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Objective: The aim of this paper was to assess the differences in clinicopathological characteristics, efficacy and prognosis of neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor2(HER2)-zero and HER2-low hormone receptor (HR)-negative breast cancer (BC) patients, and the impact of HER2-evolution on prognosis before and after NAC. Methods: 319 triple negative breast cancer (TNBC) patients who completed NAC and surgery from August 2014 to August 2018 at Tianjin Medical University Cancer Institute and Hospital were included. Clinicopathological features, efficacy of NAC and assessment of prognosis were retrospectively analysed. The evolution of HER2-zero to HER2-low after NAC is defined as HER2-gain, the evolution of HER2-low to HER2-zero after NAC is defined as HER2-loss, and HER2 unchanged after NAC is defined as HER2-stable. Results: In HR-negative BC, the pathological complete response (pCR) rate was significantly higher in HER2-zero compared with HER2-low patients, and the difference was statistically significant (38.9% vs 23.2%, p = 0.004), but there was no significant difference in the prognosis between the two groups. The overall rate of HER2-evolution after NAC was 19.7%, and there was a significant correlation between HER2-loss and histological grading, whereas HER2-gain was significantly associated with Ki-67 expression. In terms of prognosis, HER2-gain was better compared to the other two groups. Conclusion: In this study, we found that HER2-low HR-negative BC showed different clinicopathological features and response to NAC compared with HER2-zero, as well as HER2-evolution before and after NAC had a significant impact on prognosis. [ABSTRACT FROM AUTHOR]

Cholangiopathies are poorly understood disorders with no effective therapy. The extrahepatic biliary tree phenotype is less studied compared to the intrahepatic biliary injury in both human disease and Mdr2−/− mice, the established cholestatic mouse model. This study aimed to characterize the extra hepatic biliary tree of Mdr2−/− mice at various ages and to determine if injury can be repaired with the antioxidant and glutathione precursor N-acetyl-L-Cysteine treatment (NAC). We characterized extra hepatic bile ducts (EHBD)s at various ages from 2 to 40 weeks old FVB/N and Mdr2−/− mice. We examined the therapeutic potential of local NAC ex vivo using EHBD explants at early and late stages of injury; and systematic therapy by in vivo oral administration for 3 weeks. EHBD and liver sections were assessed by histology and immunofluorescent stains. Serum liver enzyme activities were analyzed, and liver spatial protein expression analysis was performed. Mdr2−/− mice developed progressive EHBD injury, similar to extrahepatic PSC. NAC treatment of ex vivo EHBD explants led to improved duct morphology. In vivo, oral administration of NAC improved liver fibrosis, and decreased liver enzyme activities. Spatial protein analysis revealed cell-type specific differential response to NAC, collectively indicating a transition from pro-apoptotic into proliferative state. NAC treatment should be further investigated as a potential therapeutic option for human cholangiopathies. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC) has established use as an antidote for acetaminophen overdose and treatment for pulmonary conditions and nephropathy. It plays a role in regulating oxidative stress and interacting with various cytokines including IL-1β, TNFα, IL-8, IL-6, IL-10, and NF-κB p65. The overexpression of reactive oxygen species (ROS) is believed to contribute to chronic pain states by inducing inflammation and accelerating disease progression, favoring pain persistence in neuropathic and musculoskeletal pain conditions. Through a comprehensive review, we aim to explore the mechanisms and inflammatory pathways through which NAC may manage neuropathic and musculoskeletal pain. Evidence suggests NAC can attenuate neuropathic and musculoskeletal pain through mechanisms such as inhibiting matrix metalloproteinases (MMPs), reducing reactive oxygen species (ROS), and enhancing glutamate transport. Additionally, NAC may synergize with opioids and other pain medications, potentially reducing opioid consumption and enhancing overall pain management. Further research is needed to fully elucidate its therapeutic potential and optimize its use in pain management. As an adjuvant therapy, NAC shows potential for chronic pain management, offering significant benefits for public health. [ABSTRACT FROM AUTHOR]

The 'No apical meristem; Arabidopsis transcription activation factor; Cup-shape cotyledon' (NAC) transcription factors are pivotal in plant development and stress response. Sucrose-non-fermenting-related protein kinase 1.2 (SnRK1) is a key enzyme in glucose metabolism and ABA signalling. In this study, we used grape (Vitis vinifera) calli to explore NAC's roles in sugar and ABA pathways and its relationship with VvSnRK1.2. We identified 19 VvNACs highly expressed at 90 days after blooming, coinciding with grape maturity and high sugar accumulation, and 11 VvNACs randomly selected from 19 were demonstrated in response to sugar and ABA treatments. VvNAC26 showed significant response to sugar and ABA treatments, and its protein, as a nucleus protein, had transcriptional activation in yeast. We obtained the overexpression (OE- VvNAC26) and RNA-inhibition (RNAi- VvNAC26) of VvNAC26 in transgenic calli by Agrobacterium tumefaciens -mediated transformation. We found that VvNAC26 negatively influenced fructose content. Under sugar and ABA treatments, VvNAC26 negatively influenced the expression of most sugar-related genes, while positively influencing the expression of most ABA pathway-related genes. Dual-luciferase reporter experiments demonstrated that VvNAC26 significantly upregulates VvSnRK1.2 promoter expression in tobacco (Nicotiana benthamiana) leaves, although this process in grape calli requires ABA. The levels of sugar content, sugar-related genes, and ABA-related genes fluctuated significantly in OE- VvNAC26 + RNAi- VvSnRK1.2 and OE- VvSnRK1.2 + RNAi- VvNAC26 transgenic calli. These findings indicated that VvNAC26 regulates sugar metabolism and ABA pathway, displaying synergistic interactions with VvSnRK1.2. The cultivation of high-quality wine grapes (Vitis vinifera) often relies on specific growth stresses, and 'No apical meristem; Arabidopsis transcription activation factor; Cup-shape cotyledon' (NAC), as plant-specific transcription factors, playing a key role in adapting to stresses. This study identified these factors influencing the grape's sugar and abscisic acid (ABA) pathways. Specifically, we discovered that the VvNAC26 significantly impacts these pathways, coordinating with VvSnRK1.2 , offering new insights into grapevine development and its adaptation to environmental challenges. [ABSTRACT FROM AUTHOR]

Skin sensitization is a key endpoint for safety assessment, especially for cosmetics and personal care products. The adverse outcome pathway for skin sensitization and the chemical and biological events driving the induction of human skin sensitization are now well understood. Several non‐animal test methods have been developed to predict sensitizer potential by measuring the impact of chemical sensitizers on these key events. In this work, we have focused on Key Event 1 (the molecular initiating step), which is based on formation of a covalent adduct between skin sensitizers and endogenous proteins and/or peptides in the skin. There exists three in‐chemico assays approved by the Organization for Economic Co‐operation and Development—(1) Direct Peptide Reactivity Assay (DPRA), (2) Amino Acid Derivative Reactivity Assay (ADRA), and (3) Kinetic Direct Peptide Reactivity Assay (kDPRA) to quantify peptide/amino acid derivative depletion after incubation with test chemicals. However, overestimated depletion of the cysteine‐based peptide/amino acid derivatives is known in such assays because of the dimerization of the thiol group. In this present work, we report the synthesis and structural confirmation of the dimer of N‐(2‐[1‐naphthyl]acetyl)‐L‐cysteine (NAC) from the ADRA assay to allow simultaneous determination of (a) peptide depletion by quantifying NAC monomer and (b) peptide dimerization by quantifying NAC dimer thereby eliminating the overestimation. We present a case study with three chemicals to demonstrate the importance of this approach. Thus, this simultaneous assay gives a more informed view of the peptide reactivity of chemicals to better identify skin sensitizers. Guidelines for skin sensitization addressing Key Event 1 include three in‐chemico methods: DPRA, ADRA, and kDPRA. However, overestimated depletion of the Cysteine‐based peptide/amino acid derivatives is known in such assays because of the dimerization of the thiol group. In this present work, we synthesized NAC dimer from the ADRA assay to allow simultaneous determination of peptide depletion and dimerization, thus eliminating the overestimation. We present a case study with three chemicals to demonstrate the importance of this approach. [ABSTRACT FROM AUTHOR]

Background: Surgical chest masculinization procedures, especially gender-affirming top surgery (GATS), are becoming increasingly prevalent in the USA. While a variety of surgical techniques have been established as both safe and effective, there is limited research examining ideal aesthetic nipple appearance and incision scar pattern. This study employs patient images to understand the public's perception on top surgery outcomes when adjusting for BMI ranges and Fitzpatrick skin types. Methods: Images from RealSelf modified via Adobe Photoshop depicted various scar types and nipple-areolar complex (NAC) sizes/positions. A Qualtrics survey was distributed utilizing Amazon Mechanical Turk. Statistical analysis was performed through JMP Pro 17 for ordinal and categorical values, with a p value less than or equal to 0.05 statistically significant. Results: A moderately sized and laterally placed NAC was preferred. A transverse scar that resembles the pectoral border between the level of the inframammary fold and pectoral insertion was deemed most masculine and aesthetic. Majority of results demonstrated that this is unaffected by Fitzpatrick skin types. Increased BMI images impacted public preferences, as a nipple placed farther from the transverse incision (p = 0.04) and a transverse scar position closer to the IMF was preferred in higher BMI patients. Conclusions: An understanding of the most popular NAC and scar choices, as well as how these factors may differ when considering a Fitzpatrick skin type or BMI categorization was attained. This validates the importance of patient-centered approach when employing surgical techniques in GATS. Future studies intend to obtain reports from actual patients considering GATS. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b−/− animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Fruit acidity and color are important quality attributes in peaches. Although there are some exceptions, blood-fleshed peaches typically have a sour taste. However, little is known about the genetic variations linking organic acid and color regulation in peaches. Results Here, we report a peach graph-based pangenome constructed from sixteen individual genome assemblies, capturing abundant structural variations and 82.3 Mb of sequences absent in the reference genome. Pangenome analysis reveals a long terminal repeat retrotransposon insertion in the promoter of the NAC transcription factor (TF) PpBL in blood-fleshed peaches, which enhances PpBL expression. Genome-wide association study identifies a significant association between PpBL and malate content. Silencing PpBL in peach fruit and ectopic overexpression of PpBL in tomatoes confirm that PpBL is a positive regulator of malate accumulation. Furthermore, we demonstrate that PpBL works synergistically with another NAC TF, PpNAC1, to activate the transcription of the aluminum-activated malate transporter PpALMT4, leading to increased malate content. Conclusions These findings, along with previous research showing that PpBL and PpNAC1 also regulate anthocyanin accumulation, explain the red coloration and sour taste in blood-fleshed peach fruits.

Acetaminophen overdose treatment in patients admitted to two tertiary centers in Oman, variation and pitfalls [SJEMed 2024; 5(2.000): 134-140]

Abstract Cholangiopathies are poorly understood disorders with no effective therapy. The extrahepatic biliary tree phenotype is less studied compared to the intrahepatic biliary injury in both human disease and Mdr2−/− mice, the established cholestatic mouse model. This study aimed to characterize the extra hepatic biliary tree of Mdr2−/− mice at various ages and to determine if injury can be repaired with the antioxidant and glutathione precursor N-acetyl-L-Cysteine treatment (NAC). We characterized extra hepatic bile ducts (EHBD)s at various ages from 2 to 40 weeks old FVB/N and Mdr2−/− mice. We examined the therapeutic potential of local NAC ex vivo using EHBD explants at early and late stages of injury; and systematic therapy by in vivo oral administration for 3 weeks. EHBD and liver sections were assessed by histology and immunofluorescent stains. Serum liver enzyme activities were analyzed, and liver spatial protein expression analysis was performed. Mdr2−/− mice developed progressive EHBD injury, similar to extrahepatic PSC. NAC treatment of ex vivo EHBD explants led to improved duct morphology. In vivo, oral administration of NAC improved liver fibrosis, and decreased liver enzyme activities. Spatial protein analysis revealed cell-type specific differential response to NAC, collectively indicating a transition from pro-apoptotic into proliferative state. NAC treatment should be further investigated as a potential therapeutic option for human cholangiopathies.

Permethrin (PMT) is a synthetic pyrethroid insecticide widely applied in the agriculture and animal husbandry industry. The current study focused on the evaluation of the oxidative damage and apoptosis induced by PMT, as well as the protective role of coenzyme Q10 and N-acetylcysteine (NAC) against PMT toxicity in the liver of male rats. In this study, rats were divided in four groups, including G1 (control), G2 (PMT), G3 (NAC + PMT), and G4 (Q10 + PMT). Levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. RT-PCR was adopted to study the expression of Bax, Bcl2, p53, Caspases-3 and -9 genes. PMT exposure significantly decreased FRAP value, whereas increased MDA content in the liver tissue (p < 0.001). While Bcl2 was downregulated (5.31-fold), permethrin increased the expression of Bax (4.84-fold), p53 (4.67-fold), Caspases-3 (6.21-fold) and Caspases -9 (6.36-fold) genes in exposed group (p

Plant transcription factors (TFs) are integral proteins associated with gene transcription. That ability arises after TFs bind to specific DNA sequences, such as promoters, responding positively or negatively to a multitude of endogenous and exogenous factors or stressors. For this reason, in plants, the vast majority of TFs are associated with growth, development, and responses to biotic and abiotic stresses. As is commonly known, the genes coding for TFs are written in uppercase italics, whereas the resulting proteins are written in lowercase, such as OsWRKY28 and OsWRKY28, respectively for a member of the WRKY TF family in rice (Oryza sativa L.). However, despite the existence of some conventions for the nomenclature of TFs, some deviation from these norms has been observed in the literature. Several cases are highlighted, primarily related to NAC TFs. These cases emphasize the need for stricter quality control of literature pertaining to the nomenclature of plant TFs.

Introduction Fluimucil, also known as N-acetylcysteine (NAC), has been used as a medicinal drug for treating Alzheimer’s and Parkinson’s disease. Recent research has shown NAC’s potential as a neuroprotective agent, preventing oxidative damage and promoting neurodegenerative treatment. This study conducted bibliometric analysis of articles related to NAC use, identifying research trends, current trends, and correlations between research and institutions. The findings can help identify unpublished research and guide future research strategies. This research not only provides public interest in NAC research but also offers valuable insights for future research. Methods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords fluimucil, nac, n-acetylcystein, and neuroprotective. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis. Results The research trend found are Documents by Year, Documents by Author, Documents by Affiliations, Documents by country or territory, Documents by funding sponsor, Factorial Map Of The Documents With The Highest Contributes, Documents by Subject Area, Network Visualization, Overlay visualization of scopus database using Vosviewer, Density Visualization, Thematic Map, and Qualitative Analysis. Conclusions Research on the neuroprotective effects of N-acetylcysteine (NAC) or fluimucil has several limitations and strengths. It uses quantitative and qualitative analysis to identify research trends and mechanisms of NAC action. However, the data may be biased and the methodology may differ. The study has significant potential for future research, particularly in treating neurodegenerative diseases like Parkinson and Alzheimer. It also contributes to the understanding of NAC mechanisms.

Changes in both lignin biosynthesis and DNA methylation have been reported to be associated with chilling stress in plants. When stored at low temperatures, red-fleshed loquat is prone to lignification, with increased lignin content and fruit firmness, which has deleterious effects on taste and eating quality. Here, we found that 5 °C storage mitigated the increasing firmness and lignin content of red-fleshed 'Dahongpao' ('DHP') loquat fruit that occurred during 0 °C storage. EjNAC5 was identified by integrating RNA sequencing with whole-genome bisulfite sequencing analysis of 'DHP' loquat fruit. The transcript levels of EjNAC5 were positively correlated with changes in firmness and negatively correlated with changes in DNA methylation level of a differentially methylated region in the EjNAC5 promoter. In white-fleshed 'Baisha' ('BS') loquat fruit, which do not undergo chilling-induced lignification at 0 °C, the transcripts of EjNAC5 remained low and the methylation level of the differentially methylated region in the EjNAC5 promoter was higher, compared with 'DHP' loquat fruit. Transient overexpression of EjNAC5 in loquat fruit and stable overexpression in Arabidopsis and liverwort led to an increase in lignin content. Furthermore, EjNAC5 interacts with EjERF39 and EjHB1 and activates the transcription of Ej4CL1 and EjPRX12 genes involved in lignin biosynthesis. This regulatory network involves different transcription factors from those involved in the lignification pathway. Our study indicates that EjNAC5 promoter methylation modulates EjNAC5 transcript levels and identifies novel EjNAC5–EjERF39– Ej4CL1 and EjNAC5–EjHB1– EjPRX12 regulatory modules involved in chilling induced-lignification. [ABSTRACT FROM AUTHOR]

Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N‐acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti‐aging effects of cysteine, we systematically reviewed and performed a meta‐analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine. [ABSTRACT FROM AUTHOR]

Key message: Overexpression of ZmNAC19, a NAC transcription factor gene from maize, improves embryo development in transgenic Arabidopsis. NAC proteins are plant-specific transcription factors that are involved in multiple aspects of plant growth, development and stress response. Although functions of many NAC transcription factors have been elucidated, little is known about their roles in seed development. In this study, we report the function of a maize NAC transcription factor ZmNAC19 in seed development. ZmNAC19 is highly expressed in embryos of developing maize seeds. ZmNAC19 localizes to nucleus and exhibits transactivation activity in yeast cells. Overexpression of ZmNAC19 in Arabidopsis significantly increases seed size and seed yield. During 3 to 7 days after flowering, embryos of ZmNAC19-overexpression Arabidopsis lines developed faster compared to Col-0, while no visible differences were detected for their endosperms. Furthermore, overexpression of ZmNAC19 in Arabidopsis leads to increased transcription levels of two embryo development-related genes YUC1 and RGE1, and several elements proven to be binding sites of NAC transcription factors were observed in promoters of these two genes. Taken together, these results suggest that ZmNAC19 acts as a positive regulator in plant embryo development. [ABSTRACT FROM AUTHOR]

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Climate change severely affects crop production. Cotton is one of the primary fiber crops in the world and its production is susceptible to various environmental stresses, especially drought and salinity. Development of stress tolerant genotypes is the only way to escape from these environmental constraints. We identified sixteen homologs of the Arabidopsis JUB1 gene in cotton. Expression of GhJUB1_3‐At was significantly induced in the temporal expression analysis of GhJUB1 genes in the roots of drought tolerant (H177) and susceptible (S9612) cotton genotypes under drought. The silencing of the GhJUB1_3‐At gene alone and together with its paralogue GhJUB1_3‐Dt reduced the drought tolerance in cotton plants. The transgenic lines exhibited tolerance to the drought and salt stress as compared to the wildtype (WT). The chlorophyll and relative water contents of wildtype decreased under drought as compared to the transgenic lines. The transgenic lines showed decreased H2O2 and increased proline levels under drought and salt stress, as compared to the WT, indicating that the transgenic lines have drought and salt stress tolerance. The expression analysis of the transgenic lines and WT revealed that GAI was upregulated in the transgenic lines in normal conditions as compared to the WT. Under drought and salt treatment, RAB18 and RD29A were strongly upregulated in the transgenic lines as compared to the WT. Conclusively, GhJUB1_3‐At is not an auto activator and it is regulated by the crosstalk of GhHB7, GhRAP2‐3 and GhRAV1. GhRAV1, a negative regulator of abiotic stress tolerance and positive regulator of leaf senescence, suppresses the expression of GhJUB1_3‐At under severe circumstances leading to plant death. [ABSTRACT FROM AUTHOR]

Drought stress is one of the most important limiting factors in crop production, and it creates major challenges for the growth and development of plants in many parts of the world. Elicitors, as key messenger compounds, play an important modulatory role in plant responses to abiotic stresses, which leads to physiological changes and triggers the expression of stress-responsive genes by the synthesis of signaling molecules. A factorial experiment was conducted with two factors in a greenhouse at the University of Zabol, Iran, during 2021. The water supply applied at three levels including 100%, 75%, and 50% of crop water requirement (as control, mild, and severe water deficit stress, respectively). The foliar sprayings were applied at six levels: control, 70% ethanol, 0.5 and 1 mM SA, and 0.5 and 1 mM MeJA. The effect of elicitors on various physiological, biochemical parameters and expression of superoxide dismutase (SOD), MYB62, and NAM/ATAF1/2/CUC2 (NAC) genes under drought stress conditions was investigated by qRT-PCR. In final the target genes, correlation rate was calculated based on the co-expression and experimental parameters, and their expression network was plotted using Cytoscape software. The results of the physiological analysis revealed that with increasing water deficit stress intensity, the amount of Chl-a, Chl-b, and total chlorophyll content decreased significantly. The utilization of elicitors also increased the carotenoid content. The analysis of anti-oxidant enzyme activity showed that the activity of the guaiacol peroxidase (GPX) increased significantly under severe stress + 1 mM MeJA application. The highest catalase (CAT) activity was also observed under severe stress + 1 mM MeJA. The expression analysis of three genes SOD, MYB62, and NAC showed that with increasing water deficit stress, the expression of all three genes increased. Based on the present results, MeJA and SA had a positive effect on increasing the expression of MYB62, proline, and carbohydrate but greatly reduced the expression of NAC. Among the spraying treatments, 0.5 mM SA showed the highest positive impact on the expression of the studied genes, while the ethanol treatment had the most negative effect. The expression analysis of genes involved in drought tolerance under elicitor applications is necessary to elucidate the relationship between physiological and enzymatic changes (osmotic adjustment, pigments, and anti-oxidant enzymes) and gene expression patterns in quinoa. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ethylene plays a vital role in the ripening process of kiwifruit. A terrific amount of transcription factors (TFs) have been shown to regulate ethylene synthesis in various fruits. RESULTS: In this research, two new NAC TFs, named AcNAC3 and AcNAC4, were isolated from kiwifruit, which belonged to NAM subfamily. Bioinformatics analysis showed that both AcNAC3 and AcNAC4 were hydrophilic proteins with similar three‐dimensional structures. The expression levels of AcNAC3, AcNAC4 and AcACO1 increased during kiwifruit ripening, as well as were induced by ethylene and repressed by 1‐methylcyclopropene (1‐MCP). Correlation analysis exhibited that ethylene production was positively correlated with the expression levels of AcNAC3, AcNAC4 and AcACO1. Moreover, both AcNAC3 and AcNAC4 acted as transcriptional activators and could bind to and activate AcACO1 promoter. CONCLUSION: All results unveiled that the ethylene‐induced AcNAC3 and AcNAC4 were transcriptional activators, and might participate in kiwifruit ripening and ethylene biosynthesis through activating AcACO1, providing a new insight of ethylene synthetic regulation during kiwifruit ripening. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Xylella fastidiosa is a multi‐host bacterium that can be detected in hundreds of plant species including several crops. Diseases caused by X. fastidiosa are considered a threat to global food production. The primary method for managing diseases caused by X. fastidiosa involves using insecticides to control the vector. Hence, it is necessary to adopt new and sustainable disease management technologies to control not only the insect but also the bacteria and plant health. We demonstrated that N‐acetylcysteine (NAC), a low‐cost cysteine analogue, is a sustainable molecule that can be used in agriculture to decrease the damage caused by X. fastidiosa and improve plant health. RESULTS: Using 15N‐NAC we proved that this analogue was absorbed by the roots and transported to different parts of the plant. Inside the plant, NAC reduced the bacterial population by 60‐fold and the number of xylem vessels blocked by bacterial biofilms. This reflected in a recovery of 0.28‐fold of the daily sap flow compared to health plants. In addition, NAC‐treated citrus variegated chlorosis (CVC) plants decreased the oxidative stress by improving the activity of detoxifying enzymes. Moreover, the use of NAC in field conditions positively contributed to the increase in fruit yield of CVC‐diseased plants. CONCLUSION: Our research not only advances the understanding of NAC absorption in plants, but also indicates its dual effect as an antimicrobial and antioxidant molecule. This, in turn, negatively affects bacterial survival while improving plant health by decreasing oxidative stress. Overall, the positive field‐based evidence supports the viability of NAC as a sustainable agricultural application. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Salinity stress adversely affects plant growth and development and causes other stresses, such as osmotic and oxidative stress. Salt-tolerant crops capable of inhabiting salty agricultural land will be useful for farming. Red beet (Beta vulgaris L.) is an economically important plant for high salt tolerance, and also contain rich in valuable ingredients including betacyanins, vitamin, antioxidant, and minerals. Exogenous treatment of chemical components facilitates the improvement of crop productivity under salt stress. N-acetyl-L-cysteine (NAC) derived from cysteine amino acid is a precursor of thiol compounds, an antioxidant, and a chelating agent. The 45-day red beets (Beta vulgaris ‘Scarlet Supreme’, B. vulgaris var. crassa ‘Ruby Queen’) were subjected to three NAC levels (100, 250, and 500 µM) and one salinity level (150 mM NaCl) for 1 week to determine the effect of applications on enzymatic and non-enzymatic antioxidant defense systems by comparing two red beets leaf extracts. NAC treatment in combination with NaCl induced an increase in total phenolic content (TPC), total flavonoid (TF), total betalain, and phenolic acid contents in ‘Ruby Queen’, while these contents decreased under the same conditions in ‘Scarlet Supreme’. The antioxidant capacity values were significantly correlated (P < 0.01) with the TPC content in both red beets. In addition, combination treatment stimulated the activity of some of the antioxidant enzymes in comparison to salt stress alone. The GSH content in the red beets was also enhanced by the combination treatments. Furthermore, TBARS values were negatively correlated with GSH or some AsA–GSH cycle enzyme activities and to some extent with POX activity in the leaves of red beets. These results suggest that NAC treatment alleviated many of the deleterious effects of salt stress in beet leaves, which was achieved by enhancing antioxidant defense system-modulating enzymatic and non-enzymatic antioxidant components. [ABSTRACT FROM AUTHOR]

The NAC(NAM, ATAF1 / 2, CUC2) protein family is one of the largest protein families in plants, and its members are detected in many plants. The NAC protein family is involved in the regulation of many plant life processes as a transcriptional regulator. NAC transcription factors (NAC TFs) generally consists of a special N-terminal DNA binding domain and a variety of C-terminal transcriptional activation / inhibition regions. The number of NAC TFs is very large and their functions are diverse, which plays an important role in regulating plant life activities. Therefore, it is of great significance to explore their biological functions and molecular regulatory networks for improving plant agronomic traits. In recent years, the research on NAC TFs has been hot. This paper systematically reviewed the research status, structural characteristics, action mode and evolution process of NAC TFs, as well as its regulation of specific plant life activities including secondary growth, biosynthesis, biotic / abiotic stress, hormone response, organ senescence, etc., and prospected its research trend. [ABSTRACT FROM AUTHOR]

Alcohol hangover (veisalgia) is a fairly common phenomenon. The pathogenesis of veisalgia is not understood and treatment has not yet been established. Occasionally, students take N-acetylcysteine (NAC) before binge drinking to alleviate hangover. The aim of this study was to evaluate the effect of NAC on serum levels of electrolytes, enzymes, oxidative stress biomarkers and symptoms of veisalgia in binge drinking. In this randomized, double-blind, placebo-controlled study, healthy students were randomly assigned into two groups: one receiving NAC and the other receiving a placebo. Blood samples were taken before drinking, 30 min after a 1.5 h long drinking session, and the subsequent morning. Serum levels of electrolytes, urea, enzymes, ethanol, 8-Hydroxydeoxyguanosine (8-OHdG) and N-epsilon-hexanoyl-lysine were measured. The participants completed the Acute Hangover Severity Scale (AHSS) assessment based on symptoms, and 40 students (20 male), aged 23 ± 2 years, were included in the study. Their mean blood ethanol concentration was 1.4 g/kg. Serum sodium levels were increased after drinking, and urea decreased the following morning compared to their levels before drinking in both groups. Serum 8-OHdG levels were increased after drinking and remained elevated until the following morning, compared to the levels before drinking, in both groups. NAC had no effect on sodium, urea and 8-OHdG levels or the symptoms of veisalgia. In conclusion, binge drinking causes a transient increase in serum sodium and as a prolonged increase in oxidative marker 8-OHdG levels. NAC had no effect on the sodium and 8-OHdG levels. [ABSTRACT FROM AUTHOR]

Abstract Smoking is one of the major contributors to airway injuries. N‐acetylcysteine (NAC) has been proposed as a treatment or preventive measure for such injuries. However, the exact nature of the smoking‐induced injury and the protective mechanism of NAC are not yet fully understood. Here, patient tissue‐derived airway organoids for modeling smoking‐induced injury, therapeutic investigation, and mechanism studies are developed. Airway organoids consist mainly of ciliated cells, together with basal cells, goblet cells, and myofibroblast‐like cells. The organoids display apical‐out and basal‐in polarity and are enriched in beating cilia, which are sensitive to smoking challenge and NAC treatment. An algorithm is developed to measure ciliary beating activity by analyzing the altered beating pattern of cilia in response to nicotine challenge and NAC treatment. Nicotinic acetylcholine receptors (nAChRs) expressed by airway organoids are involved in the mechanisms of nicotine‐induced injury through the nicotine‐nAChR pathway. In contrast to the common understanding that NAC has an antioxidative effect that mitigates airway damage, it is elucidated that NAC binding to nicotine can abolish the binding capacity of nicotine to nAChRs and thus prevent nicotine‐induced injury. This study focuses on the advances and potential of humanized organoids in understanding biological processes, mechanisms, and identifying therapeutic targets.

BackgroundThis study explores the clinical value of a machine learning (ML) model based on ultrasound radiomics features of primary foci, combined with clinicopathologic factors to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) for patients with breast cancer (BC).MethodWe retrospectively analyzed ultrasound images and clinical information from 231 participants with BC who received NAC. These patients were randomly assigned to training and validation cohorts. Tumor regions of interest (ROI) were delineated, and radiomics features were extracted. Z-score normalization, Pearson correlation analysis, and the least absolute shrinkage selection operator (LASSO) were utilized for further screening ultrasound radiomics and clinical features. Univariate and multivariate logistic regression analysis were performed to identify the CFs that were independently associated with pCR. We compared 10 ML models based on radiomics features: support vector machine (SVM), logistic regression (LR), random forest, extra trees (ET), naïve Bayes (NB), k-nearest neighbor (KNN), multilayer perceptron (MLP), gradient boosting ML (GBM), light GBM (LGBM), and adaptive boost (AB). Diagnostic performance was evaluated using the receiver operating characteristic (ROC) area under the curve (AUC), accuracy, sensitivity, and specificity, and the Rad score was calculated. Subsequently, construction of clinical predictive models and Rad score joint clinical predictive models using ML algorithms for optimal diagnostic performance. The diagnostic process of the ML model was visualized and analyzed using SHapley Additive exPlanation (SHAP).ResultsOut of 231 participants with BC, 98 (42.42%) achieved pCR, and 133 (57.58%) did not. Twelve radiomics features were identified, with the GBM model demonstrating the best predictive performance (AUC of 0.851, accuracy of 0.75, sensitivity of 0.821, and specificity of 0.698). The clinical feature prediction model using the GBM algorithm had an AUC of 0.819 and an accuracy of 0.739. Combining the Rad score with clinical features in the GBM model resulted in superior predictive performance (AUC of 0.939 and an accuracy of 0.87). SHAP analysis indicated that participants with a high Rad score, PR-negative, ER-negative and human epidermal growth factor receptor-2 (HER-2) positive were more possibly to reach pCR. Based on the decision curve analysis, it was shown that the combined model of GBM provided higher clinical benefits.ConclusionThe GBM model based on ultrasound radiomics features and routine clinical date of BC patients had high performance in predicting pCR. SHAP analysis provided a clear explanation for the prediction results of the GBM model, revealing that patients with a high Rad score, PR-negative status, ER-negative status and HER-2-positive status are more likely to achieve pCR.

AbstractThis study examines the effects of distortion of agricultural price incentives on agricultural value added in East Africa. The World Bank, IFPRI, FAO, and CSP are the sources of data. The dataset ranges from 1981 to 2018, and the error-corrected LSDV model is used to analyze the data. The results indicate that agricultural price incentives have positive and significant effects on agricultural value-added. Aggregate nominal assistance coefficient, exportable agricultural products nominal assistance coefficient, and nominal rate of protection have increased agricultural value-added significantly. Agricultural price incentives targeting different levels of value addition have larger effects than those targeting aggregate outputs. This implies that agricultural incentive policies and market conditions in support of local producers are vital to enhancing AVA in East Africa. Besides, larger areas of arable land, lower agricultural employment, a smaller population size, a larger GDP, less spending on education, and a better-performing polity contribute to a significant increase in the regional agricultural value added. The results generally imply that agricultural price incentives are vital to accelerating agricultural value addition in East Africa. Governments in this region should thus consider revising agricultural policies in a pro-agricultural way to further accelerate regional growth in agricultural value-added. Enhancing agricultural price support needs to be a crucial element of policy revisions in the region.

Objective: The aim of this paper was to assess the differences in clinicopathological characteristics, efficacy and prognosis of neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor2(HER2)-zero and HER2-low hormone receptor (HR)-negative breast cancer (BC) patients, and the impact of HER2-evolution on prognosis before and after NAC.Methods: 319 triple negative breast cancer (TNBC) patients who completed NAC and surgery from August 2014 to August 2018 at Tianjin Medical University Cancer Institute and Hospital were included. Clinicopathological features, efficacy of NAC and assessment of prognosis were retrospectively analysed. The evolution of HER2-zero to HER2-low after NAC is defined as HER2-gain, the evolution of HER2-low to HER2-zero after NAC is defined as HER2-loss, and HER2 unchanged after NAC is defined as HER2-stable.Results: In HR-negative BC, the pathological complete response (pCR) rate was significantly higher in HER2-zero compared with HER2-low patients, and the difference was statistically significant (38.9% vs 23.2%, p = 0.004), but there was no significant difference in the prognosis between the two groups. The overall rate of HER2-evolution after NAC was 19.7%, and there was a significant correlation between HER2-loss and histological grading, whereas HER2-gain was significantly associated with Ki-67 expression. In terms of prognosis, HER2-gain was better compared to the other two groups.Conclusion: In this study, we found that HER2-low HR-negative BC showed different clinicopathological features and response to NAC compared with HER2-zero, as well as HER2-evolution before and after NAC had a significant impact on prognosis.

Background The purpose of this study was to clarify fading, red, green, and blue values (RGB) change, and color reproducibility for nipple–areola complex (NAC) tattoos.

With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair. To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, and functional testing of MuSCs from young and old mice. The multiomics approach allowed us to assess which changes are causal, which are compensatory, and which are simply correlative. We identified glutathione (GSH) metabolism as perturbed in old MuSCs, with both causal and compensatory components. Contrary to young MuSCs, old MuSCs exhibit a population dichotomy composed of GSHhigh cells (comparable with young MuSCs) and GSHlow cells with impaired functionality. Mechanistically, we show that antagonism between NRF2 and NF-κB maintains this bimodality. Experimental manipulation of GSH levels altered the functional dichotomy of aged MuSCs. These findings identify a novel mechanism of stem cell aging and highlight glutathione metabolism as an accessible target for reversing MuSC aging.

N-acetyl-L-cysteine (NAC) was initially introduced as a treatment for mucus reduction and widely used for chronic respiratory conditions associated with mucus overproduction. However, the mechanism of action for NAC extends beyond its mucolytic activity and is complex and multifaceted. Contrary to other mucoactive drugs, NAC has been found to exhibit antioxidant, anti-infective, and anti-inflammatory activity in pre-clinical and clinical reports. These properties have sparked interest in its potential for treating chronic lung diseases, including chronic obstructive pulmonary disease (COPD), bronchiectasis (BE), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF), which are associated with oxidative stress, increased levels of glutathione and inflammation. NAC's anti-inflammatory activity is noteworthy, and it is not solely secondary to its antioxidant capabilities. In ex vivo models of COPD exacerbation, the anti-inflammatory effects have been observed even at very low doses, especially with prolonged treatment. The mechanism involves the inhibition of the activation of NF-kB and neurokinin A production, resulting in a reduction in interleukin-6 production, a cytokine abundantly present in the sputum and breath condensate of patients with COPD and correlates with the number of exacerbations. The unique combination of mucolytic, antioxidant, anti-infective, and anti-inflammatory properties positions NAC as a safe, cost-effective, and efficacious therapy for a plethora of respiratory conditions. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to clarify fading, red, green, and blue values (RGB) change, and color reproducibility for nipple–areola complex (NAC) tattoos. Methods NAC tattooing was performed on 60 sites in 59 Japanese patients prospectively. The evaluation was assessed using digital photo, Casmatch standardization, and RGB and luminance values preoperatively, immediately after, 1 week, 1, 3, 6, and 12 months after tattooing. RGB and luminance values changes over time, time-adjusted fading rate, and the rate of luminance at 12 months were calculated. In color reproducibility study (n = 34), RGB values after 12 months were compared with the color sample about dark/reddish and light/less reddish pigments. Results RGB varied widely from immediately after to 1 month after tattooing. For RGB and luminance, significant differences were seen between pre and immediate after, 1 and 3 months, 3 and 6 months, and 6 and 12 months. In G values, significant differences were seen between all neighboring points. The fading rate tended to decrease as time progresses, but was not significant, that is, fading continued even between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months. Color reproducibility tended to be higher with dark/reddish pigments, despite no significant differences. Conclusion The fading rate of tattooed NACs tended to decrease as time progresses, but fading still occurs between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months after. [ABSTRACT FROM AUTHOR]

Background: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Patients and Methods: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. Results: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24–38%)/GS, 26% (18–33%)], but the Kaplan–Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, −50%/−21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. Conclusions: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved. [ABSTRACT FROM AUTHOR]

Background: Position of the nipple–areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). Methods: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6–24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. Results: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. Conclusions: This study provides insights into the tendencies and characteristics of NAC malposition. [ABSTRACT FROM AUTHOR]

A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose–response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals' behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied—the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)—responds significantly (p < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals' behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area's role in response to the drug. [ABSTRACT FROM AUTHOR]

Introduction: Vitiligo is a skin pigmentation disorder caused by the selective degradation of melanocytes. This study investigates the therapeutic effects of microneedling with and without N‐acetylcysteine (NAC) in patients with persistent and limited vitiligo. Method: This research employed a clinical trial design with double‐blind randomization. Individuals affected by vitiligo and seeking treatment at Rasool Akram Medical Complex were divided into two separate treatment groups. In the intervention group, 24 affected areas underwent meso‐microneedling using 5% NAC ampoules over six sessions, in addition to the application of 4.7% NAC cream once daily on the specified area. Conversely, the control group, consisting of 22 lesions, underwent microneedling using distilled water during six sessions. The severity of lesions and the extent of repigmentation were gauged using the Modified VETI Score. Assessment of treatment efficacy was determined through both physician evaluations and patient feedback. Results: Twenty patients with a mean age of 36.4 years were recruited. The mean percentage of lesions and their intensity were significantly improved 2 weeks after the third session and 1 month after the end of the treatment (p < 0.01). There was no statistically significant difference between the intervention and control groups. Gender, age, family history, duration of disease, duration of disease stability, and history of hypothyroidism had no statistically significant relationship with patients' treatment outcomes (p > 0.05). Conclusion: Microneedling with or without the application of NAC appears to be an effective treatment option for persistent vitiligo lesions. However, despite the higher improvement rate with the application of NAC, the difference was not significant. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA–miRNA–mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA–miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance. Key message: LncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat. [ABSTRACT FROM AUTHOR]

Purpose: To assess the predictive value of an ultrasound‐based radiomics‐clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. Methods: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. Results: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound‐based radiomics‐clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. Conclusions: Ultrasound‐based radiomics‐clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients. [ABSTRACT FROM AUTHOR]

Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior. [ABSTRACT FROM AUTHOR]

The hearts of subjects with diabetes are vulnerable to ischemia–reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes. [ABSTRACT FROM AUTHOR]

Abstract In tomato (Solanum lycopersicum), the ripening of fruit is regulated by the selective expression of ripening-related genes, and this procedure is controlled by transcription factors (TFs). In the various plant-specific TF families, the no apical meristem (NAM), Arabidopsis thaliana activating factor 1/2 (ATAF1/2), and cup-shaped cotyledon 2 (CUC2; NAC) TF family stands out and plays a significant function in plant physiological activities, such as fruit ripening (FR). Despite the numerous genes of NAC found in the tomato genome, limited information is available on the effects of NAC members on FR, and there is also a lack of studies on their target genes. In this research, we focus on SlNAP1, which is a NAC TF that positively influences the FR of tomato. By employing CRISPR/Cas9 technology, compared with the wild type (WT), we generated slnap1 mutants and observed a delay in the ethylene production and color change of fruits. We employed the yeast one-hybrid (Y1H) and dual-luciferase reporter (DLR) assays to confirm that SlNAP1 directly binds to the promoters of two crucial genes involved in gibberellin (GA) degradation, namely SlGA2ox1 and SlGA2ox5, thus activating their expression. Furthermore, through a yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BIFC) and luciferase (LUC) assays, we established an interaction between SlNAP1 and SlGID1. Hence, our findings suggest that SlNAP1 regulates FR positively by activating the GA degradation genes directly. Additionally, the interaction between SlNAP1 and SlGID1 may play a role in SlNAP1-induced FR. Overall, our study provides important insights into the molecular mechanisms through which NAC TFs regulate tomato FR via the GA pathway.

Abstract Background Chalkiness is a common phenotype induced by various reasons, such as abiotic stress or the imbalance of starch synthesis and metabolism during the development period. However, the reason mainly for one gene losing its function such as NAC (TFs has a large family in rice) which may cause premature is rarely known to us. Results The Ko-Osnac02 mutant demonstrated an obviously early maturation stage compared to the wild type (WT) with 15 days earlier. The result showed that the mature endosperm of Ko-Osnac02 mutant exhibited chalkiness, characterized by white-core and white-belly in mature endosperm. As grain filling rate is a crucial factor in determining the yield and quality of rice (Oryza sativa, ssp. japonica), it's significant that mutant has a lower amylose content (AC) and higher soluble sugar content in the mature endosperm. Interestingly among the top DEGs in the RNA sequencing of N2 (3DAP) and WT seeds revealed that the OsBAM2 (LOC_Os10g32810) expressed significantly high in N2 mutant, which involved in Maltose up-regulated by the starch degradation. As Prediction of Protein interaction showed in the chalky endosperm formation in N2 seeds (3 DAP), seven genes were expressed at a lower-level which should be verified by a heatmap diagrams based on DEGs of N2 versus WT. The Tubulin genes controlling cell cycle are downregulated together with the MCM family genes MCM4 ( ↓), MCM7 ( ↑), which may cause white-core in the early endosperm development. In conclusion, the developing period drastically decreased in the Ko-Osnac02 mutants, which might cause the chalkiness in seeds during the early endosperm development. Conclusions The gene OsNAC02 which controls a great genetic co-network for cell cycle regulation in early development, and KO-Osnac02 mutant shows prematurity and white-core in endosperm.

Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b−/− animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.

Amyotrophic lateral sclerosis (ALS) is an auto-immune neurodegenerative disorder affecting the motor-neuron system. The causes of ALS are heterogeneous, and are only partially understood. We studied different aspects of immune pathogenesis in ALS and found several basic mechanisms which are potentially involved in the disease. Our findings demonstrated that ALS patients peripheral blood contains higher proportions of NK and B cells in comparison to healthy individuals. Significantly increased IFN-γ secretion by anti-CD3/28 mAbs-treated peripheral blood mononuclear cells (PBMCs) were observed in ALS patients, suggesting that hyper-responsiveness of T cell compartment could be a potential mechanism for ALS progression. In addition, elevated granzyme B and perforin secretion at a single cell level, and increased cytotoxicity and secretion of IFN-γ by patients NK cells under specific treatment conditions were also observed. Increased IFN-γ secretion by ALS patients CD8+ T cells in the absence of IFN-γ receptor expression, and increased CD8+ T cell effector/memory phenotype as well as increased granzyme B at the single cell level points to the CD8+ T cells as potential cells in targeting motor neurons. Along with the hyper-responsiveness of cytotoxic immune cells, significantly higher levels of inflammatory cytokines including IFN-γ was observed in peripheral blood-derived serum of ALS patients. Supernatants obtained from ALS patients CD8+ T cells induced augmented cell death and differentiation of the epithelial cells. Weekly N-acetyl cysteine (NAC) infusion in patients decreased the levels of many inflammatory cytokines in peripheral blood of ALS patient except IFN-γ, TNF-α, IL-17a and GMCSF which remained elevated. Findings of this study indicated that CD8+ T cells and NK cells are likely culprits in targeting motor neurons and therefore, strategies should be designed to decrease their function, and eliminate the aggressive nature of these cells. Analysis of genetic mutations in ALS patient in comparison to identical twin revealed a number of differences and similarities which may be important in the pathogenesis of the disease.