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.

Glutathione peroxidase-1 (GPx1) and cAMP/Ca2+ responsive element (CRE)-binding protein (CREB) regulate neuronal viability by maintaining the redox homeostasis. Since GPx1 and CREB reciprocally regulate each other, it is likely that GPx1-CREB interaction may play a neuroprotective role against oxidative stress, which are largely unknown. Thus, we investigated the underlying mechanisms of the reciprocal regulation between GPx1 and CREB in the male rat hippocampus. Under physiological condition, L-buthionine sulfoximine (BSO)-induced oxidative stress increased GPx1 expression, extracellular signal-regulated kinase 1/2 (ERK1/2) activity and CREB serine (S) 133 phosphorylation in CA1 neurons, but not dentate granule cells (DGC), which were diminished by GPx1 siRNA, U0126 or CREB knockdown. GPx1 knockdown inhibited ERK1/2 and CREB activations induced by BSO. CREB knockdown also decreased the efficacy of BSO on ERK1/2 activation. BSO facilitated dynamin-related protein 1 (DRP1)-mediated mitochondrial fission in CA1 neurons, which abrogated by GPx1 knockdown and U0126. CREB knockdown blunted BSO-induced DRP1 upregulation without affecting DRP1 S616 phosphorylation ratio. Following status epilepticus (SE), GPx1 expression was reduced in CA1 neurons and DGC. SE also decreased CREB activity CA1 neurons, but not DGC. SE degenerated CA1 neurons, but not DGC, accompanied by mitochondrial elongation. These post-SE events were ameliorated by N-acetylcysteine (NAC, an antioxidant), but deteriorated by GPx1 knockdown. These findings indicate that a transient GPx1-ERK1/2-CREB activation may be a defense mechanism to protect hippocampal neurons against oxidative stress via maintenance of proper mitochondrial dynamics.

Many studies showed NAC transcription factors play an important role in fruit ripening. Moreover, sucrose and starch metabolism is also closely related to fruit ripening. However, there are a few studies focus on whether NAC regulates sucrose and starch metabolism to influence fruit ripening. In this study, virus-induced gene silencing (VIGS) of SlNAP1 suppressed fruit ripening and delayed color transformation. The chlorophyll (including Chla, Chlb, and Chla + b) degradation and carotenoid synthesis in SlNAP1-silenced fruits were dramatically suppressed. Silencing SlNAP1 decreased soluble sugar and reducing sugar accumulation in fruits, and increased starch content. The activity of starch degrading enzymes, including α amylase (AMY) and β amylase (BAM) was significantly lower in SlNAP1-silenced fruits than in the control fruits, whereas denosine diphosphoglucose pyrophosphorylase (AGP) activity was significantly higher. In addition, the expression of starch degradation-related genes (SlAMY1, SlAMY2, SlBAM1, SlBAM7, SlGWD, SlPWD) in SlNAP1-silenced fruits was significantly suppressed, while starch synthesis-related genes (SlAGPase1, SlAGPase2) was significantly increased. Compared with the control fruits, SlNAP1-silenced fruits showed significantly lower sucrose and glucose content. The expression level of sucrose and glucose metabolism-related genes such as Slsus1, Slsus3, SlSPS, SlHxk1, SlHxk2, SlPK1, and SlPK2 was significantly lower in SlNAP1-silenced fruits than in the control fruits. Overall, this study revealed that SlNAP1 gene might positively regulate fruit ripening by influencing carbohydrate metabolism.

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.

Complex regional pain syndrome (CRPS) presents as a persistent and distressing pain condition often stemming from limb trauma or ischemia, manifesting as either CRPS-I (without initial nerve injury) or CRPS-II (accompanied by nerve injury). Despite its prevalence and significant impact on functionality and emotional well-being, standard treatments for CRPS remain elusive. The multifaceted nature of CRPS complicates the identification of its underlying mechanisms. In efforts to elucidate these mechanisms, researchers have turned to animal models such as chronic post-ischemic pain (CPIP), which mirrors the symptoms of CRPS-I. Various mechanisms have been proposed to underlie the acute and chronic pain experienced in CRPS-I, including oxidative stress and inflammation. Traditional treatment approaches often involve antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids. However, these methods frequently fall short of providing adequate relief. Accordingly, there is a growing interest in exploring alternative treatments, such as antioxidant supplementation, anti-inflammatory agents, and non-pharmacological interventions. Future research directions should focus on optimizing treatment strategies and addressing remaining gaps in knowledge to improve patient outcomes. This review aims to delve into the pathophysiological mechanisms implicated in the CPIP model, specifically focusing on oxidative stress and inflammation, with the ultimate goal of proposing innovative therapeutic strategies for alleviating the symptoms of CRPS-I.

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.

OBJECTIVE: To study the effects of resveratrol on heroin addiction-related behaviors and to preliminarily explore the possible intervention mechanism of resveratrol in heroin dependence.
METHODS: The effects of resveratrol on heroin withdrawal symptoms were observed by naloxone; The effect of resveratrol on heroin reward memory acquisition was detected by CPP paradigm; The effect of resveratrol on the mental excitability of heroin was tested by open field experiment; The effect of resveratrol on heroin spatial learning and memory was tested by water maze test. Western blot was used to detect Sirtuin 1 (SIRT1) Expression of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and postsynaptic density protein (PSD95).
RESULTS: The behavioral results showed that the withdrawal behavior of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05), and the shift score of the conditioned place preference test of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05) The spatial learning and memory ability of the water maze in the resveratrol intervention group was improved compared with the heroin chronic dependence group (P<0.05), and the mental excitability of the resveratrol intervention group was lower than that of the heroin chronic dependence group (P<0.05), but higher than that of the saline group (P<0.05); SIRT1 The expression levels of BDNF, GDNF and PSD95 protein were significantly increased (P<0.05).
CONCLUSIONS: The behavioral results of this study suggest that resveratrol can be used as a potential drug to treat heroin dependence. At the same time, SIRT1 The expression of BDNF, GDNF, and PSD95 increased; SIRT1, BDNF, GDNF, and PSD95 play an essential role in heroin addiction.

OBJECTIVE: MAGnetic resonance Imaging Compilation (MAGiC) is typical method of synthetic magnetic resonance imaging (MRI). The present aimed to investigate the role of MAGiC parameters of relaxation time (T1), transverse relaxation time (T2) and proton density (PD) to predict the treatment efficacy of breast cancer patients after neoadjuvant chemotherapy (NAC).
METHODS: The present prospective cohort study enrolled 120 breast cancer patients who received NAC during 2021-2023. Demographic data and clinical characteristics including tumor node metastasis (TNM) stage, pathological type, molecular classification and lymph node metastasis were collected. The levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) were measured. Patients were divided by treatment efficacy using the Miller-Payne grading as partial pathological response (pPR) group and pathological complete response (pCR). The values of MAGiC parameters of longitudinal T1, T2, and PD values were recorded.
RESULTS: In all 120 patients, 73 (60.83%) cases were with pPR and 47 (39.17%) cases were with pCR after treatment. T2 values were markedly lower in pPR patients compared with pCR patients. However, no significant difference was found for T1 and PD values. No significant correlation was observed between any of MAGiC parameters and HER-2, ER or PR. ROC curve showed T2 could be used for prediction of pPR with AUC 0.780. Lymph node metastasis and low levels of T2 were found as independent risk factors for pPR after treatment.
CONCLUSIONS: The T2 value parameter from MAGiC is an independent risk factor for pPR following NAC in breast cancer patients, suggesting its potential as a biomarker for predicting treatment efficacy.

Listening to music is a promising and accessible intervention for alleviating symptoms of major depressive disorder. However, the neural mechanisms underlying its antidepressant effects remain unclear. In this study on patients with depression, we used auditory entrainment to evaluate intracranial recordings in the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), along with temporal scalp electroencephalogram (EEG). We highlight music-induced synchronization across this circuit. The synchronization initiates with temporal theta oscillations, subsequently inducing local gamma oscillations in the BNST-NAc circuit. Critically, the incorporated external entrainment induced a modulatory effect from the auditory cortex to the BNST-NAc circuit, activating the antidepressant response and highlighting the causal role of physiological entrainment in enhancing the antidepressant response. Our study explores the pivotal role of the auditory cortex and proposes a neural oscillation triple time-locking model, emphasizing the capacity of the auditory cortex to access the BNST-NAc circuit.

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.