Discovering Novel Organophosphorus Compounds in Wastewater Treatment Plant Effluents through Suspect Screening and Nontarget Analysis.

Limited knowledge on the structure of emerging organophosphorus compounds (OPCs) hampers our comprehensive understanding of their environmental occurrence and potential risks. Through suspect and nontarget screening, combining data-dependent acquisition, data-independent acquisition, and parallel reaction monitoring modes, we identified 60 OPCs (17 traditional and 43 emerging compounds) in effluents of 14 wastewater treatment plants (WWTPs) in Beijing and Qinghai, China. These OPCs comprise 26 organophosphate triesters, 17 organophosphate diesters, 6 organophosphonates, 7 organothiophosphate esters, and 4 other OPCs. Notably, 14 suspect OPCs were newly identified in WWTP effluents, and 16 nontarget OPCs were newly discovered in environmental matrices. Specifically, the cyclic phosphonate, (5-ethyl-2-methyl-1,3,2-dioxaphosphorinan-5-yl)methyl dimethyl phosphonate P-oxide (PMMMPn), consistently appeared in all WWTP effluents, with semiquantitative concentrations ranging from 44.4 to 282 ng/L. Its analogue, di-PMMMPn, presented in 93% of wastewater samples. Compositional differences between the WWTP effluents of two cities were mainly attributed to emerging OPCs. Hazard and ecological risk assessment underscored the substantial contribution of chlorinated organophosphate esters and organothiophosphate esters to overall risks of OPCs in WWTP effluents. This study provides the most comprehensive OPC profiles in WWTP effluents to date, highlighting the need for further research on their occurrence, fate, and risks, particularly for chlorinated OPCs.

First Report on Apothecium Deformity of Morchella importuna Caused by Alternaria alternata in China.

Morel mushrooms (Morchella spp.) are highly regarded globally for their distinctive texture and savory flavor. In 2022, the cultivation area for morel mushrooms in China reached nearly 20,000 hectares, with predominant cultivars including M. sextelata, M. importuna and M. exima (Bian et al., 2024). In March 2022, however, deformities of friting bodies were observed in M. importna at morel mushroom farms in Huaihua city (28.43°N, 110.47°), China, with an incidence rate ranging from 5% to 10%. The disease symptoms begin with the invasion of the hymenium of morel mushroom by white cotton-like mycelia, ultimately resulting in halted fruiting body growth and the manifestation of anomalous fruiting body morphology. Infected samples were collected from the morel growers. Following sterilization with 75% ethanol of the surrounding tissue of infected samples, the white hyphae from the morel lesions were picked out using a dissecting needle, and incubated onto potato saccharose agar medium supplemented with 60 mg/L streptomycin at 25°C. Studies showed that seven out of nine fungal isolates exhibiting identical morphological features rapidly grew on the same culture medium described above, reaching a length of 75 mm in 4 to 5 days at 25°C. The white and thick hyphal colonies of these isolates gradually filled with brown spore powder. Generally, the conidia of the hyphal colonies were polyblastic with protrusions at the tips, measuring 75 to 165 × 36 to 50 µm (n = 30) in width and length, displaying colors varying from light reddish brown to grayish brown, and possessing one or five septa. To confirm the identity of the pathogen, the region of the internal transcribed spacer region (ITS), 28S nuclear ribosomal large subunit (LSU), and RNA polymerase II second largest subunit (rpb2) genes of the representative isolate H2 were amplified by PCR (Taguiam, et al. 2021). The generated ITS (OR338304), rpb2 (OR452112) and LSU (OR338334) from the isolate H2 had 98-100% similarity to the Alternaria alternata strains ATCC 6663 and CBS 880.95 in BLASTn analysis. ITS, rpb2 and LSU sequences were assembled using Sequence Matrix, and their homogeneity was assessed with PAUP (Vaidya et al., 2011). Bayesian (MrBayes-3.2.7a) and maximum-likelihood (RAxML1.3.1) methods, utilizing the best fit GTR+G+I model obtained from MrModeltest 2.3, were employed for phylogenetic analysis (Aveskamp et al. 2010). Based on morphological characteristics and phylogenetic analysis, the isolate H2 was identified as A. alternata. In the second year post-disease, disease-free morels, with a height of 3 cm, were cultivated in field greenhouses and used for test. A 15 ml suspension (1 × 106 conidia/ml) was applied to 15 young fruiting bodies and their corresponding substrate soil. The results showed that the reappearance of white cotton-like mycelia and deformed M. importuna fruiting bodies within 7 days post-inoculation with the spore suspension, as opposed to the controls. The isolates (H2-1, H2-2 and H2-3) were reisolated from the infected tissues and identified as A. alternata based on its morphological features and phylogenetic analyses. In this study, a similar investigation was previously conducted on cultivated quinoa (Chenopodium quinoa) in Eastern Denmark (Colque-Little et al., 2023). This study marks the first documentation of A. alternata causing deformities in M. importuna fruiting bodies. These deformities occur under conditions of high-temperature (>22°C) and high humidity (>88%). Our findings provide crucial insights for managing A. alternata in M. importuna cultivation in China.

Suspect and Nontarget Screening Reveal the Underestimated Risks of Antibiotic Transformation Products in Wastewater Treatment Plant Effluents.

Antibiotics are anthropogenic contaminants with a global presence and of deep concern in aquatic environments, while less is known about the occurrence and risks of their transformation products (TPs). Herein, we developed a comprehensive suspect and nontarget screening workflow based on high-resolution mass spectrometry to identify unknown antibiotic TPs in wastewater treatment plant effluents. We identified 211 compounds (35 parent antibiotics and 176 TPs) at confidence levels of ≥3 and 107 TPs originated from macrolides. TPs were quantified by 17 TPs standards and semiquantified by the predicted response factors and accounted for 55.6-95.1% (76.7% on average) of the total concentrations of parents and TPs. 22.2%, 63.1%, and 18.8% of the identified TPs were estimated to be more persistent, mobile, and toxic than their parent antibiotics, respectively. Further ecological risk assessment based on concentrations and toxicity to aquatic organisms revealed that the cumulative risks of TPs were generally higher than those of parents. Despite the newly formed N-oxide TPs, the tertiary treatment process (mainly ozonation) could decrease the averaged 20.3% of concentrations and 36.2% of the risks of antibiotic-related compounds. This study highlights the necessity to include antibiotic TPs in environmental scrutiny and risk assessment of antibiotics in different aquatic environments.

Cross-Feeding between Filamentous Cyanobacteria and Symbiotic Bacteria Favors Rapid Photogranulation.

Photogranules are dense algal-bacterial aggregates used in aeration-free and carbon-negative wastewater treatment, wherein filamentous cyanobacteria (FC) are essential components. However, little is known about the functional role of symbiotic bacteria in photogranulation. Herein, we combined cyanobacterial isolation, reactor operation, and multiomics analysis to investigate the cyanobacterial-bacterial interaction during photogranulation. The addition of FC to the inoculated sludge achieved a 1.4-fold higher granule size than the control, and the aggregation capacity of FC-dominant photogranules was closely related to the extracellular polysaccharide (PS) concentration (R = 0.86). Importantly, we found that cross-feeding between FC and symbiotic bacteria for macromolecular PS synthesis is at the heart of photogranulation and substantially enhanced the granular stability. Chloroflexi-affiliated bacteria intertwined with FC throughout the photogranules and promoted PS biosynthesis using the partial nucleotide sugars produced by FC. Proteobacteria-affiliated bacteria were spatially close to FC, and highly expressed genes for vitamin B1 and B12 synthesis, contributing the necessary cofactors to promote FC proliferation. In addition, Bacteroidetes-affiliated bacteria degraded FC-derived carbohydrates and influenced granules development. Our metabolic characterization identified the functional role of symbiotic bacteria of FC during photogranulation and shed light on the critical cyanobacterial-bacterial interactions in photogranules from the viewpoint of cross-feeding.

Environmental DNA metabarcoding reveals the impacts of anthropogenic pollution on multitrophic aquatic communities across an urban river of western China.

Anthropogenic activities are intensively affecting the structure and function of biological communities in river ecosystems. The effects of anthropogenic pollution on single-trophic community have been widely explored, but their effects on the structures and co-occurrence patterns of multitrophic communities remain largely unknown. In this study, we collected 13 water samples from the Neijiang River in Chengdu City of China, and identified totally 2352 bacterial, 207 algal, 204 macroinvertebrate, and 33 fish species based on the eDNA metabarcoding to systematically investigate the responses of multitrophic communities to environmental stressors. We observed significant variations in bacterial, algal, and macroinvertebrate community structures (except fish) with the pollution levels in the river. Network analyses indicated a more intensive interspecific co-occurrence pattern at high pollution level. Although taxonomic diversity of the multitrophic communities varied insignificantly, phylogenetic diversities of fish and algae showed significantly positive and negative associations with the pollution levels, respectively. We demonstrated the primary role of environmental filtering in driving the structures of bacteria, algae, and macroinvertebrates, while the fish was more controlled by dispersal limitation. Nitrogen was identified as the most important factor impacting the multitrophic community, where bacterial composition was mostly associated with NO3--N, algal spatial differentiation with TN, and macroinvertebrate and fish with NH4+-N. Further partial least-squares path model confirmed more important effect of environmental variables on the relative abundance of bacteria and algae, while macroinvertebrate and fish communities were directly driven by the algae-mediated pathway in the food web. Our study highlighted the necessity of integrated consideration of multitrophic biodiversity for riverine pollution management, and emphasized the importance of controlling nitrogen inputs targeting a healthy ecosystem.

TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5.

BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a key glycolytic enzyme, is upregulated in multiple cancers. However, expression profile and regulatory mechanism of TPI1 in breast cancer (BRCA) remain mysterious. METHODS: Western blotting and immunohistochemistry (IHC) assays were used to investigate the expression of TPI1 in BRCA specimens and cell lines. TPI1 correlation with the clinicopathological characteristics and prognosis of 362 BRCA patients was analyzed using a tissue microarray. Overexpression and knockdown function experiments in cells and mice models were performed to elucidate the function and mechanisms of TPI1-induced BRCA progression. Related molecular mechanisms were clarified using co-IP, IF, mass spectrometric analysis, and ubiquitination assay. RESULTS: We have found TPI1 is highly expressed in BRCA tissue and cell lines, acting as an independent indicator for prognosis in BRCA patients. TPI1 promotes BRCA cell glycolysis, proliferation and metastasis in vitro and in vivo. Mechanistically, TPI1 activates phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway to regulate epithelial-mesenchymal transformation (EMT) and aerobic glycolysis, which is positively mediated by cell division cycle associated 5 (CDCA5). Moreover, TPI1 interacts with sequestosome-1 (SQSTM1)/P62, and P62 decreases the protein expression of TPI1 by promoting its ubiquitination in MDA-MB-231 cells. CONCLUSIONS: TPI1 promotes BRCA progression by stabilizing CDCA5, which then activates the PI3K/AKT/mTOR pathway. P62 promotes ubiquitin-dependent proteasome degradation of TPI1. Collectively, TPI1 promotes tumor development and progression, which may serve as a therapeutic target for BRCA.

Preliminary Exploration of the Application of Vesical Imaging-Reporting and Data System (VI-RADS) in Post-treatment Patients With Bladder Cancer: A Prospective Single-Center Study.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been shown to be effective in diagnosing muscle invasion of bladder cancer (BC) in primary patients. PURPOSE: To evaluate the diagnostic efficacy of VI-RADS in a BC target population which included post-treatment patients, and to determine the repeatability. STUDY TYPE: Prospective. POPULATION: Seventy-three patients (42 with primary BC, 31 with post-treatment BC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI with propeller fast spin-echo T2 WI, echo planer imaging diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). ASSESSMENT: VI-RADS scores were independently assessed by five radiologists with different levels of experience. The diagnostic efficiency in each group (primary and post-treatment) and of each radiologist was assessed. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and area under the curve (AUC) in receiver operating characteristic curve analysis were calculated to evaluate VI-RADS diagnostic performance. Interobserver agreement was assessed using weighted Kappa statistics. A P value <0.05 was considered statistically significant. RESULTS: At the corresponding cut-off, AUC values of three groups range from 0.936 to 0.947 and AUC values of five observers range from 0.901 to 0.963. There was no significant difference between the AUCs in the primary and post-treatment groups (P = 0.870). The cut-off of the whole group and the post-treatment group was ≥4, and the cut-off of the primary group was ≥3. The Kappa values of interobserver agreements range from 0.709 to 0.923. CONCLUSIONS: After expanding the target population to include post-treatment patients, VI-RADS still has good diagnostic efficacy and repeatability. VI-RADS could potentially be a preoperative staging tool for post-treatment patients. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Transcription factor FOXC1 positively regulates SFRP1 expression in androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.

Impacts of engineered nanoparticles and antibiotics on denitrification: Element cycling functional genes and antibiotic resistance genes.

The wide presence of antibiotics and minerals warrants their combined effects on the denitrification in natural aquatic environment. Herein, we investigated the effects of two antibiotics, sulfamethazine (SMZ) and chlortetracycline (CTC), on the reduction of NO3--N and accumulation of NO2--N in the absence and presence of engineered nanoparticles (NPs) (Al2O3, SiO2, and geothite) using 16 S rRNA sequencing and high-throughput quantitative PCR. The results showed that the addition of antibiotics inhibited the reduction of NO3--N by changing the bacterial community structure and reducing the abundance of denitrification genes, while engineered NPs promoted the denitrification by increasing the abundance of denitrification genes. In the binary systems, engineered NPs alleviated the inhibitory effect of antibiotics through enriching the denitrification genes and adsorbing antibiotics. Antibiotics and its combination with engineered NPs changed the composition of functional genes related to C, N, P, S metabolisms (p < 0.01). The addition of antibiotics and/or engineered NPs altered the bacterial community structure, which is dominated by the genera of Enterobacter (40.7-90.5%), Bacillus (4.9-58.5%), and Pseudomonas (0.21-12.7%). The significant relationship between denitrification, carbon metabolism genes, and antibiotic resistance genes revealed that the heterotrophic denitrifying bacteria may host the antibiotic resistance genes and denitrification genes simultaneously. The findings underscore the significance of engineered NPs in the toxicity assessment of pollutants, and provide a more realistic insight into the toxicity of antibiotics in the natural aquatic environment.

The Competitive Effects of School Choice on Student Achievement: A Systematic Review.

School-choice policies are expected to generate healthy competition between schools, leading to improvements in school quality and better outcomes for students. However, the empirical literature testing this assumption yields mixed findings. This systematic review and meta-analysis tests this theory by synthesizing the empirical literature on the competitive effects of school choice on student achievement. Overall, we found small positive effects of competition on student achievement. We also found some evidence that the type of school-choice policy and student demographics moderated the effects of competition on student achievement. By examining whether school competition improves outcomes, our findings can inform decisions of state and local policymakers who have adopted or are considering adopting school-choice reforms.

Platelet transcriptome profiles provide potential therapeutic targets for elderly acute myelocytic leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age of 68 in clinical diagnosis. About 60% patients are over 60 years old. There are various treatment options for AML patients. But for elderly patients, the complete remission rates are disappointing due to genetic, molecular, and age-related factors. Development of next-generation sequencing technologies makes it possible to seek individual strategies for patients in different ages. This study analyzed transcriptome profiles in platelets of AML patients in different ages for the first time. METHODS: Platelet RNA sequencing in AML of ten elderly and seven young patients were performed with Illumina TruSeq Stranded mRNA library Prep Kit and Illumina HiSeq4000 sequencing instrument. With the FASTQ sequencing data obtained, statistical analyses between elderly with young AML patients were analyzed by R program. GO and KEGG enrichment analyses were performed via R package clusterProfiler. TOP 10 down-regulated/up-regulated genes in elderly patients compared to young patients were selected with the threshold of |L2FC| > 2 and padj ≤ 0.0001. The down-regulated gene ATF4 was chosen by GSEA analysis and ROC analysis with AUC > 0.95. RESULTS: We found 3059 genes with differential transcript levels (GDTLs) in AML patients of different age. Among them, 2048 genes are down-regulated and 651 genes are up-regulated in elderly patients. We found that gene transcript profiles in elderly patients is obviously different from those in young patients, including a collection of down-regulated genes related to proteins processing in endoplasmic reticulum and immunity. We further identified that genes of pathway in cancer and mitogen activated protein kinase (MAPK) pathway, involved in natural immunity and metabolism, are significantly down-regulated in elderly patients. Among all screened genes with decreased transcript levels, we believe that activating transcription factor 4 (ATF4) is a biomarker indicating different chemotherapy strategies for elderly patients. CONCLUSIONS: In summary, gene transcript profiles are different in platelets of elderly and young AML patients. And ATF4 can be a useful biomarker indicating different chemotherapy strategies for AML patients with different ages.

Spatiotemporal distribution, risk assessment and source appointment of metal(loid)s in water and sediments of Danjiangkou Reservoir, China.

Danjiangkou Reservoir is the biggest artificial reservoir in China. But spatiotemporal distribution and risks of metal(loid)s in it were still unclear after the operation of Middle Route of South-to-North Water Diversion Project. In this study, distribution pattern of fifteen metal(loid)s in the Danjiangkou Reservoir was investigated. It was shown that metal(loid)s concentrations in the water were much lower than the drinking water quality standards in China, while Sb, Co, Cd and Cr were identified as the major pollutants in the sediments. Environment-metal(loid)s correlation analysis revealed total organic carbon, sulfate, temperature, dissolved oxygen and total phosphorus markedly controlled metal(loid)s distribution in the water, while organic carbon, total phosphorus and ammonia nitrogen shaped their distribution in the sediments. Results of risk assessment further revealed that the sediments of Danjiangkou Reservoir were minor to moderate polluted, and Sb, Cd exhibited the highest potential ecological risk. Additionally, source identification showed agricultural activities (25.3%), industrial and mining activities (17.5%) and natural processes (57.2%) were the dominant sources of metal(loid)s burden in the sediments. Overall, the results are of significance to understanding the ecological risk and pollution sources in the Danjiangkou Reservoir, which is essential for the effective management of metal(loid)s pollution.

Comparing the effects of different types of inorganic nanoparticles on 17ß-estradiol adsorption by graphene oxide.

This study compared the effects of five types of inorganic nanoparticles (INPs) on the 17ß-estradiol (E2) adsorption to graphene oxide (GO). The results showed that INPs increased the equilibrium time for the adsorption of E2 to GO. Higher Brunauer-Emmett-Teller (BET) surface area of INPs resulted in lower diffusion rate of E2, and thus the adsorption rate constant (k2) calculated from pseudo-second-order kinetic model negatively correlated with the BET surface area of INPs (p = 0.037). In addition, INPs decreased the adsorption amount of E2 to GO, and the inhibition effects declined in the order of Al2O3 > ZnO > TiO2 > SiO2 > Fe2O3. This is determined by the interactions between GO and INPs. The positively charged ZnO and Al2O3 strongly heteroaggregate with GO via electrostatic attraction, and then significantly inhibited E2 adsorption to GO. In contrast, the homoaggregation of GO was superior to its heteroaggregation with negatively charged SiO2 and TiO2, and then lower inhibition of E2 adsorption to GO was induced. Fe2O3 with less negative charge (-8.48 mV) led to the lowest inhibition effect on E2 adsorption to GO because of its preferable homoaggregation. The results were further confirmed by Derjaguin-Landau-Verwey-Overbeek calculation, transmission electron microscopy, and sedimentation experiments. This study revealed how the properties of INPs influence their effects on the adsorption of E2 by GO, and the findings are critical to understand the behavior and fate of GO and pollutants in natural aquatic environment.

Enrichment of antibiotics in an inland lake water.

Inland water is very susceptible to the input of pollutants. However, little is known about the occurrence of antibiotics in inland lakes. In this study, a total of 83 target antibiotics were quantified in water and sediment samples collected from the Qinghai Lake, the largest inland lake of China located on the northeast of Qinghai-Tibet plateau, and its inflowing rivers. The results showed that 27 and 25 antibiotics were detected in water and sediments, respectively, with the summed concentrations (SUM) of 1.14-17.3 ng/L and 0.72-8.31 ng/g. Compared with the input rivers, significantly higher levels of sulfonamides (SAs), quinolones (QNs), polyethers (PEs), and SUM in water samples were observed in Qinghai Lake water. The average proportions of SAs (50.9-52.7%) and QNs (22.0-28.3%) in Qinghai Lake water nearly doubled compared to those in input rivers. An enrichment factor (EF) was proposed to reveal the enrichment degree of antibiotics in Qinghai Lake compared to its input river water. Sulfaguanidine (SGD), flumequine (FLU), and nalidixic acid (NDA) were enriched in Qinghai Lake up to several ten times based on the calculated EF values, due to their persistence in such a cold saline lake. Risk assessment showed that most antibiotics except anhydrochlortetracycline (ACTC) had insignificant risks to aquatic organisms and antibiotic resistance selection in Qinghai Lake water. This study was the first to reveal the enrichment of antibiotics in Qinghai Lake water, and suggests the urgent need to investigate the possible long-term enrichment and environmental risks of antibiotics in inland lakes.

Gender, Markets, and Inequality: A Framework.

A growing body of research examines the role of elite networks, power, and race in the advocacy for market-based reforms and their ultimate effects on students, teachers, and communities of color. Yet, less research explores how such reforms interact with gender in the workplace, especially how policies such as school choice, competition, and incentive-based pay impact female actors within K-12 schools (e.g., teachers, school leaders). The current research on marketization and privatization in education has largely overlooked the potential impact on women in schools. We review the literature on women in K-12 education and in the economy more generally, and organize it conceptually to identify areas for future inquiry. After synthesizing and summarizing themes across diverse bodies of literature, we contend that as schools privatize, we may see greater gender disparities in education leadership and teaching.

Immunotoxicity of legacy and alternative per- and polyfluoroalkyl substances on zebrafish larvae.

Hexafluoropropylene oxide dimer acid (HFPO-DA) and perfluoroethylcyclohexane sulfonate (PFECHS) are increasingly used as alternatives for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, their immunotoxicity and underlying molecular mechanisms remain poorly understood. Here, to assess immunotoxic effects, zebrafish embryos were exposed to environmentally relevant concentrations of PFOA, PFOS, HFPO-DA, and PFECHS for four days. Results revealed that all four per- and polyfluoroalkyl substances (PFAS) resulted in decreased heart rate and spontaneous movement, and induced oxidative stress in zebrafish larvae. Notably, HFPO-DA exhibited more severe oxidative stress than PFOA. Immune dysfunction was observed, characterized by elevated cytokine, complement factor, nitric oxide, and neutrophil content, along with a significant decrease in lysozyme content. Transcriptomic analysis revealed the activation of Toll-like receptor (TLR)/NOD-like receptor (NLR)/RIG-I-like receptor (RLR) and associated downstream genes, indicating their pivotal role in PFAS-induced immunomodulation. Molecular docking simulations demonstrated stable interactions between PFAS and key receptors (TLR2, NOD2 and RIG-I). Overall, HFPO-DA and PFECHS exhibited immunotoxic effects in zebrafish larvae similar to legacy PFAS, providing important information for understanding the toxic mode of action of these emerging alternatives.

CPR bacteria and DPANN archaea play pivotal roles in response of microbial community to antibiotic stress in groundwater.

The accumulation of antibiotics in the natural environment can disrupt microbial population dynamics. However, our understanding of how microbial communities adapt to the antibiotic stress in groundwater ecosystems remains limited. By recovering 2675 metagenome-assembled genomes (MAGs) from 66 groundwater samples, we explored the effect of antibiotics on bacterial, archaeal, and fungal communities, and revealed the pivotal microbes and their mechanisms in coping with antibiotic stress. The results indicated that antibiotics had the most significant influence on bacterial and archaeal communities, while the impact on the fungal community was minimal. Analysis of co-occurrence networks between antibiotics and microbes revealed the critical roles of Candidate Phyla Radiation (CPR) bacteria and DPANN archaea, two representative microbial groups in groundwater ecosystem, in coping with antibiotic resistance and enhancing network connectivity and complexity. Further genomic analysis demonstrated that CPR bacteria carried approximately 6 % of the identified antibiotic resistance genes (ARGs), indicating their potential to withstand antibiotics on their own. Meanwhile, the genomes of CPR bacteria and DPANN archaea were found to encode diverse biosynthetic gene clusters (BGCs) responsible for producing antimicrobial metabolites, which could not only assist CPR and DPANN organisms but also benefit the surrounding microbes in combating antibiotic stress. These findings underscore the significant impact of antibiotics on prokaryotic microbial communities in groundwater, and highlight the importance of CPR bacteria and DPANN archaea in enhancing the overall resilience and functionality of the microbial community in the face of antibiotic stress.

Enhancing and sustaining arsenic removal in a zerovalent iron-based magnetic flow-through water treatment system.

In areas affected by arsenicosis, zerovalent iron (ZVI)/sand filters are extensively used by households to treat groundwater, but ZVI surface passivation and filter clogging limit their arsenic (As) removal performance. Here we present a magnetic confinement-enabled column reactor coupled with periodic ultrasonic depassivation (MCCR-PUD), which efficiently and sustainably removes As by reaction with continuously generated iron (oxyhydr)oxides from ZVI oxidative corrosion. In the MCCR, ZVI microparticles self-assemble into stable millimeter-scale wires in forest-like arrays in a parallel magnetic field (0.42-0.48 T, produced by two parallel permanent magnets), forming a highly porous structure (87 % porosity) with twice the accessible reactive surface area of a ZVI/sand mixture. For a feed concentration of 100 µg/L As(III), the MCCR-PUD, with a short empty bed contact time (1.6 min), treated ca. 7340 empty bed volume (EBV) of water at breakthrough (10 µg/L), 9.4 folds higher than that of a ZVI/sand filter. Due to the large interspace between ZVI wires, the MCCR-PUD effectively prevented column clogging that occurred in the ZVI/sand filter. The high water treatment capacity was attributed to the much enhanced ZVI reactivity in the magnetic field, sustained through rejuvenation by PUD. Furthermore, most of As was structurally incorporated into the produced iron (oxyhydr)oxides (mostly ferrihydrite) in the MCCR-PUD, as revealed by Mössbauer spectroscopy, X-ray absorption spectroscopy, and sequential extraction experiments. This finding evinced a different mechanism from the surface adsorption in the ZVI/sand filter. The structural incorporation of As also resulted in much less As remobilization from the produced corrosion products during aging in water, in total ∼1 % in 28 days. Furthermore, the MCCR-PUD exihibted robust performance when treating complex synthetic groundwater containing natural organic matter and common ions (∼3700 EBV at breakthrough). Taken together, our study demonstrates the potential of the magnetic confinement-enabled ZVI reactor as a promising decentralized As treatment platform.

Causal Effects of Lipids-Related Metabolites on Androgenic Alopecia: A Mendelian Randomization Study.

Purpose: To investigate whether increased levels of lipids-related metabolites (LRMs) result in androgenic alopecia (AGA). Patients and Methods: A two-sample Mendelian randomization (MR) study was designed, and single nucleotide polymorphisms (SNPs) respectively related to nine LRMs were selected from the genome-wide association study (GWAS) dataset. An MR analysis was performed to assess the causal association between LRMs and AGA. Results: Through the fixed-effect inverse variance weighting (IVW) method, MR analysis indicated that Apolipoprotein B (ApoB), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) had a causal relationship with AGA. No obvious heterogeneity or pleiotropy was observed. Conclusion: The risk of AGA increases significantly when the serum levels of ApoB, LDL, and VLDL increase. This causal relationship is solid and free of interference from confounding factors.

Effectiveness and safety of baricitinib in patients with moderate-to-severe refractory alopecia areata in real world: An open-label, single-center study.

PURPOSE: Baricitinib is a small-molecular drug that selectively inhibits the Janus Kinase (JAK) 1 and 2. However, it showed various efficiency and safety in treating moderate-to-severe alopecia areata (AA). This study was to describe the real-world effectiveness of baricitinib in treating moderate-to-severe refractory AA. METHODS: Patients who were affected by moderate-to-severe AA and reported no shrinkage in the alopecia area after 6 months of conventional treatment were enrolled in the retrospective study. The patients were treated with baricitinib orally for at least 24 weeks. The severity of alopecia was evaluated at the end of 4, 12, and 24 weeks of treatment. RESULTS: The 32 patients included 23 females and nine males, with a median duration of AA of 14.5 months. Among them, 28 patients received baricitinib 2 mg per day for 24 weeks while the other four patients increased the daily dose from 2 to 4 mg after the first 12 weeks due to the unobvious hair restoration. SALT value showed a significant decrease from baseline at week 12 and 24 (64.45 [44.68-100.00] vs. 26.80 [13.40-62.32], p < 0.0001 and 64.45 [44.68-100] vs. 9.40 [4.85-34.95], p < 0.0001). After 24 weeks of treatment, 50% of patients had an improvement of ≥2 points in IGA scores from the baseline, and IGA scores of 68.75% of patients were less than 2. CONCLUSION: This 24-week research showed that baricitinib had favorable clinical efficacy and safety in treating moderate-to-severe AA, which is worthy of attention and expectation.