Care-seeking delay of patients with heart failure in China: a mixed-method study.

AIM: This study aims to explore the duration and influencing factors of care-seeking delay among patients with heart failure (HF) in China. METHODS AND RESULTS: A convergent mixed method containing a cross-sectional study and two parts of qualitative studies was designed, following the STROBE and COREQ guidelines. Convenience sampling was applied to recruit patients with HF from two general hospitals from December 2021 to December 2022. Purposive sampling was used to enrol healthcare professionals from two general hospitals and two community hospitals from June to November 2022. Among the 258 patients with HF in the cross-sectional study, the median duration of care-seeking delay was 7.5 days. The result integration indicated that the delay duration was influenced by the dyspnoea symptom burden, the oedema symptom burden, and the depression status. The lower dyspnoea symptom burden, the higher oedema symptom burden, and the higher depression score were related to the prolonged care-seeking delay duration. The duration was also affected by the COVID-19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers. The COVID-19 pandemic, low level of support from medical system, and limited symptom management abilities of caregivers were related to the prolonged care-seeking delay duration. CONCLUSIONS: Care-seeking delay among patients with HF needs attention in China. The duration of care-seeking delay of patients with HF was influenced by the dyspnoea symptom burden, the oedema symptom burden, and depression status, as well as the COVID-19 pandemic, level of support from medical system, and the symptom management abilities of the caregivers.

Unveiling behaviors of 8:2 fluorotelomer sulfonic acid (8:2 FTSA) in Arabidopsis thaliana: Bioaccumulation, biotransformation and molecular mechanisms of phytotoxicity.

8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.

Serum untargeted lipidomic characterization in a general Chinese cohort with residual per-/polyfluoroalkyl substances by liquid chromatography-drift tube ion mobility-mass spectrometry.

Per- and polyfluoroalkyl substances (PFAS) remain controversial due to their high persistency and potential human toxicity. Although occupational exposure to PFAS has been widely investigated, the implications of PFAS occurrence in the general population remain to be unraveled. Considering that serum from most people contains PFAS, the aim of this study was to characterize the lipidomic profile in human serum from a general cohort (n = 40) with residual PFAS levels. The geometric means of ∑PFAS (11.8 and 4.4 ng/mL) showed significant differences (P < 0.05) for the samples with the highest (n = 20) and lowest (n = 20) concentrations from the general population respectively. Reverse-phase liquid chromatography coupled to drift tube ion mobility and high-resolution mass spectrometry using dual polarity ionization was used to characterize the lipid profile in both groups. The structural elucidation involved the integration of various parameters, such as retention time, mass-to-charge ratio, tandem mass spectra and collision cross section values. This approach yielded a total of 20 potential biomarkers linked to the perturbed glycerophospholipid metabolism, energy metabolism and sphingolipid metabolism. Among these alterations, most lipids were down-regulated and some specific lipids (PC 36:5, PC 37:4 and PI O-34:2) exhibited a relatively strong Spearman correlation and predictive capacity for PFAS contamination. This study could support further toxicological assessments and mechanistic investigations into the effects of PFAS exposure on the lipidome.

Penetration pathways, influencing factors and predictive models for dermal absorption of exobiotic molecules: A critical review.

This review provides a comprehensive summary of the skin penetration pathways of xenobiotics, including metals, organic pollutants, and nanoparticles (NPs), with a particular focus on the methodologies employed to elucidate these penetration routes. The impacts of the physicochemical properties of exogenous substances and the properties of solvent carriers on the penetration efficiencies were discussed. Furthermore, the review outlines the steady-state and transient models for predicting the skin permeability of xenobiotics, emphasizing the models which enable realistic visualization of pharmaco-kinetic phenomena via detailed geometric representations of the skin microstructure, such as stratum corneum (SC) (bricks and mortar) and skin appendages (hair follicles and sebaceous gland units). Limitations of published research, gaps in current knowledge, and recommendations for future research are highlighted, providing insight for a better understanding of the skin penetration behavior of xenobiotics and associated health risks in practical application contexts.

Body mass index modifies the effect of urinary protein-to-creatinine ratio on chronic kidney disease progression.

BACKGROUND: This study aimed to determine the association between the urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression in a cohort study, and to determine whether body mass index (BMI) modifies this association. METHODS: The study population consisted of 856 hypertensive patients with CKD stages 2-5, enrolled between 2010 and 2011 in Japan. Generalized linear models with a logit link were used to evaluate the independent and combined effects of the UPCR and BMI on CKD progression RESULTS: During a median follow-up of 25 months, 242 patients developed CKD progression during follow-up. A notably higher risk of CKD progression was found in participants in tertiles 2 [odds ratio (OR): 5.46, 95% confidence interval (95% CI): 2.49-11.99] and 3 (OR 27.74, 95% CI 12.34-62.38) comparing with tertiles 1 for UPCR levels. Moreover, an interaction was found between UPCR and BMI on CKD progression (P for interaction = 0.006). Participants in both the highest tertile of UPCR and overweight (UPCR ≥ 248.9 mg/mmol and BMI ≥ 25 kg/m2) had a 45.59-times higher risk of CKD progression compared with those in the lowest tertile of UPCR and nonoverweight (UPCR < 36.2 mg/mmol and BMI < 25 kg/m2) CONCLUSIONS: The present study demonstrates that the combination of elevated UPCR and BMI may contribute to an increased risk of CKD progression.

Arsenite adsorption and oxidation affected by soil humin: The significant role of persistent free radicals and reactive oxygen species.

Humin (HM), as the main component of soil organic matter, carries various reactive groups and plays a crucial regulatory role in the transformation of arsenic (As). However, current research on the redox pathway of As and its interactions with HM is relatively limited. This study aimed to explore the impact of different HM samples on the redox characteristics of As. The results showed that HM can not only adsorb arsenite [As(III)] but also oxidize As(III) into arsenate [As(V)]. However, once As(III) is adsorbed on the HM, it cannot undergo further oxidation. HMNM (extracted from peat soil) exhibited the highest adsorption capacity of As(III), with a maximum amount of 1.95 mg/kg. The functional groups of HM involved in As complexation were primarily phenolic hydroxyl and carboxyl groups. The adsorption capacity of HM samples for As(III) was consistent with their carboxyl group contents. The oxygen-containing functional groups and environmentally persistent free radicals (EPFRs) on HM can directly oxidize As(Ⅲ) through electron transfer, or indirectly induce the production of reactive oxygen species (ROS), such as hydroxyl radicals, to further oxidize As(Ⅲ). This study provides new insight into the transport and transformation process of As mediated by soil HM, and establishes a theoretical basis for As remediation.

Development and validation of the self-volume management behaviour questionnaire for patients with chronic heart failure.

AIMS: We aim to develop and validate a questionnaire on the behaviour of self-volume management of patients with chronic heart failure. METHODS AND RESULTS: Based on the specific situation theory of heart failure self-care, the items of this questionnaire were formed through literature review and expert consultation. Content validity is judged by expert consultation. Item analysis was used for further filter entries. Cronbach's alpha and retest were used for reliability. Exploratory factor analysis and confirmatory factor analysis were used to test the structural validity. The questionnaire finally contained 3 subscales and 22 items. The Cronbach's α was between 0.732 and 0.797. The reliability of the retest was between 0.983 and 0.998. In expert consultation, the I-CVI of each item was 0.92-1, and the S-CVI of each subscale was 0.99, 1.00, and 0.99. In exploratory factor analysis, each subscale has two factors. In confirmatory factor analysis, the model fits of the three subscales were good: χ2/df < 3, RMSEA < 0.08, CFI > 0.9, TLI > 0.9, and SRMR < 0.05. CONCLUSIONS: The study has shown that the questionnaire on the behaviour of self-volume management of patients with chronic heart failure has good reliability and validity. It can be used as an evaluation tool for evaluating the self-volume management behaviour of patients with chronic heart failure.

Bayesian diagnostic test evaluation and true prevalence estimation of malnutrition in gastric cancer patients.

BACKGROUND & AIMS: Malnutrition is prevalent among gastric cancer (GC) patients, necessitating early assessment of nutritional status to guide monitoring and interventions for improved outcomes. We aim to evaluate the accuracy and prognostic capability of three nutritional tools in GC patients, providing insights for clinical implementation. METHODS: The present study is an analysis of data from 1308 adult GC patients recruited in a multicenter from July 2013 to July 2018. Nutritional status was assessed using Nutritional Risk Screening 2002 (NRS-2002), Patient-Generated Subjective Global Assessment (PG-SGA) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Bayesian latent class model (LCM) estimated the malnutrition prevalence of GC patients, sensitivity and specificity of nutritional tools. Cox regression model analyzed the relationship between nutritional status and overall survival (OS) in GC patients. RESULTS: Among 1308 GC patients, NRS-2002, PG-SGA, and GLIM identified 50.46%, 76.76%, and 68.81% as positive, respectively. Bayesian LCM analysis revealed that PG-SGA had the highest sensitivity (0.96) for malnutrition assessment, followed by GLIM criteria (0.78) and NRS-2002 (0.65). Malnutrition or being at risk of malnutrition were identified as independent prognostic factors for OS. Use any of these tools improved survival prediction in TNM staging system. CONCLUSION: PG-SGA is the most reliable tool for diagnosing malnutrition in GC patients, whereas NRS-2002 is suitable for nutritional screening in busy clinical practice. Given the lower sensitivity of NRS-2002, direct utilization of GLIM for nutritional assessment may be necessary. Each nutritional tool should be associated with a specific course of action, although further research is needed.

Macrophages regulate healing-associated fibroblasts in diabetic wound.

BACKGROUND: Recovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages. METHODS AND RESULTS: We used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1ß (IL1ß), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice. CONCLUSIONS: Macrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.

Novel Insights into the Promoted Accumulation of Nitro-Polycyclic Aromatic Hydrocarbons in the Roots of Legume Plants.

Substituted polycyclic aromatic hydrocarbons (sub-PAHs) are receiving increased attention due to their high toxicity and ubiquitous presence. However, the accumulation behaviors of sub-PAHs in crop roots remain unclear. In this study, the accumulation mechanism of sub-PAHs in crop roots was systematically disclosed by hydroponic experiments from the perspectives of utilization, uptake, and elimination. The obtained results showed an interesting phenomenon that despite not having the strongest hydrophobicity among the five sub-PAHs, nitro-PAHs (including 9-nitroanthracene and 1-nitropyrene) displayed the strongest accumulation potential in the roots of legume plants, including mung bean and soybean. The nitrogen-deficient experiments, inhibitor experiments, and transcriptomics analysis reveal that nitro-PAHs could be utilized by legumes as a nitrogen source, thus being significantly absorbed by active transport, which relies on amino acid transporters driven by H+-ATPase. Molecular docking simulation further demonstrates that the nitro group is a significant determinant of interaction with an amino acid transporter. Moreover, the depuration experiments indicate that the nitro-PAHs may enter the root cells, further slowing their elimination rates and enhancing the accumulation potential in legume roots. Our results shed light on a previously unappreciated mechanism for root accumulation of sub-PAHs, which may affect their biogeochemical processes in soils.

Stability and Biotransformation of 6:2 Fluorotelomer Sulfonic Acid, Sulfonamide Amine Oxide, and Sulfonamide Alkylbetaine in Aerobic Sludge.

The 6:2 fluorotelomer sulfonamide (6:2 FTSAm)-based compounds signify a prominent group of per- and polyfluoroalkyl substances (PFAS) widely used in contemporary aqueous film-forming foam (AFFF) formulations. Despite their widespread presence, the biotransformation behavior of these compounds in wastewater treatment plants remains uncertain. This study investigated the biotransformation of 6:2 FTSAm-based amine oxide (6:2 FTNO), alkylbetaine (6:2 FTAB), and 6:2 fluorotelomer sulfonic acid (6:2 FTSA) in aerobic sludge over a 100-day incubation period. The biotransformation of 6:2 fluorotelomer sulfonamide alkylamine (6:2 FTAA), a primary intermediate product of 6:2 FTNO, was indirectly assessed. Their stability was ranked based on the estimated half-lives (t1/2): 6:2 FTAB (no obvious products were detected) ≫ 6:2 FTSA (t1/2 ≈28.8 days) > 6:2 FTAA (t1/2 ≈11.5 days) > 6:2 FTNO (t1/2 ≈1.2 days). Seven transformation products of 6:2 FTSA and 15 products of 6:2 FTNO were identified through nontarget and suspect screening using high-resolution mass spectrometry. The transformation pathways of 6:2 FTNO and 6:2 FTSA in aerobic sludge were proposed. Interestingly, 6:2 FTSAm was hardly hydrolyzed to 6:2 FTSA and further biotransformed to perfluoroalkyl carboxylic acids (PFCAs). Furthermore, the novel pathways for the generation of perfluoroheptanoic acid (PFHpA) from 6:2 FTSA were revealed.

Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network.

With the widespread use of organophosphate esters (OPEs), the accumulation and toxicity effect of OPEs in biota are attracting more and more concern. In order to clarify the mechanism of toxicity of OPEs to organisms, this study reviewed the OPEs toxicity and systematically identified the mechanism of OPEs toxicity under the framework of adverse outcome pathway (AOP). OPEs were divided into three groups (alkyl-OPEs, aryl-OPEs, and halogenated-OPEs) and biota was divided into aquatic organism and mammals. The results showed that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) mainly caused neurotoxicity, reproductive, and hepatotoxicity in different mechanisms. According to the constructed AOP network, the toxicity mechanism of OPEs on aquatic organisms and mammals is different, which is mainly attributed to the different biological metabolic systems of aquatic organisms and mammals. Interestingly, our results indicate that the toxicity effect of the three kinds of OPEs on aquatic organisms is different, while there was no obvious difference in the mechanism of toxicity of OPEs on mammals. This study provides a theoretical basis for OPEs risk assessment in the future.

Molecular insights into microbial transformation of bioaerosol-derived dissolved organic matter discharged from wastewater treatment plant.

Wastewater treatment plants (WWTP) are important sources of aerosol-derived dissolved organic matter (ADOM) which may threaten human health via the respiratory system. In this study, aerosols were sampled from a typical WWTP to explore the chemical molecular diversity, molecular ecological network, and potential toxicities of the ADOM in the aerosols. The high fluorescence index (>1.9) and biological index (0.66-1.17) indicated the strong autogenous microbial source characteristics of the ADOM in the WWTP. DOM and microbes in the wastewater were aerosolized due to strong agitation and bubbling in the treatment processes, and contributed to 74 % and 75 %, respectively, of the ADOM and microbes in the aerosols. The ADOM was mainly composed of CHO and CHOS accounting for 35 % and 29 % of the total number of molecules, respectively, with lignin-like (69 %) as the major constituent. 49 % of the ADOM transformations were thermodynamically limited, and intragroup transformations were easier than intergroup transformations. Bacteria in the aerosols involved in ADOM transformations exhibited both cooperative and divergent behaviors and tended to transform carbohydrate-like and amino sugar/protein-like into recalcitrant lignin-like. The microbial compositions were affected by atmosphere temperature and humidity indirectly by modulating the properties of ADOM. Tannin-like, lignin-like, and unsaturated hydrocarbon-like molecules in the ADOM were primary toxicity contributors, facilitating the expression of inflammatory factors IL-ß (2.2-5.4 folds), TNF-α (3.5-7.0 folds), and IL-6 (3.5-11.2 folds), respectively.

Screening Novel Per- and Polyfluoroalkyl Substances in Human Blood Based on Nontarget Analysis and Underestimated Potential Health Risks.

Nontarget analysis has gained prominence in screening novel perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the environment, yet remaining limited in human biological matrices. In this study, 155 whole blood samples were collected from the general population in Shijiazhuang City, China. By nontarget analysis, 31 legacy and novel PFASs were assigned with the confidence level of 3 or above. For the first time, 11 PFASs were identified in human blood, including C1 and C3 perfluoroalkyl sulfonic acids (PFSAs), C4 ether PFSA, C8 ether perfluoroalkyl carboxylic acid (ether PFCA), C4-5 unsaturated perfluoroalkyl alcohols, C9-10 carboxylic acid-perfluoroalkyl sulfonamides (CA-PFSMs), and C1 perfluoroalkyl sulfonamide. It is surprising that the targeted PFASs were the highest in the suburban population which was impacted by industrial emission, while the novel PFASs identified by nontarget analysis, such as C1 PFSA and C9-11 CA-PFSMs, were the highest in the rural population who often drank contaminated groundwater. Combining the toxicity prediction results of the bioaccumulation potential, lethality to rats, and binding affinity to target proteins, C3 PFSA, C4 and C7 ether PFSAs, and C9-11 CA-PFSMs exhibit great health risks. These findings emphasize the necessity of broadening nontarget analysis in assessing the PFAS exposure risks, particularly in rural populations.

Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae.

Chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA), hydrogenated polyfluorooctane ether sulfonate (6:2 H-PFESA), and chlorinated polyfluorooctanesulfonate (Cl-PFOS) share structural similarities with the regulated perfluorooctanesulfonate (PFOS), but their toxic potential is rarely known. Here, the thyroid disrupting potential of these four compounds in zebrafish larvae has been comparably investigated. PFOS, Cl-PFOS, and 6:2 Cl-PFESA were accumulated in the larvae at similar levels, approximately 1.3-1.6 times higher than 6:2 H-PFESA. Additionally, PFOS, Cl-PFOS, and 6:2 Cl-PFESA exhibited stronger disruption than 6:2 H-PFESA on genetic regulation, particularly concerning thyroid hormone (TH) activation and action and on TH homeostasis in both free and total forms of thyroxine (T4) and 3,5,3'-triiodothyronine (T3). These results indicate that chlorination or oxygen insertion does not substantially alter the thyrotoxicity of PFOS, but hydrogenation mitigates it. Molecular docking analysis and the luciferase reporter gene assay provided mechanistic perspectives that the PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases.

Exploring Route-Specific Pharmacokinetics of PFAS in Mice by Coupling in Vivo Tests and Physiologically Based Toxicokinetic Models.

BACKGROUND: Oral ingestion, inhalation, and skin contact are important exposure routes for humans to uptake per- and polyfluoroalkyl substances (PFAS). However, nasal and dermal exposure to PFAS remains unclear, and accurately predicting internal body burden of PFAS in humans via multiple exposure pathways is urgently required. OBJECTIVES: We aimed to develop multiple physiologically based toxicokinetic (PBTK) models to unveil the route-specific pharmacokinetics and bioavailability of PFAS via respective oral, nasal, and dermal exposure pathways using a mouse model and sought to predict the internal concentrations in various tissues through multiple exposure routes and extrapolate it to humans. METHODS: Mice were administered the mixed solution of perfluorohexane sulfonate, perfluorooctane sulfonate, and perfluorooctanoic acid through oral, nasal, and dermal exposure separately or jointly. The time-dependent concentrations of PFAS in plasma and tissues were determined to calibrate and validate the individual and combined PBTK models, which were applied in single- and repeated-dose scenarios. RESULTS: The developed route-specific PBTK models successfully simulated the tissue concentrations of PFAS in mice following single or joint exposure routes as well as long-term repeated dose scenarios. The time to peak concentration of PFAS in plasma via dermal exposure was much longer (34.1-83.0 h) than that via nasal exposure (0.960 h). The bioavailability of PFAS via oral exposure was the highest (73.2%-98.0%), followed by nasal (33.9%-66.8%) and dermal exposure (4.59%-7.80%). This model was extrapolated to predict internal levels in human under real environment. DISCUSSION: Based on these data, we predict the following: PFAS were absorbed quickly via nasal exposure, whereas a distinct hysteresis effect was observed for dermal exposure. Almost all the PFAS to which mice were exposed via gastrointestinal route were absorbed into plasma, which exhibited the highest bioavailability. Exhalation clearance greatly depressed the bioavailability of PFAS via nasal exposure, whereas the lowest bioavailability in dermal exposure was because of the interception of PFAS within the skin layers. https://doi.org/10.1289/EHP11969.

The genetic landscape of histologically transformed marginal zone lymphomas.

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

Nurse-coordinated home-based cardiac rehabilitation for patients with heart failure: A scoping review.

Objectives: This study aimed to review and summarize the studies of nurse-coordinated home-based cardiac rehabilitation for patients with heart failure. Methods: The review was performed using Arksey and O'Malley's scoping review framework. A systematic search was conducted across eight databases, including PubMed, Embase, Web of Science, EBSCO, China Biomedical Literature Service System (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Science and Technology Journals (CSTJ) Database, and Chinese Clinical Trial Registry, from inception to 30 April 2023. Articles relevant to the nurse-coordinated home-based cardiac rehabilitation for patients with heart failure were included. Results: Eighteen studies were included in this review. These studies showed that nurses primarily focused on patient assessment, home-based cardiac rehabilitation planning and guidance, and follow-up. The studies also reported positive outcomes in patient safety, feasibility, and efficacy of the programs coordinated by nurses. Conclusions: Home-based cardiac rehabilitation coordinated by nurses is beneficial to patients with heart failure. Future research will explore the potential of nurses in home-based cardiac rehabilitation for patients with heart failure, determine optimal evaluation criteria, and formulate safe, effective, and economical rehabilitation programs suitable for the patients.

Nontarget Screening and Fate of Emerging Per- and Polyfluoroalkyl Substances in Wastewater Treatment Plants in Tianjin, China.

Wastewater treatment plants (WWTPs) are typical point sources of per- and polyfluoroalkyl substances (PFAS) released into the environment. The suspect and nontarget screening based on gas chromatography or liquid chromatography-high resolution mass spectrometry were performed on atmosphere, wastewater, and sludge samples collected from two WWTPs in Tianjin to discover emerging PFAS and their fate in this study. A total of 40 PFAS (14 neutral and 26 ionic) and 64 PFAS were identified in the atmosphere and wastewater/sludge, respectively, among which 5 short-chain perfluoroalkyl sulfonamide derivatives, 4 ionic PFAS, and 15 aqueous film-forming foam-related cationic or zwitterionic PFAS have rarely or never been reported in WWTPs in China. Active air sampling is more conducive to the enrichment of emerging PFAS, while passive sampling is inclined to leave out some ultrashort-chain PFAS or unstable transformation intermediates. Moreover, most precursors and intermediates could be enriched in the atmosphere at night, while the PFAS associated with aerosols with high water content or particles enter the atmosphere easily during the day. Although most emerging PFAS could not be eliminated efficiently in conventional treatment units, deep bed filtration and advanced oxidation processes could partly remove some emerging precursors.