Enhanced Degradation of Micropollutants in a Peracetic Acid/Mn(II) System with EDDS: An Investigation of the Role of Mn Species.

Extensive research has been conducted on the utilization of a metal-based catalyst to activate peracetic acid (PAA) for the degradation of micropollutants (MPs) in water. Mn(II) is a commonly employed catalyst for homogeneous advanced oxidation processes (AOPs), but its catalytic performance with PAA is poor. This study showed that the environmentally friendly chelator ethylenediamine-N,N'-disuccinic acid (EDDS) could greatly facilitate the activation of Mn(II) in PAA for complete atrazine (ATZ) degradation. In this process, the EDDS enhanced the catalytic activity of manganese (Mn) and prevented disproportionation of transient Mn species, thus facilitating the decay of PAA and mineralization of ATZ. By employing electron spin resonance detection, quenching and probe tests, and 18O isotope-tracing experiments, the significance of high-valent Mn-oxo species (Mn(V)) in the Mn(II)-EDDS/PAA system was revealed. In particular, the involvement of the Mn(III) species was essential for the formation of Mn(V). Mn(III) species, along with singlet oxygen (1O2) and acetyl(per)oxyl radicals (CH3C(O)O•/CH3C(O)OO•), also contributed partially to ATZ degradation. Mass spectrometry and density functional theory methods were used to study the transformation pathway and mechanism of ATZ. The toxicity assessment of the oxidative products indicated that the toxicity of ATZ decreased after the degradation reaction. Moreover, the system exhibited excellent interference resistance toward various anions and humid acid (HA), and it could selectively degrade multiple MPs.

Total Synthesis of Diverse Tetramic Acid Bearing cis-Decalin Natural Products.

We report herein the first total syntheses of four natural antibiotics, vermisporin, PF1052/AB4015-A, AB4015-L, AB4015-B, and one hydrogenated natural product derivative, AB4015-A2, that all feature a tetramic acid bearing cis-decalin ring. The construction of the functionalized cis-decalin ring was achieved by a diastereoselective intramolecular Diels-Alder (IMDA) reaction, which proceeded via a rare endo-boat transition state. Through an intramolecular neighboring-group-oriented strategy, the sterically hindered epoxy group in vermisporin, PF1052/AB4015-A and AB4015-L was installed efficiently. A one-pot aminolysis/Dieckmann condensation cascade using l-amino acid derivatives afforded the desired tetramic acid structure. The total synthesis led to the unambiguous verification of the absolute configuration of these natural products.

Histone methyltransferase SETDB1 inhibits TGF-ß-induced epithelial-mesenchymal transition in pulmonary fibrosis by regulating SNAI1 expression and the ferroptosis signaling pathway.

The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. Changes in histone methylation modifications of key genes play an important role in this process. As a histone methyltransferase, the regulatory mechanism and role of SET domain bifurcated 1 (SETDB1) in pulmonary fibrosis remain unclear. We found that SETDB1 inhibited EMT and that cells attenuated the expression of SETDB1 to relieve this inhibition during transforming growth factor-ß (TGF-ß)-induced EMT. Silencing SETDB1 expression significantly enhanced the mesenchymal phenotype induced by TGF-ß and the expression and deposition of fibronectin and significantly reduced the expression of E-cadherin. The decrease in E-cadherin expression and the induction of EMT led to increased lipid reactive oxygen species (ROS) and ferrous ions, which induced ferroptosis. Chromatin immunoprecipitation (ChIP) results showed that SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin. Surprisingly, when examining the effect of overexpressed SETDB1 on EMT, we found that overexpressed SETDB1 alleviated EMT and also caused ferroptosis. We suggest that the overexpression of SETDB1 partially reverses the mesenchymal phenotype to an epithelial state, while those cells that fail to reverse are depleted by ferroptosis. In conclusion, the histone methylase SETDB1 regulates Snai1 epigenetically, driving EMT gene reprogramming and ferroptosis in response to TGF-ß. However, there are unexplored links between the epigenetic reprogramming and transcriptional processes that regulate EMT in a TGF-ß-dependent manner.

Associations of Carbonaceous Compounds and Water-Soluble Inorganic Ions in Ambient PM2.5 with Renal Function in Older Individuals: The China BAPE Study.

Exposure to fine particulate matter (PM2.5) is proven to be associated with a decline in renal function. However, few studies have explored the acute renal damage from carbonaceous compounds and water-soluble inorganic ions (WSIIs), which constitute the bulk of total PM2.5 mass. We examined the acute effect of these constituents of ambient PM2.5 on renal function in older Chinese individuals. Seventy-one healthy people aged 60-69 years from Jinan, China, were enrolled and visited monthly and asked to complete survey questionnaires, undergo physical exams, and provide blood samples. The hourly concentrations of organic carbon, elemental carbon (EC), and WSIIs in ambient PM2.5 were collected from a fixed-site monitoring station. The association between PM2.5 constituents and estimated glomerular filtration rate (eGFR) was evaluated using linear mixed-effects models after controlling for a series of covariates. We observed that ambient carbonaceous compounds and WSIIs were associated with a significant decline in renal function. The interquartile range increased in the 24 h moving average of carbonaceous compounds, and WSIIs in ambient PM2.5 were associated with -13.11% [95% confidence interval (95% CI): -19.49, -6.21%] to -0.81% (95% CI: -4.17, 2.67%) changes in eGFR. We found significant associations between EC, chlorine (Cl-), sodium (Na+), and magnesium (Mg2+) and eGFR in single-pollutant, constituent-PM2.5, and residual-constituent models with a lag period of 0-24 h. This study demonstrated that carbonaceous compounds and WSIIs in PM2.5 were inversely associated with renal function.

Personal PM2.5 Elemental Components, Decline of Lung Function, and the Role of DNA Methylation on Inflammation-Related Genes in Older Adults: Results and Implications of the BAPE Study.

Epidemiological evidence of the effects of PM2.5 elements on lung function and DNA methylation is limited. We conducted a longitudinal panel study of 76 healthy older adults aged 60-69 years in Jinan, China, from September 2018 to January 2019. We periodically measured individual 72 h PM2.5 and element concentrations, lung function, and DNA methylation levels of eight inflammation-related genes. We used linear mixed-effect models to investigate the effects of exposure to personal PM2.5 elements on the lung function and DNA methylation. Mediation analysis was used to investigate the underlying effect mechanism. Negative changes in the ratio of forced expiratory volume in 1 s to forced vital capacity, ranging from -1.23% [95% confidence interval (CI): -2.11%, -0.35%] to -0.77% (95% CI: -1.49%, -0.04%), were significantly associated with interquartile range (IQR) increases in personal PM2.5 at different lag periods (7-12, 13-24, 25-48, 0-24, 0-48, and 0-72 h). Arsenic (As), nickel, rubidium (Rb), selenium, and vanadium were significantly associated with at least three lung function parameters, and IQR increases in these elements led to 0.12-5.66% reductions in these parameters. PM2.5 elements were significantly associated with DNA methylation levels. DNA methylation mediated 7.28-13.02% of the As- and Rb-related reduced lung function. The findings indicate that exposure to elements in personal PM2.5 contributes to reduced lung function through DNA methylation.

Emerging and Legacy Per- and Polyfluoroalkyl Substances in an Elderly Population in Jinan, China: The Exposure Level, Short-Term Variation, and Intake Assessment.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has gained worldwide attention due to their widespread presence in the environment and adverse health effects, but the exposure assessment in the elderly is still lacking. This study aimed to assess exposures to 3 emerging PFASs (chlorinated polyfluoroalkyl ether sulfonic acids, Cl-PFESAs) and 15 legacy PFASs. The temporal variability of internal exposures and intake amounts of these PFASs were evaluated among a population of 76 healthy elderly adults (age: 60-69) in Jinan, China over 5 consecutive months. Fifteen PFASs were detected in whole blood with the mean total concentration (ΣPFAS) at 20.1 ng/mL (range: 5.0-135.9 ng/mL) dominated by perfluorooctanoic acid (PFOA) (9.0 ng/mL), perfluorooctanesulfonic acid (PFOS) (5.3 ng/mL), and 6:2 Cl-PFESA (1.6 ng/mL). Across the 5 month assessment period, significant variation was only observed for short-chain (C4-C7) perfluoroalkyl carboxylic acids, and their variations ranged from 53 to 334%. The median intake of PFOA and PFOS was estimated to be 1.46 and 0.92 ng/kg bw/day, respectively. Regression analysis showed that dietary ingestion, especially fish, was likely an important exposure pathway for PFASs among the elderly adults. Various pathways (e.g., dietary, water, air, and dust) should thus be considered to fully understand human exposure to PFASs.

Associations between Individual Exposure to Fine Particulate Matter Elemental Constituent Mixtures and Blood Lipid Profiles: A Panel Study in Chinese People Aged 60-69 Years.

Dyslipidemia may be a potential mechanism linking fine particulate matter (PM2.5) to adverse cardiovascular outcomes. However, inconsistent associations between PM2.5 and blood lipids have resulted from the existing research, and the joint effect of PM2.5 elemental constituents on blood lipid profiles remains unclear. We aimed to explore the overall associations between PM2.5 elemental constituents and blood lipid profiles and to identify the significant PM2.5 elemental constituents in this association. Sixty-nine elderly people were recruited between September 2018 and January 2019. Each participant completed a survey questionnaire, 3 days of individual exposure monitoring, health examination, and biological sample collection at each follow-up visit. Bayesian kernel machine regression (BKMR) models were used to identify the joint effects of the 17 elemental constituents on blood lipid profiles. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly increased in older adults when exposed to the mixture of PM2.5 elemental constituents. Copper and titanium had higher posterior inclusion probabilities than other constituents, ranging from 0.76 to 0.90 (Cu) and 0.74 to 0.94 (Ti). Copper and titanium in the PM2.5 elemental constituent mixture played an essential role in changes to blood lipid levels. This study highlights the importance of identifying critical hazardous PM2.5 constituents that may cause adverse cardiovascular outcomes in the future.

Associations between Personal PM2.5 Elemental Constituents and Decline of Kidney Function in Older Individuals: the China BAPE Study.

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

Expression of Fibroblast Growth Factor 4 in a Rat Model of Polydactyly of the Thumb Induced by Cytarabine.

BACKGROUND The aim of this study was to assess the expression and mechanisms of fibroblast growth factor 4 in polydactyly of the thumb induced by cytarabine. MATERIAL AND METHODS Rats were intraperitoneally injected with cytarabine at different gestation periods (12.5 days, 13.5 days, and 14.5 days) to establish a polydactyly of the thumb model. Then, the expression of FGF4 in polydactyly was studied by whole-mount in situ hybridization. We used hematoxylin & eosin stain and cartilage stain to investigate the development of the skeleton and tissues in the embryo. Pictures were taken to determine the general shape of the deformity, then X-rays were taken to detect bone distortion of the rats born with a congenital malformation. RESULTS In the experimental group (11.5 days, 12.5 days, 13.5 days, and 14.5 days), whole-mount in situ hybridization showed that the FGF4 expression at the tip of the embryonic limb bud was significantly increased compared with the control group and FGF4 was distributed in a wider range and lasted longer than in the control group (P<0.01). HE staining and cartilage staining showed that there was an extra metacarpal bone and a phalanx in the rats with polydactyly of the thumb (P<0.01). Images of the deformed limbs showed polydactyly and syndactyly of the thumb in the rats. Further X-ray examination revealed 1 extra metacarpal bone and 1 extra phalanx. CONCLUSIONS Cytarabine can induce polydactyly and syndactyly of the thumb in rats. In this process, cytarabine can induce the expression of FGF4 on the tip of the embryonic limb bud, which further leads to abnormal development of the embryonic limb bud and eventually causes a congenital deformity.

Hypertension Among Hemorrhagic Stroke Patients in Northeast China: A Population-Based Study 2017-2019.

BACKGROUND We aimed to profile the current epidemiology of hypertension among the survivors of hemorrhagic stroke in northeast China. MATERIAL AND METHODS Our cross-sectional study included 18 796 adults aged 40 years or older and residing in northeast China. Hemorrhagic stroke was identified according to the CT and/or MRI results. Hypertension was defined based on the Chinese hypertension guidelines. RESULTS We identified 208 patients with previous hemorrhagic stroke in this population-based study. The overall prevalence of hypertension in the studied population was 88%. Out of all the survivors of hemorrhagic stroke, 80.9% were aware of their hypertensive condition, 70.5% of the patients were in antihypertensive medications treatment, and only 12% of the patients had their blood pressure under control. Furthermore, only 17.10% of the patients who took hypertensive medications achieved appropriate blood pressure. Calcium channel blockers were more commonly used than other medications. Patients with controlled hypertension had significantly higher percentages of comorbidities when compared to those with uncontrolled hypertension. In our patient sample, the rates of stage 2 and stage 3 hypertension in the hemorrhagic stroke population were 28.8% and 15.9%, respectively, and women had a significantly higher prevalence of stage 3 hypertension when compared with men (21.3% vs. 10.0%, P=0.026). CONCLUSIONS The high prevalence of uncontrolled hypertension and high rates of blood pressure at stages 2 and 3 in patients with prior hemorrhagic stroke indicated a considerable stroke burden in northeast China. Therefore, effective and long-time management of hypertension in stroke survivors should be a priority.

[Connectivity pattern of action potentials causal network in prefrontal cortex during anxiety].

Anxiety disorder is a common emotional handicap, which seriously affects the normal life of patients and endangers their physical and mental health. The prefrontal cortex is a key brain region which is responsible for anxiety. Action potential and behavioral data of rats in the elevated plus maze (EPM) during anxiety (an innate anxiety paradigm) can be obtained simultaneously by using the in vivo and in conscious animal multi-channel microelectrode array recording technique. Based on maximum likelihood estimation (MLE), the action potential causal network was established, network connectivity strength and global efficiency were calculated, and action potential causal network connectivity pattern of the medial prefrontal cortex was quantitatively characterized. We found that the entries (44.13±6.99) and residence period (439.76±50.43) s of rats in the closed arm of the elevated plus maze were obviously higher than those in the open arm [16.50±3.25, P<0.001; (160.23±48.22) s, P<0.001], respectively. The action potential causal network connectivity strength (0.017 3±0.003 6) and the global efficiency (0.044 2±0.012 8) in the closed arm were both higher than those in the open arm (0.010 4±0.003 2, P<0.01; 0.034 8±0.011 4, P<0.001), respectively. The results suggest that the changes of action potential causal network in the medial prefrontal cortex are related to anxiety state. These data could provide support for the study of the brain network mechanism in prefrontal cortex during anxiety.

Influence of surfactants on anaerobic digestion of waste activated sludge: acid and methane production and pollution removal.

The objective of this study is to summarize the effects of surfactants on anaerobic digestion (AD) of waste activated sludge (WAS). The increasing amount of WAS has caused serious environmental problems. Anaerobic digestion, as the main treatment for WAS containing three stages (i.e. hydrolysis, acidogenesis, and methanogenesis), has been widely investigated. Surfactant addition has been demonstrated to improve the efficiency of AD. Surfactant, as an amphipathic substance, can enhance the efficiency of hydrolysis by separating large sludge and releasing the encapsulated hydrolase, providing more substance for subsequent acidogenesis. Afterwards, the short chain fatty acids (SCFAs), as the major product, have been produced. Previous investigations revealed that surfactant could affect the transformation of SCFA. They changed the types of acidification products by promoting changes in microbial activity and in the ratio of carbon to nitrogen (C/N), especially the ratio of acetic and propionic acid, which were applied for either the removal of nutrient or the production of polyhydroxyalkanoate (PHA). In addition, the activity of microorganisms can be affected by surfactant, which mainly leads to the activity changes of methanogens. Besides, the solubilization of surfactant will promote the solubility of contaminants in sludge, such as organic contaminants and heavy metals, by increasing the bioavailability or desorbing of the sludge.

Single and combined removal of Cr(VI) and Cd(II) by nanoscale zero-valent iron in the absence and presence of EDDS.

This study examined the feasibility of nanoscale zero-valent iron (nZVI) for the single and combined removal of Cr(VI) and Cd(II) with or without ethylene diamine disuccinic acid (EDDS). The effects of pH and dissolved oxygen (DO) on the removal process were investigated. Results show that the single removal of either Cr(VI) or Cd(II) by nZVI was pH dependent, where the higher Cr(VI) removal was achieved under acidic conditions, whereas the higher Cd(II) removal was achieved under alkaline conditions. The presence of DO enhanced Cd(II) removal but inhibited Cr(VI) removal under alkaline conditions. In the co-existence of Cr(VI) and Cd(II), it was found that Cd(II) exerted insignificant effect on Cr(VI) removal, while the presence of Cr(VI) remarkably enhanced the Cd(II) removal. The addition of EDDS exhibited different influences on Cr(VI) and Cd(II) removal, which were associated with pH and DO. The EDDS enhanced Cr(VI) removal at pH 5.6-9.0 in the absence of DO, but decreased Cr(VI) removal at pH 9.0 in the presence of DO. For the removal of Cd(II) at pH 5.6-7.0, either facilitation or inhibition effect of EDDS was observed, depending on EDDS concentration and the co-existence of Cr(VI). However, Cd(II) removal was always significantly inhibited by EDDS at pH 9.0.

Interaction between Cu2+ and different types of surface-modified nanoscale zero-valent iron during their transport in porous media.

This study investigated the interaction between Cu2+ and nano zero-valent iron (NZVI) coated with three types of stabilizers (i.e., polyacrylic acid [PAA], Tween-20 and starch) by examining the Cu2+ uptake, colloidal stability and mobility of surface-modified NZVI (SM-NZVI) in the presence of Cu2+. The uptake of Cu2+ by SM-NZVI and the colloidal stability of the Cu-bearing SM-NZVI were examined in batch tests. The results showed that NZVI coated with different modifiers exhibited different affinities for Cu2+, which resulted in varying colloidal stability of different SM-NZVI in the presence of Cu2+. The presence of Cu2+ exerted a slight influence on the aggregation and settling of NZVI modified with PAA or Tween-20. However, the presence of Cu2+ caused significant aggregation and sedimentation of starch-modified NZVI, which is due to Cu2+ complexation with the starch molecules coated on the surface of the particles. Column experiments were conducted to investigate the co-transport of Cu2+ in association with SM-NZVI in water-saturated quartz sand. It was presumed that a physical straining mechanism accounted for the retention of Cu-bearing SM-NZVI in the porous media. Moreover, the enhanced aggregation of SM-NZVI in the presence of Cu2+ may be contributing to this straining effect.

Enhanced chalcopyrite-catalyzed heterogeneous Fenton oxidation of diclofenac by ABTS.

The widely used 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) has gained growing attention in advanced oxidation processes (AOPs), whereas there was limited knowledge regarding the feasibility of ABTS in enhancing heterogeneous Fenton oxidation so far. Hereof, ABTS was introduced into the chalcopyrite (CuFeS2)- catalyzed heterogeneous Fenton oxidation process to degrade diclofenac (DCF), and the degradation efficiency was enhanced by 25.5% compared with CuFeS2/H2O2 process. The available reactive oxygen species (ROS) and the enhanced mechanism were elaborated. Experimental results uncovered that •OH was the dominant reactive species responsible for the DCF degradation in the CuFeS2/H2O2/ABTS process, and ABTS•+ was derived from both •OH and Fe(IV). The presence of ABTS contributed significantly to the redox cycle of surface Fe of CuFeS2, and the roles of reductive sulfur species and surface Cu(I) in promoting surface Fe cycling also could not be neglected. In addition, the effects of several influencing factors were considered, and the potential practicability of this oxidation process was examined. The results demonstrate that the CuFeS2/H2O2/ABTS process would be a promising approach for water purification. This study will contribute to the development of enhancing strategies using ABTS as a redox mediator for heterogeneous Fenton oxidation of pharmaceuticals.

Essential oil from Cinnamomum cassia Presl bark regulates macrophage polarization and ameliorates lipopolysaccharide-induced acute lung injury through TLR4/MyD88/NF-κB pathway.

BACKGROUND: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). PURPOSE: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. METHODS: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. RESULTS: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1ß in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.

ACSL3 regulates breast cancer progression via lipid metabolism reprogramming and the YES1/YAP axis.

OBJECTIVE: Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers, because it sustains cancer cell survival, proliferation, and metastasis. The acyl-CoA synthetase long-chain (ACSL) family is known to activate long-chain fatty acids, yet the specific role of ACSL3 in breast cancer has not been determined. METHODS: We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples. Gain-of-function and loss-of-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo. RESULTS: ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues, and this phenotype correlated with improved survival outcomes. Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation, migration, and epithelial-mesenchymal transition. Mechanistically, ACSL3 was found to inhibit ß-oxidation and the formation of associated byproducts, thereby suppressing malignant behavior in breast cancer. Importantly, ACSL3 was found to interact with YES proto-oncogene 1, a member of the Src family of tyrosine kinases, and to suppress its activation through phosphorylation at Tyr419. The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation, and the expression of its downstream genes in breast cancer cell nuclei. CONCLUSIONS: ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming, and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways. These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.

Blood cadmium level as a risk factor for chronic pain: NHANES database 1999-2004.

Objective: The escalating prevalence of chronic pain poses a substantial socio-economic burden. Chronic pain primarily stems from musculoskeletal and nervous system impairments. Given cadmium's known toxicity to these systems, our study sought to investigate the correlation between blood cadmium levels and chronic pain. Methods: The cross-sectional study was conducted from the National Health and Nutrition Examination Survey (NHANES, 1999-2004), and comprised US adults who participated in a chronic pain interview. We employed logistic regression models and smooth curve fitting to elucidate the relationship between blood cadmium levels and chronic pain. Results: Our findings revealed a linear association between blood cadmium levels and chronic pain. Compared to the lower blood cadmium tertile 1 (<0.3 ug/dL), the adjusted odds ratios (ORs) for tertile 2 (0.3-0.4 ug/dL), and tertile 3 (≥0.5 ug/dL), were 1.11 (0.96-1.29) and 1.2 (1.03-1.39), respectively. Sensitivity analyses corroborated these results. Conclusion: Elevated levels of blood cadmium are associated with a heightened risk of chronic pain among adults in the United States. Mitigating cadmium exposure could potentially decrease the risk of chronic pain, thereby enhancing strategies for chronic pain prevention and management.