Role of per- and polyfluoroalkyl substances in the cardiorenal system: Unraveling crosstalk from the network of pollutants and phenotypes.

Although per- and polyfluoroalkyl substances (PFAS) have been frequently linked to cardiovascular and renal disease separately, evidence remains scarce regarding their systematic effect. Therefore, we recruited 546 newly diagnosed acute coronary syndrome (ACS) patients and detected seven myocardial enzymes and six kidney function biomarkers. Twelve PFAS were also assessed with ultra-high-performance liquid chromatography-tandem mass spectrometry. Generalized linear model and restricted cubic spline model were applied to single pollutant analysis. Quantile g-computation was used for mixture analysis. Network model was utilized to identify central and bridge nodes of pollutants and phenotypes. In the present study, perfluorohexane sulfonic acid was positively associated with uric acid (UA) (ß= 0.04, 95% confidence interval (CI): 0.01, 0.07), and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate (ß= -0.04, 95% CI: -0.07, -0.01) but positively associated with UA (ß= 0.03, 95% CI: 0.01, 0.06). In mixture analysis, each quantile increase in the PFAS mixture was significantly associated with UA (ß= 0.08, 95% CI: 0.04, 0.11). Network analysis revealed that perfluorooctanoate, UA, and myoglobin were denoted as bridge nodes, and the first principal component of lactate dehydrogenase and creatine kinase- myocardial band was identified as the node with the highest strength and expected influence. This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network, which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.

Legacy and alternative per- and polyfluoroalkyl substances spatiotemporal distribution in China: Human exposure, environmental media, and risk assessment.

In recent decades, China's rapid development has led to significant environmental pollution from the widespread use of chemical products. Per- and polyfluoroalkyl substances (PFAS) are among the most concerning pollutants due to their persistence and bioaccumulation. This article assesses PFAS exposure levels, distribution, and health risks in Chinese blood, environment, and food. Out of 4037 papers retrieved from November 2022 to December 31, 2023, 351 articles met the criteria. Findings show perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) as the main PFAS in both Chinese populations and the environment. The highest PFOA levels in Chinese populations were in Shandong (53.868 ng/mL), while Hubei had the highest PFOS levels (43.874 ng/mL). Similarly, water samples from Sichuan (2115.204 ng/L) and Jiangsu (368.134 ng/L) had the highest PFOA and PFOS levels, respectively. Although localized areas showed high PFAS concentrations. Additionally, developed areas had higher PFAS contamination. The researches conducted in areas such as Qinghai and Hainan remain limited, underscoring the imperative for further investigation. Temporal analysis indicates declining levels of some PFAS, but emerging alternatives require more research. Limited studies on PFAS concentrations in soil, atmosphere, and food emphasize the need for comprehensive research to mitigate human exposure.

FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models.

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Effects of Wildfire on Soil CO2 Emission and Bacterial Community in Plantations.

In order to study the effects of wildfires on soil carbon dioxide (CO2) emissions and microbial communities in planted forests, Pinus massoniana Lamb. and Cunninghamia lanceolata (Lamb.) Hook. forests were selected as the research subjects. Through a culture test with 60 days of indoor constant temperature, the soil physical and chemical properties, organic carbon mineralization, organic carbon components, enzyme activity, and microbial community structure changes of the two plantations after fire were analyzed. The results showed that wildfires significantly reduced soil CO2 emissions from the Pinus massoniana forests and Cunninghamia lanceolata forests by 270.67 mg·kg-1 and 470.40 mg·kg-1, respectively, with Cunninghamia lanceolata forests exhibiting the greatest reduction in soil CO2 emissions compared to unburned soils. Bioinformatics analysis revealed that the abundance of soil Proteobacteria in the Pinus massoniana and Cunninghamia lanceolata forests decreased by 6.00% and 4.55%, respectively, after wildfires. Additionally, redundancy analysis indicated a significant positive correlation between Proteobacteria and soil CO2 emissions, suggesting that the decrease in Proteobacteria may inhibit soil CO2 emissions. The Cunninghamia lanceolata forests exhibited a significant increase in soil available nutrients and inhibition of enzyme activities after the wildfire. Additionally, soil CO2 emissions decreased more, indicating a stronger adaptive capacity to environmental changes following the wildfire. In summary, wildfire in the Cunninghamia lanceolata forests led to the most pronounced reduction in soil CO2 emissions, thereby mitigating soil carbon emissions in the region.

Left atrial appendage thrombus is associated with a higher fractal dimension in patients with atrial fibrillation.

PURPOSE: To assess the anatomical complexity of the left atrial appendage (LAA) using fractal dimension (FD) based on cardiac computed tomography angiography (CTA) and the association between LAA FD and LAA thrombosis. MATERIALS AND METHODS: Patients with atrial fibrillation (AF) who underwent both cardiac CTA and transesophageal echocardiography (TEE) between December 2018 and December 2022 were retrospectively analyzed. Patients were categorized into normal (n = 925), circulatory stasis (n = 82), and thrombus groups (n = 76) based on TEE results and propensity score matching (PSM) was performed for subsequent analysis. FD was calculated to quantify the morphological heterogeneity of LAA. Independent risk factors for thrombus were screened using logistic regression. The diagnostic performance of FD and CHA2DS2-VaSc score for predicting thrombus was evaluated using the area under the receiver operating characteristics curve (AUC). RESULTS: LAA FD was higher in the thrombus group (1.61 [1.49, 1.70], P < 0.001) than in the circulatory stasis (1.33 [1.18, 1.47]) and normal groups (1.30 [1.18, 1.42]) both before and after PSM. LAA FD was also an independent risk factor in the thrombus (OR [odds ratio] = 570,861.15 compared to normal, 41,122.87 compared to circulatory stasis; all P < 0.001) and circulatory stasis group (OR = 98.87, P = 0.001) after PSM. The diagnostic performance of LAA FD was significantly better than the CHA2DS2-VaSc score in identifying thrombus. CONCLUSIONS: Patients with high LAA FD are more likely to develop LAA thrombus, and the use of FD provides an effective method for assessing the risk of thrombosis in AF patients, thereby guiding individualized clinical treatment.

Regulating Second-Shell Coordination in Cobalt Single-Atom Catalysts toward Highly Selective Hydrogenation.

Manipulating the local coordination environment of central metal atoms in single-atom catalysts (SACs) is a powerful strategy to exploit efficient SACs with optimal electronic structures for various applications. Herein, Co-SACs featured by Co single atoms with coordinating S atoms in the second shell dispersed in a nitrogen-doped carbon matrix have been developed toward the selective hydrogenation of halo-nitrobenzene. The location of the S atom in the model Co-SAC is verified through synchrotron-based X-ray absorption spectroscopy and theoretical calculations. The resultant Co-SACs containing second-coordination shell S atoms demonstrate excellent activity and outstanding durability for selective hydrogenation, superior to most precious metal-based catalysts. In situ characterizations and theoretical results verify that high activity and selectivity are attributed to the advantageous formation of the Co-O bond between p-chloronitrobenzene and Co atom at Co1N4-S moieties and the lower free energy and energy barriers of the reaction. Our findings unveil the correlation between the performance and second-shell coordination atom of SACs.

NMR Studies of the Interactions between Sialyllactoses and the Polysialytransferase Domain for Polysialylation Inhibition.

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

Internal water circulation mediated synergistic co-hydrolysis of PET/cotton textile blends in gamma-valerolactone.

Recycling strategies for mixed plastics and textile blends currently aim for recycling only one of the components. Here, we demonstrate a water coupling strategy to co-hydrolyze polyester/cotton textile blends into polymer monomers and platform chemicals in gamma-valerolactone. The blends display a proclivity for achieving an augmented 5-hydroxymethylfurfural yield relative to the degradation of cotton alone. Controlled experiments and preliminary mechanistic studies underscore that the primary driver behind this heightened conversion rate lies in the internal water circulation. The swelling and dissolving effect of gamma-valerolactone on polyester enables a fast hydrolysis of polyester at much lower concentration of acid than the one in the traditional hydrolysis methods, effectively mitigating the excessive degradation of cotton-derived product and undesirable product formation. In addition, the system is also applicable to different kinds of blends and PET mixed plastics. This strategy develops an attractive path for managing end-of-life textiles in a sustainable and efficient way.

Study of (k,Θ)-Hilfer fractional differential and inclusion systems on the glucose graph.

This article combines (k,Θ)-Hilfer fractional calculus with glucose molecular graph, defines fractional differential and inclusion systems on each edge of a glucose molecular graph by the assumption that 0 or 1 marks the vertices, and studies the single-valued and multi-valued (k,Θ)-Hilfer type fractional boundary value problems on the glucose molecular graph. On the one hand, the existence and uniqueness of solutions in the single-valued case are proved by using several fixed point theorems. On the other hand, in the multi-valued case, we consider that the right side of the inclusion has convex valued and non-convex value. By applying Leray-Schauder nonlinear alternative method of multi-valued maps as well as Covitz-Nadler fixed point theorem of multi-valued contractions, two existence results are obtained respectively. On this basis, we also get the topological structure of the solution set, which is a pioneering work for (k,Θ)-Hilfer fractional differential inclusion on the glucose graph. Finally, several examples are provided to verify the reliability of our proposed results.

The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs).

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.

METTL3 facilitates prostate cancer progression via inducing HOXC6 m6A modification and stabilizing its expression through IGF2BP2-dependent mechanisms.

HOXC6 (Homeobox C6) and methyltransferase-like 3 (METTL3) have been shown to be involved in the progression of prostate cancer (PCa). However, whether HOXC6 performs oncogenic effects in PCa via METTL3-mediated N6-methyladenosine (m6A) modification is not yet reported. The Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, scratch, sphere formation assays were applied for cell growth, invasion, migration and stemness analyses. Glycolysis was evaluated by measuring glucose consumption, lactate generation and ATP/ADP ratio. The N6-methyladenine (m6A) modification profile was determined by RNA immunoprecipitation (Me-RIP) assay. The proteins that interact with PGK1 (phosphoglycerate kinase 1) were confirmed by Co-immunoprecipitation assay. Tumor formation experiments in mice were conducted for in vivo assay. PCa tissues and cells showed highly expressed HOXC6 and METTL3. Functionally, the silencing of HOXC6 or METTL3 suppresses PCa cell proliferation, invasion, migration, stemness, and glycolysis. Moreover, METTL3-induced HOXC6 m6A modification to stabilize its expression. In addition, the m6A reader IGF2BP2 directly recognized and bound to HOXC6 mRNA, and maintained its stability, and was involved in the regulation of HOXC6 expression by METTL3. Furthermore, IGF2BP2 knockdown impaired PCa cell proliferation, invasion, migration, stemness, and glycolysis by regulating HOXC6. Besides that HOXC6 interacted with the glycoytic enzyme PGK1 in PCa cells. In vivo assays further showed that METTL3 silencing reduced the expression of HOXC6 and PGK1, and impeded PCa growth. METTL3 promoted PCa progression by maintaining HOXC6 expression in an m6A-IGF2BP2-dependent mechanism.

The GWAS SNP rs80207740 modulates erythrocyte traits via allele-specific binding of IKZF1 and targeting XPO7 gene.

Genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with erythrocyte traits. However, the functional variants and their working mechanisms remain largely unknown. Here, we reported that the SNP of rs80207740, which was associated with red blood cell (RBC) volume and hemoglobin content across populations, conferred enhancer activity to XPO7 gene via allele-differentially binding to Ikaros family zinc finger 1 (IKZF1). We showed that the region around rs80207740 was an erythroid-specific enhancer using reporter assays, and that the G-allele further enhanced activity. 3D genome evidence showed that the enhancer interacted with the XPO7 promoter, and eQTL analysis suggested that the G-allele upregulated expression of XPO7. We further showed that the rs80207740-G allele facilitated the binding of transcription factor IKZF1 in EMSA and ChIP analyses. Knockdown of IKZF1 and GATA1 resulted in decreased expression of Xpo7 in both human and mouse erythroid cells. Finally, we constructed Xpo7 knockout mouse by CRISPR/Cas9 and observed anemic phenotype with reduced volume and hemoglobin content of RBC, consistent to the effect of rs80207740 on erythrocyte traits. Overall, our study demonstrated that rs80207740 modulated erythroid indices by regulating IKZF1 binding and Xpo7 expression.

Oxidative Upcycling of Polyethylene to Long Chain Diacid over Co-MCM-41 Catalyst.

Plastic pollution is an emerging global threat due to lack of effective methods for transforming waste plastics into useful resources. Here, we demonstrate a direct oxidative upcycling of polyethylene into high-value and high-volume saturated dicarboxylic acids in high carbon yield of 85.9 % in which the carbon yield of long chain dicarboxylic (C10-C20) acids can reach 58.9% over cobalt-doped MCM-41 molecular sieves, in the absence of any solvent or precious metal catalyst. The distribution of the dicarboxylic acids can be controllably adjusted from short-chain (C4-C10) to long-chain ones (C10-C20) through changing cobalt loading of MCM-41 under nanoconfinement. Highly and sparsely dispersed cobalt along with confined space of mesoporous structure enables complete degradation of polyethylene and high selectivity of dicarboxylic acid in mild condition. So far, this is the first report on highly selective one-step preparation of long chain dicarboxylic acids. The approach provides an attractive solution to tackle plastic pollution and a promising alternative route to long chain diacids.

An Integrative Chemical Recycling Approach for Catalytic Oxidation of Epoxy Resin and in situ Separation of Degraded Products.

Although many approaches have been proposed to recycling waste epoxy resin (EP), the separation of mixed degraded products remains a challenge due to their similar structures. To address this, we present a catalytic oxidation strategy that enables mild degradation of EP and in situ separation of degraded products through supramolecular interactions. The oxidative degradation relies on FeIV=O radicals with strong oxidizing properties, which are generated from the electron transfer of FeCl2 with reaction reagents. As the FeIV=O radicals attacked the C-N bonds of EP, EP was broken into fragments rich in active functional groups. Meanwhile, the FeIV=O radicals were reduced to iron ions that can coordinate with the carboxyl groups on the fragments. As a result, the degraded products with different carboxyl content can be effortlessly separated into liquid and solid phase by coordinating with the catalyst. The success of this work lays the foundation for high-value application of degraded products and provides new design ideas for recycling waste plastics with complex compositions.

Extracellular vesicle-mediated communication between CD8+ cytotoxic T cells and tumor cells.

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field.

Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

Angiotoxic effects of chlorinated polyfluorinated ether sulfonate, a novel perfluorooctane sulfonate substitute, in vivo and in vitro.

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA), a substitute for perfluorooctane sulfonate (PFOS), has been widely used in the Chinese electroplating industry under the trade name F-53B. The production and use of F-53B is keep increasing in recent years, consequently causing more emissions into the environment. Thus, there is a growing concern about the adverse effects of F-53B on human health. However, related research is very limited, particularly in terms of its toxicity to the vascular system. In this study, C57BL/6 J mice were exposed to 0.04, 0.2, and 1 mg/kg F-53B for 12 weeks to assess its impact on the vascular system. We found that F-53B exposure caused aortic wall thickening, collagen deposition, and reduced elasticity in mice. In addition, F-53B exposure led to a loss of vascular endothelial integrity and a vascular inflammatory response. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were found to be indispensable for this process. Furthermore, RNA sequencing analysis revealed that F-53B can decrease the repair capacity of endothelial cells by inhibiting their proliferation and migration. Collectively, our findings demonstrate that F-53B exposure induces vascular inflammation and loss of endothelial integrity as well as suppresses the repair capacity of endothelial cells, which ultimately results in vascular injury, highlighting the need for a more thorough risk assessment of F-53B to human health.

Effect of PFDS on the immobilization of Cs+ by metakaolin-based geopolymers in complex environments.

Metakaolin-based geopolymers are very promising materials for improving the safety of low and intermediate level radioactive waste disposal, with respect to ordinary Portland cement, due to their excellent immobilization performance for Cs+ and superior chemical stability. However, their application is limited by the fact that the leaching behavior of Cs+ is susceptible to the presence of other ions in the environment. Here, we propose a way to modify a geopolymer using perfluorodecyltriethoxysilane (PDFS), successfully reducing the leaching rate of Cs+ in the presence of multiple competitive cations due to blocking the diffusion of water. The leachability index of the modified samples in deionized water and highly concentrated saline water reached 11.0 and 8.0, respectively. The reaction mechanism between PDFS and geopolymers was systematically investigated by characterizing the microstructure and chemical bonding of the material. This work provides a facile and successful approach to improve the immobilization of Cs ions by geopolymers in real complex environments, and it could be extended to further improve the reliability of geopolymers used in a range of applications.