Promising tools into oxidative stress: A review of non-rodent model organisms.

Oxidative stress is a crucial concept in redox biology, and significant progress has been made in recent years. Excessive levels of reactive oxygen species (ROS) can lead to oxidative damage, heightening vulnerability to various diseases. By contrast, ROS maintained within a moderate range plays a role in regulating normal physiological metabolism. Choosing suitable animal models in a complex research context is critical for enhancing research efficacy. While rodents are frequently utilized in medical experiments, they pose challenges such as high costs and ethical considerations. Alternatively, non-rodent model organisms like zebrafish, Drosophila, and C. elegans offer promising avenues into oxidative stress research. These organisms boast advantages such as their small size, high reproduction rate, availability for live imaging, and ease of gene manipulation. This review highlights advancements in the detection of oxidative stress using non-rodent models. The oxidative homeostasis regulatory pathway, Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), is systematically reviewed alongside multiple regulation of Nrf2-centered pathways in different organisms. Ultimately, this review conducts a comprehensive comparative analysis of different model organisms and further explores the combination of novel techniques with non-rodents. This review aims to summarize state-of-the-art findings in oxidative stress research using non-rodents and to delineate future directions.

ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-Fed ApoE-/- Mice by Regulating Lipoprotein Metabolism and Promoting Cholesterol Efflux.

BACKGROUND: Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial. Here, we comprehensively investigated the effects and the underlying molecular mechanisms of ASGR1 deficiency and overexpression on atherosclerosis and liver injury in mice. METHODS: We engineered Asgr1 knockout mice (Asgr1-/-), Asgr1 and ApoE double-knockout mice (Asgr1-/-ApoE-/-), and ASGR1-overexpressing mice on an ApoE-/- background and then fed them different diets to assess the role of ASGR1 in atherosclerosis and liver injury. RESULTS: After being fed a Western diet for 12 weeks, Asgr1-/-ApoE-/- mice exhibited significantly decreased atherosclerotic lesion areas in the aorta and aortic root sections, reduced plasma VLDL (very-low-density lipoprotein) cholesterol and LDL (low-density lipoprotein) cholesterol levels, decreased VLDL production, and increased fecal cholesterol contents. Conversely, ASGR1 overexpression in ApoE-/- mice increased atherosclerotic lesions in the aorta and aortic root sections, augmented plasma VLDL cholesterol and LDL cholesterol levels and VLDL production, and decreased fecal cholesterol contents. Mechanistically, ASGR1 deficiency reduced VLDL production by inhibiting the expression of MTTP (microsomal triglyceride transfer protein) and ANGPTL3 (angiopoietin-like protein 3)/ANGPTL8 (angiopoietin-like protein 8) but increasing LPL (lipoprotein lipase) activity, increased LDL uptake by increasing LDLR (LDL receptor) expression, and promoted cholesterol efflux through increasing expression of LXRα (liver X receptor-α), ABCA1 (ATP-binding cassette subfamily A member 1), ABCG5 (ATP-binding cassette subfamily G member 5), and CYP7A1 (cytochrome P450 family 7 subfamily A member 1). These underlying alterations were confirmed in ASGR1-overexpressing ApoE-/- mice. In addition, ASGR1 deficiency exacerbated liver injury in Western diet-induced Asgr1-/-ApoE-/- mice and high-fat diet-induced but not normal laboratory diet-induced and high-fat and high-cholesterol diet-induced Asgr1-/- mice, while its overexpression mitigated liver injury in Western diet-induced ASGR1-overexpressing ApoE-/- mice. CONCLUSIONS: Inhibition of ASGR1 inhibits atherosclerosis in Western diet-fed ApoE-/- mice, suggesting that inhibiting ASGR1 may serve as a novel therapeutic strategy to treat atherosclerosis and cardiovascular diseases.

Tuning Interfacial Molecular Asymmetry to Engineer Protective Coatings with Superior Surface Anchoring, Antifouling and Antibacterial Properties.

Multifunctional robust protective coatings that combine biocompatibility, antifouling and antimicrobial properties play an essential role in reducing host reactions and infection on invasive medical devices. However, developing these protective coatings generally faces a paradox: coating materials capable of achieving robust adhesion to substrates via spontaneous deposition inevitably initiate continuous biofoulant adsorption, while those employing strong hydration capability to resist biofoulant attachment have limited substrate binding ability and durability under wear. Herein, we designed a multifunctional terpolymer of poly(dopamine methyacrylamide-co-2-methacryloyloxyethyl phoasphorylcholine-co-2-(dimethylamino)-ethyl methacrylate) (P(DMA-co-MPC-co-DMAEMA)), which integrates desired yet traditionally incompatible functions (i.e., robust adhesion, antifouling, lubrication, and antimicrobial properties). Direct normal and lateral force measurements, dynamic adsorption tests, surface ion conductance mapping were applied to comprehensively investigate the nanomechanics of coating-biofloulant interactions. Catechol groups of DMA act as basal anchors for robust substrate deposition, while the highly hydrated zwitterion of MPC provides apical protection to resist biofouling and wear. Moreover, the antimicrobial property is conferred through the protonation of tertiary amine groups on DMAEMA, inhibiting infections under physiological conditions. This work provides an effective strategy for harmonizing demanded yet incompatible properties in one coating material, with significant implications for the development of multifunctional surfaces towards the advancement of invasive biomedical devices. STATEMENT OF SIGNIFICANCE: Multifunctional robust protective coatings have been widely utilized in invasive medical devices to mitigate host responses and infection. However, modified surface coatings often encounter a trade-off between robust adhesion to substrates and strong hydration capability for antifouling and antimicrobial properties. We propose a universal strategy for surface modification by dopamine-assisted co-deposition with a multifunctional terpolymer of P(DMA-co-MPC-co-DMAEMA) that simultaneously achieves robust adhesion, antifouling, and antimicrobial properties. Through elucidating the nanomechanics with fundamentally understanding the interactions between the coating and biomacromolecules, we highlight the role of DMA for substrate adhesion, MPC for biofouling resistance, and DMAEMA for antimicrobial activity. This approach presents a promising strategy for constructing multifunctional coatings on minimally invasive medical devices by tuning interfacial molecular asymmetricity to reconcile incompatible properties within one coating.

Deciphering the Wound-Healing Potential of Collagen Peptides and the Molecular Mechanisms: A Review.

Collagen peptides have been reported to display various bioactivities and high bioavailability. Recently, increasing evidence has revealed the excellent wound-healing activity of collagen peptides, but their molecular mechanisms remain incompletely elucidated. This review systematically evaluates the therapeutic efficacy of collagen peptides from diverse sources based on various wound models. Furthermore, the structure-activity relationships of collagen peptides and wound-healing mechanisms are discussed and summarized. Characterized by their low molecular weight and abundant imino acids, collagen peptides facilitate efficient absorption by the body to deliver nutrition throughout the wound-healing process. The specific mechanism of collagen peptide for wound healing is mainly through up-regulation of related cytokines and participation in the activation of relevant signaling pathways, such as TGF-ß/Smad and PI3K/Akt/mTOR, which can promote cell proliferation, angiogenesis, collagen synthesis and deposition, re-epithelialization, and ECM remodeling, ultimately achieving the effect of wound healing. Collagen peptides can offer a potential therapeutic approach for treating incision and excision wounds, mucosal injuries, burn wounds, and pressure ulcers, improving the efficiency of wound healing by about 10%-30%. The present review contributes to understanding of the wound-healing potential of collagen peptides and the underlying molecular mechanisms.

Changes in the Phylogenetic Structure of Alpine Grassland Plant Communities on the Qinghai-Tibetan Plateau with Long-Term Nitrogen Deposition.

Nitrogen (N) deposition rates have notably increased around the world, especially in high-altitude regions like the Qinghai-Tibetan Plateau (QTP). We conducted a six-year comprehensive experiment to simulate nitrogen deposition in an alpine grassland area near Qinghai Lake. Four levels of nitrogen depositions, i.e., 0 (CK), 8 kg N ha-1year-1 (N1), 40 kg N ha-1year-1 (N2), and 72 kg N ha-1year-1 (N3), with three replicates for each N treatment, were tested annually in early May and early July, with the meticulous collection of plant and soil samples during the peak growth period from 15 July to 15 August. We used the null model to evaluate the impact of environmental filtration and interspecific competition on the dynamics of the plant community was assessed based on the level of discrete species affinities within the plant community by constructing a phylogenetic tree. The results showed that the environmental filter was the predominant driver for the change of community's genealogical fabric. The N2 and N3 treatments increased the influence of soil factors on the change of plant community structure. Climatic factors played a crucial role on the change of plant community in the CK grassland area, while soil factors were dominant in the N1- and N3-treated grasslands.

CuO nanoparticles for glioma treatment in vitro and in vivo.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

Lipase etching effects-induced interaction between betanin nanocomplexes and polylactic acid and its 3D printing for food packaging.

Etching effects by lipase on polylactic acid (PLA) could induce the exposure of active sites and promote the attachment of betanin nanocomplexes (BR-Ch) to obtain red color. 3D printing, regarded as emerging, innovative packaging fabrication technique, was applied to potentially develop creative, red PLA products for food application. BR-Ch was prepared based on betanin and nano chitin via electrostatic interaction and hydrogen bonding, obtaining nanocomplexes with excellent thermal stability. Pre-treatments mattered greatly in PLA functionalization, and especially, lipase pre-treatment 30 min promoted BR-Ch modification on PLA. Final PLA exhibited excellent red color characteristics (CIElab, Hue-Saturation-Brightness, K/S and CMYK), elongation at break and stable thermal resistance, ultimately achieving outstanding dyeing effect. This work indicates that BR-Ch can potentially replace synthetic pigments to functionalize lipase-pretreated PLA, and the dyed PLA demonstrate the excellent packaging application prospects in food field by 3D-printed products.

Deep learning revealed the distribution and evolution patterns for invertible promoters across bacterial lineages.

Invertible promoters (invertons) are crucial regulatory elements in bacteria, facilitating gene expression changes under stress. Despite their importance, their prevalence and the range of regulated gene functions are largely unknown. We introduced DeepInverton, a deep learning model that identifies invertons across a broad phylogenetic spectrum without using sequencing reads. By analyzing 68 733 bacterial genomes and 9382 metagenomes, we have uncovered over 200 000 nonredundant invertons and have also highlighted their abundance in pathogens. Additionally, we identified a post-Cambrian Explosion increase of invertons, paralleling species diversification. Furthermore, we revealed that invertons regulate diverse functions, including antimicrobial resistance and biofilm formation, underscoring their role in environmental adaptation. Notably, the majority of inverton identifications by DeepInverton have been confirmed by the in vitro experiments. The comprehensive inverton profiles have deepened our understanding of invertons at pan-genome and pan-metagenome scales, enabling a broad spectrum of applications in microbial ecology and synthetic biology.

Enhancing Energy Density in Aqueous Ammonium-Ion Supercapacitors via CuCo2S4@MoS2 Core@Shell Heterostructure Design.

Aqueous ammonium-ion supercapacitors (AASCs) are recognized for their rapid charge-discharge capability, long cycle life, and excellent power density. However, they still confront the challenges of low energy density. To address the above issue, this work proposes a novel strategy involving the establishment of CuCo2S4@MoS2 core@shell heterostructures to enhance the capacity of electrode material. The double electric layer energy storage mechanism of the MoS2 shell facilitates the storage and provision of a substantial ammonium source for NH4 + insertion into CuCo2S4, thereby enhancing the electrochemical performance of AASCs. The density functional theory (DFT) calculations demonstrate that the CuCo2S4@MoS2 core@shell heterostructures exhibit better affinity for NH4 + and improved conductivity. Furthermore, the internal electric field at the heterojunction accelerates NH4 + transfer, thereby enhancing the pseudocapacitive behavior of CuCo2S4. Owing to the abundant active sites and pronounced pseudo-capacitance, the CuCo2S4@MoS2 electrode achieves a specific capacity of 2045 C g-1 at 1 A g-1. With activated carbon (AC) as the negative electrode, the fabricated CuCo2S4@MoS2//AC AASC device attains a specific capacity of 591 C g-1 and an energy density of 83.23 Wh kg-1. This work presents a promising new strategy for the next generation of AASCs.

Preparation, identification and α-glucosidase inhibitory activity of a high-methoxyl HG-type pectin from Liangping pomelo (Citrus maxima cv. Liangpin Yu) peel.

BACKGROUND: The peel from Liangping pomelo (Citrus maxima cv. Liangpin Yu) is generally discarded as waste during post-harvest handling and process, resulting in environmental pollution and waste. Pectin is the major component in pomelo peels and yields significant economic advantages. Thus, developing pomelo peel pectin (PPs) might be a feasible strategy to reduce environmental pollution caused by pomelo peel. RESULTS: The optimized PPs yield was 156.5 ± 2.5 g kg-1 under the inoculum size of 100 mg g-1, liquid-solid ratio of 31 mL g-1, fermentation time of 64 h, and fermentation temperature of 39 °C. PPs-6Aa, a pectin fraction from PPs purified with DEAE-52 cellulose, Sephadex G-100 and Sephadex G-75 column chromatography, showed higher α-glucosidase inhibitory activity, with an IC50 of 0.12 ± 0.03 mg mL-1. It was a high-methoxyl HG-type pectin of 42.8 kDa, and its repeat unit was →4)-α-GalpA-6-OMe-(1→4)-α-GalpA-6-OMe-(1→. Additionally, its α-glucosidase inhibitory activity might be related to hydrogen bonds formed with Lys-156, Glu-277, His-280, Asp-307, Arg-315, Asn-350, Asp-352 and Glu-411, and to hydrophobic interactions formed with Ser-157, Tyr-158, Asp-233, Gln-239, Ser-240, Phe-303, Thr-306, Leu-313, Phe-314, Gln-353 and Arg-442. CONCLUSION: These findings provide structural and bioactivity information on pectin from Liangping pomelo peel, which could be beneficial for the development of functional foods and pharmaceuticals. © 2024 Society of Chemical Industry.

Effect of cyclic topology versus linear terpolymers on antibacterial activity and biocompatibility: antimicrobial peptide avatars.

Host-defense peptides (HDPs) and their analogs hold significant potential for combating multidrug-resistant (MDR) bacterial infections. However, their clinical use has been hindered by susceptibility to proteases, high production costs, and cytotoxicity towards mammalian cells. Synthetic polymers with diverse topologies and compositions, designed to mimic HDPs, show promise for treating bacterial infections. In this study, we explored the antibacterial activity and biocompatibility of synthetic amphiphilic linear (LPs) and cyclic terpolymers (CPs) containing hydrophobic groups 2-ethylhexyl (E) and 2-phenylethyl (P) at 20% and 30% content. LPs were synthesized via RAFT polymerization and then cyclized into CPs through a hetero-Diels-Alder click reaction. The bioactivity of these terpolymers was correlated with their topology (LPs vs. CPs) and hydrophobic composition. LPs demonstrated superior antibacterial efficacy compared to CPs against four Gram-negative bacterial strains, with terpolymers containing (P) outperforming those with (E). Increasing the hydrophobicity from 20% to 30% in the terpolymers increased toxicity to both bacterial and mammalian cells. Notably, our terpolymers inhibited the MDR Gram-negative bacterial strain PA37 more effectively than gentamicin and ciprofloxacin. Furthermore, our terpolymers were able to disrupt cell membranes and rapidly eliminate Gram-negative bacteria (99.99% within 15 minutes). Interestingly, CPs exhibited higher hemocompatibility and biocompatibility with mammalian macrophage cells compared to LPs, showcasing a better safety profile (CPs > LPs). These findings underscore the importance of tailoring polymer architectures and optimizing the hydrophilic/hydrophobic balance to address challenges related to toxicity and selectivity in developing antimicrobial polymers.

Enhanced Oncolytic Potential of Engineered Newcastle Disease Virus Lasota Strain through Modification of Its F Protein Cleavage Site.

Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4+ and CD8+ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-γ, IL-15, and TNF-α, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy.

In-Depth Analysis of Molecular Network Based on Liquid Chromatography Coupled with Tandem Mass Spectrometry in Natural Products: Importance of Redundant Nodes Discovery.

The identification of molecules within complex mixtures is a major bottleneck in natural products (NPs) research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as the main tool for the high-throughput characterization of NPs. The large amount of data sets by LC-MS/MS presents a challenge for data processing and interpretation, and the LC-MS/MS molecular network (MN) is one of the most prominent tools for analyzing large MS/MS data sets, widely used for rapid classification, identification, and structural speculation of unknown compounds. However, the existence of a large number of redundant nodes leads to false-positive results. To solve this problem, we proposed the in-depth analysis of MN. In this study, in-depth analysis of MN of five NPs representing the common structures of saponin, steroid, flavonoid, alkaloid, and phenolic acid revealed the presence of redundant nodes (including other adducts, isotope, and in-source fragmentation) in addition to the normal nodes, which can lead to false-positive identification results. Additionally, the reasons for different redundant nodes are discussed and experimentally verified, and it was found that the impact of redundant nodes can be mitigated by optimizing the experimental conditions and employing Feature-Based Molecular Networking. Furthermore, Ion Identity Molecular Networking can rapidly discover and screen redundant nodes, simplifying the in-depth analysis of MN and improving the network connectivity of structurally related molecules. Finally, a combination formulation of 7 NPs is used as an example to provide a guide for in-depth analysis of MN for comprehensive characterization of complex systems. This study highlights the importance of an in-depth analysis of MN for better understanding and utilization of MS/MS data in complex systems to reduce the false-positive rate of identification by screening and filtering redundant nodes.

Design, synthesis, bioactivity and action mechanism of N-substituted N'-phenylpicolinohydrazides against phytopathogenic fungi.

N'-phenylpicolinohydrazide has been proven to be a promising lead compound for research and development of novel fungicides for agriculture in our previous study. As our continuing research, in this study, a series of N-substituted derivatives of N'-phenylpicolinohydrazide were synthesized and explored for the inhibition activity on nine phytopathogenic fungi and action mechanism. The results found that eleven of the compounds had excellent antifungal activity with more than 80% inhibition rates at 50 µg/mL on part or most of the fungi, especially A. solani and P. piricola. Compounds 5i, 5j and 5k showed EC50 values of < 8.0 µg/mL against A. solani superior to positive control carbendazim (EC50 = 36.0 µg/mL) while 5p and 5q exhibited the highest activity with EC50 values of 2.72 and 2.80 µg/mL against P. piricola superior to positive control boscalid (EC50 > 50.0 µg/mL). Furthermore, 5k also showed significant protective effect against A. solani infection on tomatoes in a concentration-dependent manner. Action mechanism research showed that 5k was able to increase the intracellular ROS level, change both MMP and permeability of cell membrane and damage mycelial morphology. Molecular docking studies showed that 5k could bind into ubiquinone-binding region of succinate dehydrogenase by hydrogen bonds, π-cation, π-π stacked, π-alkyl, and alkyl interactions. Additionally, the antibacterial activity was also investigated. Thus, N-substituted derivatives of N'-phenylpicolinohydrazide were emerged as novel and highly promising antifungal molecular skeletons to develop new fungicides for crop protection.

Systemic immunity-inflammation index is associated with body fat distribution among U.S. adults: evidence from national health and nutrition examination survey 2011-2018.

OBJECTIVE: The systemic immunity-inflammation index (SII) is a newly developed biomarker that provides an integrated measure of inflammation in the body. We aim to evaluate the relationship between SII and body fat distribution. METHODS: Adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. The SII was computed using lymphocyte (LC), neutrophil (NC), and platelet (PC) counts as its components. Body fat distribution was assessed by (total, android, gynoid) percentage fat, total abdominal fat area, subcutaneous adipose tissue area, visceral adipose tissue area, and the ratio of visceral to subcutaneous adipose tissue area (V/S ratio). Multivariable weighted linear regression and subgroup analysis were use to examine the relationships between fat distribution and SII. Restricted cubic splines (RCS) and threshold effect analysis were used to examine analyze nonlinear associations. RESULTS: After exclusions, a total of 11,192 adults with a weighted mean age of 38.46 ± 0.26 years were studied. In multivariable weighted linear regression, each level increase in log2SII was associated with increased of 0.23 SDs total percentage fat (95% CI = 0.03, 0.43) and 0.26 SDs android percentage fat (95% CI = 0.06, 0.47). Besides, the subgroup analysis showed that the positive association between SII and android percentage fat was mainly among obese individuals (BMI > 30 kg/m2) and non-obese individuals without DM or hypertension. Meanwhile, the relationship between SII and the V/S ratio was found to be significant in the female subgroup, the obese subgroup, individuals with non-alcoholic fatty liver disease (NAFLD), and those without diabetes mellitus. Finally, SII exhibited an inverted U-shaped relationship with total percentage fat, android percent fat and total abdominal fat. Accordingly, threshold effect analysis indicated a positive association between lower SII levels and total percentage fat, android percentage fat and total abdominal fat area. CONCLUSIONS: In the nationwide study, it was observed that the SII exhibited a significant correlation with higher levels of body fat, specifically android fat. This association was particularly noticeable within specific subgroups of the population.

Design, Bioactivity, and Action Mechanism of Pyridinecarbaldehyde Phenylhydrazone Derivatives with Broad-Spectrum Antifungal Activity.

Replacing old pesticides with new pesticide varieties has been the main means to solve pesticide resistance. Therefore, it is necessary to research and develop new antifungal agents for plant protection. In this study, a series of pyridinecarbaldehyde phenylhydrazone derivatives were designed and evaluated for their inhibition activity on plant pathogenic fungi to search for novel fungicide candidates. Picolinaldehyde phenylhydrazone (1) and nicotinaldehyde phenylhydrazone (2) were identified as promising antifungal lead scaffolds. The 4-fluorophenylhydrazone derivatives (1a and 2a) of 1 and 2 showed highly effective and broad-spectrum inhibition activity in vitro on 11 phytopathogenic fungi with EC50 values of 0.870-3.26 µg/mL, superior to the positive control carbendazim in most cases. The presence of the 4-fluorine atom on the phenyl showed a remarkable activity enhancement effect. Compound 1a at 300 µg/mL provided almost complete protection against infection of Alternaria solani on tomatoes over the post-treatment 9 days and high safety to germination of plant seeds. Furthermore, 1a showed strong inhibition activity with an IC50 value of 0.506 µg/mL on succinate dehydrogenase in A. solani. Molecular docking showed that both 1a and 2a can well bind to the ubiquinone-binding region of SDH by the conventional hydrogen bond, carbon-hydrogen bond, π-π or π-amide interaction, π-alkyl interaction, X---F (X = N, C, or H) interaction, and van der Waal forces. Meanwhile, scanning and transmission electron analysis displayed that 1a destroyed the morphology of mycelium and the structure of the cell membrane of A. solani. Fluorescent staining analysis revealed that 1a changed the mitochondrial membrane potential and cell membrane permeability. Thus, pyridinecarbaldehyde phenylhydrazone compounds emerged as novel antifungal lead scaffolds, and 1a and 2a can be considered promising candidates for the development of new agricultural fungicides.

Inhibition of circular JUN prevents the proliferation and invasion of glioblastoma via miR-3064-IGFBP5 axis.

Glioblastoma (GBM) remains one of the most aggressive and lethal brain tumours, characterized by rapid progression and limited treatment options. This study investigated the regulatory roles of circular RNA circJUN, and its functional interaction with microRNA miR-3064 in GBM pathogenesis. We employed bioinformatic analyses and clinical sample validation to identify circJUN as a potential target in GBM. Subsequently, we engineered GBM cell lines with stable circJUN knockout or overexpression, and transfected them with miR-3064 mimic/inhibitor or IGFBP5 small interfering RNA (siRNA)/expression vector to elucidate the molecular mechanisms governing GBM proliferation and invasion. To investigate the in vivo effects, xenograft tumour models were established in nude mice using engineered cells to assess the roles of circJUN in tumour growth regulation. Our analyses revealed significant overexpression of circJUN in GBM tissues compared to healthy controls, which strongly correlated with poor patient prognosis. In vitro and in vivo experiments demonstrated that circJUN overexpression could enhance GBM cell proliferation and invasion. Mechanistic investigations uncovered EIF4A3 as an interacting factor of circJUN which promotes circJUN expression, and circJUN modulates miR-3064 activity to regulate the malignancy of GBM cells. Furthermore, we identified IGFBP5, a crucial regulator of cell growth, as a direct target of miR-3064, thereby establishing an additional layer of control over GBM proliferation and invasion. Our study unveils a complex regulatory network involving circJUN, miR-3064 and IGFBP5 in GBM pathogenesis, underscoring their potential as novel therapeutic targets for improving patient outcomes. Our findings not only contribute to the understanding of GBM biology but also pave the way for innovative therapeutic approaches in the management of this malignancy.

Aggregation-Disruption-Induced Multi-Scale Mediating Strategy for Anticoagulation in Blood-Contacting Devices.

Minimally invasive blood-contacting interventional devices are increasingly used to treat cardiovascular diseases. However, the risk of device-related thrombosis remains a significant concern, particularly the formation of cycling thrombi, which pose life-threatening risks. To better understand the interactions between these devices and blood, the initial stages of coagulation contact activation on extrinsic surfaces are investigated. Direct force measurements reveals that activated contact factors stimulate the intrinsic coagulation pathway and promote surface crosslinking of fibrin. Furthermore, fibrin aggregation is disrupted by surface-grafted inhibitors, as confirmed by ex vivo coagulation tests. An engineered serum protein with zwitterion grafts to resist the deposition of biological species such as fibrin, platelets, and red blood cells is also developed. Simultaneously, a protease inhibitor-based coacervate is incorporated into the coating to inhibit the intrinsic pathway effectively. The loaded coacervate can be released and reloaded through modulation of catechol-amine interactions, facilitating material regeneration. The strategy offers a novel multi-scale mediation strategy that simultaneously inhibits nanoscale coagulation factors and resists microscale thrombus aggregation, providing a long-term solution for anticoagulation in blood-contacting devices.

Cu-Bi Bimetallic Catalysts Derived from Metal-Organic Framework Arrays on Copper Foam for Efficient Glycine Electrosynthesis.

Glycine as one of the most abundant amino acids in human proteins, with extensive applications in both life and industry, is conventionally synthesized through complex procedures or toxic feedstocks. In this study, we present a facile and benign electrochemical pathway for synthesis of glycine through reductive coupling of glyoxylic acid and nitrate over a copper-bismuth bimetal catalyst derived from a metal-organic framework (MOF) array on copper foam (Cu/Bi-C@CF). Remarkably, Cu/Bi-C@CF achieves a fantastic selectivity of 89%, corresponding a high Faraday efficiency of 65.9%. From control experiments, introduction of Bi caused the binding energy of Cu shift to lower state, which leads to a high selectivity towards the formation of key hydroxylamine intermediate rather than ammonia product, facilitating the formation of oxime and providing additional sites for subsequent hydrogenation reaction on the way to glycine. Moreover, the MOF array derivation ensures the effective dispersion of Bi and enhances the stability of Cu/Bi-C@CF. This innovative approach not only presents sustainable pathways for the production of value-added organonitrogen compounds utilizing readily available carbon and nitrogen sources, but also provides novel insights into the design of multistage structural catalysts for sequential reactions.

Characteristic of epicotyl dormancy and its hormonal regulation in Chinese cork oak (Quercus variabilis).

Emergence heterogeneity caused by epicotyl dormancy contributes to variations in seedling quality during large-scale breeding. However, the mechanism of epicotyl dormancy release remains obscure. We first categorized the emergence stages of Chinese cork oak (Quercus variabilis) using the BBCH-scale. Subsequently, we identified the key stage of the epicotyl dormancy process. Our findings indicated that cold stratification significantly released epicotyl dormancy by increasing the levels of gibberellic acid 3 (GA3) and GA4. Genes associated with GA biosynthesis and signaling also exhibited altered expression patterns. Inhibition of GA biosynthesis by paclobutrazol (PAC) treatment severely inhibited emergence, with no effect on seed germination. Different concentrations (50 µM, 100 µM, and 200 µM) of GA3 and GA4+7 treatments of germinated seeds demonstrated that both can promote the emergence, with GA4 exhibiting a more pronounced effect. In conclusion, this study provides valuable insights into the characterization of epicotyl dormancy in Chinese cork oak and highlights the critical role of GA biosynthesis in seedling emergence. These findings serve as a basis for further investigations on epicotyl dormancy and advancing large-scale breeding techniques.