Removal Of Reactive Oxygen Species Research Articles

NpCIPK6–NpSnRK1 module facilitates inter-subgeneric hybridization barriers in water lily (nymphaea) by reducing abscisic acid content

Abstract Pre-fertilization hybridization barriers are the main causes of inter-subgeneric hybridization challenges in water lily. However, the mechanism underlying low compatibility between pollen and stigma of water lily remains unclear. This study demonstrates that CBL-interacting protein kinase 6 (CIPK6) responded to the signaling exchange between incompatible pollen and stigma through interactions with SNF1-related kinase 1 (SnRK1) and promotes the accumulation of SnRK1 protein. Activated SnRK1 interacted with 9-cis-epoxycarotenoid dioxygenase 2 (NCED2) to promote its degradation, thereby inhibiting abscisic acid (ABA) synthesis. A decrease in ABA content in the stigma impaired the ABA-mediated removal of reactive oxygen species (ROS), ultimately resulting in the rejection of the incompatible pollen by the stigma. Our results highlight the essential role of the NpCIPK6–NpSnRK1–NpNCED2 module in conferring inter-subgeneric hybridization barriers in water lily by interfering with ABA synthesis and promoting ROS accumulation. This study offers valuable mechanistic insights into cellular signaling and reproductive barriers in water lily as well as across other biological contexts.

Exogenous silicon alleviates aluminum stress in Eucalyptus species by enhancing the antioxidant capacity and improving plant growth and tolerance quality

BackgroundAs an efficient and high-quality additive in agriculture and forestry production, silicon (Si) plays an important role in alleviating heavy metal stress and improving plant growth. However, the alleviating effect of aluminum (Al) toxicity by Si in Eucalyptus is still incomplete.ResultsHere, a study was conducted using two Al concentrations (0 and 4.5 mM) with four Si concentrations (0, 0.5, 1, and 1.5 mM) to investigate plant growth, tolerance and antioxidant defense system in four Eucalyptus species (Eucalyptus tereticornis, Eucalyptus urophylla, Eucalyptus grandis, and Eucalyptus urophylla × Eucalyptus grandis). The results showed that the stress induced by 4.5 mM Al increased oxidative damage, disturbed the balance of enzymatic and non-enzymatic antioxidant systems, and negatively affected plant growth and tolerance quality in the four Eucalyptus species. However, the addition of 0.5 mM and 1 mM Si alleviated the effects of Al toxicity on plant growth and improved plant growth quality by strengthening stress tolerance. Besides, adding Si significantly facilitated the synergistic action of enzymatic and non-enzymatic antioxidant defenses, increased the removal of reactive oxygen species, reduced lipid peroxidation, and oxidative stress, and promoted the phytoremediation rate of the four Eucalyptus species by 18.7 ~ 34.8% compared to that in the absence of Si.ConclusionsSilicon can alleviate the effect of Al toxicity by enhancing the antioxidant capacity and improving plant growth and tolerance quality. Hence, the application of Si is an effective method for the phytoremediation of Eucalyptus plantations in southern China.

A natural polyphenolic nanoparticle--knotted hydrogel scavenger for osteoarthritis therapy

Exploring highly efficient and cost-effective biomaterials for osteoarthritis (OA) treatment remains challenging, as current therapeutic strategies are difficult to eradicate the excessive reactive oxygen species (ROS) and nitric oxide (NO) at damaged sites. Tea polyphenol (TP) nanoparticles (NPs), a nature-inspired antioxidant in combination with 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a NO scavenger, could provide maximized positive therapeutic effects on OA by eradicating both ROS and NO. Notably, this combination not only improves the half-life of the TP monomer and the drug loading efficiency of carboxy-PTIO but also prevents nitrite from being harmful to tissue. Moreover, the protonation ability of carboxy-PTIO allows smart acid-responsive release in response to environmental pH, which provides conditioned treatment strategies for OA. In in vitro experiments, TP/PTIO NPs downregulated proinflammatory cytokine release via synergistic removal of ROS and NO and suppression of ROS/NF-κB and iNOS/NO/Caspase-3 signaling. For in vivo experiments, NPs were cross-linked with 4-arm-PEG-SH to form an injectable hydrogel system. The release of TP and carboxy-PTIO from the system efficiently prevents cartilage inflammation and damage via similar signaling pathways. Overall, the proposed system provides an efficient approach for OA therapy.

Bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy

Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH2 NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH2 NPs in periodontal tissues. Local injection of HMUiO-66-NH2 effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-β signaling pathways. In conclusion, HMUiO-66-NH2 exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.

Anti-inflammatory oligosaccharide licensed mesenchymal stem cells allow prolonged survival of septic rats via the promotion of glutathione synthesis

BackgroundMesenchymal stem cells (MSCs) possess the capability to mitigate multiorgan failure (MOF) and reduce mortality rates in sepsis. However, their survival is significantly limited due to oxidative stress responses triggered by excessive sepsis inflammation. Previous studies have demonstrated that the paracrine effect of MSCs can be enhanced by cytokine stimuli such as IL-1β, TNF-α, and IFN-γ, a process known as inflammatory licensing. This enhancement, however, may potentially lead to the apoptosis of MSCs. PurposeTo investigate the therapeutic effects of Fructus Lycii oligosaccharide (FLO)-nasal mucosa-derived ectodermal MSCs (EMSCs) on septic rats and the underlying mechanisms. Study design and methodsFLO was screened from 21 distinct saccharides derived from traditional Chinese medicine (TCM), utilizing macrophage lipid raft chromatography prepared by our laboratory as the primary screening method.. The comparison of EMSCs primed with/without FLO was assessed through RNA-seq. Cecal ligation and puncture (CLP) surgery was performed in the CLP, EMSCs, and FLO-EMSCs groups (n = 10). The NC group underwent cecal ligation without puncture. The therapeutic effects of EMSCs and FLO-EMSCs on septic rats were evaluated through multiple tests including RT-PCR, western blot, histochemical staining, etc. ResultsFLO promoted M2 polarization of macrophages and enhanced the paracrine effect of EMSCs, without inducing apoptosis. Furthermore, FLO promoted GSH synthesis in EMSCs, aiding in the removal of reactive oxygen species (ROS) within these cells. The FLO-treated EMSCs demonstrated enhanced protection against pyroptosis in macrophages, thereby preventing immune paralysis during sepsis. ConclusionThis study presents an innovative approach for enhancing the anti-inflammatory properties of MSCs using a TCM-derived oligosaccharide, thereby improving their therapeutic efficacy in sepsis models.

A Mechanism for Apoptotic Effects of a Planar Catechin Analog on Cancer Cells.

Catechin is one of the representative antioxidants that shows physiological activities such as an anti-cancer effect. We have developed a chemically modified catechin analog possessing a planar structure, which shows an enhanced radical-scavenging activity as well as inhibitory effects on the proliferation and migration of cancer cells, compared to the parent (+)-catechin. In this study, the mechanism for cancer cell inhibition by the planar catechin was partly elucidated using a gastric cancer cell line. The planar catechin treatment induced an enhanced expression of an apoptotic marker, cleaved caspase-3, in addition to the mitigation of the intracellular accumulation of reactive oxygen species (ROS) and NF-κB expression. Furthermore, γH2AX, a marker of double-strand breaks in DNA, was also induced by the planar catechin treatment in a dose-dependent manner. These findings suggest that the removal of ROS by the planar catechin with a higher antioxidant ability executed NF-κB suppression and/or the planar catechin-injured DNA, leading to the induction of apoptosis in cancer cells.

Antioxidative implant coating with anti-infection and osteogenesis time-dependent bifunction for synergistic promotion of osteointegration

Infection and poor osteogenesis are two major causes of implant failure. Surface modification strategy provides solutions to the above problems. However, the functional requirements at different biological stages during infectious bone repair and the oxidative stimulation caused by reactive oxygen species (ROS) in an inflammatory environment pose challenges to the existing approaches. Layer-by-layer (LbL) self-assembly realizes layer by layer superposition and time-dependent acting of different bioactive components, but is demanding to functional groups. Tannic acid (TA) owns abundant phenolic hydroxyl groups, endowing various firm chemical bindings and excellent antioxidant property. To this end, we developed a time-dependent and antioxidant multifunctional coating via TA mediated LbL self-assembly. This layer exhibited higher ROS removal capacity and stronger binding ability. Furthermore, it showed rapid and excellent antibacterial ability of over 85 % against Staphylococcus aureus and Escherichia coli at 24 h, which additionally promoted osteogenic differentiation in vitro in long term. Moreover, the coating exhibited outstanding antibacterial and bone regeneration performance in vivo as well. Thus, this study is expected to provide an antioxidant and time-dependent multifunctional platform for surface modification engineering of dental and orthopedic implantation, as well as other potential biological material designs.

Effect of central metal ion on some pharmacological properties of new Schiff base complexes. Anticancer, antioxidant, kinetic/thermodynamic and computational studies

The biological capacities of Schiff Base complexes such as anti-cancer, anti-microbial and anti-oxidant properties have been widely studied in the scientific community. However, the effect of central metal ion in the occurrence of their biological properties should be paid more attention. With this aim, novel 2-(hydroxyimino)-1-phenylpropylidene)benzohydrazide (HIPB) Schiff base ligand, and C1/palladium(II), C2/platinum(II), and C3/zinc(II) complexes derived from it were synthesized and characterized. Theoretical studies showed that C2 is more reactive and also has a higher pharmacological affinity than C1 and C3. Experimental investigations were done to compare some biological properties of the complexes. The anticancer assay showed that C1-C3 have the ability to inhibit the growth of HCT116 colon cancer cell lines, but C2 shows a relatively better effect than other. Antioxidant studies using •DPPH (2,2-diphenyl-1-picrylhydrazyl) assay presented the following trend: C2 > C1 > C3 > HIPB. Considering the importance of the antioxidant enzyme catalase in removing reactive oxygen species (ROS), the interaction of C1-C3 with Bovine Liver Catalase (BLC) was evaluated. Kinetic studies showed that C1-C3 can inhibit the catalytic performance of BLC by a similar mechanism, i.e. mixed-type inhibition. Among them, C1 was the strongest inhibitor (Activity inhibition% = 82.2). The C1-C3 quenched the BLC fluorescence emission with dynamic quenching mechanism. The binding affinity to BLC was higher for C1 and C2 than C3. The most important forces in the interaction of C1-C3 with BLC were hydrophobic interactions, which was strongly confirmed by molecular docking data. Tracking the structural changes of catalase showed that BLC undergoes structural changes in the presence of C1 more than C2 and C3.

Prognostic Significance of 18F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.

Ultraviolet-enhanced detoxification of chromate and protection of Brassica napus by Aspergillus sojae SH 20

The pervasive issue of heavy metal contamination in agricultural lands poses significant concerns and has wide-ranging implications for ecosystems. However, an encouraging solution lies in exploiting the potential of fungal endophytes to alleviate these detrimental effects. This study emphasized on improving the growth-promoting and chromium-alleviating capabilities of fungal endophytes, particularly Aspergillus sojae strain SH20, through ultraviolet (UV) irradiation. Following UV treatment, SH20 exhibited significantly enhanced growth-promoting and chromium-alleviating capabilities in comparison to its non-irradiated counterpart. Distinctly, the UV-treated SH20 strain demonstrated an improved ability to accumulate and reduce toxic chromate in the soil, effectively addressing the growth constraints imposed by elevated chromium levels in Brassica napus L. The UV-irradiated SH20 variant boosted shoot length up to 3 times that of the control. Similarly, this fungal strain displayed a remarkable increase in the total fresh weight of the seedlings, recording nearly 17 times greater than the control. The isolate treated with UV light reduced the absorption of chromium by about 3 times in the roots, helping the young plants to grow well even when exposed to chromate stress. A drop in root colonization by the UV-treated strain further resulted in reduced chromate absorption by the roots. Also, the strain showed great skill in boosting the host's antioxidant defenses by reducing the buildup of harmful reactive oxygen species (ROS), increasing the removal of ROS, and improving the plant's antioxidant levels, including phenols and flavonoids. When the host plants were exposed to 25 ppm of Cr stress, the UV-irradiated variant SH 20 stimulated the production of flavonoids (246 μg/ml) and phenols (952 μg/ml) in comparison to the control (with 220 μg/ml of flavonoids and 919 μg/ml of phenols). In conclusion, this report highlights how exposing the A. sojae strain SH20 to UV light has the potential to enhance its abilities to promote growth and bioremediate. This suggests a promising solution for addressing heavy metal contamination in agricultural lands.

Cu(II)-chelated ovalbumin mimicking the active centre of superoxide dismutase: Structure, antioxidant and antibacterial properties for food preservation application

Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.

Multifunctional human serum albumin-crosslinked and self-assembling nanoparticles for therapy of periodontitis by anti-oxidation, anti-inflammation and osteogenesis

Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity.

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity.

Microenvironment-Responsive Hydrogel Reduces Seizures After Traumatic Brain Injury in Juvenile Rats by Reducing Oxidative Stress and Hippocampal Inflammation.

Traumatic brain injury (TBI) is the primary cause of child mortality and disability worldwide. It can result in severe complications that significantly impact children's quality of life, including post-traumatic epilepsy (PTE). An increasing number of studies suggest that TBI-induced oxidative stress and neuroinflammatory sequelae (especially, inflammation in the hippocampus region) may lead to the development of PTE. Due to the blood-brain barrier (BBB), typical systemic pharmacological therapy for TBI cannot deliver berberine (BBR) to the targeted location in the early stages of the injury, although BBR has strong anti-inflammatory properties. To break through this limitation, a microenvironment-responsive gelatin methacrylate (GM) hydrogel to deliver poly(propylene sulfide)60 (PPS60) and BBR (GM/PB) is developed for regulating neuroinflammatory reactions and removing reactive oxygen species (ROS) in the brain trauma microenvironment through PPS60. In situ injection of the GM/PB hydrogel efficiently bypasses the BBB and is administered directly to the surface of brain tissue. In post-traumatic brain injury models, GM/PB has the potential to mitigate oxidative stress and neuroinflammatory responses, facilitate functional recovery, and lessen seizing. These findings can lead to a new treatment for brain injuries, which minimizes complications and improves the quality of life.

Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment.

The management of diabetic wound healing remains a severe clinical challenge due to the complicated wound microenvironments, including abnormal immune regulation, excessive reactive oxygen species (ROS), and repeated bacterial infections. Herein, we report an extracellular matrix (ECM)-mimetic coating derived from scallop byssal protein (Sbp9Δ), which can be assembled in situ within 30 min under the trigger of Ca2+ driven by strong coordination interaction. The biocompatible Sbp9Δ coating and genetically programmable LL37-fused coating exhibit outstanding antioxidant, antibacterial, and immune regulatory properties in vitro. Proof-of-concept applications demonstrate that the coating can reliably promote wound healing in animal models, including diabetic mice and rabbits, ex vivo human skins, and Staphylococcus aureus-infected diabetic mice. In-depth mechanism investigation indicates that improved wound microenvironments accelerated wound repair, including alleviated bacterial infection, lessened inflammation, appearance of abundant M2-type macrophages, removal of ROS, promoted angiogenesis, and re-epithelialization. Collectively, our investigation provides an in situ, convenient, and effective approach for diabetic wound repair.

BoPRR9, a pseudo-response regulator protein from cabbage, plays a negative regulatory role in the response to cold stress

Cold stress can adversely affect the growth, development, and yield of plants. Exploring the cabbage cold-stress-related genes and their regulatory mechanisms is crucial for cultivating high-quality varieties of cabbage. The PSEUDO RESPONSE REGULATOR (PRR) factor plays an important role in plant response to abiotic stress. However, cabbage BoPRRs in cold tolerance are rarely reported. In this study, the PRR family gene BoPRR9 was isolated from cabbage (Brassica oleracea var. capitata L) and functionally characterized in transgenic Arabidopsis and cabbage in cold stress response. BoPRR9 encodes a protein located in the nucleus. The gene was strongly induced by cold treatment, and the transcription level of BoPRR9 was up regulated under cold stress. Under cold stress, overexpression of BoPRR9 resulted in enhanced cold sensitivity in transgenic Arabidopsis and cabbage, lower antioxidant enzyme activity and maximum photosynthetic efficiency of photosystem II(Fv/Fm), and higher relative electrolyte leakage (REL) and malondialdehyde (MDA) content. Meanwhile, the ability of the transgenic plants to remove reactive oxygen species (ROS) was significantly reduced. Additionally, the expression levels of cold-related genes were downregulated in BoPRR9-overexpressing plants. The results showed that the BoPRR9 gene negatively regulates cold stress, which provides clues for further understanding of the molecular mechanism of PRR-mediated cold stress response.

The PbbHLH62/PbVHA-B1 module confers salt tolerance through modulating intracellular Na+/K+ homeostasis and reactive oxygen species removal in pear

The vacuolar H+-ATPase (V-ATPase) is a multi-subunit membrane protein complex, which plays pivotal roles in building up an electrochemical H+-gradient across tonoplast, energizing Na+ sequestration into the central vacuole, and enhancing salt stress tolerance in plants. In this study, a B subunit of V-ATPase gene, PbVHA-B1 was discovered and isolated from stress-induced P. betulaefolia combining with RT-PCR method. The RT-qPCR analysis revealed that the expression level of PbVHA-B1 was upregulated by salt, drought, cold, and exogenous ABA treatment. Subcellular localization analyses showed that PbVHA-B1 was located in the cytoplasm and nucleus. Moreover, overexpression of PbVHA-B1 gene noticeably increased the ATPase activity and the tolerance to salt in transgenic Arabidopsis plants. In contrast, knockdown of PbVHA-B1 gene in P.betulaefolia by virus-induced gene silencing had reduced resistance to salt stress. In addition, using yeast one-hybride (Y1H) and yeast two-hybride (Y2H) screens, PbbHLH62, a bHLH transcription factor, was identified as a partner of the PbVHA-B1 promoter and protein. Then, we also found that PbbHLH62 positively regulate the expression of PbVHA-B1 and the ATPase activity after salt stress treatment. These findings provide evidence that PbbHLH62 played a critical role in the salt response. Collectively, our results demonstrate that a PbbHLH62/PbVHA-B1 module plays a positive role in salt tolerance by maintain intracellular ion and ROS homeostasis in pear.

ROS-responsive nano-medicine for navigating autophagy to enhance targeted therapy of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by immune dysregulation and intestinal inflammation. Rapamycin (Ra), an mTORC1 pathway inhibitor, has shown promise for autophagy induction in IBD therapy but is associated with off-target effects and toxicity. To address these issues, we developed an oral liposome responsive to reactive oxygen species (ROS) using lipids and amphiphilic materials. We combined ketone thiol (TK) for ROS responsive and hyaluronic acid (HA) with high affinity for CD44 receptors to prepare rapamycin-loaded nanoparticle (Ra@TH). Owing to its ROS responsive characteristic, Ra@TH can achieve inflammatory colonic targeting. Additionally, Ra@TH can induce autophagy by inhibiting the mTORC1 pathway, leading to the clearance of damaged organelles, pathogenic microorganisms and oxidative stress products. Simultaneously, it also collaboratively inhibits the NF-κB pathway suppressed by the removal of ROS resulting from TK cleavage, thereby mediating the expression of inflammatory factors. Furthermore, Ra@TH enhances the expression of typical tight junction proteins, synergistically restoring intestinal barrier function. Our research not only expands the understanding of autophagy in IBD treatment but also introduces a promising therapeutic approach for IBD patients.

In-situ growth of CeO2 on biofilms: Innovative nanoparticles for photothermal therapy & multi-pronged attack on Alzheimer’s disease

Alzheimer’s disease (AD) is complex and multifactorial, and its pathogenesis involves multiple factors and processes. This study pioneered the in situ growth of cerium oxide nanoparticles on macrophage membranes (Ce-RAW). Further, carbon quantum dots (CQD) were biomimetically modified by Ce-RAW, leading to the synthesis of a multifunctional nanocomposite (CQD-Ce-RAW). Within the framework of this research, CQD-Ce-RAW was strategically combined with photothermal therapy (PTT), aiming to achieve a more significant therapeutic effect. The macrophage membrane confers the system with anti-phagocytic and anti-inflammatory biological functions. More importantly, the ultra-small size of cerium oxide grown on the membrane acts as a reactive oxygen species (ROS) scavenger and alleviates the degree of oxidative stress. Meanwhile, CQD as a photosensitizer helps dissociate amyloid-β (Aβ) aggregates and chelates excess copper ions, thus further inhibiting Aβ aggregation. Cell experiments showed that CQD-Ce-RAW combined with PTT could effectively degrade and inhibit the aggregation of Aβ, remove ROS, and improve cell survival rate. The results of in vivo photothermal experiments demonstrated that near-infrared light enhanced the efficiency of drug penetration through the blood-brain barrier and facilitated its accumulation in brain tissue. This comprehensive therapeutic approach can intervene in the disease progression from multiple pathways, providing a new prospect for treating AD.

Carboxylic acid accumulation and secretion contribute to the alkali-stress tolerance of halophyte Leymus chinensis.

Leymus chinensis is a dominant halophytic grass in alkalized grasslands of Northeast China. To explore the alkali-tolerance mechanism of L. chinensis, we applied a widely targeted metabolomic approach to analyze metabolic responses of its root exudates, root tissues and leaves under alkali-stress conditions. L. chinensis extensively secreted organic acids, phenolic acids, free fatty acids and other substances having -COOH or phosphate groups when grown under alkali-stress conditions. The buffering capacity of these secreted substances promoted pH regulation in the rhizosphere during responses to alkali stress. L. chinensis leaves exhibited enhanced accumulations of free fatty acids, lipids, amino acids, organic acids, phenolic acids and alkaloids, which play important roles in maintaining cell membrane stability, regulating osmotic pressure and providing substrates for the alkali-stress responses of roots. The accumulations of numerous flavonoids, saccharides and alcohols were extensively enhanced in the roots of L. chinensis, but rarely enhanced in the leaves, under alkali-stress conditions. Enhanced accumulations of flavonoids, saccharides and alcohols increased the removal of reactive oxygen species and alleviated oxygen damage caused by alkali stress. In this study, we revealed the metabolic response mechanisms of L. chinensis under alkali-stress conditions, emphasizing important roles for the accumulation and secretion of organic acids, amino acids, fatty acids and other substances in alkali tolerance.