Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia.

Aging of immune organs, termed as immunosenescence, is suspected to promote systemic inflammation and age-associated disease. The cause of immunosenescence and how it promotes disease, however, has remained unclear. We report that the Drosophila fat body, a major immune organ, undergoes immunosenescence and mounts strong systemic inflammation that leads to deregulation of immune deficiency (IMD) signaling in the midgut of old animals. Inflamed old fat bodies secrete circulating peptidoglycan recognition proteins that repress IMD activity in the midgut, thereby promoting gut hyperplasia. Further, fat body immunosenecence is caused by age-associated lamin-B reduction specifically in fat body cells, which then contributes to heterochromatin loss and derepression of genes involved in immune responses. As lamin-associated heterochromatin domains are enriched for genes involved in immune response in both Drosophila and mammalian cells, our findings may provide insights into the cause and consequence of immunosenescence during mammalian aging. PAPERFLICK:

Novel CAR-T cells targeting TRKB for the treatment of solid cancer.

Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating blood cancers such as B-cell malignancies, however, its effectiveness as an approach to treat solid tumors remains to be further explored. Here, we focused on the development of CAR-T cell therapies targeting tropomyosin-related kinase receptor B (TRKB), a highly expressed protein that is significantly associated with tumor progression, malignancy, and drug resistance in multiple forms of aggressive solid tumors. To achieve this, we screened brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NTF4) ligand-based CAR-T cells for their efficiency in targeting the TRKB receptor in the context of solid tumors, particularly hepatocellular carcinoma and pancreatic cancer. We demonstrated that TRKB is overexpressed not only in hepatocellular carcinoma and pancreatic carcinoma cell lines but also in cancer stem-like cells (CSCs). Notably, BDNF-CAR T and NTF4-CAR T cells could not only effectively target and kill TRKB-expressing pan-cancer cell lines in a dose-dependent manner but also effectively kill CSCs. We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.

Low field controllable continuous spin switching in the thulium-ytterbium single crystal.

We report the spin reorientation transition (SRT) and the low field controllable continuous spin switching (SSW) of the Tm0.75Yb0.25FeO3 (TYFO) single crystal in this study. The SRT, characterized by the transition from Γ2(Fx, Cy, Gz)-Γ4(Gx, Ay, Fz), occurs within the temperature range of 20-27 K. Under an external magnetic field of 50 Oe, the SSW occurs along the c-axis at approximately 98 K due to the reversal of Tm3+ magnetic moment induced by the magnetic coupling change between Tm3+ and Fe3+, transitioning from a parallel to an antiparallel alignment. Notably, a continuous SSW is observed along the a-axis at low temperatures, which has not been previously reported in rare earth orthoferrites. This unique behavior can be easily manipulated by low magnetic fields within the temperature range of 2-20 K. Both the spin reorientation transition and spin switching phenomena in the TYFO single crystal arise from interactions between rare earth ions and iron ions and can be effectively regulated by applied low magnetic fields, making it a promising material for low-field spin devices.

Distinct species turnover patterns shaped the richness of antibiotic resistance genes on eight different microplastic polymers.

Elucidating the formation mechanism of plastisphere antibiotic resistance genes (ARGs) on different polymers is necessary to understand the ecological risks of plastisphere ARGs. Here, we explored the turnover and assembly mechanism of plastisphere ARGs on 8 different microplastic polymers (4 biodegradable (bMPs) and 4 non-biodegradable microplastics (nMPs)) by metagenomic sequencing. Our study revealed the presence of 479 ARGs with abundance ranging from 41.37 to 58.17 copies/16S rRNA gene in all plastispheres. These ARGs were predominantly multidrug resistance genes. The richness of plastisphere ARGs on different polymers had a significant correlation with the contribution of species turnover to plastisphere ARGs ß diversity. Furthermore, polymer type was the most critical factor affecting the composition of plastisphere ARGs. More opportunistic pathogens carrying diverse ARGs on BMPs (PBAT, PBS, and PHA) with higher horizontal gene transfer potential may further magnify the ecological risks and human health threats. For example, the opportunistic pathogens Riemerella anatipestifer, Vibrio campbellii, and Vibrio cholerae are closely related to human production and life, which were the important potential hosts of many plastisphere ARGs and mobile genetic elements on BMPs. Thus, we emphasize the urgency of developing the formation mechanism of plastisphere ARGs and the necessity of controlling BMPs and ARG pollution, especially BMPs, with ever-increasing usage in daily life.

Extracellular vesicle-derived TP53BP1, CD34, and PBX1 from human peripheral blood serve as potential biomarkers for the assessment and prediction of vascular aging.

BACKGROUND: Vascular aging is an important pathophysiological basis for the senescence of various organs and systems in the human body, and it is a common pathogenetic trigger for many chronic diseases in the elderly. METHODS: The extracellular vesicles (EVs) from young and aged umbilical vein endothelial cells were isolated and identified by qPCR the differential expression levels of 47 mRNAs of genes closely related to aging in the two groups. RESULTS: There were significant differences in the expression levels of 18 genes (we noted upregulation in PLA2G12A, TP53BP1, CD144, PDE11A, FPGT, SERPINB4, POLD1, and PPFIBP2 and downregulation in ATP2C2, ROBO2, RRM2, GUCY1B1, NAT1-14, VEGFR2, WTAPP1, CD146, DMC1, and GRIK2). Subsequent qPCR identification of the above-mentioned genes in PBMCs and plasma-EVs from the various age groups revealed that the trend in expression levels in peripheral blood plasma-EVs of the different age groups was approximately the same as that in PBMCs. Of these mRNAs, the expression of four genes-PLA2G12A, TP53BP1, OPRL1, and KIAA0895-was commensurate with increasing age. In contradistinction, the expression trend of four genes (CREG1, PBX1, CD34, and SLIT2) was inversely proportional to the increase in age. Finally, by taking their intersection, we determined that the expression of TP53BP1 was upregulated with increasing human age and that CD34 and PBX1 were downregulated with increasing age. CONCLUSION: Our study indicates that human peripheral blood plasma-EV-derived TP53BP1, CD34, and PBX1 potentially comprise a noninvasive biomarker for assessing and predicting vascular aging.

Aging-related upregulation of the homeobox gene caudal represses intestinal stem cell differentiation in Drosophila.

The differentiation efficiency of adult stem cells undergoes a significant decline in aged animals, which is closely related to the decline in organ function and age-associated diseases. However, the underlying mechanisms that ultimately lead to this observed decline of the differentiation efficiency of stem cells remain largely unclear. This study investigated Drosophila midguts and identified an obvious upregulation of caudal (cad), which encodes a homeobox transcription factor. This factor is traditionally known as a central regulator of embryonic anterior-posterior body axis patterning. This study reports that depletion of cad in intestinal stem/progenitor cells promotes quiescent intestinal stem cells (ISCs) to become activate and produce enterocytes in the midgut under normal gut homeostasis conditions. However, overexpression of cad results in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, this study suggests that cad prevents intestinal stem/progenitor cell differentiation by modulating the Janus kinase/signal transducers and activators of the transcription pathway and Sox21a-GATAe signaling cascade. Importantly, the reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila. This study identified a function of the homeobox gene cad in the modulation of adult stem cell differentiation and suggested a potential gene target for the treatment of age-related diseases induced by age-related stem cell dysfunction.

Adar Regulates Drosophila melanogaster Spermatogenesis via Modulation of BMP Signaling.

The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.

Iodonium Initiators: Paving the Air-free Oxidation of Spiro-OMeTAD for Efficient and Stable Perovskite Solar Cells.

To date, perovskite solar cells (pero-SCs) with doped 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) hole transporting layers (HTLs) have shown the highest recorded power conversion efficiencies (PCEs). However, their commercialization is still impeded by poor device stability owing to the hygroscopic lithium bis(trifluoromethanesulfonyl)imide and volatile 4-tert-butylpyridine dopants as well as time-consuming oxidation in air. In this study, we explored a series of single-component iodonium initiators with strong oxidability and different electron delocalization properties to precisely manipulate the oxidation states of Spiro-OMeTAD without air assistance, and the oxidation mechanism was clearly understood. Iodine (III) in the diphenyliodonium cation (IP+ ) can accept a single electron from Spiro-OMeTAD and forms Spiro-OMeTAD⋅+ owing to its strong oxidability. Moreover, because of the coordination of the strongly delocalized TFSI- with Spiro-OMeTAD⋅+ in a stable radical complex, the resulting hole mobility was 30 times higher than that of pristine Spiro-OMeTAD. In addition, the IP-TFSI initiator facilitated the growth of a homogeneous and pinhole-free Spiro-OMeTAD film. The pero-SCs based on this oxidizing HTL showed excellent efficiencies of 25.16 % (certified: 24.85 % for 0.062-cm2 ) and 20.71 % for a 15.03-cm2 module as well as remarkable overall stability.

Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy.

BACKGROUND: Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive. METHODS: We generated a compendium of 3-dimensional epigenome and transcriptome maps from 101 biobanked human DCM and nonfailing heart tissues through highly integrative chromatin immunoprecipitation (H3K27ac [acetylation of lysine 27 on histone H3]), in situ high-throughput chromosome conformation capture, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin using sequencing, and RNA sequencing. We used human induced pluripotent stem cell-derived cardiomyocytes and mouse models to interrogate the key transcription factor implicated in 3-dimensional chromatin organization and transcriptional regulation in DCM pathogenesis. RESULTS: We discovered that the active regulatory elements (H3K27ac peaks) and their connectome (H3K27ac loops) were extensively reprogrammed in DCM hearts and contributed to transcriptional dysregulation implicated in DCM development. For example, we identified that nontranscribing NPPA-AS1 (natriuretic peptide A antisense RNA 1) promoter functions as an enhancer and physically interacts with the NPPA (natriuretic peptide A) and NPPB (natriuretic peptide B) promoters, leading to the cotranscription of NPPA and NPPB in DCM hearts. We revealed that DCM-enriched H3K27ac loops largely resided in conserved high-order chromatin architectures (compartments, topologically associating domains) and their anchors unexpectedly had equivalent chromatin accessibility. We discovered that the DCM-enriched H3K27ac loop anchors exhibited a strong enrichment for HAND1 (heart and neural crest derivatives expressed 1), a key transcription factor involved in early cardiogenesis. In line with this, its protein expression was upregulated in human DCM and mouse failing hearts. To further validate whether HAND1 is a causal driver for the reprogramming of enhancer-promoter connectome in DCM hearts, we performed comprehensive 3-dimensional epigenome mappings in human induced pluripotent stem cell-derived cardiomyocytes. We found that forced overexpression of HAND1 in human induced pluripotent stem cell-derived cardiomyocytes induced a distinct gain of enhancer-promoter connectivity and correspondingly increased the expression of their connected genes implicated in DCM pathogenesis, thus recapitulating the transcriptional signature in human DCM hearts. Electrophysiology analysis demonstrated that forced overexpression of HAND1 in human induced pluripotent stem cell-derived cardiomyocytes induced abnormal calcium handling. Furthermore, cardiomyocyte-specific overexpression of Hand1 in the mouse hearts resulted in dilated cardiac remodeling with impaired contractility/Ca2+ handling in cardiomyocytes, increased ratio of heart weight/body weight, and compromised cardiac function, which were ascribed to recapitulation of transcriptional reprogramming in DCM. CONCLUSIONS: This study provided novel chromatin topology insights into DCM pathogenesis and illustrated a model whereby a single transcription factor (HAND1) reprograms the genome-wide enhancer-promoter connectome to drive DCM pathogenesis.

An integrated multimedia fate modeling framework for identifying mitigation strategy of antibiotic ecological risks: A case study in a peri-urban river.

Antibiotics have been heavily used over the past decades, resulting in their frequent detections in rivers and increasing ecological risks. Recognizing characteristics of antibiotic ecological risks (AERs) and making effective strategies to mitigate the AERs are essential to ensure the safety of aquatic ecosystem and public health. In this study, an integrated technological framework has been proposed toward identifying management options for reducing AERs by jointly utilizing multimedia fugacity modelling and ecotoxicological risk assessment, and applied to characterize the AERs in a peri-urban river in Beijing. Specifically, a level III fugacity model has been successfully established to simulate the fate of antibiotics in the environment, and the manageable parameters have been screened out via sensitivity analysis of the model. Then the validated fugacity model has been used for scenario modellings to optimize mitigation strategies of AERs. Results show most of the antibiotics considered are frequently detected in the river, and pose medium or high risks to aquatic organisms. Relatively, the macrolides and fluoroquinolones present higher ecotoxicological risks than sulfonamides and tetracyclines. Furthermore, the mixture risk quotient and predictive equation of concentration addition suggest joint and synergistic/antagonistic effects of AERs for multiple or binary antibiotics in the environment. Largely, the concentrations of antibiotics in the river are determined by the source emissions into water and soil. Scenario modellings show the improvement of antibiotic removal rates would be considered preferentially to mitigate the AERs. Also, controlling human consumption is conducive to reducing the risks posed by tetracyclines, macrolides and trimethoprim, while controlling animal consumption would benefit the reduction for sulfonamides. Overall, the joint strategy presents the greatest reduction of AERs by reducing antibiotic consumption and together improving sewage treatment rate and antibiotic removal rate. The study provides us a useful guideline to make ecological risk-based mitigation strategy for reducing AERs in environment.

Biogeography and diversity patterns of antibiotic resistome in the sediments of global lakes.

Lakes act as one of the reservoirs and dispersal routes of antibiotic resistance genes (ARGs) and pathogenic resistant bacteria in aquatic environments. Previous studies reported the occurrence and distribution of ARGs in lakes worldwide; however, few investigated the biogeography and diversity patterns of antibiotic resistome in the environment. To fill this gap, a large-scale data set of sediment metagenomes was collected from globally distributed lakes and characterized comprehensively using metagenomic assembly-based analysis, aiming to shed light on the biogeography and diversity patterns of ARGs in lake ecosystems from a global perspective. Our analyses showed that abundant and diverse ARGs were found in the global lake sediments, including a set of emerging ARGs such as mcr-type and carbapenem-resistant Enterobacteriaceae related genes. Most of the identified ARGs were generally associated with the commonly used antibiotics, suggesting the role of increasing antibiotic consumptions on the resistome prevalence. Spatially, the composition and diversity of ARGs varied across geographical distances and exhibited a scale-dependent distance-decay relationship. Notably, the composition of ARGs was largely shaped by bacterial community structure, and their diversities were co-governed by stochastic process (∼48%) and deterministic process (∼52%). Findings provide a valuable insight to better understand ecological mechanisms of ARGs in lake ecosystems and have important implication for the prevention and control of resistome risk.

Green Solvent Processable, Asymmetric Dopant-Free Hole Transport Layer Material for Efficient and Stable n-i-p Perovskite Solar Cells and Modules.

The use of dopant-free hole transport layers (HTLs) is critical in stabilizing n-i-p perovskite solar cells (pero-SCs). However, these HTL materials are often processed with toxic solvents, which is not ideal for industrial production. Upon substituting them with green solvents, a trade-off emerges between maintaining the high crystallinity of the HTL materials and ensuring high solubility in the new solvents. In this paper, we designed a novel, linear, organic small molecule, BDT-C8-3O, by introducing an asymmetric polar oligo(ethylene glycol) side chain. This method not only overcomes the solubility limitations in green solvents but also enables stacking the conjugated main chains in two patterns, which further enhances crystallinity and hole mobility. As a result, the n-i-p pero-SCs based on chlorobenzene- or green (natural compound) solvent 3-methylcyclohexanone-processed BDT-C8-3O HTL that without any dopant delivered world-recorded power conversion efficiencies of 24.11 % (certified of 23.82 %) and 23.53 %, respectively. The devices also demonstrated remarkable operational and high-temperature stabilities, maintaining over 84 % and 79.5 % of their initial efficiency for 2000 h, respectively. Encouragingly, dopant-free BDT-C8-3O HTL exhibits significant advantages in large-area fabrication, achieving state-of-the-art PCEs exceeding 20 % for 5×5 cm2 modules (active area: 15.64 cm2 ), even when processed using green solvents.

Realizing 17.5% Efficiency Flexible Organic Solar Cells via Atomic-Level Chemical Welding of Silver Nanowire Electrodes.

Solution processable flexible transparent electrodes (FTEs) are urgently needed to boost the efficiency and mechanical stability of flexible organic solar cells (OSCs) on a large scale. However, how to balance the optoelectronic properties and meanwhile achieve robust mechanical behavior of FTEs is still a huge challenge. Silver nanowire (AgNW) electrodes, exhibiting easily tuned optoelectronic/mechanical properties, are attracting considerable attention, but their poor contacts at the junction site of the AgNWs increase the sheet resistance and reduce mechanical stability. In this study, an ionic liquid (IL)-type reducing agent containing Cl- and a dihydroxyl group was employed to control the reduction process of silver (Ag) in AgNW-based FTEs precisely. The Cl- in the IL regulates the Ag+ concentration through the formation and dissolution of AgCl, whereas the dihydroxyl group slowly reduces the released Ag+ to form metal Ag. The reduced Ag grew in situ at the junction site of the AgNWs in a twin-crystal growth mode, facilitating an atomic-level contact between the AgNWs and the reduced Ag. This enforced atomic-level contact decreased the sheet resistance, and enhanced the mechanical stability of the FTEs. As a result, the single-junction flexible OSCs based on this chemically welded FTE achieved record power conversion efficiencies of 17.52% (active area: 0.062 cm2) and 15.82% (active area: 1.0 cm2). These flexible devices also displayed robust bending and peeling durability even under extreme test conditions.

A new magnetic resonance imaging tumour response grading scheme for locally advanced rectal cancer.

BACKGROUND: The potential of using magnetic resonance image tumour-regression grading (MRI-TRG) system to predict pathological TRG is debatable for locally advanced rectal cancer treated by neoadjuvant radiochemotherapy. METHODS: Referring to the American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) TRG classification scheme, a new four-category MRI-TRG system based on the volumetric analysis of the residual tumour and radiochemotherapy induced anorectal fibrosis was established. The agreement between them was evaluated by Kendall's tau-b test, while Kaplan-Meier analysis was used to calculate survival outcomes. RESULTS: In total, 1033 patients were included. Good agreement between MRI-TRG and AJCC/CAP TRG classifications was observed (k = 0.671). Particularly, as compared with other pairs, MRI-TRG 0 displayed the highest sensitivity [90.1% (95% CI: 84.3-93.9)] and specificity [92.8% (95% CI: 90.4-94.7)] in identifying AJCC/CAP TRG 0 category patients. Except for the survival ratios that were comparable between the MRI-TRG 0 and MRI-TRG 1 categories, any two of the four categories had distinguished 3-year prognosis (all P < 0.05). Cox regression analysis further proved that the MRI-TRG system was an independent prognostic factor (all P < 0.05). CONCLUSION: The new MRI-TRG system might be a surrogate for AJCC/CAP TRG classification scheme. Importantly, the system is a reliable and non-invasive way to identify patients with complete pathological responses.

Geographic Dispersal Limitation Dominated Assembly Processes of Bacterial Communities on Microplastics Compared to Water and Sediment.

Microplastics provide new microbial niches in aquatic environments. Nevertheless, information on the assembly processes and potential ecological mechanisms of bacterial communities on microplastics from reservoirs is lacking. Here, we investigated the assembly processes and potential ecological mechanisms of bacterial communities on microplastics through full-length 16S rRNA sequencing in the Three Gorges Reservoir area of the Yangtze River, compared to water and sediment. The results showed that the Burkholderiaceae were the dominant composition of bacterial communities in microplastics (9.95%), water (25.14%), and sediment (7.22%). The niche width of the bacterial community on microplastics was lower than those in water and sediment. For the microplastics and sediment, distance-decay relationship results showed that the bacterial community similarity was significantly decreased with increasing geographical distance. In addition, the spatial turnover rate of the bacterial community on microplastics along the ~662-km reaches of the Yangtze River in the Three Gorges Reservoir area was higher than that in sediment. Null model analysis showed that the assembly processes of the bacterial community on microplastics were also different from those in water and sediments. Dispersal limitation (52.4%) was the primary assembly process of the bacterial community on microplastics, but variable selection was the most critical assembly process of the bacterial communities in water (47.6%) and sediment (66.7%). Thus, geographic dispersal limitation dominated the assembly processes of bacterial communities on microplastics. This study can enhance our understanding of the assembly mechanism of bacterial communities caused by the selection preference for microplastics from the surrounding environment. IMPORTANCE In river systems, microplastics create new microbial niches that significantly differ from those of the surrounding environment. However, the potential relationships between the biogeographic distribution and assembly processes of microbial communities on microplastics were still not well understood. This study could help us address the lack of knowledge about the assembly processes of bacterial communities on microplastics caused by selection from the surrounding environment. In this study, strong geographic dispersal limitation dominated assembly processes of bacterial communities on microplastics, compared to water and sediment, which may be responsible for the microplastic bacterial richness, and the niche distance was lower than those in water and sediment. In addition, sediment may be the main potential source of bacterial communities on microplastics in the Three Gorges Reservoir area, which makes higher community similarity between microplastics and sediment than between microplastics and water.

Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction.

The age-associated decline of adult stem cell function is closely related to the decline in tissue function and age-related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha-lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age-associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age-associated ISC dysfunction by promoting the activation of the endocytosis-autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti-aging compound for the treatment of ISC-dysfunction-related diseases and for the promotion of healthy aging in humans.

Thyroid Hormone Disruption by Organophosphate Esters Is Mediated by Nuclear/Membrane Thyroid Hormone Receptors: In Vitro, In Vivo, and In Silico Studies.

Earlier mechanistic studies of many prohibited flame retardants (FRs) highlighted their thyroid hormone-disrupting activity through nuclear thyroid hormone receptors (nTRs), whereas some alternative FRs such as organophosphate esters (OPEs) exerted weak nTR-disrupting effects. However, an increasing number of studies have revealed that OPEs also exert thyroid hormone-disrupting effects, and the underlying mechanism is unclear. Herein, the thyroid hormone-disrupting effects and mechanisms of 8 typical OPEs were investigated using integrated in vitro, in vivo, and in silico assays. All tested chemicals competitively bound to the membrane thyroid hormone receptor (mTR) [the 20% relative inhibitory concentration (RIC20): (3.5 ± 0.2) × 101 to (4.9 ± 1.0) × 107 nM], and Cl-OPEs and alkyl-OPEs had lower RIC20 values. In contrast, only 4 OPEs showed nTR antagonistic activities at higher concentrations [≥ (4.8 ± 0.8) × 103 nM]. Cl-OPEs and alkyl-OPEs preferentially interacted with mTR. Molecular docking illustrated that OPEs docked into mTRs, consistent with the competitive binding assay. In vivo analyses of zebrafish embryonic development confirmed that tris(1,3-dichloro-2-propyl) phosphate induced inappropriate expression of proteins, and these protein interactions might be associated with mTR according to the quantitative proteomic analysis. Based on the results, mTR might play a critical role in mediating the thyroid hormone-disrupting effects of OPEs.

Low field control of spin switching and continuous magnetic transition in an ErFeO3 single crystal.

The magnetic behavior of a rare-earth orthoferrite ErFeO3 single crystal can be controlled by low magnetic fields from a few to hundreds of Oe. Here we investigated a high-quality ErFeO3 single crystal in the temperature range of 5-120 K, with two types of spin switching in the field-cooled-cooling (FCC) and field-cooled-warming (FCW) processes below the temperature of the spin reorientation (SR) transition from Γ4 to Γ2 at 98-88 K. The magnitude of the applied magnetic fields can regulate two types of spin switching along the a-axis of the ErFeO3 single crystal but does not affect the type and temperature range of the SR transition. An interesting "multi-step" type-II spin switching is observed in FCW under low magnetic fields (H < 18 Oe) just below the SR transition temperature, which is associated with the interaction and the change of magnetic configurations from rare-earth and iron magnetic sublattices. When the magnetic field is lower than 15 Oe, the type-II spin switching in the FCW process gradually changes to a continuous magnetic transition along the a-axis of the ErFeO3 single crystal. As the magnetic field is reduced to less than 17 Oe, the type-I spin switching in the FCW process also transforms into a continuous magnetic transition. Understanding the magnetic reversal effects will help us explore the potential applications of these magnetic materials for future information devices.

Characteristics of resistome and bacterial community structure in constructed wetland during dormant period: A fullscale study from Annan wetland.

As a green technology, constructed wetlands (CWs) can provide a low-cost solution for wastewater treatment. Either as a standalone treatment or integrated with conventional treatment, nutrients, antibiotic resistant bacteria (ARB)/antibiotic resistance genes (ARGs) can be removed by CW efficiently. While, few studies have focused on characteristics of resistome and bacterial community (BC) structure in CW during dormant period. Therefore, in this study, Annan CW (a full-scale hybrid CW) was selected to characterize resistome and BC during dormant period. The profiles of bacteria / ARGs were monitored in combination of shotgun sequencing and metagenomic assembly analysis. And multidrug ARGs are the most abundant in Annan CW, and surface flow wetland had the relatively high ARG diversity and abundance compared with subsurface flow wetland and the front pond. The most dominant phylum in CW is Proteobacteria, while the other dominant phylum in three parts have different order. COD, TP, TN, ARGs, and mobile genetic genes (MGEs) were removed by subsurface flow CW with better performance, but virulent factors (VFs) were removed by surface flow CW with better performance. Based on the spatiotemporal distribution of ARGs, the internal mechanism of ARGs dynamic variation was explored by the redundancy analysis (RDA) and variation partitioning analysis (VPA). BCs, MGEs and environmental factors (EFs) were responsible for 45.6 %, 28.3 % and 15.4 % of the ARGs variations. Among these factors, BCs and MGEs were the major co-drivers impacting the ARG profile, and EFs indirectly influence the ARG profile. This study illustrates the specific functions of ARG risk elimination in different CW components, promotes a better understanding of the efficiency of CWs for the reduction of ARG and ARB, contributing to improve the removal performance of constructed wetlands. And provide management advice to further optimize the operation of CWs during dormant period.

Metagenomic binning and assembled genome analysis revealed the distinct composition of resistome and mobilome in the Ili River.

Rivers play an important role in receiving and transporting the resistome among different environmental compartments. However, the difference in resistome and mobilome between the water and sediment and their underlying mechanisms were still poorly understood. In this study, the Ili River, an important water source in the arid area of Central Asia, was selected as the studied target. The comprehensive profile of resistome and mobilome and their host in water and sediment were studied based on metagenomic binning and assembled genome (MAG) analysis. The relative abundance of resistome and mobilome in sediment were 28.0 - 67.8 × /Gb and 46.5 - 121.1 × /Gb, respectively, which were significantly higher than those in water (23.1 - 52.8 ×/Gb and 25.3 - 67.7 ×/Gb). Multidrug and macrolides-lincosamides-streptogramin (MLS) resistance genes were the main ARG types in both water and sediment from relative abundance. Transposases dominated the relative abundance of mobilome, followed by insert elements and integrases. Strong correlations were found between the relative abundance of resistome and mobilome (r > 0.6 and p < 0.01) in both water and sediment, indicating the mobilome played an important role in the propagation of resistome in the Ili River. The main hosts for multidrug resistance genes via MAG analysis differed in water (Alphaproteobacteria and Gammaproteobacteria) and sediment (Gammaproteobacteria). Distinct compositions of resistome and mobilome existed between water and sediment in the Ili River. Specificity-occupancy analysis of the differential resistome and mobilome showed that occurrence frequencies and habitat selections of the differential ARGs shaped the resistome of water and sediment. In contrast, habitat was the main driver that shaped the mobilome in the Ili River.