Adsorption removal of mercury from flue gas by metal selenide: A review.

Mercury (Hg) pollution has been a global concern in recent decades, posing a significant threat to entire ecosystems and human health due to its cumulative toxicity, persistence, and transport in the atmosphere. The intense interaction between mercury and selenium has opened up a new field for studying mercury removal from industrial flue gas pollutants. Besides the advantages of good Hg° capture performance and low secondary pollution of the mineral selenium compounds, the most noteworthy is the relatively low regeneration temperature, allowing adsorbent regeneration with low energy consumption, thus reducing the utilization cost and enabling recovery of mercury resources. This paper reviews the recent progress of mineral selenium compounds in flue gas mercury removal, introduces in detail the different types of mineral selenium compounds studied in the field of mercury removal, reviews the adsorption performance of various mineral selenium compounds adsorbents on mercury and the influence of flue gas components, such as reaction temperature, air velocity, and other factors, and summarizes the adsorption mechanism of different fugitive forms of selenium species. Based on the current research progress, future studies should focus on the economic performance and the performance of different carriers and sizes of adsorbents for the removal of Hg0 and the correlation between the gas-particle flow characteristics and gas phase mass transfer with the performance of Hg0 removal in practical industrial applications. In addition, it remains a challenge to distinguish the oxidation and adsorption of Hg0 quantitatively.

A comprehensive review of deactivation and modification of selective catalytic reaction catalysts installed in cement kilns.

After the ultralow emission transformation of coal-fired power plants, cement production became China's leading industrial emission source of nitrogen oxides. Flue gas dust contents at the outlet of cement kiln preheaters were as high as 80-100 g/m3, and the calcium oxide content in the dust exceeded 60%. Commercial V2O5(-WO3)/TiO2 catalysts suitable for coal-fired flue gas suffer from alkaline earth metal Ca poisoning of cement kiln flue gas. Recent studies have also identified the poisoning of cement kiln selective catalytic reaction (SCR) catalysts by the heavy metals lead and thallium. Investigation of the poisoning process is the primary basis for analyzing the catalytic lifetime. This review summarizes and analyzes the SCR catalytic mechanism and chronicles the research progress concerning this poisoning mechanism. Based on the catalytic and toxification mechanisms, it can be inferred that improving the anti-poisoning performance of a catalyst enhances its acidity, surface redox performance-active catalytic sites, and shell layer protection. The data provide support in guiding engineering practice and reducing operating costs of SCR plants. Finally, future research directions for SCR denitrification catalysts in the cement industry are discussed. This study provides critical support for the development and optimization of poisoning-resistant SCR denitrification catalysts.

Taurine ameliorates radiation-induced oxidative stress in bone marrow mesenchymal stromal cells and promotes osteogenesis.

Osteoradionecrosis of the jaw (ORNJ) is a severe complication following head and neck radiotherapy that significantly impacts the quality of life of patients. Currently, there is a lack of comprehensive understanding of the microenvironmental factors involved in ORNJ. In this study, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells using scRNA-Seq and demonstrate a decrease in taurine levels in irradiated bone marrow mesenchymal stromal cells (BMSCs) through metabolomics. Compared with unirradiated BMSCs, taurine uptake in irradiated BMSCs increases. Taurine concentrations in the peripheral blood and jaws of irradiated mice are significantly lower than those in unirradiated mice (P = 0.0064 and 0.0249 respectively). Supplementation with taurine promotes osteogenic differentiation, reduces oxidative stress, and decreases DNA damage in irradiated BMSCs. Oral administration of taurine significantly improves the survival rate of irradiated mice and enhances osteogenesis in irradiated jaws. Our study highlights the role of taurine in the recovery from radiation-induced jaw injury, and suggests its potential as a non-invasive therapeutic option for combating ORNJ.

MRG15 promotes cell apoptosis through inhibition of mitophagy in hyperlipidemic acute pancreatitis.

Hyperlipidemia is a common cause of acute pancreatitis (AP), often leading to more severe clinical symptoms. The mortality factor 4-like protein 1 (MORF4L1, also called MRG15) plays a crucial role in regulating lipid metabolism. Therefore, this study aimed to explore the mechanism of MRG15 in hyperlipidemic acute pancreatitis (HAP). Mendelian randomization, transcriptome analysis, and single-cell analysis were employed to explore the association between MRG15 and AP by utilizing publicly available databases. In vivo, hypertriglyceridemia mouse models were created by intraperitoneal injection of P407 or using APOE-deficient mice. Subsequently, the HAP model was induced by cerulean. In vitro, a cell model of HAP was established by initially exposing cells to palmitic acid to simulate a high-fat environment, followed by cerulein treatment. Subsequently, MRG15-related indicators were measured. Through Mendelian randomization, it was discovered that there is a positive correlation between genetic expression of MRG15 and the risk of AP. Transcriptome and single-cell analysis revealed that elevated MRG15 expression in AP contributes to lipid metabolism disorders and the activation of apoptosis pathways in pancreatic acinar cells. MRG15 is found to be significantly upregulated in cases of HAP. Knocking down MRG15 led to an increase in mitophagy and a decrease in apoptosis in pancreatic cells, and this effect was reversed when the mitochondrial Tu translation elongation factor (TUFM) was simultaneously knocked down. MRG15 inhibits mitophagy by degrading TUFM, ultimately promoting cell apoptosis and worsening the progression of HAP.

MdNAC5: a key regulator of fructose accumulation in apple fruit.

The sweetness of apple fruit is a key factor in the improvement of apple varieties, with fructose being the sweetest of the soluble sugars, playing a crucial role in determining the overall sweetness of the apple. Therefore, uncovering the key genes controlling fructose accumulation and deciphering the regulatory mechanisms of fructose are vitally important for the improvement of apple varieties. In this study, through BSA-seq and transcriptome analysis of the 'Changfu 2' × 'Golden Delicious' F1 hybrid population, MdNAC5 was identified as a key regulatory gene for fructose content. MdNAC5 was shown to significantly influence fructose accumulation in both apples and tomatoes. Furthermore, we conducted a detailed identification of sugar transporters and metabolic enzymes in apples, discovering that MdNAC5 can enhance fructose accumulation in vacuoles and the conversion of sucrose to fructose by binding to and activating the promoters of the vacuolar sugar transporter MdTST2 and the neutral invertase MdNINV6. Additionally, MdNAC5 regulated the MdEIN3.4-MdSWEET15a module, strengthening the unloading of sucrose in the phloem of the fruit. Our results reveal a new mechanism by which MdNAC5 regulates fructose accumulation in apples and provide theoretical foundations for improving apple sweetness through genetic modification.

Laoxianghuang polysaccharide promotes the anti-inflammatory cytokine interleukin-10 in colitis via gut microbial linoleic acid.

BACKGROUND: Our previous study found that the polysaccharide from Laoxianghuang (LP), fermented fruit of bergamot (traditional Chinese medicine and food), can alter gut microbiota and regulate short-chain fatty acids (SCFAs) in vitro. Nevertheless, there is a paucity of reports on the impact of LP on gut microbiota in vivo. PURPOSE: To analyze the structures of LP, investigate the influence of LP on the damaged intestinal barrier in DSS-induced colitis mice, and further explore its potential mechanisms. METHODS: We analyzed the physicochemical properties of purified LP by HPLC, SEM, and FT-IR spectrum. Then, to assess the effect of LP in DSS-induced colitis mice, we observed the damage to the colon tissue, measured inflammatory cytokines and tight junction protein expression through RT-qPCR as well as immunofluorescent staining, and investigated the influence of LP on altering gut microbiota and metabolites using 16 s rRNA sequencing and HPLC-MS/MS. Ultimately, the impact of linoleic acid on inflammatory cytokines was confirmed by the LPS-induced RAW264.7 cells. RESULTS: LP, mainly galactoglucan, could inhibit weight loss and colon shortening, decrease levels of tumor necrosis factor-α (TNF-α), increase levels of interleukin-10 (IL-10) and the intestinal acetic acid and butyric acid, and promote the expression of tight junction proteins ZO-1 and Claudin-1. Meanwhile, LP enhanced the abundance of beneficial bacteria including Romboutsia, Eubacterium_coprostanoligenes_group, and Akkermansia, and regulated linoleic acid metabolism to increase the linoleic acid level. In vitro cell experiment proved that linoleic acid could elevate the level of IL-10 and inhibit inflammatory responses. CONCLUSIONS: Our results suggested that LP effectively alleviated colitis by promoting the anti-inflammatory cytokine interleukin-10 via gut microbiota-mediated linoleic acid metabolism.

Unveiling the therapeutic potential: KBU2046 halts triple-negative breast cancer cell migration by constricting TGF-ß1 activation in vitro.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer characterized by a high rate of metastasis, poor prognosis, and lack of efficient therapies. KBU2046, a small molecule inhibitor, can inhibit cell motility in malignant tumors, including breast cancer. However, the specific targets and the corresponding mechanism of its function remain unclear. Methods: In this study, we employed (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium) (MTS) assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro. RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC. Finally, confirmed the predicted important signaling pathways through RT-qPCR and western blotting. Results: In this study, we found that KBU2046 functioned as a novel transforming growth factor-ß (TGF-ß1) inhibitor, effectively suppressing tumor cell motility in vitro. Mechanistically, it directly down-regulated leucine-rich repeat-containing 8 family, member E (LRRC8E), latent TGFß-binding protein 3 (LTBP3), dynein light chain 1 (DNAL1), and MAF family of bZIP transcription factors (MAFF) genes, along with reduced protein expression of the integrin family. Additionally, KBU2046 decreased phosphorylation levels of Raf and ERK. This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis. Conclusions: In summary, these findings advocate for the utilization of TGF-ß1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC. Furthermore, our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.

Spontaneous regression of lumbar disc herniation: four cases report and review of the literature.

Spontaneous regression of lumbar disc herniation refers to shrinkage or disappearance of herniated nucleus pulposus without invasive surgical treatments. This phenomenon has been reported and is supported by improved clinical symptoms and radiographic after conservative treatment, but the underlying mechanism remains unclear. This article reports 4 cases of disc reabsorption and reviews the distribution of several clinical and radiographic factors of disc herniation reabsorption of total 46 patients, including the four from our study, gathered from 28 recent publications. Some of these factors are present with anomalous distributions. But some factors have similar deviations in patients with lumbar disc herniation. Therefore, more research is needed to explore the correlation between those factors and disc reabsorption.

Three-Component Photochemical Cyclization/Dithiocarbamate Formation of gem-Difluoro Quinolin-2(1H)-ones.

Herein, a novel visible-light-induced 6-exo-trig difluoromethylation cyclization and subsequent carbo-thioesterification reaction is described. This protocol allows efficient access to valuable gem-difluoro quinolin-2(1H)-ones in moderate to excellent yields under mild conditions. Broad amino sources compatibility, including cyclic morpholine, thiazolidine, thiomorpholine, pyrrolidine, 1,4-oxazepane, 2,6-dimethylmorpholine, tert-butyl piperazine-1-carboxylate and noncyclic diethylamine, N-ethylpropan-1-amine, N-benzylethanamine, N-benzyl-trimethylsilanamine, dibenzylamine, and N-(4-methoxybenzyl)ethanamine, demonstrated the practicability of this strategy. A radical-radical crossover route was proposed on the basis of radical inhibition experiments, visible light irradiation on-off test, apparent quantum efficiency (AQE) calculation, and fluorescence quenching studies.

Identification of Potential Feature Genes in CRSwNP Using Bioinformatics Analysis and Machine Learning Strategies.

Purpose: The pathogenesis of CRSwNP is complex and not yet fully explored, so we aimed to identify the pivotal hub genes and associated pathways of CRSwNP, to facilitate the detection of novel diagnostic or therapeutic targets. Methods: Utilizing two CRSwNP sequencing datasets from GEO, differential expression gene analysis, WGCNA, and three machine learning methods (LASSO, RF and SVM-RFE) were applied to screen for hub genes. A diagnostic model was then formulated utilizing hub genes, and the AUC was generated to evaluate the performance of the prognostic model and candidate genes. Hub genes were validated through the validation set and qPCR performed on normal mice and CRSwNP mouse model. Lastly, the ssGSEA algorithm was employed to assess the differences in immune infiltration levels. Results: A total of 239 DEGs were identified, with 170 upregulated and 69 downregulated in CRSwNP. Enrichment analysis revealed that these DEGs were primarily enriched in pathways related to nucleocytoplasmic transport and HIF-1 signaling pathway. Data yielded by WGCNA analysis contained 183 DEGs. The application of three machine learning algorithms identified 11 hub genes. Following concurrent validation analysis with the validation set and qPCR performed after establishing the mouse model confirmed the overexpression of BTBD10, ERAP1, GIPC1, and PEX6 in CRSwNP. The examination of immune cell infiltration suggested that the infiltration rate of type 2 T helper cell and memory B cell experienced a decline in the CRSwNP group. Conversely, the infiltration rates of Immature dendritic cell and Effector memory CD8 T cell were positive correlation. Conclusion: This study successfully identified and validated BTBD10, ERAP1, GIPC1, and PEX6 as potential novel diagnostic or therapeutic targets for CRSwNP, which offers a fresh perspective and a theoretical foundation for the diagnostic prediction and therapeutic approach to CRSwNP.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Patterns and trends in asthma incidence rates in main Asian and Western countries and their prediction to 2030.

Background: The urbanization and industrialization of East and Southeast Asia in decades past has significantly altered living environment and lifestyles, which may have complicated effects on the burden of asthma. We aim to examine the patterns and trends of asthma incidence rates in six major East and Southeast Asian countries as well as five major Western countries, and predict the numbers of new cases attributed to various factors. Methods: Data on annual asthma incident cases and corresponding population by age group were drawn from 6 major selected East and Southeast Asian countries available in the Global Burden of Disease database, including China, Japan, Korea, Singapore, Philippines, and Thailand. We also collected data of five major high-income Western countries for comparative purposes. Two separate Bayesian age-period-cohort models, representing pre-COVID (model 1) and post-COVID (model 2) scenarios, were constructed to predict the asthma incidence until 2030. Results: In model 1, the age-standardized incidence rate of asthma will be the highest in the US (1970.07 per 100,000, 95% confidence interval [CI] 533.05-4455.03), while the lowest incidence rate will be found in Singapore (296.72 per 100,000, 95% CI 135.16-899.55) in 2030. Between 1990 and 2030, the incidence of asthma is projected to increase in China and Thailand, with average annual percentages changes (AAPC) ranging from 0.70% to 1.80%. The remaining four Asian countries show a declining trend, with AAPC ranging from -0.51% to -2.00%. In model 2, the US is estimated to have the highest age-standardized incidence rate (902.71 per 100,000, 95% CI 375.44-2277.24), while Korea will have the lowest incidence rate (176.46 per 100,000, 95% CI 58.77-512.09) in 2030. A decrease in asthma incidence was observed in all countries with the overall AAPC ranging from -3.42% to -0.42%. Notably, a turning point was found around 2020, after which the incidence rates dropped significantly. Conclusions: Pandemic-related factors may temporarily lower the incidence of asthma. The expected increasing asthma incidence in pre-COVID scenario (model 1) should still warrant attention from public health practitioners and call for efforts to reduce the burden of asthma.

A systematic regulatory network related to bulbil formation in Lilium lancifolium based on metabolome and transcriptome analyses.

BACKGROUND: Lilium lancifolium is a special wild triploid species native to China and can produce abundant bulbils on its stem under natural conditions, which is very valuable to study bulbil organogenesis in plants. Although similar to the lateral and tillering principles, the molecular mechanism underlying bulbil formation has remained incompletely understood. RESULTS: The metabolome and transcriptome of L. lancifolium bulbils across four development stages were analyzed. The pairwise comparison of metabolomes across the four stages identified 17 differential hormones, predominantly auxin (IAA), cytokinin (CK), and jasmonic acid (JA). Short Time-series Expression Miner (STEM) trend analysis of differential genes revealed four significant trends across these stages. The KEGG enrichment analysis of the four clusters highlighted pathways, such as plant hormone signal transduction, which were speculated to play a crucial role in development stages. these pathways were speculated to play a crucial role in development stages. To explore the key differential expressed genes and transcription factors associated with bulbil occurrence, two periods were focused on: Ll_UN and Ll_DN, which represented the stages with and without bulbils, respectively. Through correlation analysis and qRT-PCR analysis, 11 candidate differentially expressed genes and 27 candidate transcription factors were selected. By spraying exogenous hormones to validate these candidates, LlbHLH128, LlTIFY10A, LlbHLH93, and LlMYB108, were identified as the key genes for L. lancifolium bulbils. CONCLUSION: A regulatory network of L. lancifolium bulbil development was predicted. LlTIFY10A and LlbHLH93 might be involved in the JA and auxin signal transduction pathways, which jointly formed a regulatory network to affect the occurrence of L. lancifolium bulbil. This study not only provided more information about the differentially expressed genes and metabolites through transcriptome and metabolomics analyses, but also provided a clearer understanding of the effect of hormones on bulbil formation in lily.

Txnip promotes autophagic apoptosis in diabetic cardiomyopathy by upregulating FoxO1 and its acetylation.

Autophagy dysfunction and apoptosis exacerbate the risk of heart failure in patients with diabetic cardiomyopathy (DCM). However, the interactions between autophagy and apoptosis in DCM and their underlying mechanisms remain poorly understood. This study induced type 1 DCM in C57BL/6 mice via streptozotocin injection and exposed H9C2 cells to high glucose to investigate these mechanisms. The study revealed a significant elevation in autophagic vesicles and compromised autophagic flux, accompanied by pronounced myocardial cell apoptosis in the myocardium of diabetic mice. Long-term exposure to high glucose in H9C2 cells led to enhanced autophagosome formation and impaired autophagic flux, while inhibition of autophagy with 3-MA reduced cell apoptosis. Additionally, we observed an increase in Txnip expression in the myocardium of diabetic mice and in high glucose-treated H9C2 cells, which regulates autophagic apoptosis in high glucose-treated H9C2 cells. Furthermore, Txnip regulates autophagic apoptosis through the modulation of forkhead box-1 (FoxO1) expression and acetylation. Prolonged high glucose exposure resulted in increased levels of phosphorylated sirtuin 1 (SIRT1) and reduced SIRT1/FoxO1 interaction, changes that were ameliorated by Txnip knockdown. Txnip overexpression elevated FoxO1 levels, which could be suppressed by NAC and GSH. These findings revealed that Txnip mediates autophagic apoptosis in DCM by upregulating FoxO1 via ROS and enhancing FoxO1 acetylation through the suppression of SIRT1 activity. The discovery of this new mechanism provides new perspectives and potential therapeutic targets for understanding and treating DCM.

SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation.

Oral mucosal wounds exhibit accelerated healing with reduced scarring compared to cutaneous wounds, representing an optimal wound healing paradigm. However, the specific cellular subtypes orchestrating the efficient healing of mucosal tissues remain elusive. Through a comprehensive analysis integrating bulk-mRNA and single-cell sequencing data during the wound healing process in oral mucosa and skin, we have delineated a distinct set of genes markedly upregulated during tissue repair. This collection of wound healing-associated genesets was highly enriched in a specific keratinocyte subpopulation identified as STAT3-activated SPRR1B+ keratinocytes. Notably, despite the inherent rapidity of oral mucosal healing, the induction of SPRR1B+ keratinocytes is evident in both skin and mucosal wound healing processes in murine model. Intriguingly, these wound healing-promoting SPRR1B+ keratinocytes, which are induced via STAT3 activation, inherently abundant in unwounded normal mucosa but absent in normal skin. SPRR1B knockdown significantly inhibits mucosal keratinocyte migration, a critical attribute for effective wound healing. In summary, through analysis of human oral and skin wound healing processes at single-cell resolution, coupled with validation in murine model, suggests STAT3-activated SPRR1B+ keratinocytes are associated with the rapid mucosal repair process. This discovery underscores the potential application of SPRR1B+ keratinocytes in the therapeutic management of chronic or non-healing wounds.

Characterization of isoniazid resistance and genetic mutations in isoniazid-resistant and rifampicin-susceptible Mycobacterium tuberculosis in China.

Background: Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin (Hr-Rs TB) remain a neglected demographic, despite a high disease burden and poor outcomes of these patients. The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for Hr-Rs patients. Methods: Mycobacterium tuberculosis isolates (n = 4922) obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify Hr-Rs strains. The minimal inhibitory concentrations (MICs) were established for the Hr-Rs strains to determine the isoniazid resistance levels. We also identified drug-resistance-associated mutations for five drugs (fluoroquinolones, ethambutol, pyrazinamide, streptomycin, and amikacin) in the Hr-Rs strains. Results: Of the 4922 strains, 384 (7.8 %) were Hr-Rs. The subculture of seven strains failed, so 377 (98.2 %) strains underwent phenotypic MIC testing. Among the 384 genotypic Hr-Rs strains, 242 (63.0 %) contained the katG Ser315Thr substitution; 115 (29.9 %) contained the -15C>T in the promoter region of the fabG1 gene; and 16 (4.2 %) contained Ser315Asn in the katG gene. Of the 239 strains with the Ser315Thr substitution, 229 (95.8 %) had MIC ≥ 2 µg/mL, and of the 114 strains with the -15C>T mutation, 103 (90.4 %) had 0.25 µg/mL ≤ MIC ≤ 1 µg/mL. The genotypic resistance rates were 0.8 % (3/384) for pyrazinamide, 2.3 % (9/384) for ethambutol and fluoroquinolones; 39.6 % (152/384) of the strains were resistant to streptomycin, but only 0.5 % (2/384) of the strains were resistant to amikacin. Conclusion: Ser315Thr in katG was the predominant mutation conferring the Hr-Rs phenotype, followed by the fabG1 -15C>T mutation. The combination of rifampicin, pyrazinamide, ethambutol, and levofloxacin should be effective in the treatment of patients with Hr-Rs tuberculosis because the resistance rates for these drugs in China are low.

Morroniside repairs atrazine-induced skin damage by ameliorating lipid metabolism disorders and inhibiting ferroptosis.

Morroniside (MOR) has shown great potential in treating atrazine (ATZ)-induced skin damage. This study aims to elucidate MOR's mechanism of action in mitigating lipid metabolism disorders and inhibiting ferroptosis to repair ATZ-induced skin damage. Twenty C57BL/6 mice were divided into four groups: the control group, the ATZ group, the MOR-H group and the MOR-L group, each comprising five mice. Following a one-month intervention, mouse skin tissues were harvested for untargeted lipid metabolomics analysis. Subsequently, the samples were assessed for indices related to ferroptosis. Untargeted lipid metabolomics analysis showed 127 differential metabolites in the ATZ vs. Ctrl group. There were 57 differential metabolites in the MOR-L vs. ATZ group. 34 differential metabolites in the MOR-H vs. ATZ group. the most obvious lipid reversal occurred after MOR-L administration, which primarily involved phospholipids, ceramides, and sphingomyelins. The levels of GPX4, Ferritin, MDA, SOD and GSH-PX, ferroptosis-related indicators, and the levels of p21 and p53, apoptosis-related indicators, were most significantly regressed in the MOR-L group (all P < 0.05). MOR may delay cellular aging and correct skin damage by reversing ATZ-induced lipid metabolism disorders, inhibiting ferroptosis and excessive oxidative stress occurrence.

Atomistic mechanisms of the regulation of small-conductance Ca2+-activated K+ channel (SK2) by PIP2.

Small-conductance Ca2+-activated K+ channels (SK, KCa2) are gated solely by intracellular microdomain Ca2+. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling, and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in concert with Ca2+-CaM in the SK channel activation. Our computational study affords evidence for the critical role of the amino acid residue R395 in the S6 transmembrane segment, which is localized in propinquity to the intracellular hydrophobic gate. This residue forms a salt bridge with residue E398 in the S6 transmembrane segment from the adjacent subunit. Both R395 and E398 are conserved in all known isoforms of SK channels. Our findings suggest that the binding of PIP2 to R395 residue disrupts the R395:E398 salt bridge, increasing the flexibility of the transmembrane segment S6 and the activation of the channel. Importantly, our findings serve as a platform for testing of structural-based drug designs for therapeutic inhibitors and activators of the SK channel family. The study is timely since inhibitors of SK channels are currently in clinical trials to treat atrial arrhythmias.

Electroencephalography (EEG) spectral signatures of selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and vortioxetine in major depressive disorder: A systematic review.

BACKGROUND: Converging evidence suggests electroencephalography (EEG) methods may elucidate alterations in global structural and functional connectivity that underlie the pathophysiology of depressive disorders. Extant literature suggests SSRIs and SNRIs may broadly induce alterations to EEG-measured neural activity. Herein, this systematic review comprehensively evaluates changes to EEG spectral signatures associated with vortioxetine and each FDA-approved agent within the SSRI and SNRI class. METHODS: We conducted a systematic review of studies investigating changes to EEG spectral signatures associated with SSRI, SNRI, and/or vortioxetine treatment in persons with MDD. Database search occurred from database inception to May 3, 2024. RESULTS: Our search yielded 15 studies investigating overall spectral signature changes associated with SSRI- and/or SNRI-treatment. The existing literature presents with mixed findings. Notwithstanding, we did observe a pattern in which the SSRI and SNRI agents reproducibly affect EEG spectral signatures. We observed overlapping yet distinct spectral patterns for each agent within- and between-drug classes of SSRIs and SNRIs. Changes in resting/wake EEG were also observed. LIMITATIONS: The findings from our systematic review are mixed. Heterogeneity exists with sample size, composition, dosing of antidepressants, duration of antidepressant exposure, as well as the type of EEG devices used. DISCUSSIONS: Our findings provide support to the notion that although SSRIs, SNRIs and vortioxetine block reuptake of the serotonin transporter; they are different in their profile of pharmacology as evidenced by differential EEG signatures. EEG changes associated with SSRIs, SNRIs and vortioxetine are also highly replicated findings across mixed studies and populations.