MiR-183-5p inhibits lung squamous cell carcinoma survival through disrupting hypoxia adaptation mediated by HIF-1α/NDUFA4L2 axis.

Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined. The potential microRNA targeting to NDUFA4L2 was identified and its roles on LUSC cell were detected. We found that NDUFA4L2 were overexpressed in LUSC tissues, and that NDUFA4L2 expression correlated with shorter overall survival. NDUFA4L2 was regulated by HIF-1α under hypoxia, and NDUFA4L2 decreased mitochondrial reactive oxygen species (mitoROS) production through inhibiting mitochondrial complex I activity in LUSC cells. NDUFA4L2 silencing effectively suppressed LUSC cell growth and enhanced apoptosis by inducing mitoROS accumulation. Additionally, NDUFA4L2 was a target for miR-183-5p, and LUSC patients with high miR-183-5p levels had better prognoses. MiR-183-5p significantly induced mitoROS production and suppressed LUSC survival through negatively regulating NDUFA4L2 in vitro and in vivo. Our results suggested that regulation of NDUFA4L2 by HIF-1α is an important mechanism promoting LUSC progression under hypoxia. NDUFA4L2 inhibition using enforced miR-183-5p expression might be an effective strategy for LUSC treatment.

Optimized Photothermal Conversion Ability through Interband Transitions in FeCoNiCrMn High-Entropy-Alloy Nanoparticles.

High-entropy-alloy nanoparticles (HEA-NPs) composed of 3d transition metallic elements have attracted intensive attention in photothermal conversion regions due to their d-d interband transitions (IBTs). However, the effect arising from the unbalanced elemental ratio still needs more focus. In this work, FeCoNiCrMn HEA-NPs with different elemental ratios among Cr and Mn have been employed to clarify the impact of different composed elements on the optical absorption and photothermal conversion performance. It can be recognized that the unbalanced elemental ratio of HEA-NPs can reduce the photothermal performance. Density functional theory calculation demonstrated that d-d IBTs can be changed by the different composed element ratios, resulting in a number of insufficient filling regions around the Fermi level (±4 eV). As a result, the HEA-NPs (FeCoNiCr0.75Mn0.25) with a balanced elemental ratio exhibit the highest surface temperature of 97.6 °C under 1 sun irradiation, and the evaporation rate and energy conversion efficiency could reach 2.13 kg·m-2·h-1 and 93%, respectively, demonstrating effective solar steam generation behavior.

Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

Structural variations of a new fertility restorer gene, Rf20, underlie the restoration of wild abortive-type cytoplasmic male sterility in rice.

The discovery of a wild abortive-type (WA) cytoplasmic male sterile (CMS) line and breeding its restorer line have led to the commercialization of three-line hybrid rice, contributing considerably to global food security. However, the molecular mechanisms underlying fertility abortion and the restoration of CMS-WA lines remain largely elusive. In this study, we cloned a restorer gene, Rf20, following a genome-wide association study analysis of the core parent lines of three-line hybrid rice. We found that Rf20 was present in all core parental lines, but different haplotypes and structural variants of its gene resulted in differences in Rf20 expression levels between sterile and restored lines. Rf20 could restore pollen fertility in the CMS-WA line and was found to be responsible for fertility restoration in some CMS lines under high temperatures. In addition, we found that Rf20 encodes a pentatricopeptide repeat protein that competes with WA352 for binding with COX11. This interaction enhances COX11's function as a scavenger of reactive oxygen species, which in turn restores pollen fertility. Collectively, our study suggests a new action mode for pentatricopeptide repeat proteins in the fertility restoration of CMS lines, providing an essential theoretical basis for breeding robust restorer lines and for overcoming high temperature-induced fertility recovery of some CMS lines.

Nardosinone relieves metabolic-associated fatty liver disease and promotes energy metabolism through targeting CYP2D6.

BACKGROUND: Nardosinone, a major extract of Rhizoma nardostachyos, plays a vital role in sedation, neural stem cell proliferation, and protection of the heart muscle. However, the huge potential of nardosinone in regulating lipid metabolism and gut microbiota has not been reported, and its potential mechanism has not been studied. PURPOSE: To explore the regulation of nardosinone on liver lipid metabolism and gut microbiota. METHODS: In this study, the role of nardosinone in lipid metabolism was investigated in vitro and in vivo by adding it to mouse feed and HepG2 cell culture medium. And 16S rRNA gene sequencing was used to explore its regulatory effect on gut microbiota. RESULTS: Results showed that nardosinone could improve HFD-induced liver injury and abnormal lipid metabolism by promoting mitochondrial energy metabolism in hepatocytes, alleviating oxidative stress damage, and regulating the composition of the gut microbiota. Mechanistically, combined with network pharmacology and reverse docking analysis, it was predicted that CYP2D6 was the target of nardosinone, and the binding was verified by cellular thermal shift assay (CETSA). CONCLUSIONS: This study highlights a novel mechanism function of nardosinone in regulating lipid metabolism and gut microbiota. It also predicts and validates CYP2D6 as a previously unknown regulatory target, which provides new possibilities for the application of nardosinone and the treatment of metabolic-associated fatty liver disease.

Impact of National Immunization Strategies on Vaccine-Preventable Diseases - China, 1950-2021.

What is already known about this topic?: The incidences of vaccine-preventable diseases (VPDs) included in the Expanded Program on Immunization in China have decreased significantly in recent decades. What is added by this report?: This study summarizes the national incidences of nine VPDs and the seroprevalence of hepatitis B surface antigen (HBsAg) under different immunization strategies from 1950 through 2021 in China. The sharpest decreases in VPD incidence and under-5-year HBsAg seroprevalence occurred during the latest stage of the National Immunization Program. The decreases in VPD incidence were most prominent among children under five years of age. What are the implications for public health practice?: These findings provide valuable insights for vaccine value assessment and emphasize the importance of implementing immunization strategies in targeted populations.

Translatomics reveals the role of dietary calcium addition in regulating muscle fat deposition in pigs.

Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the accumulation of intramuscular fat. Additionally, calcium ions inhibit translation and reduce protein synthesis. However, the mechanism by which calcium regulates IMF deposition in muscle through translation remains largely unknown. In this study, we compared the ribosome profiles of the longissimus dorsi muscles of Duroc × Landrace × Large white pigs from the normal calcium (NC) group or calcium supplement (HC) group by Ribo-seq, and RNA-seq. By integrating multiple-omics analysis, we further discovered 437 genes that were transcriptionally unchanged but translationally altered and these genes were significantly enriched in the oxidative phosphorylation signaling pathway. Furthermore, experimental data showed that inhibiting the expression of COX10 and mtND4L increased triglyceride accumulation in C2C12 cells, providing new targets for intramuscular fat deposition. Finally, this work links dietary calcium, translation regulation and IMF deposition, providing a new strategy for both meat quality and economic performance within the pig industry.

7-Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24.

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

The landscape of super-enhancer regulates remote target gene transcription through loop domains in adipose tissue of pig.

Background: A super-enhancer (SE) is a huge cluster of multiple enhancers that control the key genes for cell identity and function. The rise of advanced chromatin immunoprecipitation sequencing (ChIP-seq) technology such as Cleavage Under Targets and Tagmentation (CUT&Tag) allows more SEs to be discovered. However, SE studies in Luchuan and Duroc pigs are very rare in animal husbandry. Results: We used the CUT&Tag technique to identify 145 and 378 SEs from the adipose tissues of Luchuan and Duroc pigs, respectively. There were significant differences in the peak coverage ratio of SE peaks in the gene promoter region between the two breeds. Not only that, peak signals at the start and end point of the SE peak profile showed obvious spikes. The proximal target genes of SE were highly expressed compared with the background genes and the typical enhancer target genes. Subsequently, in conjoint analysis with high-throughput chromosome conformation capture sequencing (Hi-C seq) data, we predicted the remote regulatory genes of SE and found that their expression level was related to the distance of SE extended to the loop's anchor, but not the length of loops. According to our prediction model, SEs can maintain promoter accessibility of partial remote target genes through loop domains. Finally, a batch of SEs closely related to fat metabolism traits were obtained by performing a coalition analysis of quantitative trait loci and SE data. Conclusions: This work enabled us to obtain hundreds of SEs from Luchuan and Duroc pigs. Our model provides a new method for predicting the SE remote target genes based on loop domains, and to further explore the potential role of super-enhancer in the regulation of fat metabolism.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Loss of function of OsL1 gene cause early flowering in rice under short-day conditions.

Heading date is one of the important agronomic traits that affects rice yield. In this study, we cloned a new rice B3 family gene, OsL1, which regulates rice heading date. Importantly, osl1-1 and osl1-2, two different types of mutants of OsL1 were created using the gene editing technology CRISPR/Cas9 system and exhibited 4 days earlier heading date than that of the wild type under short-day conditions. Subsequently, the plants overexpressing OsL1, OE-OsL1, showed a 2-day later heading date than the wild type in Changsha and a 5-day later heading date in Lingshui, but there was no significant difference in other yield traits. Moreover, the results of subcellular localization study indicated that OsL1 protein was located in the nucleus and the expression pattern analysis showed that OsL1 gene was expressed in rice roots, stems, leaves, and panicles, and the expression level was higher at the root and weak green panicle. In addition, the OsL1 gene was mainly expressed at night time under short-light conditions. The transcriptomic analysis indicated that OsL1 might be involved in the Hd1-Hd3a pathway function. Together, our results revealed that the cloning and functional analysis of OsL1 can provide new strategy for molecular design breeding of rice with suitable fertility period. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01444-1.

Dietary Betaine Improves Glucose Metabolism in Obese Mice.

BACKGROUND: Obesity caused by the overconsumption of energy-dense foods high in fat and sugar has contributed to the growing prevalence of type 2 diabetes. Betaine, found in food or supplements, has been found to lower blood glucose concentrations, but its exact mechanism of action is not well understood. OBJECTIVES: A comprehensive evaluation of the potential mechanisms by which betaine supplementation improves glucose metabolism. METHODS: Hyperglycemic mice were fed betaine to measure the indexes of glucose metabolism in the liver and muscle. To explore the mechanism behind the regulation of betaine on glucose metabolism, Ribonucleic Acid-Seq was used to analyze the livers of the mice. In vitro, HepG2 and C2C12 cells were treated with betaine to more comprehensively evaluate the effect of betaine on glucose metabolism. RESULTS: Betaine was added to the drinking water of high-fat diet-induced mice, and it was found to reduce blood glucose concentrations and liver triglyceride concentrations without affecting body weight, confirming its hypoglycemic effect. To investigate the specific mechanism underlying its hypoglycemic effect, protein-protein interaction enrichment analysis of the liver revealed key nodes associated with glucose metabolism, including cytochrome P450 family activity, insulin sensitivity, glucose homeostasis, and triglyceride concentrations. The Kyoto Encyclopedia of Genes and Genomes and gene ontogeny enrichment analyses showed significant enrichment of the Notch signaling pathway. These results provided bioinformatic evidence for specific pathways through which betaine regulates glucose metabolism. Key enzyme activities involved in glucose uptake, glycogen synthesis, and glycogenolysis pathways of the liver and muscle were measured, and improvements were observed in these pathways. CONCLUSIONS: This study provides new insight into the mechanisms by which betaine improves glucose metabolism in the liver and muscle and supports its potential as a drug for the treatment of metabolic disorders related to glucose.

High-Safety Electrolytes with an Anion-Rich Solvation Structure Tuned by Difluorinated Cations for High-Voltage Lithium Metal Batteries.

As next-generation energy storage devices, lithium metal batteries (LMBs) must offer high safety, high-voltage resistance, and a long life span. Electrolyte engineering is a facile strategy to tailor the interfacial chemistry of LMBs. In particular, the solvation structure and derived solid electrolyte interphase (SEI) are crucial for a satisfactory battery performance. Herein, a novel middle-concentrated ionic liquid electrolyte (MCILE) with an anion-rich solvation structure tuned by difluorinated cations is demonstrated to achieve ultrahigh safety, high-voltage stability, and excellent ternary-cathode compatibility. Novel gem-difluorinated cations first synthesized for prestoring fluorine on positively charged species, not only preferentially adsorb in the inner-Helmholtz layers, but also participate in regulating the Li+ solvation structure, resulting in a robust interphase. Moreover, these weak interactions in the Li+ solvation structure including anion-solvent and ionic liquid (IL) cation-solvent pairs are first revealed, which are beneficial for promoting an anion-dominated solvation structure and the desolvation process. Benefiting from the unique anion-rich solvation structure, a stable hetero-SEI structure is obtained. The designed MCILE exhibits compatibility with Li metal anode and the high-voltage ternary cathode at high temperatures (60 °C). This work provides a new approach for regulating the solvation structure and electrode interphase chemistry of LMBs via difluorinated IL cations.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

Solvation Structure and Derived Interphase Tuning for High-Voltage Ni-Rich Lithium Metal Batteries with High Safety Using Gem-Difluorinated Ionic Liquid Based Dual-Salt Electrolytes.

Stabilizing electrolytes for high-voltage lithium metal batteries (LMBs) is crucial yet challenging, as they need to ensure stability against both Li anodes and high-voltage cathodes (above 4.5 V versus Li/Li+ ), addressing issues like poor cycling and thermal runaway. Herein, a novel gem-difluorinated skeleton of ionic liquid (IL) is designed and synthesized, and its non-flammable electrolytes successfully overcome aforementioned challenges. By creatively using dual salts, fluorinated ionic liquid and dimethyl carbonate as a co-solvent, the solvation structure of Li+ ions is efficiently controlled through electrostatic and weak interactions that are well unveiled and illuminated via nuclear magnetic resonance spectra. The as-prepared electrolytes exhibit high security avoiding thermal runaway and show excellent compatibility with high-voltage cathodes. Besides, the solvation structure derives a robust and stable F-rich interphase, resulting in high reversibility and Li-dendrite prevention. LiNi0.6 Co0.2 Mn0.2 O2 /Li LMBs (4.5 V) demonstrate excellent long-term stability with a high average Coulombic efficiency (CE) of at least 99.99 % and a good capacity retention of 90.4 % over 300 cycles, even can work at a higher voltage of 4.7 V. Furthermore, the ultrahigh Ni-rich LiNi0.88 Co0.09 Mn0.03 O2 /Li system also delivers excellent electrochemical performance, highlighting the significance of fluorinated IL-based electrolyte design and enhanced interphasial chemistry in improving battery performance.

Integration of Metabolomics and Transcriptomics to Explore Dynamic Alterations in Fruit Color and Quality in 'Comte de Paris' Pineapples during Ripening Processes.

Pineapple color yellowing and quality promotion gradually manifest as pineapple fruit ripening progresses. To understand the molecular mechanism underlying yellowing in pineapples during ripening, coupled with alterations in fruit quality, comprehensive metabolome and transcriptome investigations were carried out. These investigations were conducted using pulp samples collected at three distinct stages of maturity: young fruit (YF), mature fruit (MF), and fully mature fruit (FMF). This study revealed a noteworthy increase in the levels of total phenols and flavones, coupled with a concurrent decline in lignin and total acid contents as the fruit transitioned from YF to FMF. Furthermore, the analysis yielded 167 differentially accumulated metabolites (DAMs) and 2194 differentially expressed genes (DEGs). Integration analysis based on DAMs and DEGs revealed that the biosynthesis of plant secondary metabolites, particularly the flavonol, flavonoid, and phenypropanoid pathways, plays a pivotal role in fruit yellowing. Additionally, RNA-seq analysis showed that structural genes, such as FLS, FNS, F3H, DFR, ANR, and GST, in the flavonoid biosynthetic pathway were upregulated, whereas the COMT, CCR, and CAD genes involved in lignin metabolism were downregulated as fruit ripening progressed. APX as well as PPO, and ACO genes related to the organic acid accumulations were upregulated and downregulated, respectively. Importantly, a comprehensive regulatory network encompassing genes that contribute to the metabolism of flavones, flavonols, lignin, and organic acids was proposed. This network sheds light on the intricate processes that underlie fruit yellowing and quality alterations. These findings enhance our understanding of the regulatory pathways governing pineapple ripening and offer valuable scientific insight into the molecular breeding of pineapples.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

Molecular Mechanism of Qingzaojiufei Decoction in the Treatment of Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking.

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.