Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Leaf grey spot caused by Arcopilus aureus on tobacco in China.

Tobacco (Nicotiana tabacum L.) is one of the most widely cultivated industrial crops worldwide. From April to July 2023, about 40% of tobacco seedlings in the greenhouse exhibited irregular taupe lesions in Zhengzhou, Henan Province, China. At an early stage of the lesion development, light grey spots with the diameter of 1-2 mm were observed, these spots gradually expanded and connected into large irregular lesions causing leaf wrinkling or withered. A total of 12 infected leaf tissues were sterilized with 75% ethanol for 45 s, rinsed three times in sterilized water and then plated on potato dextrose agar (PDA) medium for 10 days at 28°C in darkness. Seven fungal colonies that show the similar appearance were isolated and three of them (MB-1, MB-2 and MB-3) were used for subsequent identification. Colonies of these strains on PDA with loose mycelium and orange-red pigment on the underside, white aerial in the center and light yellow hyphae near the periphery, formed in the shape of a concentric ring pattern. Ascomata appeared from the 14th day, were black, spherical or ellipsoid with walls of textura angularis, and size was 53.8-101.1 µm × 50.3-104.3 µm (n=30). Terminal hairs were brown and straight, gradually tapering toward the tips. Asci clavate or fusiform, spore bearing part 16.2-29.2 × 7.3-11.4 µm (n=21), with 8 irregularly arranged ascospores, evanescent. Ascospores are brown at maturity, biapiculate, navicular or fusiform shapes with size of 8.7-12.8 µm × 4.8-6.9 µm (n=100), and more or less inaequilateral. Single spore strains derived from these strains exhibited the morphological features consistent with the original strains. The morphological characteristics of the fungus were consistent with the description of Arcopilus aureus (Chivers) X.W. Wang & Samson (= Chaetomium aureum Chivers) (Lee et al. 2019). Furthermore, the sequences of RPB2 region were amplified from these strains and the result sequences (GenBank accession no. OR513105-OR513108) all showed a 100.00% identity with A. aureus strain CBS 538.73 (GenBank accession no. KX976807.1). It was reported that the RPB2 gene was efficient in discriminating Arcopilus species (Tavares et al. 2022), thus a maximum likelihood (ML) phylogenetic tree based on the RPB2 gene sequences were constructed using MEGA 7.0 with 1000 replications of bootstrapping (Kumar et al. 2016), which revealed that these strains formed a well-supported clade with A. aureus strains of (CBS 153.52 and CBS538.73) (Wang et al. 2022). Pathogenicity analysis were performed on healthy flue-cured tobacco seedlings leaves (cv Y85) by using mycelial agar plugs (5 mm in diameter) and spore suspension (1×106 spores/mL), and the PDA plugs and sterile water were used for control group, respectively. Tobacco seedlings were incubated in a 25°C and 70% RH growth chamber. After seven days, the leaves showed obvious symptoms, with taupe lesions and yellow halos on the periphery, whereas no symptoms were found on the control leaves. The A. aureu was then reisolated from inoculated diseased leaves. Previously, A. aureus has been only reported to cause leaf black disease on Pseudostellaria heterophylla in China (Yuan et al. 2021). To our knowledge, this is the first reported of A. aureus causing tobacco leaf grey spot worldwide. Arcopilus aureus has been reported as a plant biocontrol fungus (Wang et al. 2013). However, due to the potential serious damage in tobacco seedlings caused by this fungus, the use of A. aureus as a plant biocontrol agent needs to be given more attention, and disease control measures of this pathogen should be developed.

Applying a Tripodal Hexaurea Receptor for Binding to an Antitumor Drug, Combretastatin-A4 Phosphate.

Phosphates play a crucial role in drug design, but their negative charge and high polarity make the transmembrane transport of phosphate species challenging. This leads to poor bioavailability of phosphate drugs. Combretastatin-A4 phosphate (CA4P) is such an anticancer monoester phosphate compound, but its absorption and clinical applicability are greatly limited. Therefore, developing carrier systems to effectively deliver phosphate drugs like CA4P is essential. Anion receptors have been found to facilitate the transmembrane transport of anions through hydrogen bonding. In this study, we developed a tripodal hexaurea anion receptor (L1) capable of binding anionic CA4P through hydrogen bonding, with a binding constant larger than 104 M-1 in a DMSO/water mixed solvent. L1 demonstrated superior binding ability compared to other common anions, and exhibited negligible cell cytotoxicity, making it a promising candidate for future use as a carrier for drug delivery.

Fucoidan alleviates high sucrose-induced metabolic disorders and enhances intestinal homeostasis through modulation of Notch signaling.

INTRODUCTION: The therapeutic potential of fucoidan (FUC), a natural polysaccharide, in metabolic disorders is recognized, yet its underlying mechanisms remain unclear. METHODS: We conducted investigations into the therapeutic mechanisms of FUC sourced from Sargassum fulvellum concerning metabolic disorders induced by a high-sucrose diet (HSD), employing Drosophila melanogaster and mice models. Drosophila larvae were subjected to HSD exposure to monitor growth inhibition, reduced pupation, and developmental delays. Additionally, we examined the impact of FUC on growth- and development-related hormones in Drosophila. Furthermore, we assessed the modulation of larval intestinal homeostasis by FUC, focusing on the regulation of Notch signaling. In mice, we evaluated the effects of FUC on HSD-induced impairments in intestinal epithelial barrier integrity and gut hormone secretion. RESULTS: FUC supplementation significantly enhanced pupal weight in Drosophila larvae and effectively countered HSD-induced elevation of glucose and triglyceride levels. It notably influenced the expression of growth- and development-related hormones, particularly augmenting insulin-like peptides production while mitigating larval growth retardation. FUC also modulated larval intestinal homeostasis by negatively regulating Notch signaling, thereby protecting against HSD-induced metabolic stress. In mice, FUC ameliorated HSD-induced impairments in ileum epithelial barrier integrity and gut hormone secretion. CONCLUSIONS: Our findings demonstrate the multifaceted therapeutic effects of FUC in mitigating metabolic disorders and maintaining intestinal health. FUC holds promise as a therapeutic agent, with its effects attributed partly to the sulfate group and its ability to regulate Notch signaling, emphasizing its potential for addressing metabolic disorders.

Flexible iontronics with super stretchability, toughness and enhanced conductivity based on collaborative design of high-entropy topology and multivalent ion-dipole interactions.

All-solid-state ionic conductive elastomers (ASSICEs) are emerging as a promising alternative to hydrogels and ionogels in flexible electronics. Nevertheless, the synthesis of ASSICEs with concomitant mechanical robustness, superior ionic conductivity, and cost-effective recyclability poses a formidable challenge, primarily attributed to the inherent contradiction between mechanical strength and ionic conductivity. Herein, we present a collaborative design of high-entropy topological network and multivalent ion-dipole interaction for ASSICEs, and successfully mitigate the contradiction between mechanical robustness and ionic conductivity. Benefiting from the synergistic effect of this design, the coordination, de-coordination, and intrachain transfer of Li+ are effectively boomed. The resultant ASSICEs display exceptional mechanical robustness (breaking strength: 7.45 MPa, fracture elongation: 2621%, toughness: 107.19 MJ m-3) and impressive ionic conductivity (1.15 × 10-2 S m-1 at 25 °C). Furthermore, these ASSICEs exhibit excellent environmental stability (fracture elongation exceeding 1400% at 50 °C or -60 °C) and recyclability. Significantly, the application of these ASSICEs in a strain sensor highlights their potential in various fields, including human-interface communication, aerospace vacuum measurement, and medical balloon monitoring.

Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.

Background: Cellular senescence is a hallmark of aging and has been implicated in Alzheimer's disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis. ABCA1 expression and its trafficking is afiltered in APOE4 and AD cellular and mouse models. However, whether ABCA1 trafficking is involved in cellular senescence in APOE4 and AD remains unknown. Methods: We examined the association between cellular senescence and ABCA1 expression in human postmortem brain samples using transcriptomic, histological, and biochemical analyses. An unbiased proteomic screening was performed to identify targets that mediate cellular ABCA1 trafficking. APOE4-TR mice, immortalized, primary and induced pluripotent stem cell (iPSC) models were used to examine the cholesterol-ABCA1-senescence pathways. Results: Bulk and single nuclei transcriptomic profiling of the human dorsolateral prefrontal cortex from the Religious Order Study/Memory Aging Project (ROSMAP) revealed upregulation of cellular senescence transcriptome signatures in AD, which was strongly correlated with ABCA1 expression. Immunofluorescence and immunoblotting analyses confirmed increased ABCA1 expression in AD brain tissues, which was associated with lipofuscin-stained lipids and mTOR phosphorylation. Using discovery proteomics, caveolin-1, a sensor of cellular cholesterol accumulation, was identified to promote ABCA1 endolysosomal trafficking. Greater caveolin-1 expression was found in both APOE4-TR mouse models and AD human brains. Cholesterol induced mTORC1 activation was regulated by ABCA1 expression or its lysosomal trapping. Reducing cholesterol by cyclodextrin in APOE4-TR mice reduced ABCA1 lysosome trapping and increased ABCA1 recycling to efflux cholesterol to HDL particles, reducing mTORC1 activation and senescence-associated neuroinflammation. In human iPSC-derived astrocytes, the reduction of cholesterol by cyclodextrin attenuated inflammatory responses. Conclusions: Cholesterol accumulation in APOE4 and AD induced caveolin-1 expression, which traps ABCA1 in lysosomes to activate mTORC1 pathways and induce cellular senescence. This study provided novel insights into how cholesterol accumulation in APOE4 and AD accelerates senescence.

Biomimetic Charge-Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in Water.

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO4 3-) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge-neutral tripodal hexaurea receptors (L1-L4), which were equipped with morpholine and polyethylene glycol terminal groups to enhance their solubility in water, were synthesized to enable the pH-triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO4 3- anion in a 1 : 1 ratio via hydrogen bonds in 100 % water solutions, with L1 exhibiting the highest binding constant (1.2×103 M-1). These represent the first neutral anion ligands to bind phosphate in 100 % water and demonstrate the potential for phosphate capture and release in water through pH-triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.

Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic - China, September 2022-August 2023.

What is already known about this topic?: Mucosal IgA plays a crucial role in host immunity against respiratory viruses. Recent studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. However, a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019 (COVID-19) pandemic is yet to be conducted. What is added by this report?: In our study involving 3,421 participants, we documented IgA responses subsequent to SARS-CoV-2 infection. A significant proportion of individuals sustained increased levels of IgA for over six months. These levels were also observed in individuals with prior infections who underwent asymptomatic reinfections, indicating an active production of IgA antibodies. Further, individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after recovery. What are the implications for public health practice?: IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 infection. These insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

Erianin alleviates LPS-induced acute lung injury via antagonizing P-selectin-mediated neutrophil adhesion function.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura et Migo, known as "Tiepi Shihu" in traditional Chinese medicine, boasts an extensive history of medicinal use documented in the Chinese Pharmacopoeia. "Shen Nong Ben Cao Jing" records D. officinale as a superior herbal medicine for fortifying "Yin" and invigorating the five viscera. Erianin, a benzidine compound, emerges as a prominent active constituent derived from D. officinale, with the pharmacological efficacy of D. officinale closely linked to the anti-inflammatory properties of erianin. AIM OF THE STUDY: Acute lung injury (ALI) is a substantial threat to global public health, while P-selectin stands out as a promising novel target for treating acute inflammatory conditions. This investigation aims to explore the therapeutic potential of erianin in ALI treatment and elucidate the underlying mechanisms. EXPERIMENTAL DESIGN: The effectiveness of erianin in conferring protection against ALI was investigated through comprehensive histopathological and biochemical analyses of lung tissues and bronchoalveolar lavage fluid (BALF) in an in vivo model of LPS-induced ALI in mice. The impact of erianin on fMLP-induced neutrophil chemotaxis was quantitatively assessed using the Transwell and Zigmond chamber, respectively. To determine the therapeutic target of erianin and elucidate their binding capability, a series of sophisticated assays were employed, including drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and molecular docking analyses. RESULTS: Erianin demonstrated a significant alleviation of LPS-induced acute lung injury, characterized by reduced total cell and neutrophil counts and diminished total protein contents in BALF. Moreover, erianin exhibited a capacity to decrease proinflammatory cytokine production in both lung tissues and BALF. Notably, erianin effectively suppressed the activation of NF-κB signaling in the lung tissues of LPS- challenged mice; however, it did not exhibit in vitro inhibitory effects on inflammation in LPS-induced human pulmonary microvascular endothelial cells (HPMECs). Additionally, erianin blocked the adhesion and rolling of neutrophils on HPMECs. While erianin did not influence endothelial P-selectin expression or cytomembrane translocation, it significantly reduced the ligand affinity between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1). CONCLUSIONS: Erianin inhibits P-selectin-mediated neutrophil adhesion to activated endothelium, thereby alleviating ALI. The present study highlights the potential of erianin as a promising lead for ALI treatment.

Molecular Mechanisms of Fucoxanthin in Alleviating Lipid Deposition in Metabolic Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is witnessing a global surge; however, it still lacks effective pharmacological interventions. Fucoxanthin, a natural bioactive metabolite derived from marine brown algae, exhibits promising pharmacological functions, particularly in ameliorating metabolic disorders. However, the mechanisms underlying its therapeutic efficacy in addressing MAFLD remain elusive. Our present findings indicated that fucoxanthin significantly alleviated palmitic acid (PA)-induced hepatic lipid deposition in vitro and obesity-induced hepatic steatosis in ob/ob mice. Moreover, at both the protein and transcriptional levels, fucoxanthin effectively increased the expression of PPARα and CPT1 (involved in fatty acid oxidation) and suppressed FASN and SREBP1c (associated with lipogenesis) in both PA-induced HepG2 cells and hepatic tissues in ob/ob mice. This modulation was accompanied by the activation of AMPK. The capacity of fucoxanthin to improve hepatic lipid deposition was significantly attenuated when utilizing the AMPK inhibitor or siRNA-mediated AMPK silencing. Mechanistically, fucoxanthin activates AMPK, subsequently regulating the KEAP1/Nrf2/ARE signaling pathway to exert antioxidative effects and stimulating the PGC1α/NRF1 axis to enhance mitochondrial biogenesis. These collective actions contribute to fucoxanthin's amelioration of hepatic steatosis induced by metabolic perturbations. These findings offer valuable insights into the prospective utilization of fucoxanthin as a therapeutic strategy for managing MAFLD.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Gigantol ameliorates DSS-induced colitis via suppressing ß2 integrin mediated adhesion and chemotaxis of macrophage.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium, recognized as "Shihu" in traditional Chinese medicine, holds a rich history of medicinal utilization documented in the Chinese Pharmacopoeia. Ancient texts like "Shen Nong Ben Cao Jing" extol Dendrobium's virtues as a superior herbal medicine fortifying "Yin" and invigorating the five viscera. Dendrobium is extensively employed for the treatment of gastrointestinal inflammatory disorders, showcasing significant therapeutic efficacy, particularly against ulcerative colitis (UC), within the realm of Chinese ethnopharmacology. Dendrobium plays crucial pharmacological roles due to its rich content of polysaccharides, alkaloids, phenanthrenes, and bibenzyls. Gigantol, a prominent bibenzyl compound, stands out as one of the most vital active constituents within Dendrobium, the gigantol content of Dendrobium leaves can reach approximately 4.79 µg/g. Its significance lies in being recognized as a noteworthy anti-inflammatory compound derived from Dendrobium. AIM OF THE STUDY: Given the pivotal role of gigantol as a primary active substance in Dendrobium, the therapeutic potential of gigantol for gastrointestinal diseases remains enigmatic. Our present investigation aimed to evaluate the therapeutic effects of gigantol on dextran sulfate sodium (DSS)-induced colitis and reveal its potential mechanism in countering UC activity. MATERIALS AND METHODS: The protective efficacy of gigantol against colitis was assessed by examining the histopathological changes and conducting biochemical analyses of colon from DSS-challenged mice. Assessments focused on gigantol's impact on improving the intestinal epithelial barrier and its anti-inflammatory effects in colonic tissues of colitis mice. Investigative techniques included the exploration of the macrophage inflammatory signaling pathway via qPCR and Western blot analyses. In vitro studies scrutinized macrophage adhesion, migration, and chemotaxis utilizing transwell and Zigmond chambers. Furthermore, F-actin and Rac1 activation assays detailed cellular cytoskeletal remodeling. The potential therapeutic target of gigantol was identified and validated through protein binding analysis, competitive enzyme-linked immunosorbent assay (ELISA), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. The binding sites between gigantol and its target were predicted via molecular docking. RESULTS: Gigantol ameliorated symptoms of DSS-induced colitis, rectified damage to the intestinal barrier, and suppressed the production of pro-inflammatory cytokines in colonic tissues. Intriguingly, gigantol significantly curtailed NF-κB signaling activation in the colons of DSS-induced colitis mice. Notably, gigantol impaired the ß2 integrin-dependent adhesion and migratory capacity of RAW264.7 cells. Moreover, gigantol notably influenced the cytoskeleton remodeling of RAW264.7 cells by suppressing Vav1 phosphorylation and Rac1 activation. Mechanistically, gigantol interacted with ß2 integrin, subsequently diminishing binding affinity with intercellular adhesion molecule-1 (ICAM-1). CONCLUSIONS: In conclusion, these findings elucidate that gigantol ameliorates DSS-induced colitis by antagonizing ß2 integrin-mediated macrophage adhesion, migration, and chemotaxis, thus it may impede macrophage recruitment and infiltration into colonic tissues. This study suggests that gigantol shows promise as a viable candidate for clinical colitis therapy.

Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.

Inflammation and immune processes underlie pulmonary hypertension progression. Two main different activated phenotypes of macrophages, classically activated M1 macrophages and alternatively activated M2 macrophages, are both involved in inflammatory processes related to pulmonary hypertension. Recent advances suggest that macrophages coordinate interactions among different proinflammatory and anti-inflammatory mediators, and other cellular components such as smooth muscle cells and fibroblasts. In this review, we summarize the current literature on the role of macrophages in the pathogenesis of pulmonary hypertension, including the origin of pulmonary macrophages and their response to triggers of pulmonary hypertension. We then discuss the interactions among macrophages, cytokines, and vascular adventitial fibroblasts in pulmonary hypertension, as well as the potential therapeutic benefits of macrophages in this disease. Identifying the critical role of macrophages in pulmonary hypertension will contribute to a comprehensive understanding of this pathophysiological abnormality, and may provide new perspectives for pulmonary hypertension management.

Glioma induces atypical depression-like behaviors in mice through the 5-HT and glutamatergic synapse pathways.

Glioma patients often undertake psychiatric disorders such as depression and anxiety. There are several clinical epidemiological studies on glioma-associated depression, but basic research and corresponding animal experiments are still lacking. Here, we observed that glioma-bearing mice exhibited atypical depression-like behaviors in orthotopic glioma mouse models. The concentrations of monoamine neurotransmitters were detected by enzyme-linked immunosorbent assay (ELISA), revealing a decrease in 5-hydroxytryptamine (5-HT) levels in para-glioma tissues. The related gene expression levels also altered, detected by quantitative RT-PCR. Then, we developed a glioma-depression comorbidity mouse model. Through sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST) and other tests, we found that the occurrence of glioma could lead to changes in depression-like behaviors in a chronic unpredictable mild stress (CUMS) mouse model. The results of RNA sequencing (RNA-seq) indicated that the altered expression of glutamatergic synapse related genes in the paratumor tissues might be one of the main molecular features of the comorbidity model. Our findings suggested that the presence of glioma caused and altered depression-like behaviors, which was potentially related to the 5-HT and glutamatergic synapse pathways.

Bidirectional Lifetime Tuning of Er 1530 nm Emission Induced by Yb.

Wide-range NIR lifetimes of lanthanide ion-doped nanocrystals are highly desired for numerous bioapplications. As one of the most promising NIR emission bands, the lifetime of Er3+ at 1.5 µm can be as long as ∼10 ms and be greatly shortened by increasing the doping level of either activator Er3+ or sensitizer Yb3+. However, the shortened lifetime is mostly accompanied by the quenching effects, highly restraining the light signal intensity. Alternatively, prolonging the lifetime of Er3+ NIR lifetime without luminescence quenching is of vital significance as it raises the upper limit of the lifetime range and maintains the effective signal intensity. In this work, we revealed that Yb3+ can bidirectionally tune the NIR lifetime of Er3+. By introducing Yb3+, in addition to the substantially improved luminescence intensities, the prolonged NIR lifetime can be generated in low-Er3+-doped NaYF4 nanocrystals, while monotonously decreased lifetime appears in Er3+ heavily doped nanocrystals. To investigate the mechanisms of this bidirectional lifetime tuning and meanwhile avoid additional structural influences, the size and morphology of nanocrystals with different doping compositions were controlled to be similar. The decay dynamics of Er3+ NIR emissions of different nanocrystals were simulated to explain the effects of Yb3+. This work provides insights into the manipulation of the NIR lifetime in Er3+/Yb3+-codoped nanocrystals.

Effects of Sophora alopecuroides in a High-Concentrate Diet on the Liver Immunity and Antioxidant Function of Lambs According to Transcriptome Analysis.

The purpose of this study was to determine the effects of Sophora alopecuroides (SA) on liver function, liver inflammatory factor levels, antioxidant indexes and transcriptome in sheep. Twenty-four 3-month-old healthy Dumont hybrid lambs weighing 25.73 ± 2.17 kg were randomly divided into three groups: C1 (the control group), fed a concentrate-to-forage ratio of 50:50; H2 (the high-concentration group), fed a concentrate-to-forage ratio of 70:30; and S3 (the SA group), fed a concentrate-to-forage ratio of 70:30 + 0.1% SA. The results showed that the rumen pH values of the C1 and S3 groups were significant or significantly higher than that of the H2 group (p < 0.05 or p < 0.01). The serum ALT, AST and LDH activities and the LPS and LBP concentrations in the sheep serum and liver in the H2 group were significantly or extremely significantly higher than those in the C1 and S3 groups (p < 0.01), and the IL-10 content and SOD, GPX-PX and T-AOC activities showed the opposite trend (p < 0.05 or p < 0.01). KEGG enrichment analysis showed that the differentially expressed genes were significantly enriched in the ECM-receptor interaction and focal adhesion pathways, which are closely related to immune and antioxidant functions (p-adjust < 0.1). In summary, SA could improve the immune and antioxidant functions of lamb livers under high-concentrate conditions and regulate the mechanism of damage on sheep livers, which is caused by high-concentrate diets and through the expression of related genes in the ECM/FAs pathway.

Tailoring Local Chemical Ordering via Elemental Tuning in High-Entropy Alloys.

Due to the large multi-elemental space desired for property screening and optimization, high-entropy alloys (HEAs) hold greater potential over conventional alloys for a range of applications, such as structural materials, energy conversion, and catalysis. However, the relationship between the HEA composition and its local structural/elemental configuration is not well understood, particularly in noble-metal-based HEA nanomaterials, hindering the design and development of nano-HEAs in energy conversion and catalysis applications. Herein, we determined precise atomic-level structural and elemental arrangements in model HEAs composed of RhPtPdFeCo and RuPtPdFeCo to unveil their local characteristics. Notably, by changing just one constituent element in the HEA (Rh to Ru), we found dramatic changes in the elemental arrangement from complete random mixing to a local single elemental ordering feature. Additionally, we demonstrate that the local ordering in RuPtPdFeCo can be further controlled by varying the Ru concentration, allowing us to toggle between local Ru clustering and distinct heterostructures in multicomponent systems. Overall, our study presents a practical approach for manipulating local atomic structures and elemental arrangements in noble-metal-based HEA systems, which could provide in-depth knowledge to mechanistically understand the functionality of noble-metal-based HEA nanomaterials in practical applications.

N and OH-Immobilized Cu3 Clusters In Situ Reconstructed from Single-Metal Sites for Efficient CO2 Electromethanation in Bicontinuous Mesochannels.

Cu-based catalysts hold promise for electrifying CO2 to produce methane, an extensively used fuel. However, the activity and selectivity remain insufficient due to the lack of catalyst design principles to steer complex CO2 reduction pathways. Herein, we develop a concept to design carbon-supported Cu catalysts by regulating Cu active sites' atomic-scale structures and engineering the carbon support's mesoscale architecture. This aims to provide a favorable local reaction microenvironment for a selective CO2 reduction pathway to methane. In situ X-ray absorption and Raman spectroscopy analyses reveal the dynamic reconstruction of nitrogen and hydroxyl-immobilized Cu3 (N,OH-Cu3) clusters derived from atomically dispersed Cu-N3 sites under realistic CO2 reduction conditions. The N,OH-Cu3 sites possess moderate *CO adsorption affinity and a low barrier for *CO hydrogenation, enabling intrinsically selective CO2-to-CH4 reduction compared to the C-C coupling with a high energy barrier. Importantly, a block copolymer-derived carbon fiber support with interconnected mesopores is constructed. The unique long-range mesochannels offer an H2O-deficient microenvironment and prolong the transport path for the CO intermediate, which could suppress the hydrogen evolution reaction and favor deep CO2 reduction toward methane formation. Thus, the newly developed catalyst consisting of in situ constructed N,OH-Cu3 active sites embedded into bicontinuous carbon mesochannels achieved an unprecedented Faradaic efficiency of 74.2% for the CO2 reduction to methane at an industry-level current density of 300 mA cm-2. This work explores effective concepts for steering desirable reaction pathways in complex interfacial catalytic systems via modulating active site structures at the atomic level and engineering pore architectures of supports on the mesoscale to create favorable microenvironments.

Chlordane exposure impairs the growth and behavior of Drosophila.

Chlordane, a previously extensively utilized insecticidal pesticide, has since been prohibited, however, owing to its limited degradability, it continues to persist significantly in soil and water reservoirs, subsequently accumulating within plant and animal organisms, representing a substantial threat to human health. Despite extensive research conducted over the past few decades to investigate the toxic effects of chlordane, there remains a notable dearth of studies focusing on its impact on sleep activity. Therefore, in this study, the effects of short-term and long-term exposure to chlordane on the activity and sleep of Drosophila were investigated. When exposed to chlordane at a concentration of 1 µM, Drosophila lost body weight, decreased body size and resulted in lipid metabolism disorders. In addition, chlordane exposure altered the arousal and sleep behaviors of Drosophila. Short-term exposure to chlordane resulted in an increase in night-time sleep duration, while long-term exposure to chlordane resulted in an increase in activity and a decrease in sleep, as evidenced by a decrease in the duration of each sleep session and the appearance of sleep fragmentation. Under conditions of long-term chlordane exposure, reactive oxygen species levels were significantly up-regulated in Drosophila. Our results suggest that long-term chlordane exposure triggers oxidative stress damage in Drosophila, leading to sleep disruption. This study offers novel insights into the harmful impacts of environmental pollutants on human sleep patterns and proposes that mitigating the presence of chlordane in the environment could potentially contribute to the reduction of global sleep disorder prevalence.

Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.