Integration of nontarget analysis with machine learning modeling for prioritization of odorous volatile organic compounds in surface water.

Assessing the odor risk caused by volatile organic compounds (VOCs) in water has been a big challenge for water quality evaluation due to the abundance of odorants in water and the inherent difficulty in obtaining the corresponding odor sensory attributes. Here, a novel odor risk assessment approach has been established, incorporating nontarget screening for odorous VOC identification and machine learning (ML) modeling for odor threshold prediction. Twenty-nine odorous VOCs were identified using two-dimensional gas chromatography-time of flight mass spectrometry from four surface water sampling sites. These identified odorants primarily fell into the categories of ketones and ethers, and originated mainly from biological production. To obtain the odor threshold of these odorants, we trained an ML model for odor threshold prediction, which displayed good performance with accuracy of 79%. Further, an odor threshold-based prioritization approach was developed to rank the identified odorants. 2-Methylisoborneol and nonanal were identified as the main odorants contributing to water odor issues at the four sampling sites. This study provides an accessible method for accurate and quick determination of key odorants in source water, aiding in odor control and improved water quality management. ENVIRONMENTAL IMPLICATION: Water odor episodes have been persistent and significant issues worldwide, posing severe challenges to water treatment plants. Unpleasant odors in aquatic environments are predominantly caused by the occurrence of a wide range of volatile organic chemicals (VOCs). Given the vast number of newly-detected VOCs, experimental identification of the key odorants becomes difficult, making water odor issues complex to control. Herein, we propose a novel approach integrating nontarget analysis with machine learning models to accurate and quick determine the key odorants in waterbodies. We use the approach to analyze four samples with odor issues in Changsha, and prioritized the potential odorants.

Co single atom coupled oxygen vacancy on W18O49 nanowires surface to construct asymmetric active site enhanced peroxymonosulfate activation.

Enhancing the activation of peroxymonosulfate (PMS) is essential for generating more reactive oxygen species in advanced oxidation process (AOPs). Nevertheless, improving PMS adsorption and expediting interfacial electron transfer to enhance reaction kinetics pose significant challenges. Herein, we construct confined W18O49 nanowires with asymmetric active centers containing Co-Vo-W (Vo: oxygen vacancy). The design incorporates surface-rich Vo and single-atom Co, and the resulting material is employed for PMS activation in water purification. By coupling unsaturated coordinated electrons in Vo with low-valence Co single atoms to construct an the "electron fountainhead", the adsorption and activation of PMS are enhanced. This results in the generation of more active free radicals (SO4•-, •OH, •O2-) and non-free radicals (1O2) for the decomposition of micropollutants. Thereinto, the degradation rate of bisphenol A (BPA) by Co-W18O49 is 32.6 times faster that of W18O49 monomer, which is also much higher than those of other transition-metal-doped W18O49 composites. This work is expected to help to elucidate the rational design and efficient PMS activation of catalysts with asymmetric active centers.

Association of serum 25-hydroxyvitamin d concentrations with all-cause and cause-specific mortality among individuals with depression: A cohort study.

BACKGROUND: Limited evidence exists on the relationship between vitamin D status and mortality in depressed patients. METHODS: This study investigates serum 25-hydroxyvitamin D [25(OH)D] concentrations in 8417 adults with depression among the National Health and Nutrition Examination Survey (NHANES, 2005-2018). Mortality outcomes were assessed through National Death Index records up to December 31, 2019. Cox proportional risk models estimated risk ratios (HR) and 95 % confidence intervals (CI) for all-cause, cardiovascular disease (CVD), and cancer mortality. Restricted cubic spline analyses explored the nonlinear association of serum 25(OH)D levels with mortality, using the likelihood ratio test for nonlinearity. RESULTS: The weighted mean serum 25(OH)D level was 66.40 nmol/L (95 % CI: 65.8, 67.0), with 36.3 % having deficient vitamin D (<50 nmol/L [20 ng/mL]). Over an average 7.16-year follow-up, 935 deaths were documented, including 296 CVD deaths and 191 cancer deaths. Higher serum 25(OH)D levels were associated with reduced all-cause mortality (HRs 0.55-1.00, p trend = 0.006) and cancer-specific mortality (HRs 0.36-1.00, p trend = 0.015) after multivariate adjustment. The relationship between serum 25(OH)D and all-cause mortality exhibited a nonlinear pattern (P for nonlinearity <0.001), with a 34 % lower risk for each unit increase in natural log-transformed 25(OH)D levels. Significant interactions were observed with age, antidepressant use, and diabetes status. CONCLUSIONS: Higher serum 25(OH)D levels were associated with decreased all-cause and cancer-specific mortality in depressed adults, particularly among younger individuals and those using antidepressants or without diabetes. Further research is essential to understand mechanisms and interventions related to vitamin D in depression.

Molecularly Imprinted Heterostructure-Based Electrochemosensor for Ultratrace and Precise Detection of 2-Methylisoborneol in Water.

Ultratrace 2-methylisoborneol (2-MIB, ∼ng/L) in source water is the main odorant in the algae-derived odor episodes, whose accurate on-site detection will have a promising application potential. Due to the chemical inertness of 2-MIB, sensitive and selective detection of 2-MIB remains much challenging. Herein, molecularly imprinted polymer cavities were polymerized on the heterostructure Ti3C2Tx@CuFc-metal-organic framework to selectively capture 2-MIB, where the heterostructure could catalyze the probe redox reaction of [Fe(CN)63-/4-] and amplify the corresponding current signals. The prepared electrochemical sensor showed higher sensitivity on 2-MIB detection than the reported ones. Excellent stability, reusability, and selectivity for 2-MIB detection were also verified. The linear range and limit of detection of our sensor for 2-MIB were optimized to 0.0001-100 µg/L and 30 pg/L, respectively, performing much better than the reported sensors. Comparable performance to gas chromatography-mass spectrometry was achieved when the sensor was applied to real water samples with or without 2-MIB standards. Overall, our research has made great progress in the application of an on-site sensor in 2-MIB detection and well advances the development of molecularly imprinted polymer-based electrochemical sensors.

Removal of Microcystis aeruginosa by manganese activated sodium percarbonate: Performance and role of the in-situ formed MnO2.

Previous studies have found that pre-oxidation of manganese salts such as potassium permanganate and potassium manganate can remove algae in water, while existing problems such as excessive oxidation and appearance of chromaticity. In this study, our objective was to induce a Fenton-like reaction by activating sodium percarbonate (SPC) with divalent manganese (Mn(II)) to pre-oxidize algae-contaminated water. The optimal dosage of Mn(II)/SPC was determined by assessing the zeta potential of the algae and the residual Mn(II) in the solution. Moreover, we conducted a characterization of the cells post-reaction and assessed the levels of dissolved organic carbon (DOC). The disinfection by-products (DBPs) (sodium hypochlorite disinfection)of the algae-containing water subsequent to Mn(II)/SPC treatment were measured. Experiments show that Mn(II)/SPC pre-oxidation at optimal dosage acquired 88% removal of algae and less damage to the cell membrane. Moreover, the Mn(II) acted not only as a catalyst but also formed MnO2 which adsorbed onto the cell surface and facilitated sedimentation. Furthermore, this technology exhibits the capability to effectively manage algal organic matters present in water, thereby mitigating the formation of nitrogen-containing DBPs. These results highlight the potential of Mn(II)/SPC treatment for treating water contaminated with algae, thus ensuring the safety and quality of water resources.

Facile synthesis of Ag/ZIF-8@ZIF-67 as an electrochemical sensing platform for sensitive detection of halonitrophenols in drinking water.

Halonitrophenols (HNPs) are an emerging type of aromatic disinfection byproduct, with detected concentrations of ∼nmol L-1 in source water and drinking water. Currently, there are no standard methods for identifying HNPs, and most of the reported methods are time-consuming and equipment-dependent. A core-shell metal-organic framework (MOF) based electrochemical sensor (Ag/ZIF-8@ZIF-67) capable of detecting 2,6-dichloro-4-nitrophenol (2,6-DCNP) is reported in this study. The electrochemical sensor obtains the concentration of 2,6-DCNP by detecting the peak current passing through the sensor. In this sensor, Ag nanoparticles (AgNPs) play a key role in electrochemical sensing by reducing nitro groups via electron transfer, and porous structure with a large surface area is offered by ZIF-8@ZIF-67. The cyclic voltammetry (CV) response of Ag/ZIF-8@ZIF-67 was found to be approximately 1.75 times and 2.23 times greater than that of Ag/ZIF-8 and Ag/ZIF-67, respectively, suggesting an ideal synergistic effect of the core-shell structures. The Ag/ZIF-8@ZIF-67 sensor exhibited exceptional sensitivity to 2,6-DCNP, exhibiting a broad linear response range (R2 = 0.992) from 240 nmol L-1 to 288 µmol L-1 and a low detection limit of 20 nmol L-1. Furthermore, the sensor exhibited good anti-interference for isomers and common distractors in water, excellent stability and reproducibility, and high recovery in actual water samples. Our reported sensor gives a novel strategy for sensitive, selective, and in situ detection of 2,6-DCNP in practical analysis.

Insights into the fate and properties of organic halamines during ultraviolet irradiation: Implications for drinking water safety.

Organic halamines compounds present a significant threat to the safety of drinking water due to their potential toxicity and stability. While Ultraviolet (UV) disinfection is commonly used for water treatment, its specific effects on organic halamines and the underlying mechanisms remain poorly understood. In this study, we investigated eight amino acid-derived organic chlor- and bromamines as representative compounds. Our findings revealed that organic halamines have a slow hydrolysis rate (<10-3 M-1 s-1) and can persist in water for extended periods (30-2000 min). However, their disinfection efficacy against Staphylococcus aureus and their ability to degrade micropollutants like carbamazepine were found to be limited. Interestingly, under UV irradiation, the N-X bonds in organic halamines were observed to break, leading to accelerated decomposition and the generation of abundant free radicals. These free radicals synergistically facilitated the removal of micropollutants and the inactivation of pathogenic microorganisms. It is worth noting that this transformation of organic halamines during UV disinfection resulted in a slight increase in the concentrations of nitrogenous disinfection byproducts. These findings shed light on the behavior and characteristics of organic halamines during UV disinfection processes, providing crucial insights for effectively managing drinking water quality impacted by these compounds. By understanding the implications of organic halamines, we can refine water treatment strategies and ensure the safety of drinking water supplies.

Pre-oxidation coupled with charged covalent organic framework membranes for highly efficient removal of organic chloramines precursors in algae-containing water treatment.

Organic chloramines in water would pose both chemical and microbiological risks. It is essential to remove the precursors of organic chloramine (amino acids and decomposed peptides/proteins) to limit its formation in disinfection. In our work, nanofiltration was chosen to remove organic chloramines precursors. To solve the "trade-off" effect and low rejection of small molecules in algae organic matter, we synthesized a thin film composite (TFC) nanofiltration (NF) membrane with a crumpled polyamide (PA) layer via interfacial polymerization on polyacrylonitrile (PAN) composite support loaded with covalent organic framework (COF) nanoparticles (TpPa-SO3H). The obtained NF membrane (PA-TpPa-SO3H/PAN) increased the permeance from 10.2 to 28.2 L m-2 h-1 bar-1 and the amino acid rejection from 24% to 69% compared to the control NF membrane. The addition of TpPa-SO3H nanoparticles decreased the thickness of PA layers, increased the hydrophilicity of the membrane, and increased the transition energy barrier for amino acids transferring through the membrane, which was identified by scanning electron microscope, contact angle test, and density functional theory computations, respectively. Finally, pre-oxidation coupled with PA-TpPa-SO3H/PAN membrane nanofiltration on the limitation of organic chloramines formation was evaluated. We found that the combined application of KMnO4 pre-oxidation and PA-TpPa-SO3H/PAN membranes nanofiltration in algae-containing water treatment could minimize the formation of organic chloramines in subsequent chlorination and maintain a high flux during filtration. Our work provides an effective way for algae-containing water treatment and organic chloramines control.

Development and validation of a novel M1 macrophage-related gene prognostic signature for lung cancer.

Background: Lung cancer (LC) is the most common cancer. Using data from The Cancer Genome Atlas (TCGA), we analyzed the functional roles of M1 macrophage status in LC patients. Methods: Clinical and transcriptome data of LC patients were obtained from the TCGA dataset. We identified M1 macrophage-related genes in LC patients and investigated the underlying molecular mechanisms of these genes in LC patients. After performing a least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the LC patients were divided into two subtypes, and the underlying mechanism of the association between them was further explored. A comparison of immune infiltration was conducted between the two subtypes. Based on gene set enrichment analysis (GSEA), the key regulators associated with subtypes were further explored. Results: M1 macrophage-related genes were identified using TCGA data, and these genes might be related to the activation of the immune response and cytokine-mediated signaling pathways in LC. A seven M1 macrophage-related gene signature (including STAT1, TAP1, UBE2L6, TAP2, CXCR6, PSMB8 and CD2) was identified in LC using LASSO Cox regression analysis. Two subtypes (low risk and high risk) of LC patients were created based on the seven M1 macrophage-related gene signature. Univariate and multivariate survival analyses further confirmed that the subtype classification was an effective independent prognostic factor. Moreover, the two subtypes were correlated with immune infiltration, and GSEA revealed that the pathways of tumor cell proliferation and immune-related biological processes (BPs) might play an important role in LC in the high-risk group and low-risk group, respectively. Conclusions: M1 macrophage-related subtypes of LC were identified and were closely associated with immune infiltration. The gene signature involved in M1 macrophage-related genes could help make a distinction and predict prognosis for LC patients.

Relationship between depressive disorders and biochemical indicators in adult men and women.

BACKGROUND: Depression is a psychiatric disorder with global public health concerns. Although a number of risk factors have been identified for depression, there is no clear relationship between biochemistry and depression. In this study, we assessed whether depressive disorders are significantly associated with biochemical indicators. METHODS: Our study included 17,561 adults (age ≥ 18 years) participating in the 2009-2018 National Health and Nutrition Examination Survey (NHANES). The relationship between depression and biochemical and obesity indicators was analyzed by logistic regression. RESULTS: As compared to the control group, men with depression showed significantly higher levels of gamma-glutamyl transferase, glucose, and triglycerides, and lower levels of albumin and total bilirubin. The depressed group had higher levels of alkaline phosphatase, bicarbonate, and sodium than the control group. CONCLUSION: Several biochemical and anthropometric indices were associated with depression in this study. It would be interesting to further analyze their cause-effect relationship. LIMITATIONS: This study is a cross-sectional study. The population is less restricted and does not exclude people with diabetes, pregnancy, etc., so it is less significant for a specific population. Dietary information was not included, as diet plays an important role in many indicators.

Vitexin Regulates Angiogenesis and Osteogenesis in Ovariectomy-Induced Osteoporosis of Rats via the VDR/PI3K/AKT/eNOS Signaling Pathway.

It is extremely important to promote angiogenesis-dependent osteogenesis and ameliorate bone loss for the prevention and treatment of osteoporosis (OP) development. Vitexin, as one of the major active components in pigeonpea leave, promoted the proliferation of osteoblast and HUVECs in hypoxia. The present study aimed to investigate the effect of vitexin on alleviating osteoporosis in ovariectomized (OVX) rats and further explore its underlying mechanisms. Herein, the OVX rat model was established and treated with vitexin (10 mg kg-1) for 3 months. After being sacrificed, we performed hematoxylin-eosin (H&E) staining and micro-computed tomography (micro-CT) to assess bone mass, which found that trabecular bone was damaged in the OVX rat model. Vitexin could repair bone injury and promote osteoblast biochemical indicators and angiogenesis indicators. Furthermore, EAhy926 cells were used to further explore the effect of vitexin on improving hypoxia-induced endothelial injury in vitro. Vitexin had a protective effect on hypoxia-treated EAhy926 cells and up-regulated vitamin D receptor (VDR) signaling and promoted phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and endothelial NO synthase (eNOS), which enhanced endothelial cell migration and tube formation. VDR small-interfering RNA (siRNA) transfection significantly decreased both VDR and p-eNOS proteins, and VDR siRNA transfection + vitexin could not further increase VDR and downstream proteins. Overall, this study presented that vitexin regulates angiogenesis and osteogenesis in ovariectomy-induced osteoporosis of rats via the VDR/eNOS signaling pathway.

Insight into the mechanisms of trichloronitromethane formation by vacuum ultraviolet: QSAR model and FTICR-MS analysis.

Vacuum ultraviolet (VUV) photolysis is recognized as an environmental-friendly treatment process. Nitrate (NO3-) and natural organic matter (NOM) are widely present in water source. We investigated trichloronitromethane (TCNM) formation during chlorination after VUV photolysis, because TCNM is an unregulated highly toxic disinfection byproduct. In this study: (1) we found reactive nitrogen species that is generated under VUV photolysis of NO3- react with organic matter to form nitrogen-containing compounds and subsequently form TCNM during chlorination; (2) we found the mere presence of 0.1 mmol/L NO3- can result in the formation of up to 63.96 µg/L TCNM; (3) we found the changes in pH (6.0-8.0), chloride (1-4 mmol/L), and bicarbonate (1-4 mmol/L) cannot effectively diminish TCNM formation; and, (4) we established the quantitative structure-activity relationship (QSAR) model, which indicated a linear relationship between TCNM formation and the Hammett constant (σ) of model compounds; and, (5) we characterized TCNM precursors in water matrix after VUV photolysis and found 1161 much more nitrogen-containing compounds with higher aromaticity were generated. Overall, this study indicates more attention should be paid to reducing the formation risk of TCNM when applying VUV photolysis process at scale.

Transfer organic chloramines to monochloramine using two-step chlorination: A method to inhibit N-DBPs formation in algae-containing water treatment.

Organic chloramines formed in chlorination of algae-containing water are typical precursors of nitrogenous disinfection byproducts (N-DPBs). The objective to simultaneously enhance the removal efficiency of organic chloramines and control DBP formation remains a challenge. In this study, we report a two-step chlorination strategy for transferring organic chloramines to monochloramine based on the decomposition mechanisms of mono- and di-organic chloramines, which could limit organic chloramines formation and inhibit N-DBPs formation. We demonstrated that two-step chlorination could decrease the organic chloramines formation by nearly 50% than conventional one-step chlorination. Furthermore, two-step chlorination not only blocked the pathway that organic chloramines decomposed to nitriles, but also led to the conversion of organic chloramines to monochloramine. During two-step chlorination of algal organic matter, the organic chloramine transfer proportion decreased by 6.5% and the monochloramine transfer proportion increased by 17.0%. The N-DBP formation, especially haloacetonitriles (HANs), decreased significantly as organic nitrogen became inorganic nitrogen (monochloramine) in two-step chlorination. This work further clarified the process from algal organic matter to N-DBPs, which could expand our understanding of algae-derived organic chloramines removal and DBPs control.

Associations between urea nitrogen and risk of depression among subjects with and without type 2 diabetes: A nationwide population-based study.

Background: Depression and type 2 diabetes (T2D) are serious public health problems with irreversible health consequences and a significant economic burden on the healthcare system. Previous studies have suggested that blood urea nitrogen (BUN) was inversely longitudinally associated with incidence of diabetes and depression in adults, but few well-designed studies have examined the effects of status of T2D on the full range of relationship between BUN and depression. Methods: The analysis sample consisted of adults aged≥20 years from the 2007-2014 National Health and Nutrition Examination Survey (NHANES) who completed the Patient Health Questionnaire-9 (PHQ-9), involving 19,005 participants. By stratifying participants according to T2D status, we further assessed the difference between BUN and risk of depression in participants with and without T2D using multivariate logistic regression (interaction test). Results: In this cross-sectional study, the association between BUN and depression prevalence appeared to differ between the T2D and non-T2D groups (OR: 1.00, 95% Cl: 0.95-1.05 vs. OR: 0.89, 95% Cl: 0.85-0.93). In addition, there was evidence of an interaction between BUN levels and T2D status in reducing the risk of depression (P value for interaction = 0.032.) The relationship between BUN and depressive symptoms was significant in non-T2D subjects (P < 0.001), but not in T2D (P = 0.940). Conclusions: Our findings suggest that there is a significant relationship between BUN and depression, and T2D status may influence the association between BUN and the risk of depression. Such findings require further prospective studies to provide more evidence.

Association Between Dietary Fiber Intake and Risk of Depression in Patients With or Without Type 2 Diabetes.

Background: Depression and type 2 diabetes (T2D) are both serious public health problems, with morbidity and mortality in people increasing year by year, resulting in a heavy economic burden. A correlation between dietary fiber and both has been reported. Nevertheless, few data are available concerning dietary fiber and the risk of depression with or without T2D, which deserve further attention. Materials and Methods: We assessed the relationship between dietary fiber intake and risk of depression with or without T2D in the 2007-2014 National Health and Nutrition Examination Survey (NHANES) population. A 24-h dietary review was used to assess fiber intake. The Patient Health Questionnaire-9 was used to assess depression. Stability of the results was assessed using restricted cubic spline models and logistic regression, as well as sensitivity analyses. Results: A total of 17,866 adults aged 20 years and older with a mean age of 49.3 ± 17.7 years were included in this study, of whom 49.5% were male. After adjusting for covariates, the association of dietary fiber intake with the risk of depression appeared to differ between non-T2D group and T2D group (OR, 0.987; 95% CI, 0.979-0.995 vs. OR, 1.003; 95% CI, 0.988-1.017). Furthermore, when dietary fiber was converted to a categorical variable, there was evidence of interaction between T2D status and fiber intake on decreasing the prevalence of depression (P-value for interaction = 0.015). Sensitivity analysis showed stable results. Conclusion: Our findings indicated that whether a patient has T2D may affect the relationship between dietary fiber intake and the risk of depression, which still needs to be confirmed by further randomized controlled trials.

Application of the clearance rate of inflammatory markers for evaluation of the therapeutic effect in adult bacterial bloodstream infection.

BACKGROUND: Bloodstream infection (BSI) is a serious systemic infectious disease. This study aimed to investigate the application of the clearance rate of interleukin-6, procalcitonin, and C-reactive protein for the evaluation of antimicrobial efficacy in adult bacterial BSI without other inflammatory factors. METHODS: Patients with positive blood culture and without other inflammatory factors in The First Hospital of Hebei Medical University from January 2017 to December 2019, who received continuous detection interleukin-6, procalcitonin, and C-reactive protein, were selected. The clearance rate of these inflammatory markers was calculated, and the consistency test (kappa test) was performed to analyze the clinical outcomes (cure, improvement, delay, deterioration, or death). RESULTS: For adult patients with bacterial BSI without other inflammatory factors, the testing speculation based on the clearance rate of interleukin-6 and C-reactive protein was consistent with the clinical outcome of the patients, with kappa values of 0.784 and 0.714, respectively (P=0.000). The testing speculation based on the procalcitonin clearance rate was generally consistent with the clinical outcome, with a kappa value of 0.685 (P=0.000). The testing speculation based on the procalcitonin clearance rate showed good consistency with the clinical outcome of patients with Gram-positive cocci infection, kappa =0.813 (P=0.000); for patients with gram-negative bacilli infection, the consistency of clinical outcomes was general, kappa =0.649 (P=0.000). CONCLUSIONS: In adult patients with bacterial BSI without other inflammatory factors, the clearance rate of interleukin-6, procalcitonin, and C-reactive protein can predict the clinical outcome within 24 hours, among which the procalcitonin clearance rate can better predict the clinical outcome of patients with Gram-negative bacilli infection. This approach can be used to evaluate the effectiveness of anti-infection treatment in early-stage BSI.

High-fat diet and alcohol induced-mice could cause colonic injury through molecular mechanisms of endogenous toxins.

Due to the complexity and diverse causes, the pathological mechanism of diet-induced colonic injury and colitis remains unclear. In this study, we studied the effects of the combination of a high-fat diet (HFD) plus alcohol on colonic injury in mice. We found HFD plus alcohol treatment induced disturbance of the gut microbiota; increased the production of intestinal toxins lipopolysaccharide (LPS), indole, and skatole; destroyed the stability of the intestinal mucosa; and caused the colonic epithelial cells damage through the activation of nuclear factor (NF)-κB and aromatic hydrocarbon receptors (AhR) signaling pathways. To mimic the effect of HFD plus alcohol in vivo, NCM460 cells were stimulated with alcohol and oleic acid with/without intestinal toxins (LPS, indole, and skatole) in vitro. Combinative treatment of alcohol and oleic acid caused moderate damage on NCM460 cells, while combination with intestinal toxins induced serious cell apoptosis. Western blot data indicated that the activation of NF-κB and AhR pathways further augmented after intestinal toxins treatment in alcohol- and oleic acid-treated colonic cells. This study provided new evidence for the relationship between diet pattern and colonic inflammation, which might partly reveal the pathological development of diet-induced colon disease and the involvement of intestinal toxins.

Gingerenone A Alleviates Ferroptosis in Secondary Liver Injury in Colitis Mice via Activating Nrf2-Gpx4 Signaling Pathway.

Patients with ulcerative colitis (UC) have been found to be frequently associated with secondary liver injury (SLI). In this study, we investigated the protective effect of GA on dextran sodium sulfate (DSS)-induced SLI in mice and its mechanism. The SLI was established by adding 4% DSS in the drinking water of mice, and the effects of GA (5, 20 mg/kg, p.o., once a day for 7 days) in hepatic tissues were analyzed. HepG2 cells were induced by lipopolysaccharide (LPS) to detect the effect of GA on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), and the level of Fe2+ in the liver were detected by kits. Cytokine levels (TNF-α, IL-1ß, and IL-6) and Gpx4 activity in the liver were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism. The results indicated that GA significantly attenuated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels and increased the antioxidant enzyme activities. Moreover, GA attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that GA activated Nrf2 in mice. Taken together, this study demonstrates that GA can alleviate ferroptosis in SLI in DSS-induced colitis mice, and its protective effects are associated with activating the Nrf2-Gpx4 signaling pathway.

Reactive Hemophagocytic Lymphohistiocytosis Secondary to Ovarian Adenocarcinoma: A Rare Case Report.

Background: Hemophagocytic lymphohistiocytosis (HLH), a syndrome of immune hyperactivation and abnormal regulation that causes life-threatening inflammation, is mainly characterized by fever, hepatosplenomegaly, cytopenia, and other symptoms. Reactive HLH (rHLH) is typically secondary to immune deregulation caused by underlying rheumatologic, infectious, or malignant conditions. Malignancy-associated HLH (M-HLH) continues to be a critical health problem worldwide. Most malignancies associated with HLH are hematologic tumors, and M-HLH in non-hematologic tumors very rarely occurs. Case Report: A 34-year-old Chinese woman had a history of persistent fever, acute dizziness, and bicytopenia. She was found to have developed bilateral ovarian cancer. Additional tests showed splenomegaly, hemophagocytes in the bone marrow, low natural killer activity, and hyperferritinemia, which met the diagnostic criteria put forth in the Histiocyte Society HLH-2004. The patient was treated with correcting anemia, increased platelets, and glucocorticoid therapy but showed no response. She progressively deteriorated and died 55 days later. Conclusion: Hemophagocytic lymphohistiocytosis related to a solid tumor is extremely rare. To the best of the authors' knowledge, the present case was the first to report rHLH secondary to ovarian adenocarcinoma. It is very significant for a better understanding of the disease mechanisms of HLH and should attract the attention of hematologists and other clinicians as the condition progresses and the cost of treating it increases.

Characteristics of non-stenotic carotid plaque in embolic stroke of undetermined source compared with cardiogenic embolism: a retrospective cross-sectional observational study.

BACKGROUND: Non-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS. METHODS: This is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People's Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS. RESULTS: We had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45-12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55-16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727-0.896; p < 0.001). CONCLUSION: Our results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.