Drug repurposing opportunities for chronic kidney disease.

The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and cost-effectiveness of traditional drug development approaches are extremely low. Utilizing large sample genome-wide association study data for drug repurposing has shown promise in many diseases but has not yet been explored in CKD. Herein, we investigated actionable druggable targets to improve renal function using large-scale Mendelian randomization and colocalization analyses. We combined two population-scale independent genetic datasets and validated findings with cell-type-dependent eQTL data of kidney tubular and glomerular samples. We ultimately prioritized two drug targets, opioid receptor-like 1 and F12, with potential genetic support for restoring renal function and subsequent treatment of CKD. Our findings explore the potential pathological mechanisms of CKD, bridge the gap between the molecular mechanisms of pathogenesis and clinical intervention, and provide new strategies in future clinical trials of CKD.

Baduanjin for ischemic heart failure with mildly reduced/preserved ejection fraction (BEAR Trial): A randomized controlled trial.

AIM: While Baduanjin, a traditional Chinese mind-body exercise, has shown potential health benefits, its efficacy in improving outcomes for heart failure patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has not been well documented. We aimed to investigate the adjunctive impact of Baduanjin on exercise capacity and quality of life for HFmrEF/HFpEF. METHODS: Patients with HFmrEF/HFpEF were enrolled in this multicenter randomized clinical trial. All participants were randomized to conventional cardiac rehabilitation with or without an additional 12-week Baduanjin exercise. The primary endpoint was the distance covered in a 6-min walk test (6MWD), while key secondary outcomes included quality of life measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and cardiopulmonary function including anaerobic threshold (VO2 AT). RESULTS: A total of 120 patients were enrolled, and 109 completed all session and tests. The mean age of the 120 patients was 60.5 years (SD, 9.21 years), and 23 (19.2%) were women. The Baduanjin group exhibited a 6.14% improvement in 6MWD compared to a 1.32% improvement in the control group (median improvement, 25.0 vs. 5.0 m; p < 0.001) at 12th week. The VO2 AT increased by 25.87% in the Baduanjin group versus 3.94% in the control group (p < 0.001). Quality of life also significantly improved in the Baduanjin group as indicated by MLHFQ score changes (-16.8% vs. -3.99%; p < 0.001). CONCLUSIONS: Adding Baduanjin to exercise-based cardiac rehabilitation for patients with ischemic HFmrEF or HFpEF are generally safe and could provide significant improvements in exercise capacity and quality of life.

[Analysis of enzyme activity and substrate specificity of dolichyl-phosphate ß-glucosyltransferase].

Protein folding and quality control processes primarily occur in the endoplasmic reticulum (ER). ER-resident molecular chaperones play a crucial role in guiding nascent polypeptides towards their correct tertiary structures. Some of these chaperones specifically recognize glucosylated N-glycan moieties on peptide. It is of great significance to study the N-glycan biosynthetic pathway and glycoprotein quality control system by analyzing the sugar donor of ER luminal glucosyltransferases, known as dolichol phosphate glucose (Dol-P-Glc), or its analogues in vitro. In this study, we investigated a range of dolichol analogues to synthesize lipid phosphate glucose, which served as substrates for dolichyl-phosphate ß-glucosyltransferase E (Alg5E) derived from Trichomonas vaginalis. The results demonstrated that the recombinant Alg5E, expressed in Escherichia coli, exhibited strong catalytic activity and the ability to recognize lipid phosphate glucose with varying chain lengths. Interestingly, the enzyme's catalytic reaction was found to be faster with longer carbon chains in the substrate. Additionally, Alg5E showed a preference for branched chain methyl groups in the lipid structure. Furthermore, our study confirmed the importance of divalent metal ions in the binding of the crucial DXD motif, which is essential for the enzyme's catalytic function. These findings lay the groundwork for future research on glucosyltransferases Alg6, Alg8, and Alg10 in the synthesis pathway of dolichol-linked oligosaccharide (DLO).

Network pharmacology and experimental verification to decode the action of Qing Fei Hua Xian Decotion against pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. METHODS: The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. RESULTS: A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1ß, STAT3, MMP-9, and TGF-ß1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-ß1/Smad2/3. CONCLUSIONS: QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-ß1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.

Mutant TP53 promotes invasion of lung cancer cells by regulating desmoglein 3.

PURPOSE: Targeted therapies have markedly improved the prognosis of lung cancer patients; nevertheless, challenges persist, including limited beneficiary populations and the emergence of drug resistance. This study investigates the molecular mechanisms of mutant TP53 in lung cancer, aiming to contribute to novel strategies for targeted therapy. METHODS: The TCGA database was employed to delineate the mutational landscape of TP53 in lung cancer patients. Differential gene expression between TP53-mutant and wild-type patients was analyzed, followed by functional enrichment. DSG3 protein expression in lung cancer patients was assessed using IHC, and its impact on prognosis was analyzed in the TCGA database. The influence of TP53 on the downstream gene DSG3 was investigated using qPCR, ChIP-qPCR, and luciferase reporter gene assays. Protein enrichment in the DSG3 promoter region was examined through IP-MS, and the regulatory role of the HIF1-α/TP53 complex on DSG3 was explored using Co-IP, luciferase assays, and ChIP-qPCR. Molecular interactions between TP53 (R273H) and HIF1-α were detected through immunoprecipitation and molecular docking. The effects and mechanisms of DSG3 on lung cancer phenotypes were assessed through WB, transwell, and wound healing assays. RESULTS: TP53 mutations were present in 47.44% of patients, predominantly as missense mutations. DSG3 exhibited high expression in TP53-mutant lung cancer patients, and this elevated expression correlated with a poorer prognosis. TP53 interference led to a reduction in DSG3 mRNA expression, with TP53 mutant P53 enriching at the P2 site of the DSG3 promoter region, a recruitment facilitated by HIF1-α. The DBD region of TP53 (R273H) demonstrated interaction with HIF1-α. DSG3, activated through Ezrin phosphorylation, played a role in promoting invasion and metastasis. CONCLUSIONS: Mutant TP53 facilitates lung cancer cell invasion by modulating desmoglein 3.

The Role of Diet in the Cardiovascular Health of Childhood Cancer Survivors-A Systematic Review.

BACKGROUND: Childhood cancer survivors (CCSs) face an increased risk of cardiovascular disease (CVD). This systematic review aims to provide the first synthesis of observational and interventional studies on the relationship between diet and cardiovascular health in CCSs. METHODS: A comprehensive search was conducted for studies published between 1990 and July 2023 in PubMed, MEDLINE, CINAHL, Child Development & Adolescent Studies, and Cochrane Library. Eligible studies included observational and interventional studies examining the associations or effects of dietary factors on CVD incidence, cardiac dysfunction, or CVD risk factors in CCSs diagnosed before age 25 years. RESULTS: Ten studies met the inclusion criteria (nine observational and one interventional). Collectively, they comprised 3485 CCSs (male, 1734; female, 1751). The outcomes examined across observational studies included characteristics of obesity, diabetes biomarkers, hypertension indicators, dyslipidaemia biomarkers, and metabolic syndrome. The evidence suggested that greater adherence to healthy diets was associated with lower body mass index, blood pressure, glucose, and triglycerides and higher high-density lipoprotein cholesterol. The 12-week lifestyle intervention study in childhood leukaemia survivors found no impact on obesity indicators. CONCLUSION: The review results indicate the potentially protective effects of healthy diets. However, the available research remains preliminary and limited, underscoring the need for more rigorous, adequately powered studies.

Degree of disorder-regulated ion transport through amorphous monolayer carbon.

Nanopore technology, re-fueled by two-dimensional (2D) materials such as graphene and MoS2, controls mass transport by allowing certain species while denying others at the nanoscale and has a wide application range in DNA sequencing, nano-power generation, and others. With their low transmembrane transport resistance and high permeability stemming from their ultrathin nature, crystalline 2D materials do not possess nanoscale holes naturally, thus requiring additional fabrication to create nanopores. Herein, we demonstrate that nanopores exist in amorphous monolayer carbon (AMC) grown at low temperatures. The size and density of nanopores can be tuned by the growth temperature, which was experimentally verified by atomic images and further corroborated by kinetic Monte Carlo simulation. Furthermore, AMC films with varied degrees of disorder (DOD) exhibit tunable transmembrane ionic conductance over two orders of magnitude when serving as nanopore membranes. This work demonstrates the DOD-tuned property in amorphous monolayer carbon and provides a new candidate for modern membrane science and technology.

Molecular mechanisms of ferroptosis and its effects on bladder cancer. / é“æ­»äº¡çš„åˆ†å­æœºåˆ¶åŠå ¶å¯¹è†€èƒ±ç™Œçš„å½±å“.

Bladder cancer (BC) is one of the 3 common malignant tumors in the urinary system, with high incidence, easy metastasis, poor therapeutic efficacy, and poor prognosis, which seriously threatens the health of human. Tumor cells exhibit a strong demand for iron, and iron overload can induce ferroptosis, which is an iron dependent cell death caused by lipid peroxidation and cell membrane damage. Therefore, ferroptosis has strong anti-tumor potential. The molecular mechanisms of ferroptosis is associated with abnormalities in cellular phospholipid metabolism and iron metabolism, and dysregulation of antioxidant and non-antioxidant systems Xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4). Ferroptosis relevant molecules play important roles in the occurrence and development, metastasis, drug resistance, and immune response of BC, and are expected to become targets for the treatment of BC.

Metabolomic analysis, extraction, purification and stability of the anthocyanins from colored potatoes.

Colored potatoes have many health benefits because they are rich in anthocyanins. However, the constituent and property of anthocyanins in colored potatoes have not been systematically studied yet. Herein, metabolomic analysis was carried out to investigate the chemical composition of anthocyanins in the four different colored potatoes. After that, the extract and purification conditions, and the stability of the anthocyanins were further studied. The results indicated that the four colored potatoes contained abundant of polyphenols, flavonoids, and anthocyanins. Cyanidin, delphinidin, and malvidin were identified as the major anthocyanidins in purple potatoes, whereas red potatoes were mainly consisted of pelargonidin and its derivatives. 84.47 mg C3GE/100 g DW of anthocyanins was obtained at the optimal conditions, which could be effectively purified macroporous resin of D101. Moreover, the anthocyanins were sensitive to pH, temperature, light, redox agents, and divalent or trivalent metal ions, but stable to sugars and univalent metal ions.

Adaptive Metabolic Responses Facilitate Blood-Brain Barrier Repair in Ischemic Stroke via BHB-Mediated Epigenetic Modification of ZO-1 Expression.

Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta-hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood-brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO-ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO-1 by enhancing local ß-hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO-ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation.

Rewritable printing of ionic liquid nanofilm utilizing focused ion beam induced film wetting.

Manipulating liquid flow over open solid substrate at nanoscale is important for printing, sensing, and energy devices. The predominant methods of liquid maneuvering usually involve complicated surface fabrications, while recent attempts employing external stimuli face difficulties in attaining nanoscale flow control. Here we report a largely unexplored ion beam induced film wetting (IBFW) technology for open surface nanofluidics. Local electrostatic forces, which are generated by the unique charging effect of Helium focused ion beam (HFIB), induce precursor film of ionic liquid and the disjoining pressure propels and stabilizes the nanofilm with desired patterns. The IBFW technique eliminates the complicated surface fabrication procedures to achieve nanoscale flow in a controllable and rewritable manner. By combining with electrochemical deposition, various solid materials with desired patterns can be produced.

Integration of Whole-Genome Resequencing and Transcriptome Sequencing Reveals Candidate Genes in High Glossiness of Eggshell.

Eggshell gloss is an important characteristic for the manifestation of eggshell appearance. However, no study has yet identified potential candidate genes for eggshell gloss between high-gloss (HG) and low-gloss (LG) chickens. The aim of this study was to perform a preliminary investigation into the formation mechanism of eggshell gloss and to identify potential genes. The eggshell gloss of 300-day-old Rhode Island Red hens was measured from three aspects. Uterine tissues of the selected HG and LG (n = 5) hens were collected for RNA-seq. Blood samples were also collected for whole-genome resequencing (WGRS). RNA-seq analysis showed that 150 differentially expressed genes (DEGs) were identified in the uterine tissues of HG and LG hens. These DEGs were mainly enriched in the calcium signaling pathway and the neuroactive ligand-receptor interaction pathway. Importantly, these two pathways were also significantly enriched in the WGRS analysis results. Further joint analysis of WGRS and RNA-seq data revealed that 5-hydroxytryptamine receptor 1F (HTR1F), zinc finger protein 536 (ZNF536), NEDD8 ubiquitin-like modifier (NEDD8), nerve growth factor (NGF) and calmodulin 1 (CALM1) are potential candidate genes for eggshell gloss. In summary, our research provides a reference for the study of eggshell gloss and lays a foundation for improving egg glossiness in layer breeding.

Seaweeds as a major source of dietary microplastics exposure in East Asia.

Microplastics (MPs) occurrence in marine ecosystems is well known, but their accumulation in seaweeds and subsequent human exposure remain understudied. This research quantifies MPs presence in two commonly consumed seaweeds, kelp (Saccharina japonica) and nori (Pyropia yezoensis), in East Asia, revealing widespread contamination dominated by microfibers (<500 µm). Based on dietary patterns, human uptake through seaweed consumption was estimated and quantified. Notably, Chinese people consume an estimated 17,034 MPs/person/year through seaweed consumption, representing 13.1% of their total annual MPs intake. This seaweeds-derived exposure surpasses all other dietary sources, contributing up to 45.5% of overall MPs intake. The highest intake was in South Korea, followed by North Korea, China, and Japan. This research identifies seaweeds as a major, previously overlooked route of dietary MPs exposure. These findings are crucial for comprehensive risk assessments of seaweed consumption and the development of mitigation strategies, particularly for populations in East Asian countries.

Life expectancy and emission trading scheme: a case study in China.

Life expectancy can reflect both health benefit and implementation cost of climate policy. Nevertheless, little research has quantified the relation between life expectancy and climate policy in literature. In this paper, we attempt to narrow the research gap by studying how life expectancy is related to the Chinese nationwide emission trading scheme (CNETS). To achieve this research target, a Computable General Equilibrium (CGE) model is employed to simulate the operation of the economic system and the policy shock from emission abatement. The CGE model results show that life expectancy is prolonged by GDP but shortened by emissions, and the GDP impact on life expectancy is larger than the emission impact. Climate policy has dual effects on life expectancy because it relieves both negative emission impacts and positive GDP impacts on lifespan; its net effect on life expectancy is positive. Life expectancy positively impacts GDP, and this impact is moderated by climate policy; specifically, climate policy reinforces the positive impact of life expectancy on GDP. Life expectancy minimally affects carbon emissions during climate policy implementation; in other words, it has minimal impacts on emission abatement. These findings imply that climate policy and life expectancy complement each other; the government could implement climate policy to increase lifespan or prolong life expectancy to facilitate policy implementation.

Interpretable machine learning model to predict surgical difficulty in laparoscopic resection for rectal cancer.

Background: Laparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models' performance. Methods: We retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model. Results: A total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors. Conclusions: This study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

Preparation of starch-palmitic acid complexes by three different starches: A comparative study using the method of heating treatment and autoclaving treatment.

Recent research emphasizes the growing importance of starch-lipid complexes due to their anti-digestibility ability, prompting a need to explore the impact of different starch sources and preparation methods on their properties. In this study, starch-palmitic acid (PA) complexes were prepared by three different starches including Tartary buckwheat starch (TBS), potato starch (PTS), and pea starch (PS) by heating treatment (HT) and autoclaving treatment (AT), respectively, and their physicochemical property and in vitro digestibility were systematically compared. The formation of the starch-PA complex was confirmed through various characterization techniques, including scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction. Among the complexes, the PTS-PA complex exhibited the highest complexation index over 80 %, while the PS-PA complex had the lowest rapid digestible starch content (56.49-59.42 %). Additionally, the complexes prepared by AT exhibited higher resistant starch content (41.95-32.46 %) than those prepared by HT (31.42-32.49 %), while the complexes prepared by HT held better freeze-thaw stability and hydration ability than those prepared by AT. This study highlights the important role of starch sources in the physicochemical and digestibility properties of starch-lipid complex and the potential application of AT in the preparation of novel resistant starch.

Adequately increasing the wheat B-starch ratio can improve the structure-properties of dough during freeze-thaw cycles: Mechanisms and conformational relations.

To reveal the influence of wheat starch particle size distribution on frozen dough quality, this study reconstituted A/B starch according to 100:0, 75:25, 50:50, 25:75 and 0:100 and prepared reconstituted dough by compounding with gluten proteins. Further, the freeze-thaw cycle of 1, 3, and 9 times for reconstituted dough was performed to investigate its ratio-regulatory role of A- and B-starch. The results showed that the freeze-thaw cycle induced gluten network breakage and starch granule exposure in doughs mainly by disrupting disulfide and hydrogen bonds between gluten protein molecules and upsetting their secondary structures, leading to a reduction in GMP and polymer protein content and an increase in freezing water content. Moreover, a moderate increase (25-50 %) in the B-starch proportion can minimize gluten protein deterioration by freeze-thaw cycles. However, excessive B-starch amounts (75-100 %) can also adversely affect gluten structure. The prepared dumpling wrappers under the 50A-50B ratio showed optimal steaming loss rate, hardness, and chewiness during the freeze-thaw cycle. Correlation analysis indicated that the B-starch ratio and its filling pattern improved dough freeze-thaw deterioration primarily by affecting dough-free sulfhydryl content, protein molecular weight distribution, secondary structure, and ΔH. The results may provide insights and guidelines for product development and storage for frozen pasta.

Reforestation regulated soil bacterial community structure along vertical profiles in the Loess Plateau.

Introduction: Reforestation is a widely used strategy for ecological restoration in areas facing ecological degradation. Soil bacteria regulate many functional processes in terrestrial ecosystems; however, how they respond to reforestation processes in surface and deep soils remains unclear. Methods: Artificial Robinia pseudoacacia plantation with different stand ages (8, 22, and 32 years) in a typical fallow forest on the Loess Plateau was selected to explore the differential response of soil bacterial community to reforestation in different soil depths (surface 0-200 cm, middle 200-500 cm, and deep 500-100 cm). Soil bacterial diversity, community composition and the co-occurrence patterns, as well as the functions were analyzed. Results and discussion: The results showed that alpha diversity and the presence of biomarkers (keynote species) decreased with the increasing soil depth, with a sharp reduction in family-level biomarker numbers in 500-1,000 cm depth, while reforestation had a positive impact on bacterial alpha diversity and biomarkers. Reforestation induced a more loosely connected bacterial community, as evidenced by an increase of 9.38, 22.87, and 37.26% in the average path length of the co-occurrence network in all three soil layers, compared to farmland. In addition, reforestation reduced the hierarchy and complexity but increased the modularity of the co-occurrence network in top and deep soil layers. Reforestation also led to enrichment in the relative abundance of functional pathways in all soil layers. This study sheds light on the strategies employed by deep soil bacteria in response to reforestation and underscores the significant potential of deep soil bacteria in terrestrial ecosystems, particularly in the context of human-induced environmental changes.

Noncoding RNAs regulating ferroptosis in cardiovascular diseases: novel roles and therapeutic strategies.

The morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health and economic burdens worldwide, and effective interventions are needed for immediate resolution of this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence and development of CVDs and are potential therapeutic targets and novel biomarkers for these diseases. Newly discovered modes of cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent cell death and ferroptosis, also play key roles in CVD progression. However, ferroptosis, which differs from the other aforementioned forms of regulated cell death in terms of cell morphology, biochemistry and inhereditability, is a unique iron-dependent mode of nonapoptotic cell death induced by abnormal iron metabolism and excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Increasing evidence has confirmed that ncRNA-mediated ferroptosis is involved in regulating tissue homeostasis and CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy and heart failure (HF). In this review, we summarize the underlying mechanism of ferroptosis, discuss the pathophysiological effects of ncRNA-mediated ferroptosis in CVDs and provide ideas for effective therapeutic strategies.

Holistic bursting cells store long-term memory in auditory cortex.

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.