Localized surface plasmon resonance (LSPR) excitation on single silver nanoring with nanoscale surface roughness.

With the expansion of the application of high-sensitivity Surface-enhanced Raman scattering (SERS) technique, micro SERS-active substrates with rich optical properties and high-level functions are desired. In this study, silver nanorings with nanoscale surface roughness were fabricated as a new type of enclosed quasi-2D micro-SERS-active substrate. Highly-crystalline spherical and hemispherical silver nanoprotrusions were densely and uniformly distributed over the entire surface of the nanorings. The SERS signals were significantly enhanced on the roughened silver nanorings which were mainly derived from the maximal localized surface plasmon resonance (LSPR) points at the junctions between adjacent coupled nanoprotrusions on the roughened nanorings. The mapping image shows a uniform and intense LSPR enhancement over the nanorings, owing to the uniform and dense distribution of silver nanoprotrusions and the resulting uniform distribution of maximal LSPR points on the roughened nanorings. The dark-field spectra further indicated that the single roughened silver nanoring had significant LSPR enhancement, a wide LSPR frequency-range response, and adaptability for SERS enhancement. Notably, both the measured and simulated results demonstrate that the maximal LSPR enhancement at the junctions between the nanoprotrusions, which are distributed on the inner surface of the silver nanoring, is higher than that on the outer surface because of the plasmon-focusing effect of the enclosed silver nanoring, which leads to the lateral asymmetrical distribution of LSPR intensity, indicating more LSPR and SERS features. These results indicate that single roughened silver nanorings exhibit excellent performance as a new type of enclosed quasi-2D silver nanoring micro-SERS-active substrate, microzone LSPR catalysis, and micro/nanodevices.

Innovative Diagnosis and Therapeutic Modalities: Engineered Exosomes in Autoimmune Disease.

Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Deconvoluting nitric oxide-protein interactions with spatially resolved multiplex imaging.

Simultaneous imaging of nitric oxide (NO) and its proximal proteins should facilitate the deconvolution of NO-protein interactions. While immunostaining is a primary assay to localize proteins in non-genetically manipulated samples, NO imaging probes with immunostaining-compatible signals remain unexplored. Herein, probe NOP-1 was developed with an NO-triggered proximal protein labeling capacity and fluorogenic signals. The trick is to fuse the native chemical ligation of acyl benzotriazole with the protein-conjugation-induced fluorogenic response of Si-rhodamine fluorophore. NOP-1 predominantly existed in the non-fluorescent spirocyclic form. Yet, its acyl o-phenylenediamine moiety was readily activated by NO into acyl benzotriazole to conjugate proximal proteins, providing a fluorogenic response and translating the transient cellular NO signal into a permanent stain compatible with immunostaining. NOP-1 was utilized to investigate NO signaling in hypoglycemia-induced neurological injury, providing direct evidence of NO-induced apoptosis during hypoglycemia. Mechanistically, multiplex imaging revealed the overlap of cellular NOP-1 fluorescence with immunofluorescence for α-tubulin and NO2-Tyr. Importantly, α-tubulin was resolved from NOP-1 labeled proteins. These results suggest that NO played a role in hypoglycemia-induced apoptosis, at least in part, through nitrating α-tubulin. This study fills a crucial gap in current imaging probes, providing a valuable tool for unraveling the complexities of NO signaling in biological processes.

Omics analysis revealed the intestinal toxicity induced by aflatoxin B1 and aflatoxin M1.

Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.

Research progress in the treatment of inflammatory bowel disease with natural polysaccharides and related structure-activity relationships.

Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.

Cryopreservation and Rapid Recovery of Differentiated Intestinal Epithelial Barrier Cells at Complex Transwell Interfaces Is Enabled by Chemically Induced Ice Nucleation.

Cell-based models, such as organ-on-chips, can replace and inform in vivo (animal) studies for drug discovery, toxicology, and biomedical science, but most cannot be banked "ready to use" as they do not survive conventional cryopreservation with DMSO alone. Here, we demonstrate how macromolecular ice nucleators enable the successful cryopreservation of epithelial intestinal models supported upon the interface of transwells, allowing recovery of function in just 7 days post-thaw directly from the freezer, compared to 21 days from conventional suspension cryopreservation. Caco-2 cells and Caco-2/HT29-MTX cocultures are cryopreserved on transwell inserts, with chemically induced ice nucleation at warmer temperatures resulting in increased cell viability but crucially retaining the complex cellular adhesion on the transwell insert interfaces, which other cryoprotectants do not. Trans-epithelial electrical resistance measurements, confocal microscopy, histology, and whole-cell proteomics demonstrated the rapid recovery of differentiated cell function, including the formation of tight junctions. Lucifer yellow permeability assays confirmed that the barrier functions of the cells were intact. This work will help solve the long-standing problem of transwell tissue barrier model storage, facilitating access to advanced predictive cellular models. This is underpinned by precise control of the nucleation temperature, addressing a crucial biophysical mode of damage.

A comparison of the effects of two protocols of concurrent resistance and aerobic training on physical fitness in middle school students.

Objective: This study aimed to compare the effects of two concurrent training (CT) protocols on the physical fitness of middle school students. Method: A 12-week quasi-experimental pre-test/post-test study was conducted with 157 middle school students (age = 12.48 ± 0.34, n = 90 females) divided into three groups: CT group A (CT-0h) received combined resistance training (RT) and aerobic training (AT) in each physical education session, CT group B (CT-48h) received RT and AT across two separate physical education classes 48 h apart, and a control group (Con) received no training. Training occurred twice a week. Test indicators included cardiorespiratory fitness (CRF) measured by estimated VO2max and 20 m shuttle run (laps), as well as muscle strength assessed through long jump, vertical jump, and handgrip strength. Results: The intervention groups exhibited significant increases in estimated VO2max and muscle strength compared to their baseline values (p < 0.05). Both CT-0h and CT-48h groups demonstrated significant improvements in 20 m shuttle run (laps) (mean difference: 8.88 laps, p < 0.01; mean difference: 4.81 laps, p < 0.01, respectively), standing long jump (mean difference: 6.20 cm, p < 0.01; mean difference: 3.68 cm, p < 0.01, respectively), vertical jump (mean difference: 4.95 cm, p < 0.01; mean difference: 4.04 cm, p < 0.01, respectively), and handgrip strength (mean difference: 11.17 kg, p < 0.01; mean difference: 6.99 kg, p < 0.01, respectively). CT-0h group exhibited significantly increased estimated VO2max (mean difference: 1.47 ml/kg/min, p < 0.01) compared to the CT-48h group. Conclusion: Both CT programs effectively improved adolescents' physical fitness indicators. However, the program that integrated RT and AT within the same physical education class demonstrated superior enhancement in adolescents' CRF.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

MRS study on the correlation between frontal GABA+/Glx ratio and abnormal cognitive function in medication-naive patients with narcolepsy.

OBJECTIVE: To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS). METHODS: MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale. All subjects recorded a 2-week sleep log as well as an overnight polysomnography within 1 week before MR scanning to understand their sleep habits and determine sleep stages. After PSG, they also underwent multiple sleep latency trials. Patient/control group differences in the individual measurements of GABA+ and Glx and the GABA+/Glx ratio and their relationship with cognition were assessed. RESULTS: The GABA+/Glx ratio and GABA + levels of patients with narcolepsy were higher than those of the control group (P＜0.0001 and P = 0.0008, respectively). However, there was no significant difference in Glx levels (P = 0.6360). The GABA+/Glx ratio negatively correlated with abnormal cognitive function (r = -0.6710, P = 0.0002). Moreover, GABA + levels were inversely proportional to rapid eye movement sleep latency (REML) in patients with narcolepsy (r = -0.5019, P = 0.0106). CONCLUSION: The GABA+/Glx ratio in the prefrontal lobe was higher in NT1 patients during N2 sleep than in normal controls, mainly caused by GABA + levels; this ratio was negatively related to abnormal cognitive function. In addition, GABA + levels were inversely proportional to REML.

Doping Ferrocene-Based Conjugated Microporous Polymers with 7,7,8,8-Tetracyanoquinodimethane for Efficient Photocatalytic CO2 Reduction.

The design and synthesis of organic photocatalysts remain a great challenge due to their strict structural constraints. However, this could be mitigated by achieving structural flexibility by constructing permanent porosity into the materials. Conjugated microporous polymers (CMPs) are an emerging class of porous materials with an amorphous, three-dimensional network structure, which makes it possible to integrate the elaborate functional groups to enhance photocatalytic performance. Here, we report the synthesis of a novel CMP, named TAPFc-TFPPy-CMP, constructed by 1,1'3,3'-tetra(4-aminophenyl)ferrocene (TAPFc) and 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) monomers. The integration of the p-type dopant 7,7,8,8-tetracyanoquinodimethane (TCNQ) into the TAPFc-TFPPy-CMP improved the light adsorption performance, leading to a decrease in the optical bandgap from 2.00 to 1.43 eV. The doped CMP (TCNQ@TAPFc-TFPPy-CMP) exhibited promising catalytic activity in photocatalytic CO2 reduction under visible light, yielding 546.8 µmol g-1 h-1 of CO with a selectivity of 96% and 5.2 µmol g-1 h-1 of CH4. This represented an 80% increase in the CO yield compared to the maternal TAPFc-TFPPy-CMP. The steady-state photoluminescence (PL) and fluorescence lifetime (FL) measurements reveal faster carrier separation and transport after the doping. This study provides guidance for the development of organic photocatalysts for the utilization of renewable energy.

Nature of Li2O2 and its relationship to the mechanisms of discharge/charge reactions of lithium-oxygen batteries.

Lithium-air batteries (LABs) are considered one of the most promising energy storage devices because of their large theoretical energy density. However, low cyclability caused by battery degradation prevents its practical use. Thus, to realize practical LABs, it is essential to improve cyclability significantly by understanding how the degradation processes proceed. Here, we used online mass spectrometry for real-time monitoring of gaseous products generated during charging of lithium-oxygen batteries (LOBs), which was operated with pure oxygen not air, with 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) tetraethylene glycol dimethyl ether (TEGDME) electrolyte solution. Linear voltage sweep (LVS) and voltage step modes were employed for charge instead of constant current charge so that the energetics of the product formation during the charge process can be understood more quantitatively. The presence of two distinctly different types of Li2O2, one being decomposed in a wide range of relatively low cell voltages (2.8-4.16 V) (l-Li2O2) and the other being decomposed at higher cell voltages than ca. 4.16 V (h-Li2O2), was confirmed by both LVS and step experiments. H2O generation started when the O2 generation rate reached a first maximum and CO2 generation took place accompanied by the decomposition of h-Li2O2. Based on the above results and the effects of discharge time and the use of isotope oxygen during discharge on product distribution during charge, the generation mechanism of O2, H2O, and CO2 during charging is discussed in relation to the reactions during discharge.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

The glass phase in the grain boundary of Na3Zr2Si2PO12, created by gallium modulation.

Na3Zr2Si2PO12 has been proven to be a promising electrolyte for solid-state sodium batteries. However, its poor conductivity prevents application, caused by the large ionic resistance created by the grain boundary. Herein, we propose an additional glass phase (Na-Ga-Si-P-O phase) to connect the grain boundary via Ga ion introduction, resulting in enhanced sodium-ion conduction and electrochemical performance. The optimized Na3Zr2Si2PO12-0.15Ga electrolyte exhibits Na+ conductivity of 1.65 mS cm-1 at room temperature and a low activation energy of 0.16 eV, with 20% newly formed glass phase enclosing the grain boundary. Temperature-dependent NMR line shapes and spin-lattice relaxation were used to estimate the Na self-diffusion and Na ion hopping. The dense glass-ceramic electrolyte design strategy and the structure-dynamics-property correlation from NMR, can be extended to the optimization of other materials.

Integrating single-cell and bulk sequencing data to identify glycosylation-based genes in non-alcoholic fatty liver disease-associated hepatocellular carcinoma.

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) has been increasing. However, the role of glycosylation, an important modification that alters cellular differentiation and immune regulation, in the progression of NAFLD to HCC is rare. Methods: We used the NAFLD-HCC single-cell dataset to identify variation in the expression of glycosylation patterns between different cells and used the HCC bulk dataset to establish a link between these variations and the prognosis of HCC patients. Then, machine learning algorithms were used to identify those glycosylation-related signatures with prognostic significance and to construct a model for predicting the prognosis of HCC patients. Moreover, it was validated in high-fat diet-induced mice and clinical cohorts. Results: The NAFLD-HCC Glycogene Risk Model (NHGRM) signature included the following genes: SPP1, SOCS2, SAPCD2, S100A9, RAMP3, and CSAD. The higher NHGRM scores were associated with a poorer prognosis, stronger immune-related features, immune cell infiltration and immunity scores. Animal experiments, external and clinical cohorts confirmed the expression of these genes. Conclusion: The genetic signature we identified may serve as a potential indicator of survival in patients with NAFLD-HCC and provide new perspectives for elucidating the role of glycosylation-related signatures in this pathologic process.

Bioactive compound schaftoside from Clinacanthus nutans attenuates acute liver injury by inhibiting ferroptosis through activation the Nrf2/GPX4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinacanthus nutans (Burm. f.) Lindau, a traditional herb renowned for its anti-tumor, antioxidant, and anti-inflammatory properties, has garnered considerable attention. Although its hepatoprotective effects have been described, there is still limited knowledge of its treatment of acute liver injury (ALI), and its mechanisms remain unclear. AIM OF THE STUDY: To assess the efficacy of Clinacanthus nutans in ALI and to identify the most effective fractions and their underlying mechanism of action. METHODS: Bioinformatics was employed to explore the underlying anti-hepatic injury mechanisms and active compounds of Clinacanthus nutans. The binding ability of schaftoside, a potential active ingredient in Clinacanthus nutans, to the core target nuclear factor E2-related factor 2 (Nrf2) was further determined by molecular docking. The role of schaftoside in improving histological abnormalities in the liver was observed by H&E and Masson's staining in an ALI model induced by CCl4. Serum and liver biochemical parameters were measured using AST, ALT and hydroxyproline kits. An Fe2+ kit, transmission electron microscopy, western blotting, RT-qPCR, and DCFH-DA were used to measure whether schaftoside reduces ferroptosis-induced ALI. Subsequently, specific siRNA knockdown of Nrf2 in AML12 cells was performed to further elucidate the mechanism by which schaftoside attenuates ferroptosis-induced ALI. RESULTS: Bioinformatics analysis and molecular docking showed that schaftoside is the principal compound from Clinacanthus nutans. Schaftoside was shown to diminish oxidative stress levels, attenuate liver fibrosis, and forestall ferroptosis. Deeper investigations revealed that schaftoside amplified Nrf2 expression and triggered the Nrf2/GPX4 pathway, thereby reversing mitochondrial aberrations triggered by lipid peroxidation, GPX4 depletion, and ferroptosis. CONCLUSION: The lead compound schaftoside counters ferroptosis through the Nrf2/GPX4 axis, providing insights into a novel molecular mechanism for treating ALI, thereby presenting an innovative therapeutic strategy for ferroptosis-induced ALI.

Dynamic alterations in physiological and biochemical indicators of Cirrhinus mrigala hatchlings: A sublethal exposure of triclosan.

Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 µg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm-1) showed a decline in α-helix and turns and an increase in ß-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.

Unlocking the mysteries of milk oligosaccharides: Structure, metabolism, and function.

Milk oligosaccharides (MOs), complex carbohydrates prevalent in human breast milk, play a vital role in infant nutrition. Serving as prebiotics, they inhibit pathogen adherence, modulate the immune system, and support newborn brain development. Notably, MOs demonstrate significant variations in concentration and composition, both across different species and within the same species. These characteristics of MOs lead to several compelling questions: (i) What distinct beneficial functions do MOs offer and how do the functions vary along with their structural differences? (ii) In what ways do MOs in human milk differ from those in other mammals, and what factors drive these unique profiles? (iii) What are the emerging applications of MOs, particularly in the context of their incorporation into infant formula? This review delves into the structural characteristics, quantification methods, and species-specific concentration differences of MOs. It highlights the critical role of human MOs in infant growth and their potential applications, providing substantial evidence to enhance infant health and development.

Nano-Cu Derived from a Copper Nitride Precatalyst for Reductive Coupling of Nitroaromatics to Azo Compounds.

The study of structural reconstruction is vital for the understanding of the real active sites in heterogeneous catalysis and guiding the improved catalyst design. Herein, we applied a copper nitride precatalyst in the nitroarene reductive coupling reaction and made a systematic investigation on the dynamic structural evolution behaviors and catalytic performance. This Cu3N precatalyst undergoes a rapid phase transition to nanostructured Cu with rich defective sites, which act as the actual catalytic sites for the coupling process. The nitride-derived defective Cu is very active and selective for azo formation, with 99.6% conversion of nitrobenzene and 97.1% selectivity to azobenzene obtained under mild reaction conditions. Density functional theory calculations suggest that the defective Cu sites play a role for the preferential adsorption of nitrosobenzene intermediates and significantly lowered the activation energy of the key coupling step. This work not only proposes a highly efficient noble-metal-free catalyst for nitroarenes coupling to valuable azo products but also may inspire more scientific interest in the study of the dynamic evolution of metal nitrides in different catalytic reactions.