Protein Corona-Directed Cellular Recognition and Uptake of Polyethylene Nanoplastics by Macrophages.

The widespread use of plastic products in daily life has raised concerns about the health hazards associated with nanoplastics (NPs). When exposed, NPs are likely to infiltrate the bloodstream, interact with plasma proteins, and trigger macrophage recognition and clearance. In this study, we focused on establishing a correlation between the unique protein coronal signatures of high-density (HDPE) and low-density (LDPE) polyethylene (PE) NPs with their ultimate impact on macrophage recognition and cytotoxicity. We observed that low-density and high-density lipoprotein receptors (LDLR and SR-B1), facilitated by apolipoproteins, played an essential role in PE-NP recognition. Consequently, PE-NPs activated the caspase-3/GSDME pathway and ultimately led to pyroptosis. Advanced imaging techniques, including label-free scattered light confocal imaging and cryo-soft X-ray transmission microscopy with 3D-tomographic reconstruction (nano-CT), provided powerful insights into visualizing NPs-cell interactions. These findings underscore the potential risks of NPs to macrophages and introduce analytical methods for studying the behavior of NPs in biological systems.

[Effect of chronic periodontitis on quality of life and severity in patients with bronchiectasis].

PURPOSE: To investigate the effects of chronic periodontitis on the quality of life and severity of the disease in patients with bronchiectasis. METHODS: A total of 80 bronchiectasis patients admitted to The Fourth Hospital of Changsha between April 2021 and April 2023 were randomly selected. Patients were divided into two groups according to whether they had moderate to severe chronic periodontitis: bronchiectasis with periodontitis group (n=45) and bronchiectasis without periodontitis group (n=35). The Qualify of Life Questionnaire for Bronchiectasi(QoL-B) was used to assess patients' quality. The severity of the disease was assessed using the Bronchiectasis Severity Index (BSI), and serum levels of hypersensitive C-reactive protein (hsCRP), tumor necrosis factor alpha(TNF-alpha), and interleukin-6(IL-6) were detected. SPSS 20.0 software package was used for data analysis. RESULTS: The QoL-B score of bronchiectasis with periodontitis group was significantly lower than that of bronchiectasis without periodontitis group, and the BSI score was significantly higher than that of bronchiectasis without periodontitis group(P＜0.05). The levels of hs-CRP, TNF-alpha and IL-6 in bronchiectasis with periodontitis were significantly higher than those in bronchiectasis without periodontitis group(P＜0.05). CONCLUSIONS: Chronic periodontitis shows significant adverse effects on both quality of life and disease severity in patients with bronchiectasis, which may be related to the common mechanism of inflammatory response between the two kinds of diseases.

HOO• as the Chain Carrier for the Autocatalytic Photooxidation of Benzylic Alcohols.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2- as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV-vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes' (or ketones) generation.

Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology.

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.

Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. OBJECTIVES: We aimed to explore the associations between HAA exposures and liver injury. METHODS: We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. RESULTS: There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (pinteraction=0.058). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage change=6.06%; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage change=-4.48%; 95% CI: -7.80%, -1.04%). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (pinteraction=0.040). CONCLUSION: Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

Urinary biomarkers of drinking-water disinfection byproducts in relation to diminished ovarian reserve risk: A case-control study from the TREE cohort.

BACKGROUND: Disinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR). OBJECTIVE: To assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk. METHODS: A total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR. RESULTS: Elevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m2), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004). CONCLUSIONS: Exposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Interactive Reweighting for Mitigating Label Quality Issues.

Label quality issues, such as noisy labels and imbalanced class distributions, have negative effects on model performance. Automatic reweighting methods identify problematic samples with label quality issues by recognizing their negative effects on validation samples and assigning lower weights to them. However, these methods fail to achieve satisfactory performance when the validation samples are of low quality. To tackle this, we develop Reweighter, a visual analysis tool for sample reweighting. The reweighting relationships between validation samples and training samples are modeled as a bipartite graph. Based on this graph, a validation sample improvement method is developed to improve the quality of validation samples. Since the automatic improvement may not always be perfect, a co-cluster-based bipartite graph visualization is developed to illustrate the reweighting relationships and support the interactive adjustments to validation samples and reweighting results. The adjustments are converted into the constraints of the validation sample improvement method to further improve validation samples. We demonstrate the effectiveness of Reweighter in improving reweighting results through quantitative evaluation and two case studies.

Screening the phytotoxicity of micro/nanoplastics through non-targeted metallomics with synchrotron radiation X-ray fluorescence and deep learning: Taking micro/nano polyethylene terephthalate as an example.

Microplastics (MPs) and nanoplastics (NPs) are global pollutants with emerging concerns. Methods to predict and screen their toxicity are crucial. Elemental dyshomeostasis can be used to assess toxicity of environmental pollutants. Non-targeted metallomics, combining synchrotron radiation X-ray fluorescence (SRXRF) and machine learning, has successfully differentiated cancer patients from healthy individuals. The whole idea of this work is to screen the phytotoxicity of nano polyethylene terephthalate (nPET) and micro polyethylene terephthalate (mPET) through non-targeted metallomics with SRXRF and deep learning algorithms. Firstly, Seed germination, seedling growth, photosynthetic changes, and antioxidant activity were used to evaluate the toxicity of mPET and nPET. It was showed that nPET, at 10 mg/L, was more toxic to rice seedlings, inhibiting growth and impairing chlorophyll content, MDA content, and SOD activity compared to mPET. Then, rice seedling leaves exposed to nPET or mPET was examined with SRXRF, and the SRXRF data was differentiated with deep learning algorithms. It was showed that the one-dimensional convolutional neural network (1D-CNN) model achieved 98.99% accuracy without data preprocessing in screening mPET and nPET exposure. In all, non-targeted metallomics with SRXRF and 1D-CNN can effectively screen the exposure and phytotoxicity of nPET/mPET and potentially other emerging pollutants. Further research is needed to assess the phytotoxicity of different types of MPs/NPs using non-targeted metallomics.

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): -17.1%, -0.37%] and 10.3% (95% CI: -18.8%, -0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.

Removal of nitrate by FeSiBC metallic glasses: high efficiency and superior reusability.

The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Associations between Urinary Concentrations of Disinfection Byproducts and in Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

BACKGROUND: Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking. OBJECTIVES: We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes. METHODS: The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers. RESULTS: The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for trends<0.05). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for trends<0.05). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women ≥30 y of age (p for interactions<0.05). DISCUSSION: Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.

A regional comparison of children's blood cadmium, lead, and mercury in rural, urban and industrial areas of six European countries, and China, Ecuador, and Morocco.

OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage.

BACKGROUND: Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men. AIM: To investigate the correlation between vascular endothelial growth factor (VEGF) and cortisol (Cor) and the prognosis of patients with hypertensive cerebral hemorrhage. METHODS: A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group. Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group. Peripheral venous blood was collected, and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay. RESULTS: A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment (P < 0.05). Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group. Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses. Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage (P < 0.05). CONCLUSION: Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

Individual and joint associations of urinary phthalate metabolites with polycystic ovary and polycystic ovary syndrome: Results from the TREE cohort.

Phthalates are widespread endocrine disrupting chemicals that adversely affect female reproductive health. We aimed to investigate the individual and joint associations of phthalate exposures measured by repeated urinary metabolites with polycystic ovary (PCO) and polycystic ovary syndrome (PCOS) (96 PCO cases, 96 PCOS cases and 370 controls). In single-pollutant analyses, mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP) and the sum of di(2-ethylhexyl) phthalate (∑DEHP) were associated with increased prevalence of PCO. Mono(2-ethylhexyl) phthalate (MEHP), MBzP and ∑DEHP were associated with elevated prevalence of PCOS. In multiple-pollutant analyses, one-quartile increase of weighted quantile sum index in phthalate metabolite mixtures was associated with increased prevalence of PCO and PCOS, and MBzP was the most major contributor. Our findings suggest a potential role for phthalate exposures, both individually and in mixtures, in the development of PCO and PCOS.

Advanced BIFs with Co, B, N, and S for Electrocatalytic Oxygen Reduction and Oxygen Evolution Reactions.

In this work, a new alkaline-stable boron imidazolate framework (BIF-90) was rationally designed and successfully synthesized by solvothermal reaction. Due to its potential electrocatalytic active sites (Co, B, N, and S) and chemical stabilities, BIF-90 was explored as a bifunctional electrocatalyst toward electrochemical oxygen reactions, namely, oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). This work will open new avenues toward the design of stable, cheap, and more active BIFs as bifunctional catalysts.

Oxidatively generated DNA damage mediates the associations of exposure to phthalates with uterine fibroids and endometriosis: Findings from TREE cohort.

BACKGROUND: Epidemiological studies on phthalate exposures in associations with uterine fibroids (UF) and endometriosis (EMT) are inconsistent. The underlying mechanisms are poorly understood. OBJECTIVES: To investigate the relationships of urinary phthalate metabolites with UF and EMT risks, and further to examine the mediating role of oxidative stress. METHODS: This study included 83 and 47 women separately diagnosed with UF and EMT, as well as 226 controls from the Tongji Reproductive and Environmental (TREE) cohort. Two spot urine samples from each woman were analyzed for two oxidative stress indicators and eight urinary phthalate metabolites. Unconditional logistic regression models or multivariate regression models were fitted to evaluate the associations among phthalate exposures, oxidative stress indicators, and the risks of UF and EMT. The potential mediating role of oxidative stress was estimated by the mediation analyses. RESULTS: We observed that each ln-unit increase in urinary mono-benzyl phthalate (MBzP) concentrations was associated with increased UF risk [adjusted OR (aOR): 1.56, 95% CI: 1.20, 2.02], and that each ln-unit increase in urinary MBzP (aOR: 1.48, 95% CI: 1.09, 1.99), mono-isobutyl phthalate (MiBP) (aOR: 1.83, 95% CI: 1.19, 2.82), and mono-2-ethylhexyl phthalate (MEHP) (aOR: 1.66, 95% CI: 1.19, 2.31) concentrations were associated with increased EMT risk (all FDR-adjusted P < 0.05). Moreover, we observed that all tested urinary phthalate metabolites were positively associated with two oxidative stress indicators [4-hydroxy-2-nonenal-mercapturic acid (4-HNE-MA) and 8-hydroxy-2-deoxyguanosine (8-OHdG)], in which 8-OHdG was associated with increased risks of UF and EMT (all FDR-adjusted P < 0.05). The mediation analyses showed that 8-OHdG mediated the positive relationships of MBzP with UF risk, and of MiBP, MBzP, and MEHP with EMT risk, with the estimated intermediary proportion ranging from 32.7% to 48.1%. CONCLUSIONS: Oxidatively generated DNA damage may mediate the positive associations of certain phthalate exposures with the risks of UF and EMT. However, further investigation is warranted to confirm these findings.

Fatal cytokine-release syndrome in a patient receiving toripalimab: a case report.

Immune checkpoint inhibitors, a type of immunotherapy, have demonstrated optimal treatment efficacy in inducing durable antitumor responses in various cancers. Cytokine-release syndrome is a rare immune-related adverse event induced by immune checkpoint inhibitors. In our case, a patient with hypopharyngeal squamous cell carcinoma received toripalimab combined with chemotherapy. On the fourth day post treatment, the patient developed fever and hypotension. Laboratory examination indicated myelosuppression, acute kidney injury and disseminated intravascular coagulation. Meanwhile, serum cytokine levels of IL-6, IL-8, IL-10, IL-1ß, IFN-γ and the level of hypersensitive C-reactive protein were markedly elevated. The patient was diagnosed with cytokine release syndrome, which progressed rapidly and led to the patient's demise on the fifth day post treatment.

Immune checkpoint inhibitors (ICIs) have shown revolutionary efficacy in the treatment of multiple cancers. Cytokine-release syndrome (CRS) is a common and lethally adverse event of chimeric antigen receptor T-cell therapy; however, this adverse effect is rare in ICI therapy. Presently, while ICI-associated CRS is reported almost exclusively in case reports, fatal outcomes are rarely observed. A patient with hypopharyngeal squamous cell carcinoma received toripalimab combined with chemotherapy. On the fourth day post treatment, the patient developed CRS, which progressed rapidly, and the patient died on the fifth day post treatment.