Comprehensive metabolic profiling of dioxin-like compounds exposure in laying hens: Implications for toxicity assessment.

The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress of experimental models based on disease pathogenesis.

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction. To date, no effective treatment exists as the exact causative mechanism remains unknown. Therefore, experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets. Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4, which is highly expressed on the membrane of astrocyte endfeet, most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes. These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders, such as aquaporin-4 loss, astrocytopathy, granulocyte and macrophage infiltration, complement activation, demyelination, and neuronal loss; however, they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders. In this review, we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro, ex vivo, and in vivo for neuromyelitis optica spectrum disorders, suggest potential pathogenic mechanisms for further investigation, and provide guidance on experimental model choices. In addition, this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders, offering further therapeutic targets and a theoretical basis for clinical trials.

Atropisomerism Observed in Galactose-Based Monosaccharide Inhibitors of Galectin-3 Comprising 2-Methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione.

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (compound 20) and 4-phenyl-4H-1,2,4-triazole (compound 15). Notably, hindered rotation caused by steric interaction between the 3-thione and ortho-trifluoromethyl group of compounds 20, 21 induced formation of thermodynamically stable atropisomers. Distinct X-ray cocrystal structures of 20 and 21 were obtained, which clearly demonstrated that the configuration of 21 proscribes a key halogen bonding σ-hole interaction of 3-chloro with carbonyl oxygen of Gly182, thereby leading to significant loss in potency. Ultimately, 20 and 15 were evaluated in mouse pharmacokinetic studies, and both compounds exhibited oral exposures suitable for further in vivo assessment.

Ultrathin Gd-Oxide Nanosheet as Ultrasensitive Companion Diagnostic Tool for MR Imaging and Therapy of Submillimeter Microhepatocellular Carcinoma.

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.

Heterogeneous Organohydrogel Toward Automated and Interference-Free Gradient Feeding of Drugs in Cell Screening.

Cell-based microarrays are widely used in the fields of drug discovery and toxicology. Precise gradient generation and automated drug feeding are essential for high-throughput screening of live cells in tiny droplets. However, most existing technologies either require sophisticated robotic equipment or cause mechanical/physiological interference with cells. Here, a heterogeneous organohydrogel is presented for automated gradient drug feeding, while ensuring minimal interference with cells. The heterogeneous organohydrogel comprises three crucial components. The bottom surface can automatically generate gradients functioning as a gradient generator, the organohydrogel bulk allows unidirectional transport of drugs without backflow, and the top surface with hydrophilic arrays can firmly anchor the cell-based droplet array to evaluate the concentration-dependent bioeffects of drugs accurately. Such a unique structure enables universal screening of different cell types and drugs dissolved in different solvents, requiring neither additional accessories nor arduous drug functionalization. The heterogeneous organohydrogel with unprecedented automation and non-interference possesses the enormous potential to be a next-generation platform for drug screening.

Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis.

Pulsed electromagnetic field (PEMF) therapy has been extensively investigated in clinical studies for the treatment of angiogenesis-related diseases. However, there is a lack of research on the impact of PEMFs on energy metabolism and mitochondrial dynamics during angiogenesis. The present study included tube formation and CCK-8 assays. A Seahorse assay was conducted to analyze energy metabolism, and mitochondrial membrane potential assays, mitochondrial imaging, and reactive oxygen species assays were used to measure changes in mitochondrial structure and function in human umbilical vein endothelial cells (HUVECs) exposed to PEMFs. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of antioxidants, glycolytic pathway-related genes, and genes associated with mitochondrial fission and fusion. The tube formation assay demonstrated a significantly greater tube network in the PEMF group compared to the control group. The glycolysis and mitochondrial stress tests revealed that PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis. Mitochondrial imaging revealed a wire-like mitochondrial morphology in the control group, and treatment with PEMFs led to shorter and more granular mitochondria. Our major findings indicate that exposure to PEMFs accelerates angiogenesis in HUVECs, likely by inducing energy metabolism reprogramming and mitochondrial fission.

Suicidal ideation in Chinese adolescents: prevalence, risk factors, and partial mediation by family support, a cross-sectional study.

Background: Suicidal ideation is a pressing public health concern, particularly among adolescents. The objective of this study was to examine the prevalence of and factors associated with suicidal ideation in Chinese adolescents, addressing an important gap in current research. Methods: This study employed an online survey of 3443 adolescents in Lianyungang, using a cross-sectional design. The assessment included the use of the Patient Health Questionnaire-9, the seven-item Generalized Anxiety Disorder instrument, and the Perceived Social Support Scale to evaluate suicidal ideation, anxiety symptoms, and social support in adolescents, respectively. Results: In adolescents, the prevalence of suicidal ideation was 22.1%, with a significantly higher proportion among female adolescents than among males (27.9% vs 16.9%, P < 0.001). Binary regression analysis identified (OR = 1.788, 95% CI: 1.467-2.177, P < 0.001), anxiety symptoms (OR = 10.035, 95% CI: 7.441-13.534, P < 0.001), total PHQ-9 scores of mothers (OR = 1.040, 95%CI: 1.003 - 1.078, P = 0.034), total GAD-7 scores of mothers (OR = 0.958, 95%CI: 0.919 - 0.998, P = 0.039), and moderate parental relationships (OR = 2.042, 95% CI: 1.630-2.557, P < 0.001) to be risk factors for suicidal ideation; family support was a protective factor (OR = 0.888, 95% CI: 0.859-0.918, P < 0.001). Furthermore, family support partially mediates the relationship between anxiety symptoms and suicidal ideation among adolescents (9.28%). Conclusions: This study highlights high adolescent suicidal ideation rates and recommends gender-specific interventions, anxiety management, and family support for improvement in mental health status.

Photoinduced Palladium-Catalyzed Radical Germylative Arylation of Alkenes with Chlorogermanes.

We describe a visible light-induced palladium-catalyzed radical germylative arylation of alkenes with easily accessible chlorogermanes. This protocol provides expedient access to germanium-substituted indolin-2-ones in good to excellent yields under mild reaction conditions. The key step for this strategy lies in the reductive activation of germanium-chloride bonds with an excited palladium complex under visible light irradiation. The involvement of germanium radicals was evidenced by electron paramagnetic resonance spectroscopy experiments.

The spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil in the terrestrial ecosystem.

Carbon(C), nitrogen(N), and phosphorus(P) are crucial elements in the element cycling in the terrestrial ecosystems. In the past decades, the spatial pattern and driving mechanism of plant and soil ecological stoichiometry have been hot topics in ecological geography. So far, many studies at different spatial and ecological scales have been conducted, but systematic review has not been reported to summarize the research status. In this paper, we tried to fill this gap by reviewing both the spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil at regional to large scale. Additionally, we synthesized researches on the relationships between plant and soil C, N and P stoichiometric characteristics. At the global scale, plant C, N, P stoichiometric characteristics exhibited some trends along latitude and temperature gradient. Plant taxonomic classification was the main factor controlling the spatial variations of plant C, N and P stoichiometric characteristics. Climate factor and soil properties showed varying impacts on the spatial variations of plant C, N, P stoichiometric characteristics across different spatial scales. Soil C, N, P stoichiometric characteristics also vary along climate gradient at large scale. Their spatial variations result from the combined effects of climate, topography, soil properties, and vegetation characteristics at regional scale. The spatial pattern of soil C, N, P stoichiometric characteristics and the driving effects from environmental factors could be notably different among different ecosystems and vegetation types. Plant C:N:P is obviously higher than that of soil, and there exists a positive correlation between plant and soil C:N:P. Their trends along longitude and latitude are similar, but this correlation varies significantly among different vegetation types. Finally, based on the issues identified in this paper, we highlighted eight potential research themes for the future studies.

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain.

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.

A novel NIR fluorescent probe for copper(ii) imaging in Parkinson's disease mouse brain.

Abnormal copper ion (Cu2+) levels are considered to be one of the pathological factors of Parkinson's disease (PD), but the internal relationship between Cu2+ and PD progression remains elusive. Visualizing Cu2+ in the brain will be pivotal for comprehending the underlying pathophysiological processes of PD. In this work, a near-infrared (NIR) fluorescent probe, DDAO-Cu, capable of detecting Cu2+ with exceptional sensitivity (about 1.8 nM of detection limit) and selectivity, rapid response (<3 min), and deep tissue penetration, was designed for quantification and visualization of the Cu2+ level. It could detect not only Cu2+ in cells but also the changes in the Cu2+ level in the rotenone-induced cell and zebrafish PD models. Moreover, DDAO-Cu can cross the blood-brain barrier to image Cu2+ in the brain of PD model mice. The imaging result showed a significant increase in Cu2+ levels in brain regions of PD model mice, including the cerebral cortex, hippocampus, and striatum. Meanwhile, Cu2+ levels in the substantia nigra region were significantly reduced in PD model mice. It revealed the nuanced relationship of Cu2+ levels in different brain regions in the disease and indicated the pathological complexity of PD. Overall, DDAO-Cu represents a novel and practical tool for investigating Cu2+-related physiological and pathological processes underlying Parkinson's disease.

Gegen Qinlian Decoction reverses oxaliplatin resistance in colorectal cancer by inhibiting YTHDF1-regulated m6A modification of GLS1.

BACKGROUND: Colorectal cancer (CRC) and its chemoresistance pose significant threats to human health. Gegen Qinlian Decoction (GQD) is frequently employed alongside chemotherapy drugs for the treatment of CRC and various intestinal disorders. Despite its widespread use, there is limited research investigating the mechanisms through which GQD reverses chemoresistance. PURPOSE: This study investigated the mechanism by which GQD reverses oxaliplatin (OXA) resistance in CRC. METHODS: A YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-knockdown OXA-resistant cell line was constructed by lentivirus to clarify YTHDF1-mediated chemoresistance through the regulation of glutaminase 1 (GLS1). The efficacy of GQD in reversing OXA resistance in CRC in vitro was evaluated by Cell Counting Kit-8, western blotting, quantitative real-time polymerase chain reaction, and glutaminase activity assays. In vivo validation was performed by constructing tumor xenografts in nude mice with OXA-resistant cells. In addition, mouse feces were collected and a 16S rDNA assay was performed to assess the regulation of intestinal flora by GQD. RESULTS: Overexpression of YTHDF1 upregulated GLS1 expression and induced OXA-resistance in CRC. GQD induced apoptosis in LoVo/OXAR, increased OXA accumulation in LoVo/OXAR, inhibited expression of YTHDF1 and GLS1 when administered alone and in combination with OXA, and suppressed GLS1 activity to reverse drug resistance with good synergistic effects. GQD and OXA combination or GLS1 inhibitor alleviated OXA toxicity, reduced the volume of tumor xenografts in nude mice, inhibited YTHDF1 and GLS1 protein expression and GLS1 activity, adjusted the intestinal flora, and significantly reversed the increased Firmicutes/Bacteroidetes ratio. CONCLUSION: GQD has shown superior efficacy in reversing OXA-resistance and increasing sensitivity. These findings indicate that the therapy combined with GQD has potential utility in the treatment of OXA-resistant CRC.

A single-centre study on abnormal antinuclear antibodies in children caused by intravenous infusion of gamma globulin.

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children. Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group. Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results. Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies.

Interfacial Electronic Interactions Promoted Activation for Nitrate Electroreduction to Ammonia over Ag-modified Co3O4.

Electrocatalytic nitrate (NO3-) reduction to ammonia (NRA) offers a promising pathway for ammonia synthesis. The interfacial electronic interactions (IEIs) can regulate the physicochemical capabilities of catalysts in electrochemical applications, while the impact of IEIs on electrocatalytic NRA remains largely unexplored in current literature. In this study, the high-efficiency electrode Ag-modified Co3O4 (Ag1.5Co/CC) is prepared for NRA in neutral media, exhibiting an impressive nitrate conversion rate of 96.86%, ammonia Faradaic efficiency of 96.11%, and ammonia selectivity of ~100%. Notably, the intrinsic activity of Ag1.5Co/CC is ~81 times that of Ag nanoparticles (Ag/CC). Multiple characterizations and theoretical computations confirm the presence of IEIs between Ag and Co3O4, which stabilize the CoO6 octahedrons within Co3O4 and significantly promote the adsorption of reactants (NO3-) as well as intermediates (NO2- and NO), while suppressing the Heyrovsky step, thereby improving nitrate electroreduction efficiency. Furthermore, our findings reveal a synergistic effect between different active sites that enables tandem catalysis for NRA: NO3- reduction to NO2- predominantly occurs at Ag sites while NO2- tends to hydrogenate to ammonia at Co sites. This study offers valuable insights for the development of high-performance NRA electrocatalysts.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Rod-Shaped Au@Ce Nano-Platforms for Enhancing Photodynamic Tumor Collaborative Therapy.

Tumor photodynamic therapy (PDT) relies on intratumoral free radicals, while the limited oxygen source and the depletion of tissue oxygen may exacerbate the hypoxia. As the treatment progresses, there will eventually be a problem of insufficient free radicals. Here, it is found that Au@CeO2 nano-rods (Au@Ce NRs), assembled by gold nano-rods (Au NRs) and ceria nanoparticles (CeO2 NPs), can efficaciously absorb near-infrared light (NIR) to promote the release of oxygen and free radicals. Au@Ce NRs exhibit a higher proportion of Ce3+ (Ce2O3) after oxygen release, while Ce3+ is subsequently oxidized to Ce4+ (CeO2) by trace H2O2. Interestingly, Au@Ce NRs re-oxidized by trace H2O2 can re-releasing oxygen and free radicals again upon NIR treatment, achieving oxygenation/oxygen evolution, similar to charging/discharging. This loop maximizes the conversion of limited oxygen source into highly cytotoxic free radicals. As a result, when B16-F10 cells are treated by NIR/Au@Ce NRs, more tumor cells undergo apoptosis, consistent with the higher level of free radicals. Importantly, NIR/Au@Ce NRs successfully suppresses tumor growth and promotes the generation of epidermal collagen fibers in the transplanted tumor model. Therefore, the rod-shaped Au@Ce NRs provide an ideal platform for maximizing the utilization of intratumoral oxygen sources and improving the treatment of melanoma.

Hepatic arterial infusion chemotherapy plus targeted therapy and immunotherapy versus systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a retrospective cohort study.

BACKGROUND: To improve the prognosis of advanced intrahepatic cholangiocarcinoma (iCCA), we retrospectively compared the effect and safety of combined hepatic arterial infusion chemotherapy (HAIC), targeted therapy and immunotherapy with systemic chemotherapy (SC) in unresectable iCCA patients. METHODS: We retrospectively enrolled 202 advanced iCCA patients treated with SC or targeted therapy, immunotherapy, and FOLFOX-HAIC combined between March 2015 and June 2023 at our institution. 202 patients were divided into two groups based on the therapeutic regimens. Baseline characteristics and prognosis were reviewed and analyzed. RESULTS: After 1-to-1 propensity score matching, 76 patients were included in each group. The triple combination therapy group demonstrated longer median overall survival (OS, 20.77 vs. 14.83 months, P=0.047), progression-free survival (PFS, 9.07 vs. 6.23 mo, P<0.001), intrahepatic PFS (11.03 vs. 6.73 mo, P<0.001), extrahepatic PFS (11.37 vs. 7.13 months, P=0.0064), and a higher objective response rate (35.5% vs. 14.5%, P=0.003) than the SC group. Fever, thrombocytopenia, elevated ALT, elevated AST, hypoalbuminemia, and hyperbilirubinemia were more common adverse events (AEs) in the triple combination therapy group, while fatigue and anemia were more prevalent in the SC group (P<0.05). For grades 3-4 AEs, the rates of elevated ALT were higher in the triple combination group (P=0.028). CONCLUSIONS: Compared with SC, triple combination therapy comprising HAIC, targeted therapy and immunotherapy appears to be an effective and safe treatment for advanced iCCA.

Electron Reservoir Effect of Adjacent Fe Nanoclusters Boosts Atomic Fe Active Sites on Porous Carbon for the Both Electrocatalytic Oxygen Reduction and CO2 Reduction Reaction.

Electrochemical oxygen reduction reaction (ORR) and carbon dioxide reduction reaction (CO2RR) are greatly significant in renewable energy-related devices and carbon-neutral closed cycle, while the development of robust and highly efficient electrocatalysts has remained challenges. Herein, a hybrid electrocatalyst, featuring axial N-coordinated Fe single atom sites on hierarchically N, P-codoped porous carbon support and Fe nanoclusters as electron reservoir (FeNCs/FeSAs-NPC), is fabricated via in situ thermal transformation of the precursor of a supramolecular polymer initiated by intermolecular hydrogen bonds co-assembly. The FeNCs/FeSAs-NPC catalyst manifests superior oxygen reduction activity with a half-wave potential of 0.91 V in alkaline solution, as well as high CO2 to CO Faraday efficiency (FE) of surpassing 90% in a wide potential window from -0.40 to -0.85 V, along with excellent electrochemical durability. Theoretical calculations indicate that the electron reservoir effect of Fe nanoclusters can trigger the electron redistribution of the atomic Fe moieties, facilitating the activation of O2 and CO2 molecules, lowering the energy barriers for rate-determining step, and thus contributing to the accelerated ORR and CO2RR kinetics. This work offers an effective design of electron coupling catalysts that have advanced single atoms coexisting with nanoclusters for efficient ORR and CO2RR.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases.

PURPOSE OF THE REVIEW: Macrophage accumulation and activation function as hallmarks of atherosclerosis and have complex and intricate dynamics throughout all components and stages of atherosclerotic plaques. In this review, we focus on the regulatory roles and underlying mechanisms of macrophage phenotypes and metabolism in atherosclerosis. We highlight the diverse range of macrophage phenotypes present in atherosclerosis and their potential roles in progression and regression of atherosclerotic plaque. Furthermore, we discuss the challenges and opportunities in developing therapeutic strategies for preventing and treating atherosclerotic cardiovascular disease. RECENT FINDINGS: Dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypealters the immuno-inflammatory response during atherosclerosis progression, leading to plaque initiation, growth, and ultimately rupture. Altered metabolism of macrophage is a key feature for their function and the subsequent progression of atherosclerotic cardiovascular disease. The immunometabolism of macrophage has been implicated to macrophage activation and metabolic rewiring of macrophages within atherosclerotic lesions, thereby shifting altered macrophage immune-effector and tissue-reparative function. Targeting macrophage phenotypes and metabolism are potential therapeutic strategies in the prevention and treatment of atherosclerosis and atherosclerotic cardiovascular diseases. Understanding the precise function and metabolism of specific macrophage subsets and their contributions to the composition and growth of atherosclerotic plaques could reveal novel strategies to delay or halt development of atherosclerotic cardiovascular diseases and their associated pathophysiological consequences. Identifying biological stimuli capable of modulating macrophage phenotypes and metabolism may lead to the development of innovative therapeutic approaches for treating patients with atherosclerosis and coronary artery diseases.