Carbon Nanomaterials for Plant Priming through Mechanostimulation: Emphasizing the Role of Shape.

The use of nanomaterials to improve plant immunity for sustainable agriculture is gaining increasing attention; yet, the mechanisms involved remain unclear. In contrast to metal-based counterparts, carbon-based nanomaterials do not release components. Determining how these carbon-based nanomaterials strengthen the resistance of plants to diseases is essential as well as whether shape influences this process. Our study compared single-walled carbon nanotubes (SWNTs) and graphene oxide (GO) infiltration against the phytopathogen Pseudomonas syringae pv tomato DC3000. Compared with plants treated with GO, plants primed with SWNTs showed a 29% improvement in the pathogen resistance. Upon nanopriming, the plant displayed wound signaling with transcriptional regulation similar to that observed under brushing-induced mechanostimulation. Compared with GO, SWNTs penetrated more greatly into the leaf and improved transport, resulting in a heightened wound response; this effect resulted from the tubular structure of SWNTs, which differed from the planar form of GO. The shape effect was further demonstrated by wrapping SWNTs with bovine serum albumin, which masked the sharp edges of SWNTs and resulted in a significant decrease in the overall plant wound response. Finally, we clarified how the local wound response led to systemic immunity through increased calcium ion signaling in distant plant areas, which increased the antimicrobial efficacy. In summary, our systematic investigation established connections among carbon nanomaterial priming, mechanostimulation, and wound response, revealing recognition patterns in plant immunity. These findings promise to advance nanotechnology in sustainable agriculture by strengthening plant defenses, enhancing resilience, and reducing reliance on traditional chemicals.

Nano-microflora Interaction Inducing Pulmonary Inflammation by Pyroptosis.

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.

Preparation of a novel antibacterial magnesium carbonate coating on a titanium surface and its in vitro biocompatibility.

Magnesium-based coatings have attracted great attention in surface modification of titanium implants due to their superior angiogenic and osteogenic properties. However, their biological effects as a carbonate-based constituent remain unrevealed. In this study, magnesium carbonate coatings were prepared on titanium surfaces under hydrothermal conditions and subsequently treated with hydrogen peroxide. Also, their antibacterial activity and in vitro cell biocompatibility were evaluated. The obtained coatings consisted of nanoparticles without cracks and exhibited excellent adhesion to the substrate. X-ray diffraction (XRD) results indicated pure magnesium carbonate coatings formed on the Ti surface after hydrothermal treatment. After hydrogen peroxide treatment, the phase composition of the coatings had no obvious change. Compared to the untreated coatings, the hydrogen peroxide-treated coatings showed increased surface roughness and hydrophilicity. Co-culture with Staphylococcus aureus (S. aureus) demonstrated that the obtained coatings had good antibacterial activity. In vitro cell culture results showed that the hydrogen peroxide-treated coatings enhanced the viability, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These findings suggest that this MgCO3-based coating exhibits excellent antibacterial performance and osteogenic potential. Based on the above, this study provides a simple method for preparing titanium implants with dual antibacterial and osteogenic capabilities, holding great promise in clinical applications.

Unveiling key mechanisms: Transcriptomic meta-analysis of diverse nanomaterial applications addressing biotic and abiotic stresses in Arabidopsis Thaliana.

The potential applications of nanomaterials in agriculture for alleviating diverse biotic and abiotic stresses have garnered significant attention. The reported mechanisms encompass promoting plant growth and development, alleviating oxidative stress, inducing defense responses, modulating plant-microbe interactions, and more. However, individual studies may not fully uncover the common pathways or distinguish the effects of different nanostructures. We examined Arabidopsis thaliana transcriptomes exposed to biotic, abiotic, and metal or carbon-based nanomaterials, utilizing 24 microarray chipsets and 17 RNA-seq sets. The results showed that: 1) from the perspective of different nanostructures, all metal nanomaterials relieved biotic/abiotic stresses via boosting metal homeostasis, particularly zinc and iron. Carbon nanomaterials induce hormone-related immune responses in the presence of both biotic and abiotic stressors. 2) Considering the distinct features of various nanostructures, metal nanomaterials displayed unique characteristics in seed priming for combating abiotic stresses. In contrast, carbon nanomaterials exhibited attractive features in alleviating water deprivation and acting as signaling amplifiers during biotic stress. 3) For shared pathway analysis, response to hypoxia emerges as the predominant and widely shared regulatory mechanism governing diverse stress responses, including those induced by nanomaterials. By deciphering shared and specific pathways and responses, this research opens new avenues for precision nano-agriculture, offering innovative strategies to optimize plant resilience, improve stress management, and advance sustainable crop production practices.

Zinc oxide nanoparticles enhance plasmid transfer among growth-promoting endophytes in Arabidopsis thaliana.

Nanoparticles (NPs) hold great promise for agricultural applications, yet their potential impact on exogenous gene transfer within plant remains poorly understood. In this study, we utilized the non-conjugative plasmid pCAMBIA1300, harboring the bialaphos resistance (bar) gene expressed in plant and the kanamycin resistance (kanR) gene as selectable marker in bacteria. Our results revealed a significant increase in the transfer of plasmid (via carrier Escherichia coli DH5α), both intra- and inter-species within the endophyte, when Arabidopsis thaliana was exposed to environmentally relevant level of zinc oxide (ZnO) NPs at a concentration of 0.7 µg/mL throughout its lifespan. Intriguingly, the plasmid exhibited selective transfer to growth-promoting endophytes, such as Enterobacter, Serratia, and Achromobacter, with the presence of ZnO NPs expanding the pool of potential recipients. This result is due to the facilitation of an endophytic and mutualistic lifestyle of invasive E. coli DH5α and the enrichment of beneficial bacteria aided by ZnO NPs. The plant's descendant generations did not express the bar gene, and the endophytes carrying the exogenous plasmid did not transmit it to sub sequent generation. This research provides crucial insights for assessing the potential risks associated with gene contamination and ensuring the safe and sustainable use of NPs in agriculture.

New insights into nanotherapeutics for periodontitis: a triple concerto of antimicrobial activity, immunomodulation and periodontium regeneration.

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.

Cell response and bone ingrowth to 3D printed Ti6Al4V scaffolds with Mg-incorporating sol-gel Ta2O5 coating.

In recent years, additive manufacturing techniques have been used to fabricate 3D titanium (Ti)-based scaffolds for production of desirable complex shapes. However, insufficient osteointegration of porous Ti-based scaffolds can elicit long-term complications (e.g., aseptic loosening) and need further revision surgery. In this study, a magnesium (Mg)-incorporating tantalum (Ta) coating was deposited on a 3D Ti6Al4V scaffold using a sol-gel method for enhancing its osteogenic properties. To evaluate the biofunction of this surface, bone mesenchymal stem cells and rabbit femoral condyle were used to assess the cell response and bone ingrowth, respectively. Ta2O5 coatings and Mg-incorporating Ta2O5 coatings were both homogeneously deposited on porous scaffolds. In vitro studies revealed that both coatings exhibit enhanced cell proliferation, ALP activity, osteogenic gene expression and mineralization compared with the uncoated Ti6Al4V scaffold. Especially for Mg-incorporating Ta2O5 coatings, great improvements were observed. In vivo studies, including radiographic examination, fluorochrome labeling and histological evaluation also followed similar trends. Also, bone ingrowth to scaffolds with Mg-incorporating Ta2O5 coatings exhibited the most significant increase compared with uncoated and Ta2O5 coated scaffolds. All the above results indicate that Mg-doped Ta2O5 coatings are an effective tool for facilitating osteointegration of conventional porous Ti6Al4V scaffolds.

Open reduction and internal fixation of irreducible displaced femoral neck fracture with femoral Neck System: a preliminary study.

BACKGROUND: Most displaced femoral neck fractures can achieve satisfactory anatomical reduction by closed reduction, but there are still some that cannot reset satisfactorily after closed reduction, and open reduction are required. Such fractures that cannot be repositioned successfully by closed reduction are called irreducible displaced femoral neck fractures in this study. The objective of our study was to evaluate the efficacy of direct anterior incision with the Femoral Neck System in the treatment of irreducible displaced femoral fractures. METHODS: A total of 16 young and middle-aged patients with irreducible displaced femoral neck fractures involving Garden type III and IV were treated using Femoral Neck System fixation by open reduction through Direct Anterior Approach between January 2020 to September 2021. Functional outcomes and postoperative complications were assessed during follow-up. Clinical outcomes were evaluated by the Hip Harris score. The postoperative reduction was evaluated by the Garden Index. Observe postoperative complications. RESULTS: All patients were followed up with a mean follow-up time of 21.1(12-30) months, and according to radiological results, all patients achieved fracture healing, with a mean healing time of 4.25 months. All 16 patients received grade Garden I and II reductions, and there was no significant difference in the anteroposterior Garden reduction index between the first day after surgery (166.13 ± 5.61) and the 12th month after surgery(164.94 ± 4.49) (P>0.05) and no significant difference in lateral Garden index between the first day after surgery(171.06 ± 4.46) and the 12th month after surgery(169.38 ± 3.98) (P<0.05). According to the Hip Harris score scale, 13 patients received excellent and 3 patients received good. The postoperative Hip Harris Score(17.19 ± 4.8) was significantly higher than the preoperative score(92.19 ± 3.4), and the difference was statistically significant (P < 0.05). No or mild femoral neck shortness occurred in 12 (75%) patients, moderate shortening occurred in 3 (18.75%) patients, and severe shortening occurred in 1 (6.25%) patient. None of the patients experienced femoral head necrosis, fracture nonunion, or incision infection. One patient developed deep venous thrombosis of the lower extremity. CONCLUSIONS: The Direct Anterior Approach combined with Femoral Neck System is an excellent treatment for irreducible displaced femoral neck fracture and achieved good functional outcomes and anatomical reduction with low complications.

Prediction of base editor off-targets by deep learning.

Due to the tolerance of mismatches between gRNA and targeting sequence, base editors frequently induce unwanted Cas9-dependent off-target mutations. Here, to develop models to predict such off-targets, we design gRNA-off- target pairs for adenine base editors (ABEs) and cytosine base editors (CBEs) and stably integrate them into the human cells. After five days of editing, we obtain valid efficiency datasets of 54,663 and 55,727 off-targets for ABEs and CBEs, respectively. We use the datasets to train deep learning models, resulting in ABEdeepoff and CBEdeepoff, which can predict off-target sites. We use these tools to predict off-targets for a panel of endogenous loci and achieve Spearman correlation values varying from 0.710 to 0.859. Finally, we develop an integrated tool that is freely accessible via an online web server http://www.deephf.com/#/bedeep/bedeepoff . These tools could facilitate minimizing the off-target effects of base editing.

Bacterial memory in antibiotic resistance evolution and nanotechnology in evolutionary biology.

Bacterial memory refers to the phenomenon in which past experiences influence current behaviors in response to changing environments. It serves as a crucial process that enables adaptation and evolution. We first summarize the state-of-art approaches regarding history-dependent behaviors that impact growth dynamics and underlying mechanisms. Then, the phenotypic and genotypic origins of memory and how encoded memory modulates drug tolerance/resistance are reviewed. We also provide a summary of possible memory effects induced by antimicrobial nanoparticles. The regulatory networks and genetic underpinnings responsible for memory building partially overlap with nanoparticle and drug exposures, which may raise concerns about the impact of nanotechnology on adaptation. Finally, we provide a perspective on the use of nanotechnology to harness bacterial memory based on its unique mode of actions on information processing and transmission in bacteria. Exploring bacterial memory mechanisms provides valuable insights into acclimation, evolution, and the potential applications of nanotechnology in harnessing memory.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

PURPOSE: Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. METHODS: To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. RESULTS: Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. CONCLUSION: The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.

Advances in the application of Mxene nanoparticles in wound healing.

Skin is the largest organ of the human body. It plays a vital role as the body's first barrier: stopping chemical, radiological damage and microbial invasion. The importance of skin to the human body can never be overstated. Delayed wound healing after a skin injury has become a huge challenge in healthcare. In some situations, this can have very serious and even life-threatening effects on people's health. Various wound dressings have been developed to promote quicker wound healing, including hydrogels, gelatin sponges, films, and bandages, all work to prevent the invasion of microbial pathogens. Some of them are also packed with bioactive agents, such as antibiotics, nanoparticles, and growth factors, that help to improve the performance of the dressing it is added to. Recently, bioactive nanoparticles as the bioactive agent have become widely used in wound dressings. Among these, functional inorganic nanoparticles are favored due to their ability to effectively improve the tissue-repairing properties of biomaterials. MXene nanoparticles have attracted the interest of scholars due to their unique properties of electrical conductivity, hydrophilicity, antibacterial properties, and biocompatibility. The potential for its application is very promising as an effective functional component of wound dressings. In this paper, we will review MXene nanoparticles in skin injury repair, particularly its synthesis method, functional properties, biocompatibility, and application.

Exploring the molecular mechanism of Nux Vomica in treating ischemic stroke using network pharmacology and molecular docking methods.

BACKGROUND: Nux Vomica (NV) has the effects of dredging collaterals, relieving pain, dispersing knots, and detumescence, and has a verified effect in treating ischemic stroke (IS), but its molecular mechanism for treating IS remains unclear. In this study, network pharmacology and molecular docking methods were adopted to explore the pharmacological mechanism of NV in treating IS. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the HERB database were searched to screen the active components and targets of NV. IS disease targets were retrieved from the DisGeNET, DrugBank, GeneCards, and Therapeutic Target Database. Venn diagram and intersection targets were obtained from the Venny website. Subsequently, the STRING database was employed to analyze the interrelationship of the intersection targets. Metascape database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection targets. Furthermore, Cytoscape was employed to plot a drug-component-target network, and other networks, and molecular docking method was adopted to predict the effective components and targets of NV for treating IS. RESULTS: A total of 14 active compounds and 59 targets of NV were screened, of which 35 targets were related to IS. Stigmasterol, brucine, isobrucine, isostrychnine N-oxide (I), (S)-stylopine, icaride A, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one were the main active ingredients, and SLC6A4, NR3C1, SLC6A3, HTR3A, CHRNA7, MAOA, PTGS2, ESR1, catalase (CAT), ADRB2, and AR were the core targets. Molecular docking shows that these compounds bind well to the core targets. In addition, the treatment of IS by NV may mainly involve salivary secretion, serotonergic synapse, calcium signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. CONCLUSIONS: This study revealed that NV exerts its therapeutic effect on IS through multi-component, multi-target, and multi-pathway, which provides a basis for clinical treatment of IS.

BP@Au undergoes rapid degradation and releases singlet oxygen under dark conditions: Doping effect and detrimental effects on superoxide-producing marine algae.

Black phosphorus (BP) shows encouraging utility in many fields, and metal doping has been suggested as an efficient way to improve stability. However, controversial results and inconsistent mechanisms have been reported for doping modulation and stability change. We observed the unforeseen evolution of singlet oxygen (1O2) from BP integrated with gold nanoparticles (BP@Au) under dark conditions, and this led to rapid BP deterioration, even though enhanced stability is commonly thought via surface doping. Briefly, the BP reacted with oxygen and water to yield superoxide (O2•-) and hydrogen peroxide. Au0 acted as an enzyme mimic and catalyzed the conversion of these derivatives, and Au0 was converted to a mixture of Au3+ and Au+. The O2•- was converted to 1O2 via direct donation of electrons to the Au3+/+. The Au-catalyzed redox reactions accelerated the degradation of the BP nanosheets. BP@Au showed significant toxicity toward marine alga that produce O2•- in the dark, as indicated by a more than 30% reduction in cell viability after 12 h of incubation with 7.56 mg/L BP@Au. The novelty of this work lies in the demonstration of a dopant-related degradation pathway of BP that shows unrevealed toxicity toward O2•--producing marine algae.

Deep muscle stimulator in the treatment of post-stroke spasticity: A protocol for systematic review and meta-analysis.

BACKGROUND: Spasticity is one of the most common complications and sequelae of stroke, with the main clinical manifestations being increased muscle tension, pain, stiffness, and other disorders. It not only increases the length of hospitalization and medical costs but also affects the quality of daily life and the stress of returning to society, increasing the burden on patients and their families. At present, 2 driver types of deep muscle stimulator (DMS) have been used in the clinical treatment of post-stroke spasticity (PSS) with good clinical results, but there is no evidence of clinical efficacy and safety. Therefore, this study aims to integrate direct and indirect comparative clinical evidence through a systematic review and network meta-analysis (NMA). According to the data, different driver types for DMS with the same body of evidence will be collected, analyzed, and sequenced in a quantitative and comprehensive manner and then screened for the optimal driver type of DMS device for PSS treatment. The study also aims to provide reference value and an evidence-based theoretical basis for the clinical optimization of DMS equipment selection. METHODS: A comprehensive retrieval of China National Knowledge Infrastructure, Chinese scientific journal database, China biological feature database, Wanfang Chinese databases and the Cochrane Library, PubMed, Web of Science, and Embase foreign databases will be conducted. Randomized controlled trials of these 2 driver types of DMS devices combined with conventional rehabilitation training of PSS will be searched and published. The retrieval time is from the establishment of the database to December 20, 2022. The 2 first authors will screen references that meet the inclusion criteria, independently extract data according to predesigned rules, and assess the quality of the included studies and the risk of bias according to the Cochrane 5.1 Handbook criteria. R programming and Aggregate Data Drug Information System software will be used to perform a combined NMA of the data and to evaluate the probability of ranking for all interventions. RESULTS: The NMA and probability ranking will determine the best driver type of DMS device for PSS. CONCLUSION: This study will offer a comprehensive evidence-based approach to DMS therapy and assist doctors, PSS patients, and decision-makers in selecting a more efficient, secure, and cost-effective treatment option.

Creating a Nanoscale Lateral Junction in a Semiconductor Monolayer with a Large Built-in Potential.

The ability to engineer atomically thin nanoscale lateral junctions is critical to lay the foundation for future two-dimensional (2D) device technology. However, the traditional approach to creating a heterojunction by direct growth of a heterostructure of two different materials constrains the available band offsets, and it is still unclear if large built-in potentials are attainable for 2D materials. The electronic properties of atomically thin semiconducting transition metal dichalcogenides (TMDs) are not static, and their exciton binding energy and quasiparticle band gap depend strongly on the proximal environment. Recent studies have shown that this effect can be harnessed to engineer the lateral band profile of a monolayer TMD to create a lateral electronic junction. Here we demonstrate the synthesis of a nanoscale lateral junction in monolayer MoSe2 by intercalating Se at the interface of an hBN/Ru(0001) substrate. The Se intercalation creates a spatially abrupt modulation of the local hBN/Ru work function, which is imprinted directly onto an overlying MoSe2 monolayer to create a lateral junction with a large built-in potential of 0.83 ± 0.06 eV. We spatially resolve the MoSe2 band profile and work function using scanning tunneling spectroscopy to map out the nanoscale depletion region. The Se intercalation also modifies the dielectric environment, influencing the local band gap renormalization and increasing the MoSe2 band gap by ∼0.26 ± 0.1 eV. This work illustrates that environmental proximity engineering provides a robust method to indirectly manipulate the band profile of 2D materials outside the limits of their intrinsic properties.

Correction: Mixing behavior of p-terphenyl-3,5,3',5'-tetracarboxylic acid with trimesic acid at the solid-liquid interface.

Correction for 'Mixing behavior of p-terphenyl-3,5,3',5'-tetracarboxylic acid with trimesic acid at the solid-liquid interface' by Wei Li et al., Phys. Chem. Chem. Phys., 2021, 23, 25896-25900, https://doi.org/10.1039/D1CP04770A.

Curcumin's mechanism of action against ischemic stroke: A network pharmacology and molecular dynamics study.

Ischemic stroke (IS) is one of the major global causes of death and disability. Because blood clots block the neural arteries provoking ischemia and hypoxia in the brain tissue, IS results in irreversible neurological damage. Available IS treatments are currently limited. Curcumin has gained attention for many beneficial effects after IS, including neuroprotective and anti-inflammatory; however, its precise mechanism of action should be further explored. With network pharmacology, molecular docking, and molecular dynamics (MD), this study aimed to comprehensively and systematically investigate the potential targets and molecular mechanisms of curcumin on IS. We screened 1096 IS-related genes, 234 potential targets of curcumin, and 97 intersection targets. KEGG and GO enrichment analyses were performed on these intersecting targets. The findings showed that the treatment of IS using curcumin is via influencing 177 potential signaling pathways (AGE-RAGE signaling pathway, p53 signaling pathway, necroptosis, etc.) and numerous biological processes (the regulation of neuronal death, inflammatory response, etc.), and the AGE-RAGE signaling pathway had the largest degree of enrichment, indicating that it may be the core pathway. We also constructed a protein-protein interaction network and a component-target-pathway network using network pharmacology. From these, five key targets were screened: NFKB1, TP53, AKT1, STAT3, and TNF. To predict the binding conformation and intermolecular affinities of the key targets and compounds, molecular docking was used, whose results indicated that curcumin exhibited strong binding activity to the key targets. Moreover, 100 ns MD simulations further confirmed the docking findings and showed that the curcumin-protein complex could be in a stable state. In conclusion, curcumin affects multiple targets and pathways to inhibit various important pathogenic mechanisms of IS, including oxidative stress, neuronal death, and inflammatory responses. This study offers fresh perspectives on the transformation of curcumin to clinical settings and the development of IS therapeutic agents.

Nitrate sink function of riparian zones induced by river stage fluctuations.

River stage fluctuation (RSF) induced by tides, dam releases, or storms may lead to enhanced nitrogen cycling (N cycling) in riparian zones (RZ). We conducted a laboratory water table manipulation experiment and applied a multiphase flow and transport model (TOUGHREACT) to investigate the role of RSF in N cycling in the RZ. Coupled nitrification and denitrification occur in the water table fluctuation zone under alternating aerobic and anaerobic conditions. Nitrate removal was enhanced in the saturated and unsaturated zones of the RZ. The net nitrate reduction rate in groundwater increased with the increasing number of RSF, as a result, the cumulative water influx. The RZ nitrate sink function became stronger with increasing RSF amplitude and soil organic matter (SOM) content, and weaker with increasing [NH4+]/[NO3-] ratio and mineralization rate. RSF generally creates a hot moment for net nitrate removal in the RZ. However, a hot moment for the nitrate source function might occur if the [NH4+]/[NO3-] ratio of groundwater is much greater than 1 and/or if a large pool of nitrate accumulates in the topsoil over a prolonged dry period. The absence of oxygen diffusion in the model would overestimate the nitrate removal capacity of the RZ.