% of 154).
Although up to 26% of TKI-naïve EGFR-mutant-positive NSCLC harbor high MET CNG by fluorescence in situ hybridization, this did not significantly affect response to TKI, except in patients identified as MET-amplified. Our data underscore the limitations of adopting arbitrary copy number thresholds and the need for cross-assay validation to define therapeutically tractable MET pathway dysregulation in EGFR-mutant-positive NSCLC.
Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic ...relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.
We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no ...evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.
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