Ubiquitous nanocolloids suppress the conjugative transfer of plasmid-mediated antibiotic resistance in aqueous environment.

Nanocolloids (Nc) are widespread in natural water environment, whereas the potential effects of Nc on dissemination of antibiotic resistance remain largely unknown. In this study, Nc collected from the Yellow River in Henan province was tested for its ability to influence the conjugative transfer of resistant plasmid in aqueous environment. The results revealed that the conjugative transfer of RP4 plasmid between Escherichia coli was down-regulated by 52%-91% upon exposure to 1-10 mg/L Nc and the reduction became constant when the dose became higher (20-200 mg/L). Despite the exposure of Nc activated the anti-oxidation and SOS response in bacteria through up-regulating genes involved in glutathione biosynthesis and DNA recombination, the inhibition on the synthesis and secretion of extracellular polysaccharide induced the prevention of cell-cell contact, leading to the reduction of plasmid transfer. This was evidenced by the decreased bacterial adhesion and lowered levels of genes and metabolites relevant to transmembrane transport and D-glucose phosphorylation, as clarified in phenotypic, transcriptomics and metabolomics analysis of E. coli. The significant down-regulation of glycolysis/gluconeogenesis and TCA cycle was associated with the shortage of ATP induced by Nc. The up-regulation of global regulatory genes (korA and trbA) and the reduction of plasmid genes (trfAp, trbBp, and traG) expression also contributed to the suppressed conjugation of RP4 plasmid. The obtained findings remind that the role of ubiquitous colloidal particles is nonnegligible when practically and comprehensively assessing the risk of antibiotic resistance in the environment.

Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis.

Tris(2,4-di-tert-butylphenyl)phosphate (AO168 =O), a novel organophosphate ester, is prevalent and abundant in the environment, posing great exposure risks to ecological and public health. Nevertheless, the toxicological effects of AO168 =O remain entirely unknown to date. The results in this study indicated that acute exposure to AO168 =O at 10 and 100 µg/L for 5 days obviously impaired cardiac morphology and function of zebrafish larvae, as proofed by decreased heartbeat, stroke volume, and cardiac output and the occurrence of pericardial edema and ventricular hypertrophy. Transcriptomics, polymerase chain reaction, and molecular docking revealed that the strong interaction of AO168 =O and transferrin receptor 1 activated the transportation of ferric iron into intracellular environment. The release of free ferrous ion to cytoplasmic iron pool also contributed to the iron overload in heart region, thus inducing ferroptosis in larvae via generation of excessive reactive oxygen species, glutathione peroxidase 4 inhibition, glutathione depletion and lipid peroxidation. Ferroptosis inhibitor (Fer-1) co-exposure effectively relieved the cardiac dysfunctions of zebrafish, verifying the dominant role of ferroptosis in the cardiotoxicity caused by AO168 =O. This research firstly reported the adverse impact and associated mechanisms of AO168 =O in cardiomyogenesis of vertebrates, underlining the urgency of concerning the health risks of AO168 =O.

Interactions of monolayer molybdenum disulfide sheets with metalloid antimony in aquatic environment: Adsorption, transformation, and joint toxicity.

The tremendous application potentiality of transitional metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2) nanosheets, will unavoidably lead to increasing release into the environment, which could influence the fate and toxicity of co-existed contaminants. The present study discovered that 59.8 % of trivalent antimony [Sb(III)] was transformed by MoS2 to pentavalent Sb [Sb(V)] in aqueous solutions under light illumination, which was due to hole oxidation on the nanosheet surfaces. A synergistic toxicity between MoS2 and Sb(III, V) to algae (Chlorella vulgaris) was observed, as demonstrated by the lower median-effect concentrations of MoS2 + Sb(III)/Sb(V) (13.1 and 20.9 mg/L, respectively) than Sb(III)/Sb(V) (38.8 and 92.5 mg/L, respectively) alone. Particularly, MoS2 at noncytotoxic doses notably increased the bioaccumulation of Sb(III, V) in algae, causing aggravated oxidative damage, photosynthetic inhibition, and structural alterations. Metabolomics indicated that oxidative stress and membrane permeabilization were primarily associated with down-regulated amino acids involved in glutathione biosynthesis and unsaturated fatty acids. MoS2 co-exposure remarkably decreased the levels of thiol antidotes (glutathione and phytochelatins) and aggravated the inhibition on energy metabolism and ATP synthesis, compromising the Sb(III, V) detoxification and efflux. Additionally, extracellular P was captured by the nanosheets, also contributing to the uptake of Sb(V). Our findings emphasized the nonignorability of TMDs even at environmental levels in affecting the ecological hazard of metalloids, providing insight into comprehensive safety assessment of TMDs.

Toxicity of hexagonal boron nitride nanosheets to freshwater algae: Phospholipid membrane damage and carbon assimilation inhibition.

Hexagonal boron nitride (h-BN) nanomaterials have attracted numerous attentions for application in various fields, including environmental governance. Understanding the environmental implications of h-BN is a prerequisite for its safe and sustainable use; nevertheless, information on the negative effect of h-BN on aquatic organisms and the underlying toxicity mechanisms is scarce. The present study found that low exposure doses (0.1-1 µg/mL) of micron-sized h-BN lamella apparently suppressed (maximally 45.3%) the growth of Chlorella vulgaris (a freshwater alga) via membrane damages and metabolic reprogramming. Experimental and simulation results verified that h-BN can penetrate into and then extract phospholipids from the cell membrane of algae due to the strong hydrophobic interactions between h-BN nanosheets and lipids, resulting in membrane permeabilization and integrity reduction. Oxidative stress-triggered lipid peroxidation also contributes to membrane destruction of algae. Metabolomics assay demonstrated that h-BN down-regulated the CO2-fixation associated Calvin cycle and glycolysis/gluconeogenesis pathways in algae, thereby inhibiting energy synthesis and antioxidation process. Despite releasing soluble B inside cells, the B species exhibited negligible toxicity. These findings highlight the phenomena and mechanisms of h-BN toxicity in photosynthetic algae, which have great implications for guiding their safe use under the scenarios of global carbon neutrality.

An immune and epigenetics-related scoring model and drug candidate prediction for hepatic carcinogenesis via dynamic network biomarker analysis and connectivity mapping.

Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality. This study aimed to build a prognostic signature for HCC patients based on immune-related genes (IRGs) and epigenetics-related genes (EPGs). RNA-seq data from Gene Expression Omnibus were used for dynamic network biomarker (DNB) analysis to identify 56 candidate IRG-EPG-DNBs and their first-neighbor genes. These genes were screened using LASSO-Cox regression analysis to finally obtain five candidate genes-RNF2, YBX1, EZH2, CAD, and PSMD1-which constituted the prognostic signature panel. According to this panel, patients in The Cancer Genome Atlas and International Cancer Genome Consortium were divided into high- and low-risk groups. The prognosis, clinicopathological features, and immune cell infiltration significantly differed between the two risk groups. The prognostic ability of the signature panel and expression profiling were further validated using online databases. We used an independent cohort of patients to validate the expression profiles of the five genes using reverse transcription-PCR. CMap and CellMiner predicted four small molecule drug-protein pairs based on the five prognostic genes. Of them, two market drugs approved by the Food and Drug Administration (AT-13387 and KU-55933) have emerged as candidates for HCC study. This new signature panel may serve as a potential prognostic marker, engendering the possibility of novel personalized therapy with classification of HCC patients.

Differential developmental and proinflammatory responses of zebrafish embryo to repetitive exposure of biodigested polyamide and polystyrene microplastics.

Microplastics (MPs) have attracted global concern and are at the forefront of current research on environmental pollution, whereas, little is known about the degradation of ingested MPs in the gastrointestinal environment and repetitive exposure-associated risk of egested MPs to organisms. The present study revealed that polyamide (PA) and polystyrene (PS) MPs exhibited remarkably differential biodegradations in the gastric and intestinal fluids of a model fish (Siniperca chuatsi). Significant disintegration of the skeleton structure, size reduction (from 27.62 to 9.17 µm), benzene ring scission, and subsequent biogenic corona coating and surface oxidation occurred during in vitro digestion, thus increasing the hydrophilicity and agglomeration of PS. Conversely, PA MPs exhibited high resistance to enzymolysis with slight surface erosions and protein adsorption. Relative to the pristine form, the bioaccumulation of digested PS elevated and the musculoskeletal deformity and mortality of juvenile zebrafish were obviously enhanced, but these changes were unobservable for PA. Lipopolysaccharide-triggered inflammation and apoptosis via Toll-like receptor signaling pathways and reduction of extracellular matrix secretions driven by oxidative stress contributed to the aggravated inhibitory effects of digested PS on larval development. These findings emphasize the necessity of concerning the biota digestion in MP risk assessments in natural waters.

A randomized controlled trial of group CBT with positive psychotherapy intervention for university students with maladaptive perfectionism in China.

Objective: The primary objective of this randomized controlled trial was to find a more economical and feasible intervention for maladaptive perfectionism, which is a risk and maintenance mechanism for various psychopathologies. Methods: In total, 64 university students who met the total inclusion criteria were randomly assigned to either group CBT with positive psychotherapy intervention or a 16-week waitlist (WL). The intervention group received 2 h of therapy for eight weekly sessions. Measurements of maladaptive perfectionism and the symptoms of depression and anxiety were conducted at baseline, post-intervention, and follow-up. Results: There was no statistically significant difference in the scores of the Frost Multidimensional Perfectionism Scale, Self-Rating Depression Scale, and Self-Rating Anxiety Scale between the intervention group and the waitlist group at baseline (all p > 0.05). The intervention group had a significant main effect of time and a time × group interaction effect of the maladaptive aspects of perfectionism, Concern over Mistakes and Doubts about Actions, and depression and anxiety scores in comparison with the waitlist group at the post-intervention and 8-week follow-up and had no statistically significant effects on the scores for Personal Standards, Parental Expectation, and Parental Criticism. The analysis showed that group intervention reduced symptoms of depression and anxiety while reducing maladaptive aspects of perfectionism. Conclusion: This study added to the literature on CBT interventions for maladaptive perfectionism and indicated that group CBT with positive psychotherapy intervention had substantial long-term effects on the maladaptive perfectionism of university students in China. Moreover, the results indicated that the intervention increased participants' self-acceptance.

Componential and molecular-weight-dependent effects of natural organic matter on the colloidal behavior, transformation, and toxicity of MoS2 nanoflakes.

The potential widespread applications in water processing have rendered the necessity for investigations of the fate and hazard of molybdenum disulfide (MoS2) nanosheets. Herein, it was found that humic acid (HA) had better performances toward stabilizing pure 2H phase MoS2 and chemical-exfoliated MoS2 (ce-MoS2) in electrolyte solutions than fulvic acid (FA), and molecular weight (MW)-dependent manners were disclosed due to steric repulsions. Compared with darkness, the extent to which the aggregation and sedimentation of ce-MoS2 facilitated by visible light irradiation was greater in the presence of HA and FA fractions, likely due to the introduction of stronger plasmonic dipole-dipole interaction and Van der Waals attraction forces. HA-triggered structural disintegration of nanosheets was performed after irradiation and it was observed to be more significant with the increase in MWs, whereas the MW-dependent dissolution of MoS2 caused by FA was much quicker than that by HA owing to the higher generation of singlet oxygen. Moreover, FA lowered the bioavailability of MoS2 and relieved its toxicity to zebrafish more effectively than HA. Our findings boost the insights into the effects of organic molecules on the fates and hazards of MoS2, providing guidance for the MoS2-based nanotechnological development on environment.

Promotion effects and mechanisms of molybdenum disulfide on the propagation of antibiotic resistance genes in soil.

The rapid development of nanotechnology has aroused considerable attentions toward understanding the effects of engineered nanomaterials (ENMs) on the propagation of antibiotic resistance. Molybdenum disulfide (MoS2) is an extensively used ENM and poses potential risks associated with environmental exposure; nevertheless, the role of MoS2 toward antibiotic resistance genes (ARGs) transfer remains largely unknown. Herein, it was discovered that MoS2 nanosheets accelerated the horizontal transfer of RP4 plasmid across Escherichia coli in a dose-dependent manner (0.5-10 mg/L), with the maximum transfer frequency 2.07-fold higher than that of the control. Integration of physiological, transcriptomics, and metabolomics analyses demonstrated that SOS response in bacteria was activated by MoS2 due to the elevation of oxidative damage, accompanied by cell membrane permeabilization. MoS2 promoted bacterial adhesion and intercellular contact via stimulating the secretion of extracellular polysaccharides. The ATP levels were maximally increased by 305.7 % upon exposure to MoS2, and the expression of plasmid transfer genes was up-regulated, contributing to the accelerated plasmid conjugation and increased ARG abundance in soil. Our findings highlight the roles of emerging ENMs (e.g., MoS2) in ARGs dissemination, which is significant for the safe applications and risk management of ENMs under the development scenarios of nanotechnology.

Diagnostic value of combining preoperative inflammatory markers ratios with CA199 for patients with early-stage pancreatic cancer.

BACKGROUND: An early diagnosis of pancreatic cancer (PC) is extremely difficult because of the lack of sensitive liquid biopsy methods and effective biomarkers. We attempted to evaluate whether circulating inflammatory marker could complement CA199 for the detection of early-stage PC. METHODS: We enrolled 430 patients with early-stage PC, 287 patients with other pancreatic tumors (OPT), and 401 healthy controls (HC). The patients and HC were randomly divided into a training set (n = 872) and two testing sets (n1 = 218, n2 = 28). The receiver operating characteristic (ROC) curves were investigated to evaluate the diagnostic performance of circulating inflammatory markers ratios, CA199, and combinations of the markers ratios in the training set, which would then be validated in the two testing sets. RESULTS: Circulating fibrinogen, neutrophils, and monocytes in patients with PC were significantly higher while circulating albumin, prealbumin, lymphocytes, and platelets of patients with PC were significantly lower compared to those of HC and OPT (all P < 0.05). The fibrinogen-to-albumin (FAR), fibrinogen-to-prealbumin (FPR), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), and fibrinogen-to-lymphocyte (FLR) ratios were significantly higher while the prognostic nutrition index values (PNI) were lower in patients with PC than in HC and OPT (all P < 0.05). Combining the FAR, FPR, and FLR with CA199 exhibited the best diagnostic value for distinguishing patients with early-stage PC from HC with an area under the curve (AUC) of 0.964, and for distinguishing patients with early-stage PC from OPT with an AUC of 0.924 in the training sets. In the testing set, compared with HC, the combination markers had powerful efficiency for PC with an AUC 0.947 and AUC 0.942 when comparing PC with OPT. The AUC was 0.915 for the combination of CA199, FAR, FPR, and FLR for differentiating between patients with pancreatic head cancer (PHC) and other pancreatic head tumors (OPHT), and 0.894 for differentiating between patients with pancreatic body and tail cancer (PBTC) and other pancreatic body and tail tumors (OPBTT). CONCLUSION: A combination of FAR, FPR, FLR, and CA199 may serve as a potential non-invasive biomarker for differentiating early-stage PC from HC and OPT, especially early-stage PHC.

Systematic stress persistence and recovery patterns of rice (Oryza sativa L.) roots in response to molybdenum disulfide nanosheets.

The increasing application of engineered nanomaterials (ENMs) unavoidably leads to environmental release and biological exposure. Understanding the potential hazards of ENMs on crops is essential for appropriate utilization and management. Herein, rice seedlings were hydroponically exposed to molybdenum sulfide (MoS2, a typical ENM) nanosheets at 5-20 mg/L for 7 days and then depurated for another 7 days in a fresh culture medium. Exposure to MoS2 triggered irreversible reductions in root length (by 26.3%-69.9%) and tip number (by 22.2%-66.0%). Integration of biochemical assays, transcriptomic and metabolomics found that oxidative stress induced by MoS2 in roots was persistent, whereas the activation of aquaporins, ionic transportation, and energy synthesis was normalized due to the recovery of nutrient uptake. The down-regulated levels of genes and metabolites associated with peroxidases, hemicellulose synthesis, expansins, and auxins caused persistent structural damages (sclerosis and rupture) of root cell walls. Approximately 64.5%-84.8% of internalized MoS2 nanosheets were degraded, and the successive up-regulation of genes encoding cytochrome P450s and glutathione S-transferases reflected the biotransformation and detoxification of MoS2 in the depuration period. These findings provide novel insights into the persistence and recovery of MoS2 phytotoxicity, which will help advance the risk assessment of MoS2 application on environment.

Molecular Dynamics Simulations of the Mechanical Properties of Cellulose Nanocrystals-Graphene Layered Nanocomposites.

Cellulose nanocrystals (CNCs) have received a significant amount of attention due to their excellent physiochemical properties. Herein, based on bioinspired layered materials with excellent mechanical properties, a CNCs-graphene layered structure with covalent linkages (C-C bond) is constructed. The mechanical properties are systematically studied by molecular dynamics (MD) simulations in terms of the effects of temperature, strain rate and the covalent bond content. Compared to pristine CNCs, the mechanical performance of the CNCs-graphene layered structure has significantly improved. The elastic modulus of the layered structure decreases with the increase of temperature and increases with the increase of strain rate and covalent bond coverage. The results show that the covalent bonding and van der Waals force interactions at the interfaces play an important role in the interfacial adhesion and load transfer capacity of composite materials. These findings can be useful in further modeling of other graphene-based polymers at the atomic scale, which will be critical for their potential applications as functional materials.

Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma.

Background: Systemic inflammation is important in the development of extrahepatic cholangiocarcinoma (ECC). The aim of this study was to compare the prognostic power of preoperative peripheral blood inflammatory markers and the novel FLR-N score in patients with resectable ECC. Methods: A total of 140 patients with resectable ECC and 140 healthy controls (HCs) were recruited for the study. The Mann-Whitney U test was used to evaluate the differences in inflammatory markers between groups. Kaplan-Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative fibrinogen, albumin, prealbumin, bilirubin, neutrophils, lymphocytes, monocytes, platelets, fibrinogen-to-lymphocyte ratio (FLR), fibrinogen-to-albumin ratio (FAR), fibrinogen-to-prealbumin ratio (FPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), FLR-neutrophil (FLR-N) score, and CA19-9 in patients with resectable ECC. Nomogram was developed based on the results of multivariate Cox analyses. Results: Patients with resectable ECC had significantly higher levels of neutrophils, monocytes, fibrinogen, FLR, FAR, FPR, NLR, PLR, and MLR and lower levels of lymphocytes, albumin, and prealbumin than HCs (all P < 0.01). Albumin, prealbumin, and FPR had a good ability to distinguish between ECC patients with total bilirubin < 34 µmol/L and HCs (AUCs of 0.820, 0.827, and 0.836, respectively). Kaplan-Meier analysis showed that high neutrophil, fibrinogen, FLR, FAR, PLR, MLR, and FLR-N score values were associated with poor survival in patients with resectable ECC. Multivariate analyses indicated that neutrophils (P = 0.022), FLR (P = 0.040), FLR-N score (P < 0.0001), and positive lymph node metastasis (P = 0.016) were independent factors for overall survival (OS). Nomogram were developed to predict OS for patients with ECC. Conclusion: The prognostic roles of inflammatory markers in patients with resectable ECC were different. The preoperative neutrophil count, FLR and FLR-N score could serve as noninvasive markers for predicting the prognosis of resectable ECC.

MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.

The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.

Enhanced removal of organic contaminants by novel iron-carbon and premagnetization: Performance and enhancement mechanism.

Iron-carbon (Fe-C) microelectrolysis has attracted considerable attention in wastewater treatment due to its excellent ability to remove contaminants. Herein, novel Fe-C granules were synthesized by simple calcination method for removing organic contaminations, and a cost-effective and environmentally friendly method, namely pre-magnetization, was used to improve the micro-electrolysis performance of Fe-C. Batch experiments proved that premagnetized iron-carbon (pre-Fe-C) could significantly improve the removal of methyl orange (MO) at different Fe-C mass ratios (1:2-2:1), material dosages (1.0-2.5 g/L), initial pH values (3.0-5.0), and MO concentrations (10.0-50.0 mg/L). Electrochemical analysis showed that premagnetization could increase the current density and reduce the charge transfer resistance of the microelectrolysis system, making Fe-C more susceptible to electrochemical corrosion. Characterizations confirmed that the corrosion products of the materials included FeO, Fe2O3, and Fe3O4, and more corrosion products were formed in the pre-Fe-C system. Radical quenching experiments and electron spin resonance spectroscopy verified that •OH, 1O2, and O2-• were all involved in pollutant removal, and premagnetization could promote the generation of more reactive oxygen species. Overall, the pre-Fe-C process could effectively remove various organic pollutants, exhibit good adaptability to complex water environments, and hold potential for industrial applications.

Aging relieves the promotion effects of polyamide microplastics on parental transfer and developmental toxicity of TDCIPP to zebrafish offspring.

Understanding the role of microplastics (MPs) in the biological fate and toxicity of organic pollutants in food webs is vital for its risk assessment. However, contradictory results and the neglect of MP aging as a factor have led to a research gap, which needs to be filled. Our study discovered that polyamide (PA, a ubiquitous MP in water) MPs clearly facilitated bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in the F0 zebrafish gonads and parental transfer of TDCIPP to the F1 offspring. Rapid TDCIPP desorption in the gut and intestine barrier dysfunction triggered by MPs were the causes for the phenomenon. In contrast to the pristine forms, aged PA with higher hydrophilcity exhibited stronger binding and polar interactions with TDCIPP, and the intestine damage was neglectable, resulting in increased intestinal immobilization and prevented parental transfer of TDCIPP. Additionally, the aggravated body weight loss and decreased length of TDCIPP offspring were relieved after PA aging. The recovery of subintestinal venous plexus angiogenesis, yolk lipid utilization, and ATP synthesis were responsible for the mitigated transgenerational toxicity. Our results highlight the significance of aging on the role of MPs with respect to coexisting pollutants and have great implications for understanding MP-associated risks.

Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation.

Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically, Ezh2 functions through its SANT2 domain to maintain the enrichment of H3K27 acetylation in the promoter region of the long noncoding RNA (lncRNA) Neat1, thereby promoting chromatin accessibility and facilitating p65-mediated transcription of Neat1, which is a critical mediator of inflammasome assembly and activation. In addition, the tumour suppressor protein p53 competes with Ezh2 for the same binding region in the Neat1 promoter and thus antagonises Ezh2-induced Neat1 transcription and inflammasome activation. Therefore, loss of Ezh2 strongly promotes the binding of p53, which recruits the deacetylase SIRT1 for H3K27 deacetylation of the Neat1 promoter and thus suppresses Neat1 transcription and inflammasome activation. Overall, our study demonstrates an epigenetic mechanism involved in modulating inflammasome activation through an Ezh2/p53 competition model and highlights a novel function of Ezh2 in maintaining H3K27 acetylation to support lncRNA Neat1 transcription.

Mitigation Effects and Associated Mechanisms of Environmentally Relevant Thiols on the Phytotoxicity of Molybdenum Disulfide Nanosheets.

Thorough investigations of the environmental fate and risks are necessary for the safe application of engineered nanomaterials. Nevertheless, the current understanding of potential transformations of MoS2 (an intensively studied two-dimensional nanosheet) upon interactions with ubiquitous environmentally relevant thiols (ERTs) in water is limited. This study revealed that two ERTs, l-cysteine and mercaptoacetic acid, could modify MoS2 by covalently grafting thiol groups on S atoms of 1T phases, improving the colloidal persistence and chemical stability of MoS2. Compared with the pristine form, MoS2-thiols with higher dispersity exhibited significantly mitigated envelopment and ultrastructural damage to microalgae. MoS2-triggered growth inhibition, upregulation of reactive oxygen species, photosynthetic injury, and metabolic perturbation in algae were remarkably attenuated by ERTs. The diminished capability for MoS2 to generate reactive intermediates and glutathione oxidation driven by ERTs caused the weakness of oxidative stress and negative effects. Additionally, molecular dynamics simulations demonstrated that ERTs altered the extent of the influence of MoS2 on the secondary structures and functions of adsorbed intracellular proteins, which also contributed to the lower phytotoxicity of MoS2. Our findings provide evidence for the crucial role of specific organic ligands in the risk of MoS2 in aquatic environments.

Impact of sulfhydryl ligands on the transformation of silver ions by molybdenum disulfide and their combined toxicity to freshwater algae.

The transformation of silver ions (Ag+) mediated by engineered nanomaterials (ENMs) influences the biosafety of Ag-containing products in natural environments. Actually, modification of biomolecules to ENMs in aquatic ecosystems alters their interactions with Ag+. This study discovered that surface functionalization of glutathione (GSH, a sulfhydryl compound ubiquitous in natural waters) on molybdenum disulfide (MoS2) nanoflakes suppressed the redox reaction between 1 T components and Ag+, inhibiting the MoS2-mediated reduction of Ag+ to Ag nanoparticles (AgNPs) in aqueous phase in the dark. However, AgNPs formation (from 2.32 ± 0.35-3.25 ± 0.29 mg/L per day, pH 7.0) and oxidation of MoS2 were remarkably accelerated after GSH binding under light conditions. The dominant electron donator of MoS2 to Ag+ was transformed from the electron-hole pairs to surface ligands driven by the introduction of chromophoric groups was authenticated as the cause for the elevated Ag+ reduction. These processes also occurred between Ag+ and MoS2 at low levels (50 µg/L). Additionally, the joint algal toxicity of GSH-modified MoS2 with Ag+ was weaker than that of pristine MoS2 due to increased retention of free Ag+ and AgNPs formation. Our findings improve the understanding of the interaction between ENMs and Ag+ in aquatic ecosystems.

Attentional resource allocation among individuals with different fluid intelligence: The integrated control hypothesis and its evidence from pupillometry.

To clarify the effects of individual differences in fluid intelligence (Gf) on attentional resource allocation, the present study proposes a new hypothesis (i.e., the integrated control hypothesis) based on previous studies and provides preliminary empirical evidence through a pupillometry study. The results showed that both task type and task difficulty play crucial roles in the relationship between Gf and attentional resource allocation when participants perform visuospatial-domain tasks. In particular, in the exploitation task, higher Gf individuals allocated fewer attentional resources than those with average Gf at all the difficulty levels. In contrast, in the exploration task, those with higher intelligence allocated equivalent resources in the low- and medium-difficulty trials and more resources in the high-difficulty trials; this phenomenon was more significant among the male subjects. In conclusion, this study suggests that high Gf individuals tend to control their attention state in tasks with diverse demands, allowing them to dynamically optimize the use of attentional resources and flexibly adapt to changing conditions.