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Cisplatin (CDDP) serves as a vital component in the chemotherapeutic approach to treat esophageal squamous cell carcinoma (ESCC). However, prolonged CDDP application frequently culminates in resistance, compromising therapeutic outcomes. Through genome-wide CRISPR library screening, our study elucidates the mechanisms underlying this resistance, pinpointing CYFIP2 as a pivotal mediator. Notably, the involvement CYFIP2 is characterized by pronounced autophagic activity and the modulation of multiple cellular pathways. Empirical validation was achieved by treating ESCC cell lines with CDDP, which resulted in an upsurge of CYFIP2 expression. The functional impact of CYFIP2 was further delineated through knockdown experiments, where a marked suppression in cell proliferation was observed, alongside a discernible decline in reactive oxygen species levels. This was complemented by a suite of assays and microscopic techniques, including GFP-LC3, mRFP-GFP-LC3, electron microscopy and western blot, which collectively affirmed the inhibitory effect of CYFIP2 knockdown on autophagic processes, particularly impeding autophagosome formation and their subsequent fusion with lysosomes. In vivo studies have also confirmed that CYFIP2 knockdown limits tumor progression and increases CDDP efficacy. Conclusively, our findings introduce CYFIP2 as a novel contributor to CDDP resistance in ESCC, underscoring its potential as a therapeutic target. This revelation not only deepens our understanding of resistance mechanisms but also paves the way for novel oncotherapeutic strategies, promising enhanced treatment efficacy against ESCC. [ABSTRACT FROM AUTHOR]

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration. [ABSTRACT FROM AUTHOR]

Background: Although the exact role of mitophagy in the pathogenesis of diabetic cardiomyopathy (DCM) caused by type 2 diabetes mellitus (T2DM) remains controversial, recent studies revealed inhibition of mitophagy exacerbates cardiac injury in DCM. The zinc transporter ZIP7 has been reported to be upregulated by high glucose in cardiomyocytes and ZIP7 upregulation leads to inhibition of mitophagy in mouse hearts in the setting of ischemia/reperfusion. Nevertheless, little is known about the role of ZIP7 and its relationship with mitophagy in DCM caused by T2DM. Methods: T2DM was induced with high-fat diet (HFD) and streptozotocin. The cardiac-specific ZIP7 conditional knockout (ZIP7 cKO) mice were generated by adopting CRISPR/Cas9 system. Cardiac function was evaluated with echocardiography. Mitophagy was assessed by detecting mito-LC3II, mitoKeima, and mitoQC. Reactive oxygen species (ROS) were detected with DHE and mitoB. Results: ZIP7 was upregulated by T2DM in mouse hearts and ZIP7 cKO reduced mitochondrial ROS generation in mouse hearts with T2DM. Mitophagy was suppressed by T2DM in mouse hearts, which was prevented by ZIP7 cKO. T2DM inhibited PINK1 and Parkin accumulation in cardiac mitochondria, an effect that was prevented by ZIP7 cKO, pointing to that ZIP7 upregulation mediates T2DM-induced suppression of mitophagy by inhibiting the PINK1/Parkin pathway. T2DM induced mitochondrial hyperpolarization and decrease of mitochondrial Zn2+ and this was blocked by ZIP7 cKO, indicating that upregulation of ZIP7 leads to mitochondrial hyperpolarization by reducing Zn2+ within mitochondria. Finally, ZIP7 cKO prevented cardiac dysfunction and fibrosis caused by T2DM. Conclusions: ZIP7 upregulation mediates the inhibition of mitophagy by T2DM in mouse hearts by suppressing the PINK1/Parkin pathway. Reduction of mitochondrial Zn2+ due to upregulation of ZIP7 accounts for the inhibition of the PINK1/Parkin pathway. Prevention of ZIP7 upregulation is essential for the treatment of T2DM-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

The roles of plant-specific transcription factor family YABBY may vary among different members. OsYABBY6 is a rice YABBY gene, whose function is not well elucidated so far. In this paper, we show that OsYABBY6 is a nucleus-localized protein with transcriptional activation activity. OsYABBY6 is predominantly expressed in the palea and lemma, as well as in the sheath, culm and node. OsYABBY6 RNA interference (RNAi) plants exhibited altered plant height and larger grain size. Under cold treatment, OsYABBY6 overexpression (OE) plants had up-regulated expression of cold responsive genes, and accumulated less reactive oxygen species but more proline compared to wild type, resulting in improved cold tolerance. On the other hand, RNAi plants showed enhanced drought tolerance compared to the wild type by slower water loss, less reactive oxygen species but more proline and soluble sugar accumulation. In addition, endogenous abscisic acid (ABA) level was reduced in OsYABBY6 RNAi plants, and RNAi and OE plants were more and less sensitive to ABA treatment, respectively. Accordingly, we deduce that OsYABBY6 positively regulates cold response but negatively regulates drought response through different pathways. Our study reveals the crucial roles of OsYABBY6 in plant architecture and grain development, as well as in abiotic stress response, providing new insights into the functions of YABBYs in rice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent type of dementia. Its causes are not fully understood, but it is now known that factors like mitochondrial dysfunction, oxidative stress, and compromised ion channels contribute to its onset and progression. Flickering light therapy has shown promise in AD treatment, though its mechanisms remain unclear. In this study, we used a rat model of streptozotocin (STZ)-induced AD to evaluate the effects of 40 Hz flickering light therapy. Rats received intracerebroventricular (ICV) STZ injections, and 7 days after, they were exposed to 40 Hz flickering light for 15 min daily over seven days. Cognitive and memory functions were assessed using Morris water maze, novel object recognition, and passive avoidance tests. STZ-induced AD rats exhibited cognitive decline, elevated reactive oxygen species, amyloid beta accumulation, decreased serotonin and dopamine levels, and impaired mitochondrial function. However, light therapy prevented these effects, preserving cognitive function and synaptic plasticity. Additionally, flickering light restored mitochondrial metabolites and normalized ATP-insensitive mitochondrial calcium-sensitive potassium (mitoBKCa) channel activity, which was otherwise downregulated in AD rats. Our findings suggest that 40 Hz flickering light therapy could be a promising treatment for neurodegenerative disorders like AD by preserving synaptic and mitochondrial function. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy characterized by dysregulated cellular metabolism leading to aberrant glucose metabolism, fatty acid accumulation, and excessive reactive oxygen species production. ccRCC cells exhibit an augmented oxidative stress response. Complex interactions between iron metabolism and lipid homeostasis in ccRCC cells require a counteracting response that enables ferroptosis evasion and survival maintenance. Additionally, abnormal GA-binding protein transcription factor subunit alpha (GABPA) expression is associated with ccRCC occurrence and development, but its impact on ferroptosis-related molecular mechanisms remains unclear. Herein, we examined the impact of the GABPA–ACSL4 pathway on ferroptosis in ccRCC through bioinformatics analysis, as well as in vitro and in vivo experiments. In contrast to that in adjacent normal tissues, GABPA expression was significantly downregulated in ccRCC tissues, and this downregulation was linked to poor overall survival. Increased GABPA expression suppressed ccRCC cell proliferation, migration, and invasion. Moreover, GABPA overexpression increased the susceptibility of ccRCC cells to ferroptosis. Additionally, GABPA directly bound to the promoter region of ACSL4, promoting ferroptosis. Thus, inducing the GABPA–ACSL4 pathway activates ferroptosis, inhibits proliferation or metastasis, and exerts anticancer activity in ccRCC. These findings have important implications for regulating ccRCC occurrence and development. [ABSTRACT FROM AUTHOR]

Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2′:6′,2′′-terpyridine-metal complexes possess these properties. The high level of activity (IC50 = 0.605 µM) of 2,2′:6′,2′′-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2′:6′,2′′-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis. [ABSTRACT FROM AUTHOR]

With the rapid emergence of antibiotic‐resistant pathogens, nanomaterial‐assisted catalytic sterilization has been well developed to combat pathogenic bacteria by elevating the level of reactive oxygen species including hydroxyl radical (·OH). Although promising, the ultra‐short lifetime and limited diffusion distance of ·OH severely limit their practical antibacterial usage. Herein, the rational design and preparation of novel virus‐like copper silicate hollow spheres (CSHSs) are reported, as well as their applications as robust artificial bacteriophages for localized bacterial capture and enhanced catalytic sterilization in the treatment of oral infectious diseases. During the whole process of capture and killing, CSHSs can efficiently capture bacteria via shortening the distance between bacteria and CSHSs, produce massive ·OH around bacteria, and further iinducing the admirable effect of bacterial inhibition. By using mucosal infection and periodontitis as typical oral infectious diseases, it is easily found that the bacterial populations around lesions in animals after antibacterial treatment fall sharply, as well as the well‐developed nanosystem can decrease the inflammatory reaction and promote the hard or soft tissue repair. Together, the high Fenton‐like catalytic activity, strong bacterial affinity, excellent antibacterial activity, and overall safety of the nanoplatform promise its great therapeutic potential for further catalytic bacterial disinfection. [ABSTRACT FROM AUTHOR]

Abstract\nKEY POLICY HIGHLIGHTSIron is necessary for life, but the simultaneous iron-catalyzed formation of reactive oxygen species (ROS) is involved in pathogenesis of many diseases. One of them is diabetes mellitus, a widespread disease with severe long-term complications, including neuropathy, retinopathy, and nephropathy. Much evidence points to methylglyoxal, a potent glycating agent, as the key mediator of diabetic complications. In diabetes, there is also a peculiar dysregulation of iron homeostasis, leading to an expansion of redox-active iron. This in vitro study focuses on the interaction of methylglyoxal with ferritin, which is the main cellular protein for iron storage. Methylglyoxal effectively liberates iron from horse spleen ferritin, as well as synthetic iron cores; in both cases, it is partially mediated by superoxide. The interaction of methylglyoxal with ferritin increases the production of hydrogen peroxide, much above the generation of peroxide by methylglyoxal alone, in an iron-dependent manner. Glycation with methylglyoxal results in structural changes in ferritin. All of these findings can be demonstrated with pathophysiologically relevant (submillimolar) methylglyoxal concentrations. However, the rate of iron release by ascorbate, the ferroxidase activity, or the diameter of gated pores even in intensely glycated ferritin is not altered. In conclusion, although the functional features of ferritin resist alterations due to glycation, the interaction of methylglyoxal with ferritin liberates iron and markedly increases ROS production, both of which could enhance oxidative stress in vivo. Our findings may have implications for the pathogenesis of long-term diabetic complications, as well as for the use of ferritin as a nanocarrier in chemotherapy. Ferritin with methylglyoxal generates both Fenton reagents, ferrous iron, and hydrogen peroxide.Methylglyoxal produces structural modifications in ferritin that are detectable even in excess of another protein.Even heavily glycated ferritin has been found to resist functional alteration.Ferritin with methylglyoxal generates both Fenton reagents, ferrous iron, and hydrogen peroxide.Methylglyoxal produces structural modifications in ferritin that are detectable even in excess of another protein.Even heavily glycated ferritin has been found to resist functional alteration. [ABSTRACT FROM AUTHOR]

SUMMARY Arsenic (As) is extremely toxic to plants, posing a serious concern for food safety. Identification of genes responsive to As is significative for figuring out this issue. Here, we identified a bHLH transcription factor OsbHLH6 that was involved in mediating the processes of As tolerance, uptake, and root‐to‐shoot translocation in rice. The expression of OsbHLH6 gene was strongly induced after 3 and 48 h of arsenite [As(III)] treatment. The OsbHLH6‐overexpressed transgenic rice (OE‐OsbHLH6) was sensitive to, while the knockout mutant of OsbHLH6 gene (Osbhlh6) was tolerant to As(III) stress by affecting the contents of reactive oxygen species (ROS) and non‐protein thiols (NPT), etc. Knockout of OsbHLH6 gene increased significantly the As concentration in roots, but decreased extensively As accumulation in shoots, compared to that in OE‐OsbHLH6 and WT plants. The transcripts of phytochelatins (PCs) synthetase encoding genes OsPCS1 and OsPCS2, as well as As(III) transporter encoding genes OsLsi1 and OsABCC1 were greatly abundant in Osbhlh6 mutants than in OE‐OsbHLH6 and WT plants under As(III) stress. In contrast, the expression of OsLsi2 gene was extensively suppressed by As(III) in Osbhlh6 mutants. OsbHLH6 acted as a transcriptional activator to bind directly to the promoter and regulate the expression of OsPrx2 gene that encodes a peroxidase precursor. Moreover, overexpression of OsbHLH6 gene resulted in significant change of expression of amounts of abiotic stress‐related genes, which might partially contribute to the As sensitivity of OE‐OsbHLH6 plants. These findings may broaden our understanding of the molecular mechanism of OsbHLH6‐mediated As response in rice and provide novel useful genes for rice As stress‐resistant breeding. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) stands out as a highly promising modality for tumor treatment, yet previous works have primarily centered around either boosting the production of reactive oxygen species (ROS) in tumor tissues or restricting it in normal tissues. The current challenge lies in the urgent need to achieve precise modulation of ROS production by simultaneously controlling both aspects. To achieve this goal, a precise PDT platform through a “locking‐unlocking‐boosting” ROS production strategy is presented, in which the generation of ROS is modulated by bidirectionally regulating the upconversion luminescence (UCL) of lanthanide‐doped nanoparticles (LnNPs), thus ROS production is “locked” in normal tissues but “boosted” in tumor tissues. In detail, by introducing an energy acceptor BHQ3, the UCL is initially quenched to prevent Chlorin e6 (Ce6) from generating ROS. However, under the tumor microenvironment with overexpressed miR‐21, LnNPs are sequestered from BHQ3 to “unlock” ROS generation and then assembled with QDs@B2, which functions as an antenna to sensitize LnNPs luminescence, to further “boost” ROS generation. With the assistance of spherical nucleic acids, this therapeutic agent effectively traverses the blood‐brain barrier (BBB), enabling efficient PDT for glioblastoma. [ABSTRACT FROM AUTHOR]

ABSTRACT Bivalve mollusks frequently experience salinity fluctuations that may drive oxidative stress (OS) in the organism. Here we investigated OS markers and histopathological changes in gills and hemolymph of Mediterranean mussels Mytilus galloprovincialis Lamarck, 1819 exposed to a wide range of salinities (6, 10, 14, 24, and 30 ppt). Mussels were captured at the shellfish farm with the salinity 18 ppt and then exposed to hypo‐ and hypersaline conditions in the laboratory. Indicators of redox balance in hemocytes (intracellular reactive oxygen species (ROS) levels, DNA damage) and gills (thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The effect of salinity stress on microstructure of gills has been evaluated as well. The results revealed induction of OS in tissues and cells of mussels for both experimental increase and decrease salinity modelings. Hemocytes showed higher sensitivity to osmotic stress compared to gills. In gills TBARS were stable in all experimental groups and PC increased only at salinity 6 ppt. The activity of SOD, CAT and GPx in gills decreased only in mussels acclimated to salinity 24 ppt and further salinisation up to 30 ppt was associated with the recovery of the activity of all enzymes. Major histopathological changes in gills upon salinity fluctuations included inflammatory reactions, circulatory alterations, regressive and progressive changes. Our findings clearly indicate that salinity fluctuations promote OS at cellular and tissue level and also affect microstructure of gills in mussels. The results provide new insights into the mechanisms of osmotic stress in bivalves. [ABSTRACT FROM AUTHOR]

Upconversion nanoparticles (UCNPs) have been used as a potential nanocarrier for photosensitizers (PSs), which have demonstrated a great deal of promise in achieving an effective photodynamic therapy (PDT) for deep-seated tumors. However, overcoming biological barriers to achieve mitochondria-targeted PDT remains a major challenge. Herein, CD44- and mitochondria-targeted photodynamic nanosystems were fabricated through the self-assembly of hyaluronic acid-conjugated-methoxy poly(ethylene glycol)-diethylenetriamine-grafted-(chlorin e6-dihydrolipoic acid-(3-carboxypropyl)triphenylphosphine bromide) polymeric ligands (HA-c-mPEG-Deta-g-(Ce6-DHLA-TPP)) and NaErF4:Tm@NaYF4 core–shell UCNPs (termed CMPNs). The CMPNs presented ideal physiological stability, a good drug loading capacity and an improved capacity for the generation of singlet oxygen (1O2) based on the FRET mechanism. Significantly, confocal images revealed that CMPNs not only facilitated cellular uptake through CD44-receptor-targeted endocytosis, subsequently enabling rapid evasion from endo-lysosomal sequestration, but also specifically targeted mitochondria, ultimately inducing a profound disruption of mitochondrial membrane potential, which triggered apoptosis upon laser irradiation, thereby significantly enhancing the therapeutic effect. Furthermore, in vitro antitumor experiments further confirmed the substantial enhancement in cancer cell killing efficiency achieved by treating with CMPNs upon near-infrared (NIR) laser irradiation. This innovative approach holds promise for the development of NIR-laser-activated photodynamic nanoagents specifically designed for mitochondria-targeted PDT, thus addressing the limitations of the current PDT treatments. [ABSTRACT FROM AUTHOR]

Photoaging damages the skin layers. The tumor necrosis factor-alpha (TNF-α) plays a crucial role in the central mechanism of photoaging. TNF-α production leads to direct damage to skin cells and facilitates the degradation of vital extracellular matrix (ECM) proteins. TNF-α stimulates matrix metalloproteinase-1 (MMP-1) activation This accelerates the loss of skin elasticity and wrinkle formation. Thus, preventing photoaging and delaying the skin aging process are important research objectives, and the development of new anti-aging substances that target the TNF-α and MMP-1 pathways is promising. In this context, the efficacies of four extracts derived from two types of Cephalotaxus harringtonia (CH) buds (CH-10Y-buds, CH-200Y-buds) and leaves (CH-10Y-leaves, CH-200Y-leaves) were investigated, exhibiting a significant reduction in reactive oxygen species (ROS). Among the four extracts, CH-10Y-buds was the most effective in reducing ROS and exhibited the highest amounts of harringtonine and homoharringtonine. The activities of harringtonine, homoharringtonine, and ginkgetin were evaluated; harringtonine exhibited a high efficacy in inhibiting TNF-α-induced inflammatory responses and MMP-1 activation, thereby reducing collagen degradation. These findings suggest that CH-10Y-buds and their components herringtonin are promising candidates for preventing damage caused by photoaging. Our results can facilitate the development of new methods for maintaining skin health and inhibiting the skin aging process. Further research is necessary to comprehensively evaluate the potential efficacy of these candidate substances and investigate their applicability to actual skin. Such studies will aid in the development of more effective anti-aging strategies in the future. [ABSTRACT FROM AUTHOR]

Background: In recent years, more severe droughts have occurred frequently in many parts of the world, drought stress is the primary abiotic stress factor restricting the growth and quality of flue-cured tobacco. Therefore, screening dryland cultivation-compatible flue-cured tobacco varieties will help reduce the negative impact of drought. Methods: Tobacco varieties were selected: Qinyan 96 (Q96), Zhongyan 101 (Z101), Yunyan 87 (Y87), and Yunyan 116 (Y116). A pot experiment was conducted with four water supply gradients: sufficient, mild stress, moderate stress, and severe stress. The aim was to analyze inter-varietal differences in agronomic traits, photosynthetic traits, reactive oxygen species (ROS) metabolism, and antioxidant enzyme system under drought stress. Additionally, the drought resistance of four flue-cured tobacco varieties was evaluated using principal component analysis and membership function analysis. Results: The results showed that drought intensification inhibited seedling growth and development across all varieties, with Q96 showing the least decrease and Y116 the greatest. With the increasing degree of drought stress, photosynthetic rates (Pn), transpiration rate (Tr), and stomatal conduction (Gs) have shown gradually decreasing trends, while substomatal cavity CO2 concentration (Ci) showed a growing trend. Severe drought corresponded with lower chlorophyll content and decreased the maximal photochemical efficiency (Fv/Fm), photosystem II (PSII), and photochemical quenching coefficient (qP) in all varieties, while steady-state non-photochemical quenching (NPQ) increased. Increased drought stress led to significantly higher reactive oxygen species (ROS) and malondialdehyde (MDA) content accumulation in tobacco seedlings. The antioxidant enzyme activities in, Q96, Z101, and Y87 increased under mild drought stress, whereas Y116 showed decreased activity. Conclusion: The drought resistance ranking among the four varieties is as follows: Q96 > Z101 > Y87 > Y116. Therefore, Q96 is a promising drought-tolerant breeding material that can be used as a reference for dryland cultivation of flue-cured tobacco. [ABSTRACT FROM AUTHOR]

Plant growth-promoting rhizobacteria colonize the rhizosphere through dynamic and intricate interactions with plants, thereby providing various benefits and contributing to plant growth. Moreover, increasing evidence suggests that plant growth-promoting rhizobacteria affect plant tolerance to abiotic stress, but the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect of Bacillus velezensis strain GH1-13 on drought stress tolerance in rice. Phenotypical analysis, including the measurement of chlorophyll content and survival rate, showed that B. velezensis GH1-13 enhances rice tolerance to drought stress. Additionally, visualizing ROS levels and quantifying the expression of ROS-scavenging genes revealed that GH1-13 treatment reduces ROS accumulation under drought stress by activating the expression of antioxidant genes. Furthermore, the GH1-13 treatment stimulated the jasmonic acid response, which is a key phytohormone that mediates plant stress tolerance. Together with the result that jasmonic acid treatment promotes the expression of antioxidant genes, these findings indicate that B. velezensis GH1-13 improves drought tolerance in rice by reducing ROS accumulation and suggest that activation of the jasmonic acid response is deeply involved in this process. [ABSTRACT FROM AUTHOR]

Calcium-Dependent Protein Kinases (CDPKs) are a class of serine/threonine protein kinases encoded by several gene families that play key roles in biotic and abiotic stresses response and plant growth and development. However, snow lotus (Saussurea involucrata kar L.) CDPKs has rarely been reported. In this study, 20 CDPK genes in snow lotus were identified based on transcriptome data and classified into four groups (I-IV) based on their structural features and phylogenetic analyses. Among them, the transcript levels of SikCDPK1 were significantly induced by low temperature and multiple hormone treatments, and SikCDPK1 gene was found to have different expression in snow lotus seeds, leaves, stems and roots. The full-length promoter activity of SikCDPK1 gene was higher than that of the 5' end deletion fragment, and the promoter fragment containing the low temperature inducing element had increased activation after low temperature treatment. The promoter activity of SikCDPK1 gene was mainly expressed in roots and rosette leaves. In addition, overexpressing plants of SikCDPK1 were more tolerant compared to the wild type after being subjected to low temperature stress. Physiological analyses indicated that SikCDPK1 improved plant tolerance to low temperature stress by maintaining cell membrane stability and reducing the accumulation of reactive oxygen species (ROS). These findings provided insights into CDPK gene families in snow lotus and broaden our understanding of the biological role of SikCDPK1 and the mechanism of low temperature stress tolerance in snow lotus. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Introduction: Rice is a vital staple food for many countries, and its yield is known to be significantly affected by various abiotic stresses, which are expected to intensify with climate change, posing a threat to global food security. Abscisic acid (ABA), a crucial plant growth regulator, plays a crucial role in plant responses to these abiotic stresses. It influences several processes, such as seed dormancy, leaf gas exchange, reactive oxygen species (ROS) scavenging, ion toxicity reduction, and root elongation, all of which contribute to enhancing plant survival under stress. Methods: This article reviews recent research on ABA-mediated gene responses and expressions involved in rice plant architecture and its response to abiotic stress. Results and discussion: Abscisic acid responses were primarily driven by changes in gene expression. Expression analyses of the gene related to ABA biosynthesis or catabolism indicated several changes in plant architecture, such as changes in leaf angle, delayed flowering, and modifications in growth regulators. Additionally, tolerance-related mechanisms, such as increased ROS scavenging, reduced membrane leakage, and vacuolar compartmentation of toxic radicals, were activated under single or multiple stress conditions. While these adaptations may improve plant survival and yield sustainability under stress, they may not necessarily enhance yield potential in environments affected by drought, salinity, or heat stress. ABA expression was also associated with improved pollen viability, grain-filling potential, and seed setting under abiotic stresses such as heat, which could enhance seed yield in such challenging environments. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a leading cause of infection related mortality. Isoniazid is one of the frontline drugs for anti-TB therapy. Hepatotoxicity induced by isoniazid is a major cause of drug-discontinuation which may lead to development of resistant TB or increased mortality. Purpose: To characterize pharmacological properties of plant-based prescription medicine, Livogrit Vital (LVV) against isoniazid-induced liver injury (IILI) using HepG2 cells. Method: Phytometabolite characterization of LVV was performed by High-performance liquid chromatography (HPLC). The effects of LVV on cytosafety, IC50 shift, oxidative stress, ER stress, apoptosis, liver injury markers, and accumulation of isoniazid and hydrazine was performed on HepG2 cells induced with isoniazid. Silymarin was used as the positive control. Results: HPLC based phytometabolite characterization of LVV revealed the presence of several anti-oxidant, anti-apoptotic, and hepatoprotective compounds. In isoniazid-induced HepG2 cells, LVV reduced cytotoxicity of isoniazid and shifted its IC50 value. Treatment with LVV reduced ROS generation and lipid peroxidation; enhanced GSH enzyme levels in isoniazid-induced HepG2 cells. As per the mechanistic evaluation, LVV modulated gene expression level of Caspase-3, FGF21, and IRE-1α. LVV treatment also normalized isoniazid-induced elevated Caspase-3 activity and cPARP1 protein levels, indicating its potentials to regulate liver cell apoptosis. Concomitantly, biomarkers of hepatotoxicity, ALT and GGT, also decreased by LVV treatment. Interestingly, LVV treatment reduced intracellular accumulation of isoniazid and its toxic metabolite hydrazine, in isoniazid-stimulated HepG2 cells. Conclusion: Treatment of hepatic cells with the herbo-vitamin medicine, Livogrit Vital, regulates IILI by modulation of oxidative and ER stress, apoptosis, and bioaccumulation of isoniazid and hydrazine. Collectively, Livogrit Vital could well be explored as an adjuvant hepatoprotective agent alongwith anti-TB medicines. [ABSTRACT FROM AUTHOR]

Background: Breast cancer seriously affects physical and mental health of women. Despite advances in the clinical use of different treatments, breast cancer remains a major cause of mortality. Therefore, it is imperative to identify promising treatment options. In the present study, we investigated the effects of shikonin on 4T1 breast cancer cells and its potential mechanisms of action. Methods: BALB/c-derived mouse breast cancer 4T1 is very close to human breast cancer in growth characteristics and systemic response, so 4T1 cells were selected for further experiments. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial activity, and cellular calreticulin (CRT) exposure were assessed to evaluate the antitumor effects and mechanisms of shikonin in vitro. Orthotopic tumor growth inhibition and splenic immune cell regulation by shikonin were evaluated in 4T1 breast cancer orthotopic mice in vivo. Results: In vitro, shikonin could inhibit cell proliferation, cause apoptosis, disrupt mitochondrial activity, and induce ROS production and CRT exposure. In vivo, shikonin inhibited tumor growth, increased the proportion of CD8+ T cells, and reduced the proportion of regulatory cells (CD25+ Foxp3+ T cells) in the spleen. Conclusions: Shikonin inhibits the growth of 4T1 breast cancer cells by disrupting mitochondrial activity, promoting oxidative stress, and regulating immune function. [ABSTRACT FROM AUTHOR]

Background: During diabetes, prorenin is highly produced by the renal collecting ducts. The binding of prorenin to (pro)renin receptor (PRR) on the apical plasma membrane triggers intracellular profibrotic genes, including TGF-β and CTGF. However, the underlying mechanisms contributing to the stimulation of these pathways remain unclear. Hence, we hypothesize that the glucose transporter-1 (GLUT1) favors the PRR-dependent stimulation of TGF-β and CTGF in the distal nephron segments during high glucose (HG) conditions. Methods: To test this hypothesis, primary cultured renal inner medullary collecting duct (IMCD) cells were treated with normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 h in the presence or absence of the GLUT1-specific inhibitor BAY 876 (2 nM). Additionally, IMCD cells were treated with the PRR antagonist PRO20. The expression of TGF-β and CTGF was quantified by immunoblot and qRT-PCR. Results: HG increased GLUT1 mRNA and protein abundance, while BAY 876 inhibited these responses. HG treatment upregulated PRR, but the concomitant treatment with BAY 876 partially prevented this effect. TGF-β and CTGF expressions were augmented in IMCD cells treated with HG. However, PRO20 prevented the increases in TGF-β but not those of CTGF. GLUT1 inhibition partially prevented the increases in reactive oxygen species (ROS) during HG while PRO20 did not. ROS scavenging impaired CTGF upregulation during HG conditions. Additionally, long-term exposure to HG increases lipid peroxidation and reduced cell viability. Conclusions: The data indicate that glucose transportation via GLUT1 is implicated in the PRR-dependent upregulation of TGF-β while CTGF is mediated mainly via a mechanism depending on ROS formation in renal medullary collecting duct cells. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most efficient therapeutic options available to cure many hematological malignancies. However, severe complications derived from this procedure, including graft-versus-host disease (GVHD) and infections, can limit its success and negatively impact survival. Previous studies have shown that alterations in the microbiome are associated with the development of allo-HSCT-derived complications. However, most studies relied on single techniques that can only analyze a unique aspect of the microbiome, which hinders our ability to understand how microbiome alterations drive allo-HSCT-associated diseases. Results: Here, we have applied multiple "omic" techniques (16S rRNA and shotgun sequencing, targeted and un-targeted metabolomics) in combination with machine learning approaches to define the most significant microbiome changes following allo-HSCT at multiple modalities (bacterial taxa, encoded functions, and derived metabolites). In addition, multivariate approaches were applied to study interactions among the various microbiome modalities (the interactome). Our results show that the microbiome of transplanted patients exhibits substantial changes in all studied modalities. These include depletion of beneficial microbes, mainly from the Clostridiales order, loss of their bacterial encoded functions required for the synthesis of key metabolites, and a reduction in metabolic end products such as short chain fatty acids (SCFAs). These changes were followed by an expansion of bacteria that frequently cause infections after allo-HSCT, including several Staphylococcus species, which benefit from the reduction of bacteriostatic SCFAs. Additionally, we found specific alterations in all microbiome modalities that distinguished those patients who subsequently developed GVHD, including depletion of anti-inflammatory commensals, protective reactive oxygen detoxifying enzymes, and immunoregulatory metabolites such as acetate or malonate. Moreover, extensive shifts in the homeostatic relationship between bacteria and their metabolic products (e.g., Faecalibacterium and butyrate) were detected mainly in patients who later developed GVHD. Conclusions: We have identified specific microbiome changes at different modalities (microbial taxa, their encoded genes, and synthetized metabolites) and at the interface between them (the interactome) that precede the development of complications associated with allo-HSCT. These identified microbial features provide novel targets for the design of microbiome-based strategies to prevent diseases associated with stem cell transplantation. Bx_7phuTozz8yFUTR9cZV4 Video Abstract [ABSTRACT FROM AUTHOR]

Background: As a feed additive, medium-chain fatty acids (MCFAs)/medium-chain fatty acid triglycerides (MCTs) have been used in ruminant production, but mostly added in the form of mixed esters. Studies have shown that MCTs may have a positive effect on feed intake or oxidative stress in animals, but it is unclear which MCT could play a role, and the mechanism has not been elucidated. In this study, the effects of individual MCT on growth performance, serum intake-related hormones, and oxidative stress indices in finishing bulls were investigated and further studied the effects of MCT supplementation on gastrointestinal tract bacteria and rumen fluid metabolomics. Results: Four ruminally fistulated Yanbian cattle (bulls) were selected in 4 × 4 Latin square designs and allocated to four treatment groups: a control group (CON) fed a basal diet (total mixed ration, TMR), three groups fed a basal diet supplemented with 60 g/bull/day glycerol monocaprylin (GMC, C8), glycerol monodecanoate (GMD, C10), and glycerol monolaurate (GML, C12), respectively. Compared with the CON group, GMD tended to increase the dry matter intake (DMI) of finishing bulls (P = 0.069). Compared with the CON group, GMD significantly increased the concentration of ghrelin O-acyl transferase (GOAT), total ghrelin (TG), acylated ghrelin (AG), and orexins (P < 0.05) and significantly decreased the concentrations of hydrogen peroxide (H2O2), malondialdehyde, reactive oxygen species (ROS), and lipopolysaccharides (LPS) in the serum of finishing bulls (P < 0.05). Compared with the CON group, GMD and GML significantly increased the concentrations of total antioxidant capacity (T-AOC), catalase, glutathione peroxidase (GSH-PX), glutathione reductase (GR), and nitric oxide (NO) in the serum of finishing bulls (P < 0.05). Compared with the CON group, there were 5, 14, and 6 significantly different bacteria in the rumen digesta in the C8, C10, and C12 groups, respectively; there were 3, 10, and 5 significantly different bacteria in the rumen fluid in the C8, C10, and C12 groups, respectively; and only one differential bacteria (genus level) in the feces among the four treatment groups. Compared with the CON group, there were 3, 14, and 15 significantly differential metabolites identified under positive ionization mode in the C8, C10, and C12 groups, respectively, while under negative ionization mode were 3, 11 and 14, respectively. Correlation analysis showed that there was a significant correlation between DMI, GOAT, AG, GSH-PX, LPS, gastrointestinal tract bacteria, and rumen fluid metabolites. Conclusions: Our findings revealed that different types of MCTs have different application effects in ruminants. Among them, GMD may improve the feed intake of finishing bulls by stimulating the secretion of AG. GMD and GML may change gastrointestinal tract microorganisms and produce specific rumen metabolites to improve the oxidative stress of finishing bulls, and ghrelin may also be involved. This study enlightens the potential mechanisms by which MCT improves feed intake and oxidative stress in finishing bulls. 5d9kULzJFQsQ3ajLfa--XD Video Abstract [ABSTRACT FROM AUTHOR]

Tomato is the second most valuable vegetable crop, and its susceptibility to tropospheric ozone (O3) varies on the cultivar. Eight tomato cultivars with documented O3 sensitivity were reevaluated using ethylenediurea (400 ppm EDU) to determine the effectiveness of EDU in assessing O3 sensitivity under heavily O3-polluted tropical conditions. EDU helped in amending the growth, photosynthetic pigments, photosynthetic rate, stomatal conductance, and yield characteristics in the tomato cultivars. EDU reduced the lipid peroxidation and reactive oxygen species content, while enzymatic and non-enzymatic antioxidant responses differed across cultivars. The cultivar Superbug and Sel-7 (O3 susceptible) performed better by employing more biomass and yield and exhibiting more potent antioxidative defense machinery mainly non-enzymatic antioxidants after EDU treatment. The higher value of total antioxidative potential (TAP) in O3 susceptible cultivars suggested the adaptive resilience through EDU application against O3 stress. EDU application greatly enhanced the photosynthetic rate in O3 susceptible cultivars by increasing the stomatal conductance. Hence, both biophysical and biochemical responses were involved in protection against O3 provided by EDU. Kashi chayan and VRT02 (O3 tolerant) cultivars showed least response to EDU, due to their efficient inherent mechanisms in alleviating O3 stress. Thus, EDU may be used as an efficient biomonitoring tool against O3-sensitive cultivars. [ABSTRACT FROM AUTHOR]

Heavy metals (HMs) contamination has gained much attention due to its high degree of toxicity for living organisms. Therefore, different techniques are underway to eradicate HMs from the environment. Among the biological techniques, phytoremediation is a suitable method, but owing to the slow rate and chance of HMs penetration into the food chain, alternative techniques are needed to reduce their phytotoxicity, and biochar is one of them. Due to the diverse characteristics, biochar immobilizes HMs in the soil by improving soil pH, ion exchange, electrostatic interactions, complexation, precipitation, surface adsorption, and microbial activation. Thereby, amendment of biochar in the HMs-contaminated soils reduces HMs toxicity to plants and limits their penetration into the food chain. In contrast, some biochars have also been studied to induce metal availability in soils and subsequently its uptake by plants. This dual role of biochar depends on the feedstock of biochar, incineration temperature, and the rate of application. Moreover, biochar treatments enhance plant growth under HMs stress by improving nutrient availability, water retention capacity, scavenging of reactive oxygen species, and photosynthetic efficiency. Owing to the beneficial characteristics of biochar in HMs-contaminated sites, the number of publications has tremendously increased. Additionally, the plant species and the types of HMs that have been tested frequently under biochar treatments in these articles have been studied. Overall, the current study would help in understanding the mechanisms of how biochar influences phytoremediation of HMs and improves plant growth in HMs-polluted soils and the current scenario of the available literature. [ABSTRACT FROM AUTHOR]

Tobacco, a warm-season crop originating from the Americas, is highly susceptible to cold stress. The utilization of symbiotic fungi as a means to bolster crops' resilience against abiotic stresses has been proven to be a potent strategy. In this study, we investigated the effect of endophytic fungus Piriformospora indica on the cold resistance of tobacco. When exposed to cold stress, the colonization of P.indica in tobacco roots effectively stimulates the activity of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). This, in turn, reduces the accumulation of reactive oxygen species (ROS), thereby mitigating oxidative damage. Additionally, P. indica elevates the levels of osmolytes, such as soluble sugars, proline, and soluble proteins, thus facilitating the restoration of osmotic balance. Under cold stress conditions, P. indica also induces the expression of cold-responsive genes. Furthermore, this fungus not only enhances photosynthesis in tobacco by stimulating the synthesis of photosynthetic pigments, strengthening Rubisco activity, and elevating PSII efficiency, but also fortifies tobacco's nitrogen assimilation by inducing the expression of nitrate transporter gene and activating enzymes related to nitrogen assimilation. Consequently, this synergistic optimization of nitrogen and carbon assimilation provides a solid material and energetic foundation for tobacco plants to withstand cold stress. Our study demonstrates that a mycorrhizal association between P. indica and tobacco seedlings provides multifaceted protection to tobacco plants against low-temperature stress and offers a valuable insight into how P. indica enhances the cold tolerance of tobacco. [ABSTRACT FROM AUTHOR]

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Objective: Sorafenib, a multikinase inhibitor, is currently the standard treatment for advanced liver cancer. However, its application has become limited by the development of drug resistance. We intended to explore the mechanisms underlying the development of sorafenib resistance, therefore identifying an effective strategy to overcome sorafenib resistance remain challenges. Methods: Here, the follow-up of liver cancer patients undergoing sorafenib therapy, as well as animal tumor challenge and treatment were performed. The sorafenib-resistant liver cancer cell lines Huh7/SOR and HepG2/SOR were also established. miRNA and mRNA microarray analyses, TargetScan prediction, dual luciferase reporter assay, RNA pull-down assay, co-mmunoprecipitation (Co-IP) and pull-down assays, a transcription factor-specific NRF2 assay, an iron detection assay, a lipid peroxidation quantification assay, a ROS measurement assay, and GSH/GSSG and GSH-px standard quantitative assays were used. Results: We showed that upregulation of the provirus-integrating site for Moloney murine leukemia virus 3 (Pim-3) predicted poor response and unsatisfactory prognosis in sorafenib-treated liver cancer patients. Similarly, Pim-3 expression was positively associated with sorafenib resistance in liver cancer cells. Furthermore, microRNA-936 (miR-936) targeted the 3'-noncoding region (3'-UTR) of Pim-3 but exhibited lower expression in sorafenib-resistant liver cancer cells than in their parental cells. The high expression of Pim-3 mediated by miR-936 insufficiency activated the ANKRD18A/Src/NRF2 pathway which rearranged the expression of the indicated markers involved in iron distribution and lipid peroxidation homeostasis. MiR-936 overexpression and GV102-Pim-3-shRNA significantly attenuated the activity of the ANKRD18A/Src/NRF2 pathway to decrease the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A), Src, and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), especially decreasing NRF2 nuclear retention and transcriptional activity. The transcriptional activity of NRF2 prompted cell ferroptosis because the transfection of miR-936 mimics, GV102-Pim-3-shRNA and GV102-NRF2-shRNA plasmid increased the expression of transferrin receptor 1 (TFR1) and divalent metal transporter 1 (DMT1) but decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), thus facilitating the accumulation of intracellular Fe2+, lipid peroxides, and reactive oxygen species (ROS) but reducing the glutathione (GSH) level. Moreover, the elevated expression of Pim-3, resulting from the absence of miR-936 enhances sorafenib resistance in liver cancer by inhibiting cell ferroptosis. Conclusion: Pim-3 can be regarded as a target in the treatment of sorafenib-resistant liver cancer. [ABSTRACT FROM AUTHOR]

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro , accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer. [ABSTRACT FROM AUTHOR]

The anti-Acanthamoeba properties of riboflavin and its enhanced amoebicidal effects when combined with ultraviolet A (UVA) radiation were investigated in vitro. The viability of cultured Acanthamoeba castellanii was assessed by adding varying concentrations (0 ~ 0.2% w/v) of riboflavin to the culture medium or after combined riboflavin and UVA treatment (30 min, 3 mW/cm2) over 1, 3, 5, and 7 days. Intracellular reactive oxygen species (ROS) levels were measured following a 30-minute exposure to riboflavin. Additionally, the cysticidal effects of riboflavin, UVA, and their combination were evaluated. Gene transcription in Acanthamoeba was analyzed using RNA-seq. Riboflavin demonstrated dose-dependent toxicity on Acanthamoeba, accompanied by an increase in intracellular ROS. Exposure to 0.2% riboflavin reduced Acanthamoeba viability by over 50% within one day. UVA treatment alone also reduced viability by over 50%. Combined treatment with 0.2% riboflavin decreased trophozoite survival by more than 80%, and approximately 60% of cysts were killed when 0.1% riboflavin was combined with UVA. RNA-seq analysis indicated significant changes in gene expression after exposure to riboflavin, UVA, and their combination, particularly affecting oxidoreductase activity, cystathionine β synthase, and serine-threonine kinase activity. These findings indicate that riboflavin exhibits dose-dependent toxicity in Acanthamoeba, primarily through increased ROS generation. Combining riboflavin and UVA did not fully eradicate trophozoites and cysts of Acanthamoeba, but was able to partially inactivate them. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) is a newly identified, potent, and selective inhibitor of the Keap1-Nrf2 interaction. This study aimed to explore the protective effects and mechanisms of C7 on RM in vitro and in vivo. Methods: Western blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) and mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, and tissue staining were employed to explore the protective effects and underlying mechanisms of C7 in radiation-induced primary rat microglia and BV2 cells, as well as RM rat models. Results: In this study, we found that C7 inhibited the production of pro-inflammation cytokines and oxidative stress induced by irradiation in vitro. Further, the data revealed that radiation worsened the locomotor functions in rats, and C7 significantly improved histological and functional recovery in RM rats. Mechanically, C7 activated Nrf2 signaling and promoted the microglia transformation from M1 to M2 phenotype. Conclusion: C7 could ameliorate RM by boosting Nrf2 signaling and promoting M2 phenotype microglia polarization in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Noninvasive control over the reversible generation of singlet oxygen (1O2) has found the enormous practical implications in the field of biomedical science. However, metal‐free pure organic emitters, connected with a photoswitch, capable of generating "on‐demand" 1O2via triplet harvesting remain exceedingly rare; therefore, the utilization of these organic materials for the reversible control of singlet oxygen production remains at its infancy. Herein, an ambient triplet mediated emission in quinoline‐dithienylethene (DTE)‐core‐substituted naphthalene diimide (cNDI) derivative is unveiled via delayed fluorescence. The quinoline‐DTE‐cNDI triad displayed enhanced photoswitching efficiency via double FRET mechanism. It was found to have direct utilization in controlled photosensitized organic transformations via efficient generation of singlet oxygen (yield ΦΔ~0.55 in DCM and 0.73 in methanol). The designed molecule exhibits a long‐lived emission (τ∼1.1 μs) and very small singlet‐triplet splitting (ΔEST) of 0.13 eV empowering it to display delayed fluorescence. Comprehensive steady state and time‐resolved emission spectroscopy (TRES) analyses along with DFT calculations offer detailed understandings into the excited‐state manifolds of organic compound and energy transfer (ET) pathways involved in 1O2 generation. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are physiological byproducts of neuronal metabolism. However, an imbalance between ROS generation and antioxidant capacity, often driven by dysregulated pro-oxidant enzymes like nicotinamide adenine dinucleotide phosphate oxidases (NOX), can result in deleterious oxidative stress. This oxidative stress is a critical factor in the pathogenesis of neurodegenerative diseases. While interventions with broad-spectrum antioxidants have demonstrated limited efficacy, the modulation of endogenous antioxidant mechanisms presents a promising therapeutic avenue. Here, we investigated the potential of the neuroprotective hormone prolactin to mitigate oxidative stress and subsequent neuronal cell death. Prolactin protected primary mouse hippocampal neurons from hydrogen peroxide (H2O2)-induced oxidative damage. Prolactin reduced ROS levels, lipid peroxidation, and apoptosis, and its effects were occluded by a specific prolactin receptor antagonist (G129R-hPRL). Mechanistically, prolactin suppressed H2O2-induced mRNA upregulation of pro-oxidative Nox4 and pro-apoptotic Bax. Moreover, prolactin induced nuclear factor kappa B (NF-κB) nuclear translocation, and the inhibition of the NF-κB signaling pathway abolished the neuroprotective and transcriptional effects of prolactin, indicating its central role in prolactin-mediated protection. Our findings indicate that prolactin exerts potent antioxidant and neuroprotective effects by modulating the expression of Nox4 and Bax, thereby reducing ROS generation and neuronal apoptosis. This study underscores the therapeutic potential of prolactin in attenuating oxidative stress and suggests a possible role in the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) releasing materials are increasingly used in nanomedicines due to their effectiveness against a broad spectrum of microbes. However, most ROS‐releasing materials rely on external stimuli such as photoirradiation, either through photodynamic or photocatalytic processes, which limits their practical applications. Herein, this work presents a novel nanoclay mediated self‐promoted ROS releasing material called oxygen vacancies‐rich ZnO/kaolinite (Ov‐rich ZnO/Kaol). Both experiments and density functional theory (DFT) calculations reveal that the introduction of kaolinite increases the content of Ov in ZnO, and the change in the electronic structure promotes the process of oxygen adsorption and activation, resulting in the generation of ·O2−through oxygen reduction without photoirradiation. Molecular dynamics simulations confirm that Ov enhances the interaction between the material and bacterial membrane, promoting the bacterial‐killing effect of ·O2−. More importantly, Ov‐rich ZnO/Kaol is successfully prepared on a pilot scale and used to manufacture antibacterial gauze, which showed at least 99% antibacterial activity against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in the absence of light. The as‐prepared material also exhibited satisfactory biocompatibility and biosafety. This method can offer a more benign approach to address the limitations of traditional photoirradiation‐dependent photosensitizers for antimicrobial gauze. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is promising for combating deep‐seated infectious diseases by generating substantial reactive oxygen species (ROS) through the profound tissue penetration capabilities of ultrasound. However, the compact protective structures of bacterial biofilms present a formidable challenge, impeding ROS efficacy. Given that ROS have a limited diffusion range and current sonosensitizers struggle to infiltrate biofilms, complete eradication of pathogenic bacteria often remains unachieved. In this study, mesoporous titanium dioxide (TiO2) nanoparticles are engineered asymmetrically coated with a thin layer of Ag and loaded with L‐arginine (LA) to construct ultrasound‐propelled nanomotors. These Ag‐TiO2‐LA Janus nanoparticles demonstrate robust self‐propulsion upon ultrasonic activation, allowing for deeper penetration into biofilm matrices and enhancing localized biofilm disruption through improved SDT outcomes. Additionally, the incorporation of Ag not only broadens TiO2's absorption spectrum but also confers photothermal capabilities upon NIR laser excitation at 808 nm. The Ag‐TiO2‐LA nanomotor amalgamates TiO2's sonodynamic potential with Ag's photothermal properties, forging a versatile antimicrobial agent capable of efficient biofilm penetration and a synergistic antibacterial effect when subjected to dual NIR and ultrasound stimuli. This innovative, singularly‐structured nanoparticle stands out as an effective combatant against bacterial biofilms and accelerates the healing process of infected wounds, showcasing potential for multifaceted clinical applications. [ABSTRACT FROM AUTHOR]

The exploitation of effective and nontoxic materials with antioxidant activity to mitigate or inhibit the damage caused by elevated levels of free radicals has attracted considerable attention across diverse fields. Herein, this study demonstrates that a biocompatible MgAl‐layered double hydroxide (LDH) can be activated for multiple types of free radical scavenging with unexpected activity through amorphization (a‐MgAl‐LDH). Detailed characterization reveals that numerous oxygen defects are introduced after amorphization. Mechanistic studies and theoretical simulations indicate that amorphization‐induced oxygen defects in a‐MgAl‐LDH promote radical adsorption and reduce the reaction energy barriers, thereby resulting in enhanced radical scavenging activities. Consequently, a‐MgAl‐LDH demonstrated remarkable efficiency in mitigating the oxidative injury induced by Rosup in cells and provided thermal stabilization of polyvinyl chloride against degradation. This study demonstrates the transformation of inert MgAl‐LDH into a promising, nontoxic, and cost‐effective nano‐antioxidant option for antioxidative therapy or polymer stabilization and highlights the significance of crystallinity engineering of nanomaterials for efficient free radical scavenging. [ABSTRACT FROM AUTHOR]

The scientific community is actively engaged in the development of innovative nanomaterials with broad‐spectrum virucidal properties, particularly those capable of producing reactive oxygen species (ROS), to combat upcoming pandemics effectively. The generation of ROS capable of inhibiting viral activity on high‐touch surfaces can prove an effective means of reducing pathogenic and viral infections, while avoiding the exacerbation of antibiotic resistance resulting from the extensive use of chemical disinfectants. Carbon dots (C‐dots), in particular, are a class of nanomaterials that under specific conditions is able to generate reactive species. They are, therefore, excellent candidates for fabricating light‐activated functional antiviral devices. Pro‐oxidant C‐dots have been developed via microwave synthesis using an amino acid, glycine (Gly), and 1,5‐diaminonaphtalene (DAN) as precursors. The formation of C‐dots has been obtained by reacting the precursors in microwave using two different acid catalysts, H3BO3 or HCl. The HCl catalyst promotes the formation of a copolymer while using H3BO3 the precursors preferentially self‐condense. The boron‐catalyzed samples have shown to contain radical centers whose intensity increases upon illumination by UV and also visible light. They also show the capability of generating singlet oxygen through energy transfer to oxygen molecules when irradiated. The C‐dots exhibit effective virucidal activity and have been tested in vitro using two different variants of SARS‐CoV‐2, the original strain, and Omicron. Antiviral C‐dots have been finally used to functionalize a model surface, inducing a strong virucidal activity against the SARS‐CoV‐2 coronavirus with both ultraviolet (UV) and visible (VL) light. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, a major health concern globally, often faces challenges in the non-invasive elimination of cancer cells. This has prompted researchers to explore alternative strategies, such as photothermal therapy (PTT), which takes advantage of the location of breast cancer lesions. Additionally, the tumor microenvironment with high hydrogen peroxide (H2O2) provides a key prerequisite for treating tumors with nanozymes, especially those with peroxidase (POD)-like activity. However, the overexpression of TrxR1, which maintains redox homeostasis in tumor cells, limits reactive oxygen species (ROS)-based cytotoxic therapy. This study aims to present molybdenum selenide nano urchins (MoSe2 NUs) with excellent photothermal conversion efficiency, POD-like activity and selective inhibition of TrxR1 to achieve photothermal enhanced nanocatalytic therapy for combating breast cancer. Methods: The characterization of MoSe2 NUs synthesized by the hydrothermal method was identified by TEM, XRD, Zeta potential and DLS. Whether MoSe2 NUs in conjunction with NIR possessed POD-like activities or not was identified via a TMB colorimetric method. The photothermal characteristics of MoSe2 NUs excited by near-infrared were recorded by an infrared thermal imaging camera. The antitumor effect of MoSe2 NUs was detected by cell death staining, apoptosis assay and animal experiments. TrxR1 and apoptosis-related protein expression were identified by Western blot and Immunohistochemistry. Results: MoSe2 NUs possessed excellent photothermal conversion efficiency, peroxidase (POD)-like activity, and selective inhibition of TrxR1. Furthermore, the photothermal effect of MoSe2 NUs can enhance their POD-like activity, allowing for accurate cancer treatment under near-infrared (NIR) light. MoSe2 NUs plus NIR and MoSe2 NUs alone exhibited in vivo tumor inhibition rates of 69.7% and 35.1%, respectively. Mechanistically, NIR-regulated MoSe2 NUs induced potent apoptosis of cancer cells by downregulating the TrxR1 and elevating intracellular ROS, thereby leading to caspase-3 cleavage. Conclusions: This study demonstrated that MoSe2 NUs under NIR irradiation can precisely and efficiently treat breast cancer and have great potential for clinical application. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is susceptible to various abiotic stresses, such as salt, cold, and drought. Therefore, there is an urgent need to explore the relevant genes that enhance tolerance to these stresses. In this study, we identified a gene, OsNCED4 (9-cis-epoxycarotenoid dioxygenase 4), which regulates tolerance to multiple abiotic stresses. OsNCED4 encodes a chloroplast-localized abscisic acid (ABA) biosynthetic enzyme. The expression of OsNCED4 gene was significantly induced by 150 mM NaCl and cold stress. Disruption of OsNCED4 by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9-mediated mutagenesis resulted in significant sensitivity to NaCl and cold stress. The salt and cold sensitivity of osnced4 mutant was due to the reduction of ABA content and the excessive accumulation of reactive oxygen species (ROS) under stress. Moreover, OsNCED4 also regulates drought stress tolerance of rice seedlings. Taken together, these results indicate that OsNCED4 is a new regulator for multiple abiotic stress tolerance in rice, and provided a potential target gene for enhancing multiple stress tolerance in the future. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii's extensive antibiotic resistance makes its infections difficult to treat, so effective strategies to fight this bacterium are urgently needed. This study aims to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) mediated by Rutin-Gal(III) complex and Quercetin against A. baumannii. Absorbance spectra, fluorescence spectra, and minimum inhibitory concentration (MIC) of Rutin-Gal(III) complex and Quercetin were determined. The intracellular reactive oxygen species (ROS), extracellular polymeric substances (EPS), cell membrane permeability, expression of ompA and blaOXA−23, anti-biofilm activity, and anti-metabolic activity of Rutin-Gal(III) complex- and Quercetin-mediated aPDT were measured. Rutin-Gal(III) complex and Quercetin revealed absorption peaks in the visible spectra. Quercetin and Rutin-Gal(III) complex displayed fluorescence peaks at 524 nm and 540 nm, respectively. MIC values for the Rutin-Gal(III) complex and Quercetin were 64 µg/mL and 256 µg/mL, respectively. Quercetin- and Rutin-Gal(III) complex-mediated aPDT significantly reduced the colony forming units/mL (58.4% and 67.5%), EPS synthesis (47.4% and 56.5%), metabolic activity (30.5% and 36.3%), ompA (5.5- and 10.5-fold), and blaOXA−23 (4.1-fold and 7.8-fold) genes expression (respectively; all P < 0.05). Quercetin- and Rutin-Gal(III) complex-mediated aPDT enhanced notable biofilm degradation (36.2% and 40.6%), ROS production (2.55- and 2.90-folds), and membrane permeability (10.8– and 9.6-folds) (respectively; all P < 0.05). The findings indicate that Rutin-Gal(III) complex- and Quercetin-mediated aPDT exhibits antibacterial properties and could serve as a valuable adjunctive strategy to conventional antibiotic treatments for A. baumannii infections. One limitation of this study is that it was conducted solely on the standard strain; testing on clinical isolates would allow for more reliable interpretation of the results. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic non‐specific inflammatory disease of the intestines with a high prevalence. Polymer‐prepared nanoparticles are well‐targeted, highly biocompatible, and have high potential for personalized therapy. Polymer nanoparticles are able to achieve localized therapy through their unique design. First, this review compares the advantages and disadvantages of natural and synthetic polymeric materials as well as describes the application of polymeric nanoparticles in UC therapy. Then, the preparation, characterization methods, and current challenges of common polymer nanoparticles are presented. Next, one‐by‐one examples of polymer nanoparticle‐targeted drug delivery strategies for the treatment of UC are presented. In addition, polymer nanoparticle‐based therapeutic approaches for UC, including anti‐inflammatory therapies, reactive oxygen species scavenging therapies, and intestinal flora modulation therapies, are presented. Finally, future research directions for polymer nanoparticles in UC therapy are discussed and current challenges are identified. The aim of this paper is to provide valuable references and guidance for researchers to design and develop novel UC therapies. [ABSTRACT FROM AUTHOR]

Age‐related declines in oocyte quality and ovarian function are pivotal contributors to female subfertility in clinical settings. Yet, the mechanisms driving ovarian aging and oocyte senescence remain inadequately understood. The present study evaluated the alterations in N‐glycoproteins associated with ovarian aging and noted a pronounced elevation in N221 glycopeptides of cathepsin L (Ctsl) in the ovaries of reproductive‐aged mice (8–9 months and 11–12 months) compared to younger counterparts (6–8 weeks). Subsequent analysis examined the involvement of Ctsl in oocyte aging and demonstrated a significant elevation in Ctsl levels in aged oocytes. Further, it was revealed that the overexpression of Ctsl in young oocytes substantially diminished their quality, while oocytes expressing an N221‐glycosylation mutant of Ctsl did not suffer similar quality degradation. This finding implies that the N221 glycosylation of Ctsl is pivotal in modulating its effect on oocyte health. The introduction of a Ctsl inhibitor into the culture medium restored oocyte quality in aged oocytes by enhancing mitochondrial function, reducing accumulated reactive oxygen species (ROS), lowering apoptosis, and recovering lysosome capacity. Furthermore, the targeted downregulation of Ctsl using siRNA microinjection in aged oocytes enhanced fertilization capability and blastocyst formation, affirming the role of Ctsl knockdown in fostering oocyte quality and embryonic developmental potential. In conclusion, these findings underscore the detrimental effects of high expression of N‐glycosylated Ctsl on oocyte quality and its contribution to oocyte senescence, highlighting it as a potential therapeutic target to delay ovarian aging and enhance oocyte viability. [ABSTRACT FROM AUTHOR]

ABSTRACT Plants are an intrinsic part of the soil community, which is comprised of a diverse range of organisms that interact in the rhizosphere through continuous molecular communications. The molecular dialogue within the plant microbiome involves a complex repertoire of primary and secondary metabolites that interact within different liquid matrices and biofilms. Communication functions are likely to involve membrane‐less organelles formed by liquid−liquid phase separation of proteins and natural deep eutectic solvents that play a role as alternative media to water. We discuss the chemistry of inter‐organism communication and signalling within the biosphere that allows plants to discriminate between harmful, benign and beneficial microorganisms. We summarize current information concerning the chemical repertoire that underpins plant−microbe communication and host‐range specificity. We highlight how the regulated production, perception and processing of reactive oxygen species (ROS) is used in the communication between plants and microbes and within the communities that shape the soil microbiome. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion The aim of this study is to explore the mechanism of benzylurea in the inflammatory injury of human periodontal ligament fibroblasts (hPDLFs).An inflammation model of hPDLFs was established using LPS. Nuclear transport of nuclear transcription factor‐κB (NF‐κB), secretion of cytokines, and the morphology and distribution of F‐actin were determined. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP), and reactive oxygen species (ROS) levels. The expression of mitochondrial carrier homolog 2 (MTCH2) and Cytochrome b5 type B (CYB5B) was detected.Benzylurea alleviated the effects of lipopolysaccharide (LPS) on the proliferation and apoptosis of hPDLFs. It reduced the release of inflammatory cytokines and inhibited NF‐κB nuclear translocation. Benzylurea improved mitochondrial function by regulating MMP and preventing excessive mPTP opening. Furthermore, LPS elevated the expression of MTCH2 and reduced the expression of CYB5B in hPDLFs. However, these effects can be inhibited by benzylurea. The altered expression of MTCH2 directly affected CYB5B expression, the release of inflammatory cytokines, and the activation of nuclear translocation of NF‐κB.CYB5B may act as an effector of MTCH2, with benzylurea enhancing mitochondrial function and protecting hPDLFs from LPS‐induced injury through MTCH2. [ABSTRACT FROM AUTHOR]

Conventional photosensitizers for tumor phototherapy are greatly limited by their reliance on a single‐cell death process, leading to insufficient therapeutic effects and restricted biomedical applications. To address these limitations, multifunctional fluorophores, BTA and BTB, are designed based on an electron donor‐π‐acceptor system. By adjusting the strength of the intramolecular charge transfer through varying electron‐donating moieties, their optical properties are tailored. BTA emits bright near‐infrared II (NIR‐II) fluorescence and exhibits typical aggregation‐induced emission (AIE) characteristics, a large Stokes shift (>250 nm), good photostability, satisfactory biocompatibility, and remarkable mitochondria‐targeting capabilities. Notably, it demonstrates potent photodynamic and photothermal properties. BTA as an effective photosensitizer and a photothermal agent, generates various cytotoxic Type I and II reactive oxygen species and photothermal energy to effectively destroy tumor cell mitochondria and suppress tumor growth. Importantly, the molecular mechanisms underlying combination phototherapy are elucidated, revealing that it induces synergistic cell apoptosis and pyroptosis. These results highlight the potential of multifunctional AIE materials with bright NIR‐II fluorescence and mitochondria‐targeting characteristics for the synergistic phototherapy of breast tumors, offering new insights for future therapeutic developments. [ABSTRACT FROM AUTHOR]

Given the unique anatomy and location of inflammatory bowel disease (IBD), oral pharmacological treatment is the mainstay for managing IBD because of its convenience and direct accessibility to the gastrointestinal tract. However, efficient delivery systems must be designed to navigate the harsh gastrointestinal environment during application. Here, an innovative oral drug delivery system was proposed using nanomotor (NM)‐loaded soluble microcapsules for treating IBD. MnO2‐Au‐mSiO2 NMs incorporate partially encapsulated MnO2 antennas that convert reactive oxygen species into oxygen, autonomously propelling the NMs. Astaxanthin (AST), known for its anti‐inflammatory properties, is loaded into the mesoporous silica (mSiO2) of NMs (AST@NMs). AST effectively reduces inflammation and shifts macrophages from a proinflammatory (M1) phenotype to an anti‐inflammatory (M2) phenotype. To protect the nanomotors from harsh digestive conditions and achieve intestinal‐responsive release, using photocurable 3D printing, we fabricated enteric‐coated oral microcapsules (MCs). Additionally, to prevent leakage of AST@NMs, a calcium alginate shell was cured in situ on the surface of the microcapsules (AST@NMs@MCs). In vitro and in vivo, AST@NMs@MCs effectively reduced inflammation, repaired the intestinal barrier, and modulated the gut microbiota. These findings underscore the protective effects of the microcapsules on AST@NM, highlighting their potential as a promising strategy for treating colitis. [ABSTRACT FROM AUTHOR]

ABSTRACT The photosensitizer mechanism by the psoralen (PSO) reacts to produce reactive oxygen species has not been thoroughly studied; thus, this work was carried out a study of the reaction and mechanism involved in the photosensitizer activity of PSO, employing M06‐2X/6‐311++G(d,p) of the density functional theory. There is a competition between the generation of radical anion superoxide (type I mechanism) and the singlet oxygen molecule (type II mechanism) in lipid media; therefore, the ROS anion superoxide and singlet oxygen could be formed as products of the reaction involved in the photosensitizer activity of PSO in lipid media. In aqueous media, the reaction involved in the photosensitizer activity of PSO was only attributed to the type I mechanism; hence, in aqueous media, the photosensitizer activity of PSO yielded the anion superoxide. The present study supports the photosensitizer activity of the PSO in lipid and aqueous media. It enhances the knowledge of these reactions in different media and their application to reactivity, including the physiology media. [ABSTRACT FROM AUTHOR]

The strategy of in vivo self‐assembly has been developed for improved enrichment and long‐term retention of anticancer drug in tumor tissues. However, most self‐assemblies with non‐covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling‐induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation‐responsive peptide‐porphyrin conjugate P1 is synthesized, which self‐assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2‐fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria‐targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies. [ABSTRACT FROM AUTHOR]

Helicenes represent a class of fascinating π compounds with fused yet folded backbones. Despite their broad structural diversity, harnessing helicenes to develop well‐defined materials is still a formidable challenge. Here we report the synthesis of crystalline porous helicene materials by exploring helicenes to synthesize covalent 2D lattices and layered π frameworks. Topology‐directed polymerization of [6]helicenes and porphyrin creates 2D covalent networks with alternate helicene‐porphyrin alignment along the x and y directions at a 1.5‐nm interval and develops [6]helicene frameworks through reversed anti‐AA stack along the z direction to form segregated [6]helicene and porphyrin columnar π arrays. Notably, this π configuration enables the frameworks to be highly red luminescent with benchmark quantum yields. The [6]helicene frameworks trigger effieicnt intra‐framework singlet‐to‐singlet state energy transfer from [6]helicene to porphyrin and facilitate intermolecular triplet‐to‐triplet state energy transfer from frameworks to molecular oxygen to produce reactive oxygen species, harvesting a wide range of photons from ultraviolet to near‐infrared regions for light emitting and photo‐to‐chemical conversion. This study introduces a new family of extended frameworks, laying the groundwork for exploring well‐defined helicene materials with unprecedented structures and functions. [ABSTRACT FROM AUTHOR]