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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and requires better treatment. N-acetylcysteine (NAC) is known to be beneficial under such conditions owing to its antioxidant potential and insulin-sensitizing properties. The effect of NAC on the reproductive outcomes of PCOS patients was examined in this meta-analysis. Methods: In accordance with PRISMA standards, this meta-analysis included studies that compared N-acetylcysteine, metformin, clomiphene citrate, and a placebo in patients with POCS. The main indicators were follicular growth, endometrial thickness, and hormone level. The risk of bias was evaluated using the Cochrane ROB2 tool. Results: Twenty-two studies (n = 2515) were included. NAC was associated with a statistically significant increase in progesterone (SMD 0.95, 95% CI: 0.13–1.77, p = 0.02) and endometrial thickness (SMD 0.58, 95% CI: 0.10–1.06, p = 0.02) compared to the placebo and other drugs (SMD 0.71, 95% CI: 0.48–0.94, p < 0.0001). LH levels were significantly increased by NAC compared to metformin (SMD 0.67, 95% CI: 0.23–1.12, p = 0.003). However, no significant differences were observed in the estradiol, SHBG, or FSH levels. Conclusions: NAC had a major effect on progesterone, endometrial thickness, and LH levels in women with PCOS. Therefore, it may be a potential treatment option. [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.

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.

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.

PVP and 4-MBA were used as ligands to synthesize 4-MBA@PVP-CuNCs under simple conditions. Hg2+ was able to reduce its fluorescence by static quenching, and then NAC restored the fluorescence of the CuNCs by taking away Hg2+ through chelation. The 4-MBA@PVP-CuNCs-Hg probe was prepared for the detection of NAC with a low limit of detection (16 nM), and its action mechanism was explored in detail. Besides, the probe was extended to the assays of NAC in real samples. [Display omitted] • Analyzing effects of single/double ligands and temperature on the synthesis of 4-MBA@PVP-CuNCs. • Discussing effects of metal ion types and Hg2+ doses for the 4-MBA@PVP-CuNCs-Hg probe construction. • Investigating the action mechanisms of 4-MBA@PVP-CuNCs-Hg and 4-MBA@PVP-CuNCs-Hg-NAC systems. • The probe was successfully utilized to test NAC in real samples. N-acetyl-L-cysteine (NAC) as a class of thiols is commonly used in the treatment of lung diseases, detoxification and prevention of liver damage. In this paper, 4-mercaptobenzoic acid (4-MBA) coated and polyvinylpyrrolidone (PVP) attached copper nanoclusters (4-MBA@PVP-CuNCs) were successfully synthesized using a simple one-pot method with an absolute quantum yield of 10.98 %, and its synthetic conditions (like effects of single/double ligands and temperature) were studied intensively. Then Hg2+ could quench the fluorescence of the 4-MBA@PVP-CuNCs and its fluorescence was restored with the addition of NAC. Based on the above principles, an off–on switching system was established to detect NAC. That is, the 4-MBA@PVP-CuNCs-Hg probe was prepared by adding Hg2+ to switch off the fluorescence of the CuNCs by static quenching, and then NAC was added to switch on the fluorescence of the probe based on the chelation of NAC and Hg2+. Moreover, the effects of metal ion types and mercury ion doses for the probe construction were also further discussed. The method showed excellent linearity in the range of 0.05–1.25 µM and low detection limit of 16 nM. Meanwhile, good recoveries in real urine, tablets and pellets were observed, which proved the reliability of the method and provided a convenient, fast and sensitive method for NAC detection. [ABSTRACT FROM AUTHOR]

• Controversy remains regarding adjuvant therapy (AT) in patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer. • Determining variables that may affect cancer-specific survival (CSS) for nonresponsiveness to NAC may aid in identifying patients who may require AT after RC. • In this multicentric retrospective study, only ypN status was shown to be an independent prognostic indicator of CSS in patients who did not respond to NAC. • ypN+ may be an important prognostic indicator that should be evaluated and may favor AT when considering AT or observation options for locally advanced disease in NAC-non-responsive patients. To investigate the risk factors affecting cancer-specific survival (CSS) in nonresponsive disease to neoadjuvant chemotherapy (NAC) among patients with muscle-invasive bladder cancer (MIBC) who were treated with NAC and radical cystectomy (RC). Patients with MIBC who underwent NAC and RC were retrospectively examined. By comparing clinical and pathological stages, patients whose pathological stage was lower than clinical stage were categorized as "NAC-responsive" and the remainder as "NAC-non-responsive." Apart from pathologic staging, variables compared between groups included age, gender, Eastern Cooperative Oncology Group (ECOG) score, clinical stages, NAC type and cycle number, durations between MIBC diagnosis and NAC initiation and RC, presence of hydronephrosis, number of lymph nodes removed, and variant histology of urothelial bladder cancer. CSS analysis was performed by construction of Kaplan–Meier survival curves and multivariable Cox regression was performed to identify the prognosticators in the NAC-non-responsive-group. Ninety-two patients were included with a mean age was 61.5 ± 8.5 years, of whom 84.8% were men. The NAC regimen used was predominantly gemcitabine-cisplatin (88%) and the median cycle number was 4. Fifty-six (60.9%) patients were NAC-non-responsive. There was a significantly lower proportion of patients receiving ≥4 cycles (46.4% vs. 66.7%) and a higher rate of patients with ECOG score ˃1 (33.9% vs. 11.1%) in the NAC-non-responsive-group compared to the NAC-responsive-group (both P < 0.05). Other variables were similar between groups. In multivariable analysis, only ypN+ was found to be an independent prognosticator for CSS in NAC-non-responsive-group (HR: 2.725, CI95%:1.017–7.303). Although higher ECOG scores and lower cycle numbers appears to be associated factors in NAC-non-responsive disease, only ypN(+) status was a prognosticator for CSS in this population. [ABSTRACT FROM AUTHOR]

The dopamine D3 receptor (D3R), principally confined to the nucleus accumbens (NAc), is involved in regulating natural and drug rewards; however, the molecular mechanisms underlying the associated process remain unclear. Earlier research has reported the concurrent influence of D3R and miR-29c expressed in the NAc on methamphetamine (METH)-induced reward behaviors and microglial activation, hinting at regulatory roles in reward processing. Herein, we performed viral manipulation-mediating D3R/miR-29c overexpression and inhibition in the whole NAc in male D3R knockout and wild-type mice to investigate this potential relationship. Behavioral responses to the rewarding stimuli were assessed using sucrose preference score, METH-induced locomotor sensitization, and METH-induced conditioned place preference tests. Overall, we observed a notable decrease in the behavioral response to sucrose and METH in D3R-deficient mice, accompanied by the downregulation of miR-29c expression in the NAc. Diminished responses to those rewarding stimuli in D3R-deficient mice primarily stemmed from the reduction of GSK3β activity and subsequent down-regulation of miR-29c in the NAc. Microglial activation in the NAc mediates the effect of D3R-miR-29c deficiency on the reward effects of sucrose and METH. Pharmacological suppression of microglial activity rescued the reduced response in mice lacking D3R-miR-29c in the NAc. Overall, this study revealed the mechanism by which D3R regulates both natural and drug rewards via miR-29c in the murine NAc, highlighting the role of the NAc D3R-miR-29c pathway as a critical regulator of rewards, and providing new insights into the role of NAc D3R-miR-29c in encoding rewarding experiences. [Display omitted] • D3R deficiency reduces mice's rewarding response by decreasing miR-29c in NAc. • D3R regulated miR-29c expression in NAc via modulating GSK3β activity. • Decreasing miR-29c in NAc activates microglia, releasing pro-inflammatory cytokines. • Inhibiting microglial activation rescued impaired rewards from D3R-miR-29c deficit. [ABSTRACT FROM AUTHOR]

Objective: Organophosphorus Nerve Agent, VX [(O-Ethyl S-diisopropylaminomethyl) methylphosphonothioate] compound interferes with acetylcholine signaling by targeting the AChE enzyme. Studies suggest that in nerve agents poisoning, non-cholinergic effects are also responsible for damage in peripheral tissues including long term damage in brain. Present study reports cholinergic and non-cholinergic effects of VX poisoning and their prevention by use of N-acetylcysteine (NAC) in addition to conventional antidotes atropine sulphate and 2-PAM chloride as an antioxidant. NAC was chosen being an approved drug for medical conditions including oxidative damage and as mucolytic., Results: Results of the study showed that after 1x LD 50 exposure to VX and standard atropine and oxime therapy resulted in recovery of cholinesterase activity up to 51%, while additional NAC administration resulted in increased recovery up to 89% in brain cholinesterase activity. NAC also helped in maintaining intracellular and tissue GSH level, reduced ROS generation and lipid peroxidation. NAC treatment could able to reduce the lipid peroxidation (MDA) levels in liver of NAC administered groups as compared to standard treatment of atropine sulphate and PAM chloride at 10 LD 50 VX. Likewise, a 20% higher level of GSH was found in NAC treated group at 1x LD 50 dose in brain. Cell cycle analysis and histopathological results showed that NAC prevents VX induced damage., Conclusion: it was found that use of antioxidant agent NAC along with standard atropine-oxime treatment is helpful in reducing the cholinergic and oxidative stress mediated toxicity induced by VX., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)