Spexin inhibits excessive autophagy-induced ferroptosis to alleviate doxorubicin-induced cardiotoxicity by upregulating Beclin 1.

BACKGROUND AND PURPOSE: Doxorubicin is widely used in the treatment of malignant tumours, but doxorubicin-induced cardiotoxicity severely limits its clinical application. Spexin is a neuropeptide that acts as a novel biomarker in cardiovascular disease. However, the effects of spexin on doxorubicin-induced cardiotoxicity is unclear. EXPERIMENTAL APPROACH: We established a model of doxorubicin-induced cardiotoxicity both in vivo and in vitro. Levels of cardiac damage in mice was assessed through cardiac function assessment, determination of serum cardiac troponin T and CKMB levels and histological examination. CCK8 and PI staining were used to assess the doxorubicin-induced toxicity in cultures of cardiomyocytes in vitro. Ferroptosis was assessed using FerroOrange staining, determination of MDA and 4-HNE content and ferroptosis-associated proteins SLC7A11 and GPX4. Mitochondrial membrane potential and lipid peroxidation levels were measured using TMRE and C11-BODIPY 581/591 probes, respectively. Myocardial autophagy was assessed by expression of P62 and Beclin1. KEY RESULTS: Spexin treatment improved heart function of mice with doxorubicin-induced cardiotoxicity, and attenuated doxorubicin-induced cardiotoxicity by decreasing iron accumulation, abnormal lipid metabolism and inhibiting ferroptosis. Interestingly, doxorubicin caused excessive autophagy in cardiomyocyte in culture, which could be alleviated by treatment with spexin. Knockdown of Beclin 1 eliminated the protective effects of spexin in mice with DIC. CONCLUSION AND IMPLICATIONS: Spexin ameliorated doxorubicin-induced cardiotoxicity by inhibiting excessive autophagy-induced ferroptosis, suggesting that spexin could be a drug candidate against doxorubicin-induced cardiotoxicity. Beclin 1 might be critical in mediating the protective effect of spexin against doxorubicin-induced cardiotoxicity.

Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose/Lipid Metabolism and the Gut Microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.

Superhydrophobic Tensile Designability of Silicone Rubber Composites.

Silicone rubber has broad applications in the field of industrial engineering due to its stable physical and chemical properties. However, the superhydrophobic properties, of silicone rubber, especially large deformation superhydrophobic properties, were not satisfactory for many harsh application environments and complex engineering structures. Here, we report the preparation of superhydrophobic tensile designable silicone rubber composites by a mixed deposition process that included powder deposition and smoke deposition. The infrared test showed that the deposited powder from silicone rubber combustion was mainly composed of SiO2 and short chain siloxane. The mixed deposited surface with a rich micro-nanostructure, which was the key to the formation of superhydrophobic properties. The water contact angle (WCA) and sliding angle (SA) of coating surface could reach 157.6° and 5° ± 1°, respectively, and the tensile designability of superhydrophobic surface is closely related to the prestretched process. In addition, bounce tests, high temperature tests, and solvent resistance tests showed the application potential of modified silicone rubber composites in the field of engineering.

Adaptive enzyme-responsive self-assembling multivalent apelin ligands for targeted myocardial infarction therapy.

Microvascular dysfunction following myocardial infarction exacerbates coronary flow obstruction and impairs the preservation of ventricular function. The apelinergic system, known for its pleiotropic effects on improving vascular function and repairing ischemic myocardium, has emerged as a promising therapeutic target for myocardial infarction. Despite its potential, the natural apelin peptide has an extremely short circulating half-life. Current apelin analogs have limited receptor binding efficacy and poor targeting, which restricts their clinical applications. In this study, we utilized an enzyme-responsive peptide self-assembly technique to develop an enzyme-responsive small molecule peptide that adapts to the expression levels of matrix metalloproteinases in myocardial infarction lesions. This peptide is engineered to respond to the high concentration of matrix metalloproteinases in the lesion area, allowing for precise and abundant presentation of the apelin motif. The changes in hydrophobicity allow the apelin motif to self-assemble into a supramolecular multivalent peptide ligand-SAMP. This self-assembly behavior not only prolongs the residence time of apelin in the myocardial infarction lesion but also enhances the receptor-ligand interaction through increased receptor binding affinity due to multivalency. Studies have demonstrated that SAMP significantly promotes angiogenesis after ischemia, reduces cardiomyocyte apoptosis, and improves cardiac function. This novel therapeutic strategy offers a new approach to restoring coronary microvascular function and improving damaged myocardium after myocardial infarction.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Evaluation of nintedanib efficacy: Attenuating the lens fibrosis in vitro and vivo.

PURPOSE: Organ fibrosis is a huge challenge in clinic. There are no drugs for fibrotic cataracts treatments in clinic. Nintedanib is approved by the FDA for pulmonary fibrosis treatments. This study aims to investigate the efficacy and mechanism of nintedanib on fibrotic cataracts. METHODS: Drug efficacy was validated through TGFß2-induced cell models and injury-induced anterior subcapsular cataract (ASC) mice. A slit lamp and the eosin staining technique were applied to access the degree of capsular fibrosis. The CCK-8 assay was used to evaluate the toxicity and anti-proliferation ability of the drug. The cell migration was determined by wound healing assay and transwell assay. The anti-epithelial mesenchymal transition (EMT) and anti-fibrosis efficacy were evaluated by qRT-PCR, immunoblot, and immunofluorescence. The inhibition of nintedanib to signaling pathways was certified by immunoblot. RESULTS: Nintedanib inhibited the migration and proliferation of TGFß2-induced cell models. Nintedanib can also repress the EMT and fibrosis of the lens epithelial cells. The intracameral injection of nintedanib can also allay the anterior subcapsular opacification in ASC mice. The TGFß2/ Smad and non-Smad signaling pathways can be blocked by nintedanib in vitro and in vivo. CONCLUSION: Nintedanib alleviates fibrotic cataracts by suppressing the TGFß2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.

Proportion and risk factors of zonulopathy in patients with age-related cataract.

Purpose: To investigate the proportion of zonulopathy in patients with age-related cataract, and further explore demographics and ocular characteristics, as well as potential risk factors. Methods: Hospital-based, observational, cross-sectional study. We enrolled consecutive patients who were 45 years or older and diagnosed with age-related cataract and underwent surgery between October 2022 and April 2023 at the Division of Cataract, Beijing Tongren Hospital. Zonulopathy was diagnosed based on intraoperative signs. We calculated the total proportion, age, and gender specific proportions of zonulopathy. We compared the demographic and ocular characteristics between the cases with and without zonulopathy. Univariate and multivariate logistic regression analyses were employed to determine the risk factors associated with the presence of zonulopathy in patients with age-related cataract. Results: A total of 640 age-related cataract patients with a median age of 70.0 (64.0-77.0) were enrolled. Zonulopathy was diagnosed intraoperatively in 70 patients (10.9%). Compared with the patients having no zonulopathy, those with zonulopathy were likely to be older (P < 0.001), have a shallower central ACD (P < 0.001), a thicker lens (P < 0.001) and a shorter AL (P = 0.010). Logistic regression analyses showed that the risk predictors associated with the presence of zonulopathy in patients with age-related cataract were older age (OR, 1.042; P = 0.035) and shallower central ACD (OR, 0.834; P < 0.001). Conclusion: Zonulopathy in age-related cataract patients is not an uncommon finding. Clinicians should be mindful of zonulopathy in patient population with advanced age and shallower ACD.

The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis.

Myocardial ischemia-reperfusion (I/R) injury stands out among cardiovascular diseases, and current treatments are considered unsatisfactory. For cardiomyocytes (CMs) in ischemic tissues, the upregulation of Limb-bud and Heart (LBH) and αB-crystallin (CRYAB) and their subsequent downregulation in the context of cardiac fibrosis have been verified in our previous research. Here, we focused on the effects and mechanisms of activated LBH-CRYAB signaling on damaged CMs during I/R injury, and confirmed the occurrence of mitochondrial apoptosis and ferroptosis during I/R injury. The application of inhibitors, ectopic expression vectors, and knockout mouse models uniformly verified the role of LBH in alleviating both apoptosis and ferroptosis of CMs. p53 was identified as a mutual downstream effector for both LBH-CRYAB-modulated apoptosis and ferroptosis inhibition. In mouse models, LBH overexpression was confirmed to exert enhanced cardiac protection against I/R-induced apoptosis and ferroptosis, suggesting that LBH could serve as a promising target for the development of I/R therapy.

MicroRNA-7 attenuates secondary brain injury following experimental intracerebral hemorrhage via inhibition of NLRP3.

BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying brain injury resulting from intracerebral hemorrhage (ICH) remain incompletely elucidated, and efficacious therapeutic interventions to enhance the prognosis of ICH patients are currently lacking. Previous research indicates that MicroRNA-7 (miR-7) can suppress the expression of Nod-like receptor protein 3 (NLRP3), thereby modulating neuroinflammation in Parkinson's disease pathogenesis. However, the potential regulatory effects miR-7 on NLRP3 inflammasome after ICH are yet to be established. This study aims to ascertain whether miR-7 mitigates secondary brain injury following experimental ICH by inhibiting NLRP3 and to investigate the underlying mechanisms. METHODS: An ICH model was established by stereotaxically injecting 100 µL of autologous blood into the right basal ganglia of Sprague-Dawley (SD) rats. Subsequently, these rats were allocated into three groups: sham, ICH + Vehicle, and ICH + miR-7, each comprising 18 animals. Twelve hours post-modeling, rats received intraventricular injections of 10 µL physiological saline, 10 µL phosphate, and 10 µL phosphate-buffered saline solution containing 0.5 nmol of miR-7 mimics, respectively. Neurological function was assessed on day three post-modeling, followed by euthanasia for brain tissue collection. Brain water content was determined using the dry-wet weight method. The expression of inflammatory cytokines in cerebral tissues surrounding the hematoma was analyzed through immunohistochemistry and Western blot assays. These cytokines were re-evaluated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Moreover, bioinformatics tools were employed to predict miR-7's binding to NLRP3. A wild-type luciferase reporter gene vector and a corresponding mutant vector were constructed, followed by transfection of miR-7 mimics into HEK293T cells to assess luciferase activity. RESULTS: Our study demonstrates that the administration of miR-7 mimics markedly reduced neurological function scores and attenuated brain edema in rats following ICH. A significant upregulation of NLRP3 expression in microglia/macrophage adjacent to the hematoma was observed, substantially reduced after the treatment with miR-7 mimics. Furthermore, this intervention ameliorated neurodegenerative changes and effectively decreased the protein and mRNA levels of pro-inflammatory cytokines, namely TNF-α, IL-1ß, IL-6, and Caspase1, in the cerebral tissues proximate to the hematomas. In addition, miR-7 mimics distinctly inhibited the luciferase activity associated with the wild-type reporter gene, an effect not mirrored in its mutant variant. CONCLUSIONS: The miR-7 suppressed NLRP3 expression in microglia/macrophage to reduce the production of inflammatory cytokines, leading to conducting certain neuroprotection post-ICH in rats.

Noxa inhibits oncogenesis through ZNF519 in gastric cancer and is suppressed by hsa-miR-200b-3p.

While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan-Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3'-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.

Microwave synthesis of amino-functionalized MCM-41 from coal gasification fine slag for efficient bidirectional adsorption of anionic and cationic dyes.

Coal based solid waste has been recognized as a sustainable raw material for the preparation of high added value materials for wastewater treatment. In this paper, a preparation route was designed for the rapid, efficient, and low-cost preparation of MCM-41 zeolite using coal gasification fine slag as raw material. Functionalization modification of MCM-41 was carried out by grafting amino groups on its surface to improve its application performance. Moreover, the prepared functionalized material is used for bidirectional adsorption of anionic and cationic dyes. The experimental results indicate that MCM-41 zeolite with highly ordered pore structure was rapidly prepared using the advantages of fast heating and strong permeability of microwave synthesis method, with a specific surface area of up to 862.03 m2/g. Amine functionalized MCM-41 exhibits strong adsorption capacity for both cationic and anionic dyes, with maximum adsorption capacities for methylene blue and Congo red being 292.40 mg/g and 354.61 mg/g, respectively. The study of adsorption kinetics and adsorption mechanism indicate that the adsorption process is mainly controlled through chemical adsorption, including electrostatic attraction, hydrogen bonding, and π-π interactions. The results of this study will provide useful references for the use of coal based solid waste to prepare functional materials for the treatment of organic wastewater.

Inhibition of miR-29a-3p Alleviates Apoptosis of Lens Epithelial Cells via Upregulation of CAND1.

PURPOSE: Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved. METHODS: In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis. RESULT: Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p. CONCLUSION: These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts.

The burden of vision loss due to cataract in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To provide a reference for future policy and measure formulation by conducting a detailed analysis of the burden of vision loss due to cataract by year, age, and gender in China from 1990 to 2019. METHODS: Data on the prevalence and disability-adjusted life-years (DALYs) due to cataract in China and neighboring and other G20 countries were extracted from the 2019 Global Burden of Disease (GBD) study to observe the changing trends of vision loss. RESULTS: The number and rate of all-age prevalence and DALYs for cataract in China increased significantly from 1990 to 2019. The age-standardized DALYs rate witnessed a slowly declining trend by 10.16%. And the age-standardized prevalence increased by 14.35% over the 30-year period. Higher prevalence and DALYs were observed in female population from 1990 through 2019, with little improvement over the decades(all p < 0.001). The disease burden of cataract is higher in middle-aged and elderly people. Blindness accounted for the largest proportion of vision impairment burden caused by cataract in China. The age-standardized prevalence and DALY rate of cataract in China were lower than those in India and Pakistan, but higher than those in Russia, South Korea, North Korea, Singapore, and Japan. CONCLUSIONS: In the past 30 years, although the age-standardized DALYs rate has decreased slightly in China, the all-age prevalence and DALYs have both increased. This study highlights the importance of reducing cataract burden by providing timely and easily accessible quality care, especially in females and the elderly population.

Biomineralization-Inspired Copper Sulfide Decorated Aramid Textiles via In Situ Anchoring toward Versatile Wearable Thermal Management.

Designing smart textiles for personal thermal management (PTM) is an effective strategy for thermoregulation and energy saving. However, the manufacture of versatile high-performance thermal management textiles for complex real-world environments remains a challenge due to the limitations of functional integration, material properties, and preparation procedures. In this study, an aramid fabric based on in situ anchored copper sulfide nanostructure is developed. The textile with excellent solar and Joule heating properties can effectively keep the body warm even at low energy inputs. Meanwhile, the reduced infrared emissivity of the textile decreases the thermal radiation losses and helps to maintain a constant body temperature. Impressively, the textile integrates superb electromagnetic shielding, near-complete UV protection properties, and ideal resistance to fire and bacteria. This work provides a simple strategy for fabricating multi-functional integrated wearable devices with flexibility and breathability, which is highly promising in versatile PTM applications.

Correlation between Flow Temperature and Average Molar Ionic Potential of Ash during Gasification of Coal and Phosphorus-Rich Biomass.

The co-gasification of biomass and coal is helpful for achieving the clean and efficient utilization of phosphorus-rich biomass. A large number of alkali and alkaline earth metals (AAEMs) present in the ash system of coal (or biomass) cause varying degrees of ash, slagging, and corrosion problems in the entrained flow gasifier. Meanwhile, phosphorus is present in the slag in the form of PO43-, which has a strong affinity for AAEMs (especially for Ca2+) to produce minerals dominated by calcium phosphates or alkaline Ca-phosphate, effectively mitigating the aforementioned problems. To investigate the changing behavior of the slag flow temperature (FT) under different CaO/P2O5 ratios, 72 synthetic ashes with varying CaO/P2O5 ratios at different Si/Al contents and compositions were prepared, and their ash fusion temperatures were tested. The effects of different CaO/P2O5 ratios on the FT were analyzed using FactSage thermodynamic simulation. A model for predicting slag FT at different CaO/P2O5 ratios was constructed on the basis of the average molar ionic potential (Ia) method and used to predict data reported from 19 mixed ashes in the literature. The results showed that Ia and FT gradually increased with a decreasing CaO/P2O5 ratio, and the main mineral types shifted from anorthite → mullite → berlinite, which reasonably explained the decrease in ash fusion temperatures in the mixed ash. The established model showed good adaptability to the prediction of 19 actual coal ash FTs in the literature; the deviation of the prediction was in the range of 40 °C. The model proposed between FT and Ia based on the different CaO/P2O5 ratios can be used to predict the low-rank coal and phosphorus-rich biomass and their mixed ashes.

Transcriptome sequencing and microRNA-mRNA regulatory network construction in the lens from a Na2SeO3-induced Sprague Dawley rat cataract model.

BACKGROUND: A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression. METHODS: Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes' targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape. RESULT: In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis. CONCLUSION: We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.

Bile duct hamartoma in a dog.

An 11-year-old female Collie presented with a significantly increased abdominal circumference. Computed tomography of the abdomen revealed that the left lateral lobe of the liver contained a large mass, which was excised via laparotomy. Histologically, many small, dilated, cystic luminal structures were anastomosed and connected to a net-like structure. Immunohistochemistry revealed cytokeratin 19-immunopositive areas, representing bile duct structures in the cystic lumen. Based on these results, the tumour was diagnosed as a bile duct hamartoma. To our knowledge, this is the first report of a bile duct hamartoma in a dog.

Development and Psychometric Properties of Work Information Anxiety Questionnaire.

Purpose: The purpose of this study is to develop and validate the Work Information Anxiety Questionnaire (WIAQ), and to report on the psychometric properties of the WIAQ. Methods: Based on the Approach-Avoidance Conflict theory, and combining previous literature reviews and open-ended interviews, initial scale items for the Work Information Anxiety Questionnaire were developed. Using 324 full-time corporate employees as subjects (Sample 1), an exploratory structural examination of work information anxiety was conducted, including item analysis, exploratory factor analysis, and network analysis. An additional 210 corporate employees were selected for formal testing (Sample 2), and the obtained data underwent structural validation, including confirmatory factor analysis, validity testing, and reliability testing. Results: The WIAQ (9 items) exhibited a two-factor structure of reception anxiety and missing out anxiety, with a cumulative variance contribution rate of 67.56%. The confirmatory factor model showed good model fit, with cross-group and cross-measurement stability. The Cronbach's α of the WIAQ was 0.899, and the McDonald's ω of the two factors were 0.906 and 0.831 respectively. The WIAQ demonstrated good criterion-related validity with the SAS and DASS. Conclusion: The factor structure of the WIAQ is clear, and its reliability and validity indicators meet psychometric requirements. It can serve as an effective tool for measuring work information anxiety.

Genome-wide association study of ear tip barrenness in waxy maize.

Ear tip-barrenness (ETB), which results from aborted kernels or infertile florets at the ear tip, is an undesirable factor affecting the yield and quality of waxy maize. To uncover the genetic basis of ETB, a genome-wide association study (GWAS) was conducted using the genotype with 27,354 SNPs and phenotype with three environments. Five SNPs that distributed on chromosomes 1, 3 and 6, were identified to be significantly associated with ETB based on the threshold of false discovery rate (FDR) at 0.05. Among these significant loci, three SNPs were clustered together and colocalized with genomic regions previously reported. The average length of ETB decreased almost linearly from the inbred lines containing no favorable alleles across the three loci (1.75 cm) to those with one (1.18 cm), two (0.94 cm) and three (0.65 cm) favorable alleles. Moreover, three important genes, Zm00001d030028, Zm00001d041510 and Zm00001d038676 were predicted for three significant QTLs, respectively. These results promote the understanding genetic basis for ETB and will be useful for breeding waxy maize varieties with high-quality and high-yield.

Fucoxanthin alleviated myocardial ischemia and reperfusion injury through inhibition of ferroptosis via the NRF2 signaling pathway.

Background: Myocardial ischemia and reperfusion injury (MIRI) is a severe complication of revascularization therapy in patients with myocardial infarction. Therefore, there is an urgent requirement to find more therapeutic solutions for MIRI. Recently, ferroptosis, which is characterized by lipid peroxidation, was considered a critical contributor to MIRI. Fucoxanthin (FX), a natural antioxidant carotenoid, which is abundant in brown seaweed, exerts protective effects under various pathological conditions. However, whether FX alleviates MIRI is unclear. This study aims to clarify the effects of FX on MIRI. Methods: Mice with left anterior descending artery ligation and reperfusion were used as in vivo models. Neonatal rat cardiomyocytes (NRCs) induced with hypoxia and reperfusion were used as in vitro models. TTC-Evans blue staining was performed to validate the infarction size. Transmission electron microscopy was employed to detect mitochondrial injury in cardiomyocytes. In addition, 4 weeks after MIRI, echocardiography was performed to measure cardiac function; fluorescent probes and western blots were used to detect ferroptosis. Results: TTC-Evans blue staining showed that FX reduced the infarction size induced by MIRI. Transmission electron microscopy showed that FX ameliorated the MIRI-induced myofibril loss and mitochondrion shrinkage. Furthermore, FX improved LVEF and LVFS and inhibited myocardial hypertrophy and fibrosis after 4 weeks in mice with MIRI. In the in vitro study, calcein AM/PI staining and TUNEL staining showed that FX reduced cell death caused by hypoxia and reperfusion treatment. DCFH-DA and MitoSOX probes indicated that FX inhibited cellular and mitochondrial reactive oxygen species (ROS). Moreover, C11-BODIPY 581/591 staining, ferro-orange staining, MDA assay, Fe2+ assay, 4-hydroxynonenal enzyme-linked immunosorbent assay, and western blot were performed and the results revealed that FX ameliorated ferroptosis in vitro and in vivo, as indicated by inhibiting lipid ROS and Fe2+ release, as well as by modulating ferroptosis hallmark FTH, TFRC, and GPX4 expression. Additionally, the protective effects of FX were eliminated by the NRF2 inhibitor brusatol, as observed from western blotting, C11-BODIPY 581/591 staining, and calcein AM/PI staining, indicating that FX exerted cardio-protective effects on MIRI through the NRF2 pathway. Conclusion: Our study showed that FX alleviated MIRI through the inhibition of ferroptosis via the NRF2 signaling pathway.