Phthalate alternatives and their monoesters in indoor dust from several regions, China and implications for human exposure.

Household products, in response to regulations, increasingly incorporate phthalate (PAE) alternatives instead of traditional PAEs. However, limited information exists regarding the fate and exposure risk of these PAE alternatives and their monoesters in indoor environments. The contamination levels of PAE alternatives and their monoesters in indoor dust might vary across regions due to climate, population density, industrial activities, and interior decoration practices. By analyzing indoor dust samples from six geographical regions across China, this study aims to shed light on concentrations, profiles, and human exposure to 12 PAE alternatives and 9 their monoesters. Bis(2-ethylhexyl) benzene-1,4-dicarboxylate (DEHTP), tributyl 2-acetyloxypropane-1,2,3-tricarboxylate (ATBC), and tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (TOTM) were the main PAE alternatives in dust across all regions. The total concentrations of 12 PAE alternatives ranged from 0.125 to 4160 µg/g in indoor dust. High molecular weight PAE alternatives had significantly correlated concentrations (p < 0.05) based on Spearman analysis, suggesting their co-use in heat-resistant plastic products. A collective of nine monoesters were identified in most samples, with total concentrations ranging from 0.048 to 29.6 µg/g. The median concentrations of PAE alternatives were highest in North China (66.8 µg/g), while those of monoesters were highest in Southwest China (6.93 µg/g). A significant correlation (p < 0.05) between the concentrations of DEHTP and its monoester suggested that degradation could be a potential source of monoesters. Although hazard quotients (HQs) have been calculated to suggest that the current exposure is unlikely to pose a significant health risk, the lack of toxicity threshold data and the existence of additional exposure pathways necessitate a further confirmation.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

Phthalate acid esters: A review of aquatic environmental occurrence and their interactions with plants.

The increasing use of phthalate acid esters (PAEs) in various applications has inevitably led to their widespread presence in the aquatic environment. This presents a considerable threat to plants. However, the interactions between PAEs and plants in the aquatic environment have not yet been comprehensively reviewed. In this review, the properties, occurrence, uptake, transformation, and toxic effects of PAEs on plants in the aquatic environment are summarized. PAEs have been prevalently detected in the aquatic environment, including surface water, groundwater, seawater, and sediment, with concentrations ranging from the ng/L or ng/kg to the mg/L or mg/kg range. PAEs in the aquatic environment can be uptake, translocated, and metabolized by plants. Exposure to PAEs induces multiple adverse effects in aquatic plants, including growth perturbation, structural damage, disruption of photosynthesis, oxidative damage, and potential genotoxicity. High-throughput omics techniques further reveal the underlying toxicity molecular mechanisms of how PAEs disrupt plants on the transcription, protein, and metabolism levels. Finally, this review proposes that future studies should evaluate the interactions between plants and PAEs with a focus on long-term exposure to environmental PAE concentrations, the effects of PAE alternatives, and human health risks via the intake of plant-based foods.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

Neurotoxicities induced by micro/nanoplastics: A review focusing on the risks of neurological diseases.

Pollution of micro/nano-plastics (MPs/NPs) is ubiquitously prevalent in the environment, leading to an unavoidable exposure of the human body. Despite the protection of the blood-brain barrier, MPs/NPs can be transferred and accumulated in the brain, which subsequently exert negative effects on the brain. Nevertheless, the potential neurodevelopmental and/or neurodegenerative risks of MPs/NPs remain largely unexplored. In this review, we provide a systematic overview of recent studies related to the neurotoxicity of MPs/NPs. It covers the environmental hazards and human exposure pathways, translocation and distribution into the brain, the neurotoxic effects, and the possible mechanisms of environmental MPs/NPs. MPs/NPs are widely found in different environment matrices, including air, water, soil, and human food. Ambient MPs/NPs can enter the human body by ingestion, inhalation and dermal contact, then be transferred into the brain via the blood circulation and nerve pathways. When MPs/NPs are present in the brain, they can initiate a series of molecular or cellular reactions that may harm the blood-brain barrier, cause oxidative stress, trigger inflammatory responses, affect acetylcholinesterase activity, lead to mitochondrial dysfunction, and impair autophagy. This can result in abnormal protein folding, loss of neurons, disruptions in neurotransmitters, and unusual behaviours, ultimately contributing to the initiation and progression of neurodegenerative changes and neurodevelopmental abnormalities. Key challenges and further research directions are also proposed in this review as more studies are needed to focus on the potential neurotoxicity of MPs/NPs under realistic conditions.

Hydrodeoxygenation of furfural to 2-methylfuran over Cu-Co confined by hollow carbon cage catalyst enhanced by optimized charge transfer and alloy structure.

Hydrodeoxygenation of furfural over non-noble metal catalyst is an effective route to synthesis 2-methylfuran, but the reaction is often hampered by the low activity and selectivity of the catalyst. Herein, a bimetallic catalyst with CuCo alloy encapsulated in a hollow nitrogen-doped carbon cages (CuCo/NC) are fabricated by using ZIF-67 as a sacrificial template, which exhibited superior catalytic performance and a full conversion of furfural with a 95.7 % selectivity towards 2-methylfuran was achieved at an under relatively mild reaction conditions (150 ℃, 1.5 MPa H2 and 4.0 h). The characterizations and density functional theory calculations clearly evidenced that the introduced Cu species acts as a switch to regulate the activity and selectivity of the catalyst via two aspects. On the one hand, the Cu species perturb the Co electronic structure leading to adsorption configuration of furfural change from flat to vertical on the catalyst surface, which successfully hindered the hydrogenation of furan ring, resulting high selectivity towards 2-methylfuran. On the other hand, the formed CuCo (111) sites promotes the dissociation of hydrogen, cleavage of the CO bond and reduces the diffusion barrier of hydrogen so as to advance the formation of 2-methylfuran. This work may provide a feasible strategy for the design of nanoalloy catalyst for the hydrodeoxygenation of biomass platforms to value-added chemicals.

Highly Hydrophilic Zirconia Composite Anion Exchange Membrane for Water Electrolysis and Fuel Cells.

To prepare anion exchange membranes with high water electrolysis and single fuel cell performance, an inorganic-organic composite (IOC) strategy with click cross-linked membranes coated with different contents of hydrophilic polar nanozirconia is proposed to fabricate composite membranes (CM) PBP-SH-Zrx. The performance test results showed that the CM PBP-SH-Zr4 not only has good through-plane ionic conductivity (167.7 mS cm-1, 80 °C), but also exhibits satisfactory dimensional stability (SR 16.5%, WU 206.4%, 80 °C), especially demonstrating excellent alkaline stability with only 16% degradation (2 M NaOH for 2200 h). In water electrolysis, the "microgap" between the membrane and catalyst layer (solid-solid interface) is alleviated, and the membrane electrode assembly (MEA) interfacial compatibility (liquid-solid-solid interface) is enhanced. The CM PBP-SH-Zr4 showed the lowest charge transfer resistance (Rct, 0.037 Ω cm2) and a high current density of 2.5 A cm-2 at 2.2 V, while the voltage drop was 0.361 mV h-1 after 360 h of endurance (six start-stop cycles) at 60 °C and 500 mA cm-2, proving a good water electrolysis durability. Moreover, an acceptable peak power density of 0.464 W cm-2 at 80 °C is achieved in a H2/O2 fuel cell with a PBP-SH-Zr4-AEM. Therefore, the IOC strategy can enhance the membrane's comprehensive performance and interface compatibility of MEA and may promote the development of anion exchange membranes (AEMs) for water electrolysis and fuel cells.

Enhancement of PRMT6 binding to a novel germline GATA1 mutation associated with congenital anemia.

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function and the broader role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.

Twisted Poly(p-terphenyl-co-m-terphenyl)-Based Anion Exchange Membrane for Water Electrolysis.

In order to improve the mechanical and water electrolysis performance of anion exchange membranes (AEMs), we adjusted the ratio between p-terphenyl and m-terphenyl to balance the backbone conformation, which gives it a better suitability for a better combination with cations. The results showed that poly(m-terphenyl-co-p-terphenyl)-based AEMs have excellent mechanical properties. Among them, the m-p-TP-40-BOP-ASU membrane has the highest tensile strength and elongation at break (75.72 MPa and 16.07%). The ionic conductivity reaches 137.14 mS cm-1 at 80 °C owing to the fact that efficient ion-conducting channels are formed by well-balanced molecular structures. The current density of the m-p-TP-40-BOP-ASU membrane reached 1.96 A cm-2 (1 M KOH aq, 2.0 V and 60 °C). After testing for 112 h under a current density of 500 mA cm-2, the voltage increased by 102 mV compared to the initial electrolysis voltage. All results have shown that m-p-TP-x-BOP-ASU has excellent electrolysis performance and electrochemical durability and has a promising application prospect in AEM water electrolyzers.

Combining a lung microfluidic chip exposure model with transcriptomic analysis to evaluate the inflammation in BEAS-2B cells exposed to cigarette smoke.

BACKGROUND: Typically, in vitro studies on the exposure of complex gaseous substances are performed in multi-well plate experiments by trapping and redissolving them, which could introduce potential bias into the results due to the use of inadequate trapping methods. Therefore, a more effective method is to expose complex gaseous substances in gaseous form online, such as using microfluidic chips in experiments. To address these challenges, we introduce a methodology that integrates a self-designed bionic-lung chip with transcriptome analysis to assess the impact of cigarette smoke (CS) exposure on changes in BEAS-2B cells cultured on-chip. RESULTS: After the microfluidic chip underwent online gas exposure, total RNA was extracted via in situ cell lysis, and RNA-Seq transcriptome analysis was conducted. And the RNA-Seq findings revealed the significant involvement of the MAPK signaling pathway associated with the inflammatory response in the cellular effects induced by CS exposure. Moreover, the validation of inflammatory response-related biomarkers through in situ fluorescence corroborated the outcomes of the transcriptome analysis. Besides, the experiment involving the inhibition of inflammation by DEX on the microfluidic chip provided additional confirmation of the previous experimental findings. SIGNIFICANT: In this study, we present an analytical strategy that combines microfluidic-based CS in situ exposure method with RNA-Seq technology. This strategy offers an experimental scheme for in situ exposure to complex gases, transcriptome analysis, and in situ fluorescence detection. Through the integration of the comprehensiveness of transcriptome analysis with the chip's direct and intuitive in situ fluorescence detection with the stability and reliability of RT-PCR and Western blot experiments, we have successfully addressed the challenges associated with in vitro risk assessment for online exposure to complex gaseous substances.

Phlebitis in Takayasu arteritis: A case-based literature review.

Takayasu arteritis (TAK) is the main type of large vessel arteritis in young adults, which mainly affects the aorta and its main branches, leading to clinical manifestations such as syncope, intermittent limb claudication, hypertension, and abdominal pain. Among them, venous involvement is rarely reported. Here we show a case of TAK presenting as phlebitis. This was a 27-year-old woman, who initially admitted to our hospital with myalgia of the upper and lower extremities and night sweats. She was diagnosed as TAK according to the 1990 American College of Rheumatology TAK criteria. Surprisingly, vascular ultrasonography revealed wall thickening as indicated by macaroni sign of the multiple veins. TAK phlebitis appeared at the active phase, while disappearing rapidly at remission. Phlebitis might have a close relationship with disease activity. By retrospective study in our department, the estimated incidence rate of phlebitis might be 9.1% in TAK. With the literature review, it revealed that phlebitis might be an ignored manifestation in active TAK. However, due to the smaller sample size, it should be noted that a direct cause-effect relationship cannot be established.

Hydrophilic Chitosan-Doped Composite Diaphragm Reducing Gas Permeation for Alkaline Water Electrolysis Producing Hydrogen.

The present paper studied the chitosan-doped composite diaphragm by the phase exchange method with the objective of developing a composite diaphragm that complies with the alkaline water electrolysis requirements, as well as tested the electrolytic performance of the diaphragm in alkaline water electrolysis. The structure and morphology are characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The performance of chitosan-doped composite diaphragms was tested; CS3Z12 composite diaphragm with a low area resistance (0.20 Ω cm2), a high bubble point pressure (2.75 bar), and excellent electrochemical performance (current density of 650 mA cm-2 at 1.83 V) shows the best performance. Moreover, the performance of the synthesized composite diaphragm is significantly elevated compared to commercial diaphragms (Zirfon PERL), which is promising for practical application in alkaline electrolytic cells.

Opportunities and Challenges for ChatGPT and Large Language Models in Biomedicine and Health.

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction, and medical education, and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Associations of urinary di(2-ethylhexyl) phthalate metabolites with lipid profiles among US general adult population.

Background: Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. Methods: In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005-2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. Results: A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend <0.05), but there was no notable association with MEHP. RCS demonstrated a linear relationship of DEHP metabolites with HDL-C, TC, TG, and LDL-C (all P for nonlinearity >0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [ß = -0.26, 95%CI (-0.43, -0.09), P = 0.002], TC [ß = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [ß = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Conclusion: Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

A scoping review on multimodal deep learning in biomedical images and texts.

Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.

Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis.

BACKGROUND AND AIM: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y-box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. METHODS: We studied the characteristics of UXT-V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT-V1 in the colonic epithelium was investigated using lentivirus-mediated shRNA in vitro and ex vivo. Through endogenous Co-immunoprecipitation and LC-MS/MS, we identified ZONAB as a UXT-V1-interactive protein. RESULTS: Herein, we report that UXT-V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT-V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT-V1 in NCM-460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT-V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT-V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation-related genes, including AML1 and KLF4. CONCLUSION: Taken together, our study reveals a potential role of UXT-V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.

A scoping review on multimodal deep learning in biomedical images and texts.

OBJECTIVE: Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. METHODS: In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. RESULT: This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. CONCLUSION: Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.