Molecular transformation of dissolved organic matter in manganese ore-mediated constructed wetlands for fresh leachate treatment.

The organic matter (OM) and nitrogen in Fresh leachate (FL) from waste compression sites pose environmental and health risks. Even though the constructed wetland (CW) can efficiently remove these pollutants, the molecular-level transformations of dissolved OM (DOM) in FL remain uncertain. This study reports the molecular dynamics of DOM and nitrogen removal during FL treatment in CWs. Two lab-scale vertical-flow CW systems were employed: one using only sand as substrates (act as a control, CW-C) and the other employing an equal mixture of manganese ore powder and sand (experimental, CW-M). Over 488 days of operation, CW-M exhibited significantly higher removal rates for chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and dissolved organic matter (represented by dissolved organic carbon, DOC) at 98.2 ± 2.5%, 99.2 ± 1.4%, and 97.9 ± 1.9%, respectively, in contrast to CW-C (92.8 ± 6.8%, 77.1 ± 28.1%, and 74.7 ± 9.5%). The three-dimensional fluorescence excitation-emission matrix (3D-EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses unveiled that the influent DOM was predominantly composed of readily biodegradable protein-like substances with high carbon content and low unsaturation. Throughout treatment, it led to the degradation of low O/C and high H/C compounds, resulting in the formation of DOM with higher unsaturation and aromaticity, resembling humic-like substances. CW-M showcased a distinct DOM composition, characterized by lower carbon content yet higher unsaturation and aromaticity than CW-C. The study also identified the presence of Gammaproteobacteria, reported as Mn-oxidizing bacteria with significantly higher abundance in the upper and middle layers of CW-M, facilitating manganese cycling and improving DOM removal. Key pathways contributing to DOM removal encompassed adsorption, catalytic oxidation by manganese oxides, and microbial degradation. This study offers novel insights into DOM transformation and removal from FL during CW treatment, which will facilitate better design and enhanced performance.

Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study.

Purpose: To explore the effect of AFN on knee function and complications in patients after TKA. Methods: We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results: Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson's correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC (r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS (r = -0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS (ß = 5.974, 95% CI: 3.968-7.981, P < 0.001) and ΔWOMAC (ß = 6.356, 95% CI: 4.223-8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain (ß = 5.974, 95% CI: 3.968-7.981, P < 0.05). Conclusion: Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

GPR39 Agonist TC-G 1008 Promoted Mitochondrial Biogenesis and Improved Antioxidative Capability via CREB/PGC-1α Pathway Following Intracerebral Hemorrhage in Mice.

Mitochondrial dysfunction and excessive reactive oxygen species production due to impaired mitochondrial biogenesis have been proven to exacerbate secondary brain injury after intracerebral hemorrhage (ICH). The G-protein-coupled receptor 39 (GPR39) agonist TC-G 1008 has been shown to exert anti-oxidative stress effect in acute hypoxic brain injury. Herein, our study aimed to investigate the potential effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress in a mouse model of ICH and explore the underlying mechanisms. A total of 335 male C57/BL6 mice were used to establish an autologous blood-induced ICH model. Three different dosages of TC-G 1008 were administered via oral gavage at 1 h, 25 h, and 49 h post-ICH. The GPR39 siRNA and cAMP response element-binding protein (CREB) inhibitor 666-15 were administered via intracerebroventricular injection before ICH insult to explore the underlying mechanisms. Neurobehavioral function tests, Western blot, quantitative polymerase chain reaction, immunofluorescence staining, Fluoro-Jade C staining, TUNEL staining, dihydroethidium staining, transmission electron microscopy, and enzyme-linked immunosorbent assay were performed. Expression of endogenous GPR39 gradually increased in a time-dependent manner in the peri-hematoma tissues, peaking between 24 and 72 h after ICH. Treatment with TC-G 1008 significantly attenuated brain edema, hematoma size, neuronal degeneration, and neuronal death, as well as improved neurobehavioral deficits at 72 h after ICH. Moreover, TC-G 1008 upregulated the expression of mitochondrial biogenesis-related molecules, including PGC-1α, NRF1, TFAM, and mitochondrial DNA copy number, associated with antioxidative stress markers, such as Nrf2, HO-1, NQO1, SOD, CAT, and GSH-Px. Furthermore, treatment with TC-G 1008 preserved neuronal mitochondrial function and structure post-ICH. Mechanistically, the protective effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress were partially reversed by GPR39 siRNA or 666 -15. Our findings indicated that GPR39 agonist TC-G 1008 promoted mitochondrial biogenesis and improved antioxidative capability after ICH, partly through the CREB/PGC-1α signaling pathway. TC-G 1008 may be a potential therapeutic agent for patients with ICH.

Pseudostellaria heterophylla improves intestinal microecology through modulating gut microbiota and metabolites in mice.

BACKGROUND: Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. RESULTS: The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. CONCLUSION: We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

Extending the Cycle Lifetime of Solid-State Zinc-Air Batteries by Arranging Stable Zinc Species Channels.

The solid-state zinc-air batteries have attracted extensive attention due to their high theoretical energy density, high safety, and the compact structure. In this work, a novel hydrogel solid-state electrolyte was developed that was equipped with an interpenetrating network of zinc polyacrylate (PAZn) and polyacrylamide (PAM). At the same time, a cyclodextrin derivative with sulfonate groups was introduced as an additive. From the design of anionic groups in the network, effective and stable channels for zinc species have been established. The unique structure of the additives regulates the uniform deposition of zinc. After using this solid-state electrolyte, the cycle lifetime of solid-state zinc-air batteries assembled have been significantly extended. The byproducts were greatly suppressed and generated the smooth zinc electrode surface after the charge-discharge cycling.

Radical relay cyclization/C-C bond formation of allyloxy-tethered aryl iodides with quinoxalin-2(1H)-ones via polysulfide anion photocatalysis.

A visible-light-induced radical relay cyclization/C-C bond formation of quinoxalin-2(1H)-ones with allyloxy-tethered aryl iodides using polysulfide anions as a photocatalyst is described. This protocol allows efficient access to a variety of complicated molecules bearing both quinoxalin-2(1H)-one and 2,3-dihydrobenzofuran motifs in high yields under mild reaction conditions with a broad range of substrates.

A novel nomogram for prediction of intrahepatic recurrence-free survival in patients with HCC followed by radiofrequency ablation.

OBJECTIVE: Although radiofrequency ablation (RFA) has been considered as the favourable treatment option for hepatocellular carcinoma (HCC), there still exist some challenges for new recurrence after RFA. The present study aims to determine the factors affecting recurrence and develop an effective model to predict intrahepatic recurrence-free survival (RFS). METHODS: Patients with HCC followed by RFA between 2000 and 2021 were included in this study. Multivariable Cox regression analysis was used to determine the independent prognostic factors and establish the nomogram predicting intrahepatic RFS after RFA. The predictive performance of the nomogram was assessed according to the C-index, calibration plots, and Kaplan-Meier curves stratified by the tertiles. RESULTS: A total of 801 sessions in 660 patients (including 1155 lesions) were enrolled into this study. Intrahepatic new recurrence was observed in all patients during the follow-up, and the mean intrahepatic RFS was 21.9 months in the present cohort. According to multivariate COX regression analysis, five independent prognostic factors affecting intrahepatic RFS were determined, including age, Child-Pugh class, tumour distribution, number of tumours, and a-fetoprotein (AFP). Based on all independent prognostic factors, the nomogram model was developed and evaluated, which achieved favourable discrimination and calibration. CONCLUSION: This study established five independent prognostic factors and constructed a nomogram model to predict intrahepatic RFS for HCC patients followed by RFA. It could better help clinicians select RFA candidates, as well as offering the important information about whether patients need receive comprehensive treatment to prevent new recurrence after RFA. ADVANCES IN KNOWLEDGE: (1) In this study, 5 preoperative clinic-pathological variables were determined as the independent prognostic factors affecting RFS after RFA in the current largest sample size. (2) Based on these independent prognostic factors, a prognostic nomogram predicting RFS after RFA was established, which may be used to select patients who benefit from RFA and could help both surgeons and patients provide useful information for choosing the personalized treatment.

Hydrogen Sulfide and Functional Therapy: Novel Mechanisms from Epigenetics.

Hydrogen sulfide (H2S) is a gasotransmitter with significant physiological effects, including anti-inflammatory properties, regulation of oxidative stress, and vasodilation, thus regulating body functions. Functional therapy involves using treatments that target the underlying cause of a disease, rather than simply treating symptoms. Epigenetics refers to changes in gene expression that occur through modifications to DNA, to the proteins that package DNA, or to noncoding RNA mechanisms. Recent research advances suggest that H2S may play a role in epigenetic regulation by altering DNA methylation patterns and regulating histone deacetylases, enzymes that modify histone proteins, or modulating microRNA mechanisms. These critical findings suggest that H2S may be a promising molecule for functional therapy in various diseases where epigenetic modifications are dysregulated. We reviewed the relevant research progress in this area, hoping to provide new insights into the epigenetic mechanisms of H2S. Despite the challenges of clinical use of H2S, future research may lead to the progress of new therapeutic approaches. Antioxid. Redox Signal. 40, 110-121.

Using microalgae to reduce the use of conventional fertilizers in hydroponics and soil-based cultivation.

The intensive use of agrochemicals has led to nutrient loss, greenhouse gas emissions, and resource depletion, thus the development of sustainable agricultural solutions is required. Microalgal biomass has the potential to provide nutrients such as nitrogen, phosphorus, and potassium, along with various plant growth promoters, to enhance crop productivity and impart disease resistance. This study provides a comprehensive assessment of the potential applications of microalgal extracts and biomass in the contexts of seed germination, hydroponic systems, and soil-based crop cultivation. The results revealed that the extracts from Chlorella sp. and Anabaena sp. have no significant impact on the germination of wheat seeds. High concentrations of Chlorella sp. and Anabaena sp. cell extracts in hydroponics enhanced the length of cucumber seedling stems by 81.7 % and 58.3 %, respectively. Additionally, the use of microalgal cell extracts hindered root elongation while stimulating the growth of lateral and fibrous roots. Furthermore, the study compared the performance of 5 different fertilizers: 1) inorganic fertilizer (IF), 2) organic fertilizer (OF), 3) microalgae-based biofertilizer (MF), 4) inorganic fertilizer + microalgae-based biofertilizer (IM), 5) organic fertilizer + microalgae-based biofertilizer (OM). The findings indicate that the plant growth and soil physicochemical properties in the groups supplied with different fertilizers are comparable and significantly higher than those in the control group. The levels of protein, chlorophyll A, and chlorophyll B in the MF group increased significantly by 40 %, 29.2 %, and 33.5 %, respectively, compared to the control group. However, it remained notably lower compared to groups supplied with inorganic and organic fertilizers (p < 0.05). Combining microalgae with organic fertilizer can simultaneously enhance the yield and quality of Chinese cabbage, representing a promising source of crop nutrition. In conclusion, this study suggests that it is promising to use microalgae to reduce the use of conventional fertilizers in hydroponics and soil-based cultivation.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors.

OBJECTIVES: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). METHODS: Between March 2011 and November 2022, 34 patients (16 males; age range, 25-72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1-5.2) cm. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. RESULTS: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0-45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8-159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. CONCLUSIONS: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Apportioning Atmospheric Ammonia Sources across Spatial and Seasonal Scales by Their Isotopic Fingerprint.

Mitigating ammonia (NH3) emissions is a significant challenge, given its well-recognized role in the troposphere, contributing to secondary particle formation and impacting acid rain. The difficulty arises from the highly uncertain attribution of atmospheric NH3 to specific emission sources, especially when accounting for diverse environments and varying spatial and temporal scales. In this study, we established a refined δ15N fingerprint for eight emission sources, including three previously overlooked sources of potential importance. We applied this approach in a year-long case study conducted in urban and rural sites located only 40 km apart in the Shandong Peninsula, North China Plain. Our findings highlight that although atmospheric NH3 concentrations and seasonal trends exhibited similarities, their isotopic compositions revealed significant distinctions in the primary NH3 sources. In rural areas, although agriculture emerged as the dominant emission source (64.2 ± 19.5%), a previously underestimated household stove source also played a considerably greater role, particularly during cold seasons (36.5 ± 12.5%). In urban areas, industry and traffic (33.5 ± 15.6%) and, surprisingly, sewage treatment (27.7 ± 11.3%) associated with high population density were identified as the major contributors. Given the relatively short lifetime of atmospheric NH3, our findings highlight the significance of the isotope approach in offering a more comprehensive understanding of localized and seasonal influences of NH3 sources compared to emissions inventories. The refined isotopic fingerprint proves to be an effective tool in distinguishing source contributions across spatial and seasonal scales, thereby providing valuable insights for the development of emission mitigation policies aimed at addressing the increasing NH3 burden on the local atmosphere.

Astragalus polysaccharide restores insulin secretion impaired by lipopolysaccharides through the protein kinase B /mammalian target of rapamycin/glucose transporter 2 pathway.

BACKGROUND: Lipopolysaccharide (LPS)-induced dysfunction of pancreatic ß-cells leads to impaired insulin (INS) secretion. Astragalus polysaccharide (APS) is a bioactive heteropolysaccharide extracted from Astragalus membranaceus and is a popular Chinese herbal medicine. This study aimed to elucidate the mechanisms by which APS affects INS secretion from ß-cells under LPS stress. METHODS: Rat insulinoma (INS-1) cells were treated with LPS at a low, medium, or high concentration of APS. Glucose-stimulated insulin secretion (GSIS) was evaluated using an enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was used to assess genome-wide gene expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the signaling pathways affected by APS. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to evaluate the gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK), pancreatic duodenal homeobox-1 (PDX-1), and INS. Western blot analysis was used to detect the protein expression of phosphorylated protein kinase B (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), total mTOR (t-mTOR), and GLUT2. RESULTS: LPS decreased GLUT2, GCK, PDX-1, and INS expression and reduced GSIS. These LPS-induced decreases in gene expression and GSIS were restored by APS treatment. In addition, transcriptome sequencing in combination with KEGG enrichment analysis revealed changes in the INS signaling pathway following APS treatment. LPS decreased p-Akt and p-mTOR expression, which was restored by APS treatment. The restorative effects of APS on GSIS as well as on the expression of GLUT2, GCK, PDX-1, and INS were abolished by treatment with the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin (RPM). CONCLUSIONS: APS restored GSIS in LPS-stimulated pancreatic ß-cells by activating the Akt/mTOR/GLUT2 signaling pathway.

Electrophilic Halospirocyclization of N-Benzylacrylamides to Access 4-Halomethyl-2-azaspiro[4.5]decanes.

An electrophilic spirocyclization of N-benzylacrylamides with N-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize a wide variety of 4-halomethyl-2-azaspiro[4.5]decanes with satisfactory yields. The approach is further highlighted through gram-scale synthesis and diverse transformations of the spiro products.

Self-assembled electrochemically active biofilms doped with carbon nanotubes: Electron exchange efficiency and cytotoxicity evaluation.

Thick electrochemically active biofilms (EABs) will lead to insufficient extracellular electron transfer (EET) rate because of the limitation of both substrate diffusion and electron exchange. Herein, carbon nanotubes (CNTs)-doped EABs are developed through self-assembly. The highly conductive biofilms (internal resistance of ∼211 Ω) are efficiently enriched at CNTs dosage of 1 g L-1, with the stable power output of 0.568 W m-2 over three months. The embedded CNTs can act as electron tunnel to accelerate the EET rate in thick biofilm. Self-charging/discharging experiments and Nernst-Monod model stimulation demonstrate a higher net charge storage capacity (0.15 C m-2) and more negative half-saturation potential (-0.401 V) for the hybrid biofilms than that of the control (0.09 C m-2, and -0.378 V). Enzyme activity tests and the observation of confocal laser scanning microscopy by live/dead staining show a nearly negligible cytotoxicity of CNTs, and non-targeted metabonomics analysis reveals fourteen differential metabolites that do not play key roles in microbial central metabolic pathways according to KEGG compound database. The abundance of typical exoelectrogens Geobacter sp. is 2-fold of the control, resulting in a better bioelectrocatalytic activity. These finding provide a possible approach to prolong electron exchange and power output by developing a hybrid EABs doped with conductive material.

An evaluation of 20-year survival of radiofrequency ablation for hepatocellular carcinoma as first-line treatment.

OBJECTIVES: To evaluate the changes in clinical characteristics, overall survival (OS), and progression-free survival (PFS) by investigating a 20-year cohort of patients with HCC who underwent RFA treatment. METHODS: From 2000 to 2020, 505 consecutive patients with HCC underwent ultrasound-guided percutaneous RFA as first-line therapy at a tertiary cancer hospital. We divided the cohort according to the time when hepatitis-B antiviral therapy was covered by national medical insurance coverage (early 2011), including the first decade (2000-2010) and second decade (2011-2020). The prognostic factors for OS were analyzed by the Cox proportional hazard model. OS and PFS in different groups were compared using the Kaplan-Meier method. To reduce selection bias, matched groups of patients were selected using the propensity score matching (PSM) method. RESULTS: In total, 726 RFA sessions were performed to treat 867 HCC lesions. Patients treated in the second decade were younger (p =.047), had smaller tumors (p <.001), had lower Child-Pugh scores (p <.001), and had a higher proportion of antiviral treatment (p <.001). A total of 96.0% of patients achieved technical efficacy from the initial RFA. After PSM analysis, improved PFS was found for the second decade (median, 68 vs. 49 months, p =.003), but no significant difference in OS was observed between the two groups (median, 71 vs. 65 months, p =.20). CONCLUSIONS: This study demonstrated that improved PFS was achieved in patients with HCC receiving RFA as first-line treatment in the second decade. However, long-term OS was not significantly increased compared to the first decade suggesting that while RFA treatment has improved, it still might not substantially affect OS results.

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

Background: Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets. Method and results: we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltration of M2 macrophages and neutrophils was associated with poor prognosis. Next, we identified NR4A1 as a potential therapeutic target based on its protective effect in two predict models. Using cancer therapeutics response analysis, we found that high expression levels of NR4A1 were sensitive to OSI-930, a tyrosine kinase inhibitor with anti-tumor effects. Conclusion: Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach.

Noncausal effects between tea intake and migraine risk: a Mendelian randomization study.

Observational studies have yielded conflicting results regarding the relationship between tea intake and migraine risk. Residual confounders and potential reverse causality are unavoidable in traditional observational studies. To provide evidence for establishing viable disease screening and prevention strategies, a Mendelian randomization study (MR) was conducted to determine the causal inference between tea intake and migraine. We obtained 28 single-nucleotide polymorphisms (SNPs) for any migraine (AM), 25 SNPs for migraine with aura (MA), and 27 SNPs for migraine without aura (MO) associated with tea intake derived from a large genome-wide association study (GWAS) of the UK Biobank (UKBB) (containing 447,485 samples). The largest migraine GWAS performed by the International Headache Genetics Consortium (IHGC), including 29,209 cases and 172,931 controls, provided data on migraines and their subtypes (MA and MO). We used the method of inverse variance weighting (IVW) with fixed effects as the first-string MR selection. Sensitivity analysis and MR-pleiotropy residual sum and outlier (MR-PRESSO) method further assessed the robustness of the findings. Based on the conclusion of IVW in the fixed effects model, we found that tea intake had no causal relationship with AM risk (odds ratio (OR), 0.94; 95% confidence interval (CI), 0.70-1.25; P = 0.65), MA risk (OR, 0.93; 95% CI, 0.51-1.72; P = 0.83), or MO risk (OR, 0.90; 95% CI, 0.52-1.54; P = 0.69). Sensitivity analyses and MR-PRESSO showed no directional pleiotropy or heterogeneity. Our two-sample MR investigation found no causality between tea intake and migraine risk in European populations, implying that attempts to change tea drinking habits may not lead to a reduced risk of migraine.