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Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus , and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo , CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. Cutibacterium acnes , which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

Steel slag has been investigated as a potential aggregate for pavement-wearing courses in road engineering. The volume stability, resistance to high and low temperatures, and water stability for asphalt mixtures containing steel slag have been widely studied. As for the skid resistance, previous studies have primarily focused on the initial performance. The relationship between the steel slag's appearance morphology and skid resistance during the wearing process remains to be further explored. It is essential to undertake a comparative study on the long-term skid resistance of steel slag and conventional aggregates to address the differences. This research picked two steel slags and two types of conventional aggregates (granite and limestone) as research samples. The chosen aggregate samples underwent various degrees of wear treatment with the Los Angeles abrasion machine, and their angularity was examined utilizing an aggregate image measurement system (AIMS). Based on the polishing pre-treatment, the micro-texture of the aggregates was observed with the assistance of a laser confocal microscope, and its correlation with skid resistance was determined. British pendulum number (BPN) tests were also conducted and analyzed at various polishing durations. The results show that steel slag has a low abrasion rate and higher initial angularity and abrasion resistance compared to natural stones. The micro-texture analysis demonstrates that steel slags have a coarser roughness, more contact points, and more durable abrasion resistance. Additionally, the fluctuations in BPN further prove that steel slag has superior initial and sustained skid resistance. Overall, steel slag can be a promising alternative for pavement-wearing course aggregate due to its superior long-term skid resistance. [ABSTRACT FROM AUTHOR]

Newly synthesized chemicals are being introduced into the environment without undergoing proper toxicological evaluation, particularly in terms of their effects on the vulnerable neurodevelopment. Thus, it is important to carefully assess the developmental neurotoxicity of these novel environmental contaminants using methods that are closely relevant to human physiology. This study comparatively evaluated the potential developmental neurotoxicity of 19 prevalent environmental chemicals including neonicotinoids (NEOs), organophosphate esters (OPEs), and synthetic phenolic antioxidants (SPAs) at environment-relevant doses (100 nM and 1 μM), using three commonly employed in vitro neurotoxicity models: human neural stem cells (NSCs), as well as the SK-N-SH and PC12 cell lines. Our results showed that NSCs were more sensitive than SK-N-SH and PC12 cell lines. Among all the chemicals tested, the two NEOs imidaclothiz (IMZ) and cycloxaprid (CYC), as well as the OPE tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), generated the most noticeable perturbation by impairing NSC maintenance and neuronal differentiation, as well as promoting the epithelial-mesenchymal transition process, likely via activating NF-κB signaling. Our data indicate that novel NEOs and OPEs, particularly IMZ, CYC, and TDCIPP, may not be safe alternatives as they can affect NSC maintenance and differentiation, potentially leading to neural tube defects and neuronal differentiation dysplasia in fetuses. [Display omitted] • The developmental neurotoxicity of 19 emerging environmental chemicals was assessed. • Neural stem cells were more sensitive to the chemicals than the SK-N-SH and PC12 cell lines. • Among the chemicals tested, IMZ, CYC, and TDCIPP exhibited the most adverse effects. • IMZ, CYC, and TDCIPP impaired NSC maintenance and differentiation, likely via NF-κB. • This study provides valuable insights for the safe use of emerging environmental chemicals. [ABSTRACT FROM AUTHOR]

Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosis-like cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress. [Display omitted] • PCP exposure triggered bacterial apoptosis-like cell death and necrosis. • Cd exposure caused severe bacterial oxidative damage and cell necrosis. • The co-exposure caused bacterial oxidative stress and apoptosis-like cell death. • Bacterial cell membrane depolarization can be a potential ultrasensitive indicator. [ABSTRACT FROM AUTHOR]

Background: To distinguish preinvasive (adenocarcinoma in situ/atypical adenomatous hyperplasia) and minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IA) appearing as solitary subsolid nodules (SSNs) less than 3 cm based on thin-section computed tomography (TSCT) features to guide therapeutic approaches.Methods: A total of 154 lesions that were histopathologically confirmed to have pre/minimally invasive adenocarcinoma (hereafter pre/MIA) and IA presenting as part-solid nodules (PSNs) or pure ground-glass nodules (pGGNs) were retrospectively reviewed. The TSCT features, including diameter, area, CT value, shape, air bronchogram, margins, and location, were compared and assessed. Receiver operating characteristic analyses were conducted to determine the cut-off values for the qualitative variables and their diagnostic performances.Results: Of 154 nodules, 89 IA, 53 MIA, eight adenocarcinoma in situ, and four atypical adenomatous hyperplasia lesions were found. Univariate and multivariate logistic regression of the pre/MIA and IA lesions were compared and analyzed among PSNs and pGGNs. Among pGGNs, a significant difference was found in the area (p = 0.004, odds ratio [OR] = 0.124, 95% confidence interval [CI] = 0.300-0.515) between the pre/MIA and IA groups. In PSNs, significant differences were found in the diameter (p = 0.001, OR = 0.171, 95% CI = 0.063-0.467) and CT value (p = 0.001, OR = 0.996, 95% CI = 0.993-0.998) between the pre/MIA and IA groups. According to the corresponding receiver operating characteristic curves, the optimal cut-off tumor area in pGGNs to differentiate pre/MIA from IA was 0.595 cm2. A higher CT value of the lesion (≥ -298.500 HU) and a larger diameter (≥1.450 cm) in PSNs were significantly associated with IA.Conclusion: Imaging features from TSCT contribute to distinguishing pre/MIA from IA in solitary subsolid nodules and may contribute to guide the clinical management of these lesions. [ABSTRACT FROM AUTHOR]

Abstract Exposure to airborne particulate matter (PM) 2.5 induced various adverse health effects, such as metabolic syndrome, systemic inflammation and respiratory infection. However, a global influence of PM 2.5 -induced metabolic and proteomic disorders remains confusing, and the underlying mechanism is still under-explored. Herein, LC-MS/MS-based metabolomics, lipidomics and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics were applied to analyze the toxicological characteristics of PM 2.5 from Taiyuan City in China (Taiyuan-PM 2.5) on human lung carcinoma cells (A549) after the 24-h treatment. Metabolites, lipids and proteins that have distinctive differences were screened by SIEVE, LipidSearch and Proteome Discoverer, respectively. The abundance of 56 metabolites (40 increased and 16 decreased), 22 lipids (19 increased and 3 decreased) and 81 proteins (55 up-regulated and 26 down-regulated) were significantly changed upon the PM 2.5 treatment. Among the proteomics analysis, 16 proteins were specifically related to RNA splicing, mainly including up-regulated serine/arginine-rich splicing factor 1 (SRSF1), SRSF2, small nuclear ribonucleoprotein 70 kDa (snRNP70), small nuclear ribonucleoprotein polypeptide B (SNRPB), SNRPC, SNRPE and down-regulated heterogeneous nuclear ribonucleoprotein U-like 2 (hnRNP UL2). At the metabolic level, PM 2.5 exposure significantly altered the sphingolipid metabolism, including ceramide, serine, sphingosine and sphingomyelin. It was proposed that excessive accumulation of ceramide and expression of key enzymes (ceramide synthases, phingomyelinase, sphingosine kinase types 2 and protein phosphatase-1) induced the secretion of pro-inflammatory cytokines, generation of lipotoxicity and alterations of RNA splicing in PM 2.5 -treated A549 cells. In general, our results demonstrated that ceramide accumulation and altered RNA splicing could becritical contributors to PM 2.5 -induced cytotoxicity at metabolic and proteomic level, which might be considered as potential markers for toxicological evaluation of PM 2.5 samples. Graphical abstract Image 1 Highlights • PM 2.5 induced ceramide accumulation in A549 cell line. • PM 2. 5 disturbed RNA splicing pathway and related protein expression. • PM 2.5 promoted the secretion and expression of pro-inflammatory cytokines. • Multi-omics plays a significant role in exploring the toxicity mechanism of PM 2.5. PM 2.5 induced toxicity by regulating the ceramide accumulation and RNA splicing in human lung carcinoma cells. [ABSTRACT FROM AUTHOR]

This study investigated the characteristics of air multi-pollutants emitted during typical electronic waste (e-waste) dismantling processes and assessed their risks to the environment and human health. Concentrations of total volatile organic compounds (TVOCs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) in a typical e-waste dismantling workshop were 137 μg/m3, 135 ng/m3 and 42 ng/m3, respectively, which were lower than those without emission control measures. The partial removal of pollutants due to the emission control measures also decreased the ozone formation potential and non-cancer risk of volatile organic compounds (VOCs). In the workshop, the lifetime cancer risk (LCR) of VOCs (8.1 × 10−5) was close to the recommended values. Conversely, the LCR of PAHs (3.6 × 10−5) and the total exposure index of PBDEs (19 ng/d) were remarkably lower than the recommended values of 10−3 and that without emission control measures, respectively. Meanwhile, the concentrations of TVOCs, polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), PBDEs, and PAHs in the outlet were approximately 10–30 times higher than those in the workshop. In addition, the LCR of TVOCs within a 5-km radius area remained higher than the accepted value (10−6), and the inhalation exposure risk of PCDD/Fs within a 20-km radius area was five times higher than the recommended value. Therefore, the emissions from e-waste recycling processes should be considered as an important source of air pollution, and more efficient control measures should be taken in the future. The pollution characteristic and risk assessment on environment and human health of multi-pollutants from typical e-waste dismantling activities were systematically investigated. The TVOCs, PBDEs and PAHs concentration in workshop were well controlled. In contrast, the emission can be regarded as an important source of air pollution and more efficient control measures should be taken in the future. [Display omitted] • The levels of pollutants from outlet were 10–30 times higher than those in workshop. • Risks of specific compounds within certain area were higher than acceptable values. • E−waste dismantling activities substantially contributed to local air pollution. [ABSTRACT FROM AUTHOR]

Dimethyl sulfide (DMS) related to solar radiation and greenhouse effect is one of the most important volatile sulfides and its' oxidation products are also important contributors to acid rain. It is of great importance to study the consumption and reactions of DMS in the atmosphere. In this work, atmospheric-like particulate TiO 2 was selected to study the reaction mechanism of DMS on TiO 2 with the purpose to explore the possible heterogeneous oxidation of DMS. The results showed that the heterogeneous reaction of DMS with TiO 2 occurred under the condition of illumination, which is a first-order-like reaction with the rate constant K = 2.83 × 10−4/s, the initial reaction uptake coefficient and the steady reaction uptake coefficient indicated the occupation of products and by-products on the surface of TiO 2. The heterogeneous reaction mechanism of DMS studied by aerosol time-of-flight mass spectrometry (ATOFMS) suggested that DMS underwent a series of complex chemical reactions with sulfate and various sulfur-containing gas products, in which hydroxyl radicals might play an important role. • Simplify the research system by using model oxidized particulates with a single component. • Study the heterogeneous reaction of DMS on model particulates by smog chamber. • Reveal reaction mechanism of DMS on atmospheric-like particulates by ATOFMS. [ABSTRACT FROM AUTHOR]

Combating global climate change calls for all countries to accelerate emissions reductions, and equity is an important guiding principle. A new indicator – the carbon Palma ratio, extended from the income Palma ratio and defined as the ratio of the total emissions of the top 10% emitters to those of the bottom 40% – is proposed, which provides a new perspective to inform the international community and the public of the distribution inequality of carbon emissions among individuals. The ratio is quantified within and across countries, by applying an elastic relationship between individual emissions and income. Results show that the carbon Palma ratios within most developing countries are overall high, suggesting them to focus more on coordinating regional and income differences and mainly guide high emitters to mitigate, so as to improve emissions and income equity simultaneously. The carbon Palma ratios within developed countries are comparatively smaller; however, the greater historical responsibilities to warming suggest them to substantially reduce emissions of all citizens, so as to enhance national mitigation contributions systematically. At a global scope, the current carbon Palma ratio is observably higher than within any country, reflecting an extremely severe inequality when looking at individual emissions beyond territorial limitations. The regional decomposition of emitters further suggests developed countries to take the lead in the post-Paris era in ratcheting up mitigation and climate finance ambition. Image 1 • Carbon Palma ratio is proposed to measure individual emissions inequality. • The ratio provides a new perspective to quantify and inform inequality. • The ratios in developed countries are overall lower than in developing countries. • The global ratio reflects an extremely severe inequality across the world. • Decomposition suggests developed countries to enhance mitigation and finance. [ABSTRACT FROM AUTHOR]

This study conducts a comprehensive experimental and numerical investigation on the in-plane structural behavior of trapezoidal corrugated-web arches (TCWA) under uniform vertical loads. Three TCWA specimens were tested to examine their failure modes, stress distributions, and in-plane ultimate bearing capacities. The experimental results indicate that flanges primarily resist axial compression and bending moments, while the trapezoidal corrugated webs bear shear forces. The specimens failed due to flange yielding at sections experiencing maximum compression or bending moments. Using a finite element model validated against test data, this study further investigates the influence of various parameters on the in-plane structural behavior of TCWAs, including cross-sectional dimensions, geometric imperfections, corrugation dimensions, rise-to-span ratios, and in-plane slenderness ratios. The numerical analysis identified three failure modes of TCWAs: in-plane global buckling, flange compression buckling, and web shear buckling. It was found that the global geometric imperfection amplitude significantly affects the in-plane bearing capacity under full-span loading but has a minor impact under half-span loading. Additionally, when the in-plane global buckling governs the failure mode, the impact of corrugation dimensions is negligible. These findings establish a foundation for future design methods of TCWAs. • A novel steel arch —trapezoidal corrugated-web arch (TCWA)—was proposed, and its fabrication process was introduced. • Three TCWA specimens were investigated experimentally, revealing their stress distributions and failure modes. • The effect of various parameters on the in-plane structural behavior of TCWA was discussed. [ABSTRACT FROM AUTHOR]

We previously reported a fluorescence anisotropy (FA) approach for small molecules using tetramethylrhodamine (TMR) labeled aptamer. It relies on target-binding induced change of intramolecular interaction between TMR and guanine (G) base. TMR-labeling sites are crucial for this approach. Only terminal ends and thymine (T) bases could be tested for TMR labeling in our previous work, possibly causing limitation in analysis of different targets with this FA strategy. Here, taking the analysis of adenosine triphosphate (ATP) as an example, we demonstrated a success of conjugating TMR on other bases of aptamer adenine (A) or cytosine (C) bases and an achievement of full mapping various labeling sites of aptamers. We successfully constructed aptamer fluorescence anisotropy (FA) sensors for adenosine triphosphate (ATP). We conjugated single TMR on adenine (A), cytosine (C), or thymine (T) bases or terminals of a 25-mer aptamer against ATP and tested FA responses of 14 TMR-labeled aptamer to ATP. The aptamers having TMR labeled on the 16th base C or 23rd base A were screened out and exhibited significant FA-decreasing or FA-increasing responses upon ATP, respectively. These two favorable TMR-labeled aptamers enabled direct FA sensing ATP with a detection limit of 1 µM and the analysis of ATP in diluted serum. The comprehensive screening various TMR labeling sites of aptamers facilitates the successful construction of FA sensors using TMR-labeled aptamers. It will expand application of TMR-G interaction based aptamer FA strategy to a variety of targets. [ABSTRACT FROM AUTHOR]

Abnormal elevation of indispensable steroid hormone estrogens and exposure to exogenous estrogen-like compounds pose adverse health effects to aquatic animals and human alike. These compounds generally display functionally important estrogenic activity even at extremely low picomolar concentrations. In this study we identified one critical but lethal gene (TAF1) that remarkably represses estrogenic activity. This gene is selected as a candidate for genetically modulating an estrogen-responding cell line. To overcome its lethality, instead of adopting a gene knockout strategy, we developed a transient TAF1 depletion strategy using a designed small interfering RNA. By the transient knockdown of TAF1 in the estrogen-responding reporter cell line, the maximum induction signals for endogenous estrogen 17β-estradiol (E2) and environmental estrogens 17α-ethynyl estradiol (EE2) and bisphenol compounds were enhanced by 4.8–13.3 folds. The limit of detection for EE2 is about 8 × 10−15 mol/L. Moreover, by the established method, trace estrogenic activity (14.7–24.2 pg E2 equivalents (E2Eq)/L) can be detected in a portion of Tap water samples. [Display omitted] • By siRNA knockdown of TAF1, the established reporter displays enhanced response to estrogenic compounds by 4.8–13.3 folds. • The TAF1-knockdown enhanced reporter assay can be used to measure estrogenic activity down at the picomolar concentrations. • This improved assay can be applied for analysis of drinking water in a small detection volume (1 mL) with simple pretrement. [ABSTRACT FROM AUTHOR]

The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates epiblast development in vivo during the peri-implantation period of mouse embryo development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events that occur during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knockin cell models, we identify the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, which is dependent on the formation of R-loops in ZFP281-targeted gene promoters, undergoes a "high-low-high" bimodal pattern regulating dynamic DNA methylation and gene expression during the naive-formative-primed transitions. ZFP281 also safeguards DNA methylation in maintaining primed pluripotency. Our study demonstrates a previously unappreciated role for ZFP281 in coordinating DNMT3A/3B and TET1 functions to promote pluripotent state transitions. [Display omitted] • ZFP281 activates Dnmt3a/3b in pluripotent stem cells in vitro and epiblast in vivo • ZFP281 and TET1 undergo bimodal chromatin occupancy in pluripotent state transitions • ZFP281 and TET1 chromatin binding depends on the formation of R-loops at promoters • ZFP281 is necessary for the establishment and maintenance of primed pluripotency The naive, formative, and primed pluripotent states and their interconversions recapitulate the pluripotency continuum during early development. Huang et al. investigate the transcriptional programs and identify an essential role for ZFP281 in coordinating DNMT3A/3B and TET1 to establish the DNA methylation and gene expression programs during the pluripotent state transitions. [ABSTRACT FROM AUTHOR]

• This study investigated fatigue behavior of CWGs using CWTs to lower the cost of fatigue tests. • The comparative tests demonstrated that it was reasonable to investigate the fatigue behavior of a CWG using a CWT. • Fatigue tests were carried out on CWT specimens with two different waveform radii of R30 and R60. • Fatigue behaviour of CWT specimens were investigated based on hot spot stress concept to consider the stress concentration. • S-N curve was recommended for calculating the fatigue strength of the CWG based on the hot spot stress range. Fatigue of steel corrugated-web girders (CWGs) is a new research topic. This study uses trapezoidal corrugated-web T-section members (CWTs) to lower the cost of fatigue tests when investigating the fatigue behavior of a trapezoidal CWG. First, static tests were conducted, and the CWG under a bending moment and CWT under an axial force were compared, which verified that the flanges had the same stress distribution characteristics under equivalent loads. This demonstrates that it is suitable to investigate the fatigue behavior of a CWG using a CWT. Second, fatigue tests were performed on trapezoidal CWT specimens with two different waveform radii, R30 and R60, and their hot spot stress concentration factors at the fatigue critical location of CWG (the intersection between a parallel fold and an inclined fold of a web) were obtained, which reached 1.63 and 1.54, respectively. Of the 18 CWT specimens that experienced fatigue failure, 72 % of the initial cracks occurred at point S, indicating that this location was the most susceptible to fatigue cracking. The same S-N curve (log 10 N = 12.928-3log 10 Δ σ hs) could be applied in calculating the fatigue strengths of CWTs with different wave radii (R30 and R60) when the hot spot stress range that considered the stress concentration factor (SCF) was used. [ABSTRACT FROM AUTHOR]

• Finite element models were established for analysing the linear elastic behaviour of IGTCWs under uniform bending. • The distribution characteristic and mechanism of normal stresses in flanges of IGTCWs were investigated in detail. • A secondary transverse moment theory was improved. • The formulae were proposed for calculating normal stresses in flanges of different cross-sections of IGTCWs under uniform bending. I-girders with corrugated webs (IGCWs) are a new type of structure that has been increasingly used in engineering. The normal stress distribution in flanges of IGCWs is quite complicated compared with that of conventional I-girders under in-plane loads. This study numerically and theoretically investigates the normal stress distribution rules and mechanisms in flanges of I-girders with trapezoidal corrugated webs (IGTCWs) under uniform bending in the elastic stage. First, finite element (FE) modelling was developed using ABAQUS software and verified by the available experimental results. Based on the verified FE models, a detailed analysis of the normal stress distribution in flanges of IGTCWs was performed. The results show that the normal stresses are nearly uniformly distributed over the flange in cross-sections with inclined web folds. Normal stresses in cross-sections with parallel web folds are approximately linearly distributed along the flange width, with stresses away from the corrugated web side being much larger than those near it. Its mechanism is explored using a secondary transverse moment theory, which is improved and completed by considering the proposed effective cross-section coefficient and equivalent width coefficient for the action of shear flow. The reliability of this theory was verified through comparison with the normal stress difference and distribution results of the supplementary FE models. Finally, the formulae for calculating the normal stresses in flanges of different cross-sections of IGTCWs under uniform bending are presented. These formulae suggest that secondary normal stresses generated by secondary transverse moments in cross-sections with parallel web folds account for 7% to 13% of the total normal stresses and cannot be ignored in the stress analysis. [ABSTRACT FROM AUTHOR]

Donor factors, in addition to HLA matching status, have been associated with recipient survival in unrelated donor (URD) hematopoietic cell transplantation (HCT); however, there is no hierarchical algorithm that weights the characteristics of individual donors against each other in a quantitative manner to facilitate donor selection. The goal of this study was to develop and validate a donor selection score that prioritizes donor characteristics associated with better survival in 8/8 HLA-matched URDs. Two separate patient/donor cohorts, the first receiving HCT between 1999 and 2011 (n = 5952, c1), and the second between 2012 and 2014 (n = 4510, c2) were included in the analysis. Both cohorts were randomly spilt, 2:1, into training and testing sets. Despite studying over 10,000 URD transplants, we were unable to validate a donor selection score. The only donor characteristic associated with better survival was younger age, with 2-year survival being 3% better when a donor 10 years younger is selected. These results support previous studies suggesting prioritization of a younger 8/8 HLA-matched donor. This large dataset also shows that none of the other donor clinical factors tested were reproducibly associated with survival, and hence flexibility in selecting URDs based on other characteristics is justified. These data support a simplified URD selection process and have significant implications for URD registries. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) has been extensively explored as a promising nanomaterial for applications in biology because of its unique properties. Therefore, systematic investigation of GO toxicity is essential to determine its fate in the environment and potential adverse effects. In this study, acute toxicity, oxidative stress and immunotoxicity of GO were investigated in zebrafish. No obvious acute toxicity was observed when zebrafish were exposed to 1, 5, 10 or 50 mg/L GO for 14 days. However, a number of cellular alterations were detected by histological analysis of the liver and intestine, including vacuolation, loose arrangement of cells, histolysis and disintegration of cell boundaries. As evidence for oxidative stress, malondialdehyde levels and superoxide dismutase and catalase activities were increased and glutathione content was decreased in the liver after treatment with GO. GO treatment induced an immune response in zebrafish, as demonstrated by increased expression of tumor necrosis factor α, interleukin-1 β, and interleukin-6 in the spleen. Our findings demonstrated that GO administration in an aquatic system can cause oxidative stress and immune toxicity in adult zebrafish. To our knowledge, this is the first report of immune toxicity of GO in zebrafish. [ABSTRACT FROM AUTHOR]

There is a potential risk to the environment from persistent estrogenic compounds in sewage sludge. In this study, eight bisphenols (BPs) were identified in sewage sludge collected from wastewater treatment plants in 15 cities in China. The estrogenic potencies of the eight BPs and the estrogenic activities of sludge samples were evaluated using a bioluminescence yeast estrogen screen (BLYES) assay. All sludge samples elicited considerable estrogenic activity at a range of 2.8–4.7 ng E2 g −1 dry weight (dw). All BPs exhibited estrogenic activity in the BLYES assay, but there were significant differences between the potency of individual chemicals. Bisphenol AF had the highest activity, followed by tetrachlorobisphenol A, bisphenol F, bisphenol A, bisphenol E, bisphenol S and 2,4-dihydroxybenzophenone. Tetrabromobisphenol A showed weak estrogenic activity at 1 × 10 4 nM, but significant cytotoxicity above this concentration. The total estradiol equivalency quantities (EEQs) of BPs were in the range of 2.16–49.13 pg E2 g −1 dw, accounting for 0.05–1.47% of the total EEQs in sewage sludge samples. The results indicate that BPs made a minor contribution to the estrogenic activity of the investigated sewage sludge. Nevertheless, our results suggest that considerable attention should be directed to the estrogenic potentials of emerging organic pollutants because of their widespread use and their potential to persist in the environment. [ABSTRACT FROM AUTHOR]

Halogenated bisphenol A (H-BPAs), widely used in industrial production, have been identified in various environmental matrices and detected in human serum and breast milk. The persistence and prevalence of H-BPAs in the environment underscore the need to in-depth understand their adverse effects to humans and other organisms. In the present study, zebrafish embryos/larvae were used as models to investigate the developmental toxicities of three H-BPAs, namely tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and bisphenol AF (BPAF). The half lethal concentration (LC50) values indicated that the rank order of toxicities of the chemicals were TCBPA>TBBPA>BPAF. Three H-BPAs exposure resulted in a variety of developmental lesions in the embryos/larvae, such as a delay in time to hatch, edema, and hemorrhage. The estrogenic activities of H-BPAs were determined by means of in vivo vitellogenin (vtg) assay and in vitro MVLN assay. Here only BPAF specifically shows a stronger estrogenic activity than BPA both in in vivo and in vitro. These data suggest that TCBPA, TBBPA, and BPAF are more potent toxicants than BPA, and indicate that further research of the mechanisms on their toxicities is required. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) can dampen the antitumor activity of T cells, yet the underlying mechanism remains incompletely understood. Here, we show that C1q+ TAMs are regulated by an RNA N 6-methyladenosine (m6A) program and modulate tumor-infiltrating CD8+ T cells by expressing multiple immunomodulatory ligands. Macrophage-specific knockout of an m6A methyltransferase Mettl14 drives CD8+ T cell differentiation along a dysfunctional trajectory, impairing CD8+ T cells to eliminate tumors. Mettl14 -deficient C1q+ TAMs show a decreased m6A abundance on and a higher level of transcripts of Ebi3 , a cytokine subunit. In addition, neutralization of EBI3 leads to reinvigoration of dysfunctional CD8+ T cells and overcomes immunosuppressive impact in mice. We show that the METTL14 -m6A levels are negatively correlated with dysfunctional T cell levels in patients with colorectal cancer, supporting the clinical relevance of this regulatory pathway. Thus, our study demonstrates how an m6A methyltransferase in TAMs promotes CD8+ T cell dysfunction and tumor progression. [Display omitted] • m6A on mRNA directly controls the specification and function of the C1q+ TAM • Mettl14 depletion in C1q+ TAM promotes the growth of diverse solid tumors • Macrophage-derived Ebi3 transcript with decreased m6A level drives T cell dysfunction • Mettl14 level in human tumor stroma is inversely correlated with T cell dysfunction Dong et al. discover an mRNA m6A-mediated post-transcriptional regulatory mechanism in C1q+ tumor-associated macrophages. The loss of Mettl14 encoding an m6A "writer" in these macrophages promotes the accumulation of Ebi3 mRNA in an m6A-dependent manner, thereby leading to CD8+ T cell dysfunction and tumor growth. [ABSTRACT FROM AUTHOR]

• BPS induced the splenic morphological alterations and inflammation. • BPS induced the perturbation of spatial distribution of lipids in splenic white pulp. • MS imaging plays a significant role in exploring the toxicity mechanism of bisphenols. The widespread use of bisphenol A (BPA) substitutes has aroused great attention towards their toxicological evaluation in vivo and in vitro. Considering the intimate correlation between BPA and metabolic diseases, we explored whether bisphenol S (BPS), a major substitute to BPA, could cause the splenic toxicity by disturbing the lipid metabolism in mouse model. We investigated the splenic injury by combing the mass spectrometry (MS)-based lipidomics and imaging analysis, as well as molecular biological methods. Mice were divided into three groups (control-olive oil, 10 and 100 μg-BPS/kg body weight/day group) and treated by BPS in 56 days. Two of BPS-treated concentrations induced the splenic morphological alterations and inflammation, including the decreased numbers and cellularity in the periarteriolar lymphoid sheath (T cell zone) and paucicellular primary lymphoid follicles (B cell zone) in splenic white pulp. Lipidome profiling of spleen after BPS treatment was also changed with up-regulated sphingosine [So], neutral glycosphingolipids [CerG], cholesteryl ester [ChE], diacylglycerols [DAG], lysophosphatidylcholine [LPC], lysophosphatidylethanolamine [LPE], phosphatidylglycerols [PG], phosphatidylinositols [PI] and phosphatidylserine [PS] as well as down-regulated ceramide [Cer], phosphatidylethanolamines [PE] and sphingomyelin [SM] compared to the control group. More importantly, significant different lipids in abundance and spatial distribution also implicated that white pulp were more sensitive to BPS treatment than other splenic sub-structures. Signaling lipids such as So (d18:0), Cer (d18:1/24:0), Cer (d18:1/22:0), SM (d18:1/22:1) and SM (d18:1/24:2) associated with inflammation were remarkable changed and co-localized in the splenic white pulp. Our finding indicated that BPS exposure promoted the splenomegaly, pro-inflammatory activation and morphological alterations, as well as induced the lipidome perturbation in the immune cells of white pulp, which might be expected to contribute a new perspective of bisphenol-induced organ injury. [ABSTRACT FROM AUTHOR]