M6A-mediated hsa_circ_0061179 inhibits DNA damage in ovarian cancer cells via miR-143-3p/TIMELESS.

Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice.

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.

Ursonic acid attenuates spermatogenesis in oligozoospermia mice through inhibiting ferroptosis.

Ursonic acid (UNA) is a natural pentacyclic triterpene found in some medicinal plants and foods. The reproductive protective effect of UNA was evaluated in a mouse model of oligozoospermia induced by busulfan (BUS) at 30 mg/kg b.w.. The mice were initially divided into groups with UNA concentrations of 10, 30, 50, 100 mg/kg. Subsequently, based on sperm parameters, the optimal concentration of 50 mg/kg was identified. As a control, an additional group was supplemented with ursolic acid at a concentration of 50 mg/kg. The results indicated that BUS caused the loss of spermatogenic cells in testis, the decrease of sperm in epididymis, the disorder of testicular cytoskeleton, the decrease of serum sex hormones such as testosterone which induced an increase in feedback of androgen receptor and other testosterone-related proteins, the increase of malondialdehyde and reactive oxygen species levels and the increase of ferroptosis in testis while UNA successfully reversed these injuries. High-throughput sequencing revealed that UNA administration significantly upregulated the expression of genes associated with spermatogenesis, such as Tnp1, Tnp2, Prm1, among others. These proteins are crucial in the histone to protamine transition during sperm chromatin remodeling. Network pharmacology analysis reveals a close association between UNA and proteins related to the transformation of histones to protamine. Molecular docking studies reveal that UNA can interact with the ferroptosis-inhibiting gene SLC7A11, thereby modulating ferroptosis. Taken together, UNA alleviated BUS-induced oligozoospermia by regulating hormone secretion, mitigating oxidative stress and promoting recovery of spermatogenesis by inhibiting the ferroptosis.

Comprehensive effects of traditional Chinese medicine treatment on heart failure and changes in B-type natriuretic peptide levels: A meta-analysis.

BACKGROUND: Heart failure (HF), a common cardiovascular condition, is characterized by significant morbidity and mortality. While traditional Chinese medicine (TCM) is often used as a complementary approach in HF management, systematic evaluations of its impact on clinical outcomes, TCM syndrome scores, and B-type natriuretic peptide (BNP) levels are lacking. This study fills this gap through a comprehensive analysis of randomized controlled trials (RCTs) focusing on TCM for HF treatment. It encompasses an assessment of methodological quality, a meta-analysis, and an evaluation of evidence quality based on established standards. The results offer crucial insights into the potential advantages and constraints of TCM in HF management. AIM: To systematically analyze the effects of TCM on the clinical comprehensive outcomes, TCM syndrome scores, and BNP levels in patients with HF and evaluated the quality of evidence for these trials. METHODS: RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Science and Technology Journal, and PubMed. Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool, and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software. Finally, the quality of evidence was rated according to the GRADE criteria. RESULTS: A total of 1098 RCTs were initially retrieved. After screening, 16 RCTs were finally included in our study, which were published between 2020 and 2023. These RCTs involved 1660 HF patients, including 832 in the TCM group [TCM combined with conventional Western medicine (CMW) treatment] and 828 in the CWM group (CWM treatment). The course of treatments varied from 1 wk to 3 months. TCM syndrome differentiation was analyzed in 11 of the included RCTs. In all included RCTs, outcome indicators included comprehensive clinical outcomes, TCM syndrome scores, and BNP levels. The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes [risk ratio = -0.54; 95% confidence interval (CI) = -0.61, -0.47; P < 0.00001], TCM syndrome scores [weighted mean difference (WMD) = -142.07; 95%CI = -147.56, -136.57; P < 0.00001], and BNP levels (WMD = -142.07; 95%CI = -147.56, -136.57; P < 0.00001). According to the GRADE criteria, RCTs where "TCM improves clinical comprehensive outcomes" were rated as low-quality evidence, and RCTs where "TCM reduces TCM syndrome scores" or "TCM decreases BNP levels" were rated as medium-quality evidence. CONCLUSION: TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients. Given the low and medium quality of the included RCTs, the application of these results should be cautious.

5- methylcytidine effectively improves spermatogenesis recovery in busulfan-induced oligoasthenospermia mice.

The function and regulatory mechanisms of 5-methylcytidine (m5C) in oligoasthenospermia remain unclear. In this study, we made a mouse model of oligoasthenospermia through the administration of busulfan (BUS). For the first time, we demonstrated that m5C levels decreased in oligoasthenospermia. The m5C levels were upregulated through the treatments of 5-methylcytidine. The testicular morphology and sperm concentrations were improved via upregulating m5C. The cytoskeletal regenerations of testis and sperm were accompanying with m5C treatments. m5C treatments improved T levels and reduced FSH and LH levels. The levels of ROS and MDA were significantly reduced through m5C treatments. RNA sequencing analysis showed m5C treatments increased the expression of genes involved in spermatid differentiation/development and cilium movement. Immunofluorescent staining demonstrated the regeneration of cilium and quantitative PCR (qPCR) confirmed the high expression of genes involved in spermatogenesis. Collectively, our findings suggest that the upregulation of m5C in oligoasthenospermia facilitates testicular morphology recovery and male infertility via multiple pathways, including cytoskeletal regeneration, hormonal levels, attenuating oxidative stress, spermatid differentiation/development and cilium movement. m5C may be a potential therapeutic agent for oligoasthenospermia.

Comparative study on chain conformations, physicochemical and rheological properties of three acidic polysaccharides from Opuntia dillenii Haw. fruits.

In this study, three acidic polysaccharides (OFPP-1, OFPP-2 and OFPP-3) were isolated from the pulps of Opuntia dillenii Haw. fruits, and their chain conformations, physicochemical and rheological properties were investigated. The molecular weight and conformational parameters (Mw, Mn, Mz, Rg and Rh) of OFPPs in 0.1 M NaNO3 solution were detected by HPSEC-MALLS-RI. In addition, based on the parameters ρ and v, it was concluded that these three polysaccharide chains exhibited sphere-like conformation in 0.1 M NaNO3 solution, which was consistent with AFM and TEM observations. Furthermore, the Congo Red experiment showed that OFPP-2 had a triple-helix structure, which may be conducive to its biological activity. This study also found that OFPPs were semi-crystalline structures with high thermal and pH stability. The rheological analyses indicated that the apparent viscosity of OFPPs solutions exhibited concentration-, temperature-, and pH-dependence, and the viscoelasticity of them was affected by molecular characteristics and concentration. The results of this study are helpful to elucidate the structure-activity relationship of OFPPs. Moreover, this study can provide theoretical reference for the application of OFPPs as bioactive ingredients or functional materials in the food, pharmaceutical and cosmetic industries and the development and utilization of the O. dillenii Haw. fruits resource.

Effect of pre-drying and post-frying holding treatments on the oil absorption and quality of fried batter-coated peanuts.

In this study, the effect of pre-drying and post-frying holding treatments on the oil absorption and the quality of the fried batter-coated peanuts were explored. The results showed that hot air drying and microwave drying induced the gelatinization of starch in the batter before frying. The thermodynamic properties of starch in the batter after frying indicated that pre-drying could protect the orderliness of the starch. CLSM images showed that the pre-drying treatment reduced the number of large oil spots on the surface of batter of fried batter-coated peanuts. SEM observation revealed that the structure of the batter treated with pre-drying was denser and the number of large pores was reduced after frying. The post-frying holding treatment improved the color and texture of the batter-coated peanuts. In conclusion, the pre-drying and post-frying holding treatment can reduce the oil content and improve the fracturability of the fried batter-coated peanuts.

Pretreatment with low-frequency magnetic fields can improve the functional properties of pea globulin amyloid-like fibrils.

Plant protein fibrils have recently attracted considerable attention due to their superior mechanical and interfacial properties. The objective of this study was to evaluate the feasibility of low-frequency magnetic field (LF-MF) pretreatment in enhancing the conversion and functional characteristics of the amyloid-like fibrils derived from pea globulin (PG), which was considered a sustainable hypoallergenic protein. The results showed that LF-MF-treated PG (MPG) assembled into longer amyloid-like fibrils compared with native PG (NPG). The MPG presented similar gelling, emulsifying, and foaming properties to the NPG, while the fibril samples exhibited significantly improved functional properties. Moreover, the amyloid-like fibrils generated from the MPG (MPGF) showed large aspect ratios accompanied by superior solubility, molecular flexibility, emulsion stability, and gelling properties. The improved functional properties of the amyloid-like fibrils generated from the MPG can provide a promising outlook for expanding the applications of the PG in food, medicine and other fields.

The addition of resistant starch and protein to the batter reduces oil uptake and improves the quality of the fried batter-coated nuts.

The batter compositions can affect the oil uptake and texture of fried batter-coated nuts. In this study, the oil uptake and quality of fried batter-coated peanuts and sunflower seeds added with resistant starch and protein were investigated. The results demonstrated that the addition of resistant starch increased the batter hardness and fracturability of the fried batter-coated peanuts by 34.36 % and 33.73 %, respectively. The oil content of fried batter-coated peanuts and sunflower seeds were decreased by 17.98 % and 15.69 %, respectively, with the addition of protein. The microstructure and roughness of the batter revealed that the batter added with protein became denser and uniform. Furthermore, the protein in the batter added with 6 % soy protein isolate had a high surface hydrophobicity. In summary, the addition of resistant starch and protein in batter will be a promising strategy for reducing the oil content and improving the quality of fried batter-coated nuts.

Physicochemical properties and solution conformation of polysaccharides from Toona sinensis (A. Juss) Roem leaves.

In this study, two polysaccharide fractions (TSP-1 and TSP-2) were isolated from Toona sinensis leaves. The physicochemical properties and solution conformations of TSP-1 and TSP-2 were investigated. DSC and TG results showed that TSP-1 and TSP-2 had thermal stability. The intrinsic viscosities of TSP-1 and TSP-2 solutions were 11.42 and 6.13 mL/g, respectively. Rheological results showed that the viscosities of TSP-1 and TSP-2 solutions were affected by polysaccharide concentration, Ca2+ and extreme pH. Furthermore, TSP-1 exhibited a weak gel behavior at the concentrations of 0.5 %-2.0 %, while TSP-2 showed a weak gel behavior at the concentration of 2 %. HPSEC-MALLS analysis revealed that the Rg values of TSP-1 and TSP-2 were 96.8 nm and 56.2 nm, respectively. Conformation analysis indicated that TSP-1 behaved as a sphere, while TSP-2 behaved like a rigid rod. These results suggest that TSP-1 and TSP-2 can be used as additives in food, pharmaceutical and cosmetic industries.

Deficiency of N-linked glycosylation impairs immune function of B7-H6.

B7-H6 is a novel immune checkpoint molecule that triggers NK cell cytotoxicity, but the role of N-glycosylation in B7-H6 is poorly understood. We here identified the existence of N-glycosylation of B7-H6 in different cell lines and exogenous expression cells by PNGase F digestion and tunicamycin blockage. Subsequently, we demonstrated that B7-H6 contains 6 functional N-linked glycosylation sites by single site mutation and electrophoresis. Phylogenetical and structural analysis revealed that N43 and N208 glycan are conserved in jawed vertebrates and may thus contribute more to the biological functions. We further demonstrated that N43 and N208 glycosylation are essential for B7-H6 to trigger NK cell activation. Mechanistically, we found that N43 and N208 glycan contributed to the stability and membrane expression of B7-H6 protein. Lack of N208 glycosylation led to membrane B7-H6 shedding, while N43 mutation resulted in impaired B7-H6/NKp30 binding affinity. Together, our findings highlight the significance of N-linked glycosylation in B7-H6 biological functions and suggest potential targets for modulating NK cell-mediated immunity.

Development of arachin and basil seed gum composite gels for the encapsulation and controlled release of vitamin D3.

In this study, the textural and rheological properties of arachin and basil seed gum composite gels (ABG) were successfully regulated by the addition of sodium chloride (NaCl) and transglutaminase (TGase). The texture profile analysis (TPA) results showed that the hardness and springiness of the ABG were significantly enhanced by adding TGase (p < 0.05). Particularly, the composite gel added with NaCl first and subsequently crosslinked by TGase (ABG-Na+-TG) showed a higher hardness value of 186.0 ± 6.1 g. ABG-Na+-TG showed a higher amplitude of strain with lower compliance in the creep and recovery test and exhibited a better elastic behavior. These composite gels were employed as new delivery systems to encapsulate and deliver vitamin D3 (VD3). ABG-Na+-TG showed a higher VD3 encapsulation efficiency of 91.7 % and a better protection of VD3 under different temperatures or UV light, as well as an improved storage stability of VD3. Furthermore, the release of VD3 in the simulated gastric digestion could be controlled by ABG-Na+-TG and the bioaccessibility after digestion was 32.9 %. These results suggest that ABG-Na+-TG can be utilized as a promising delivery system of VD3.

Predicting post-stroke cognitive impairment using machine learning: A prospective cohort study.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a serious complication of stroke that warrants prompt detection and management. Consequently, the development of a diagnostic prediction model holds clinical significance. OBJECTIVE: Machine learning algorithms were employed to identify crucial variables and forecast PSCI occurrence within 3-6 months following acute ischemic stroke (AIS). METHODS: A prospective study was conducted on a developed cohort (331 patients) utilizing data from the Affiliated Zhongda Hospital of Southeast University between January 2022 and August 2022, as well as an external validation cohort (66 patients) from December 2022 to January 2023. The optimal model was determined by integrating nine machine learning classification models, and personalized risk assessment was facilitated by a Shapley Additive exPlanations (SHAP) interpretation. RESULTS: Age, education, baseline National Institutes of Health Scale (NIHSS), Cerebral white matter degeneration (CWMD), Homocysteine (Hcy), and C-reactive protein (CRP) were identified as predictors of PSCI occurrence. Gaussian Naïve Bayes (GNB) model was determined to be the optimal model, surpassing other classifier models in the validation set (area under the curve [AUC]: 0.925, 95 % confidence interval [CI]: 0.861 - 0.988) and achieving the lowest Brier score. The GNB model performed well in the test sets (AUC: 0.919, accuracy: 0.864, sensitivity: 0.818, and specificity: 0.932). CONCLUSIONS: The present study involved the development of a GNB model and its elucidation through employment of the SHAP method. These findings provide compelling evidence for preventing PSCI, which could serve as a guide for high-risk patients to undertake appropriate preventive measures.

Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

Infiltration of a Unique CD8+CD274+ Cell Subgroup in Hepatocellular Carcinoma is Associated with Poor Clinical Outcomes.

Introduction: Immune checkpoint (IC) inhibitor-related immunotherapies have attracted considerable attention in hepatocellular carcinoma (HCC). High IC expression and high tumor infiltrating lymphocyte levels are the current indicators of sensitivity to IC inhibitors. Thus, it is imperative to apply precision medicine strategies for patient selection. Methods: Six independent HCC cohorts were used for analysis at the single-cell and tissue levels. Multiplex immunofluorescence and immunochemistry staining assays were used to validate our results. A series of methodologies were used for immune-related evaluations. Results: Herein, we uncovered a unique CD8+CD274+ cell subpopulation that is associated with tumor progression and poor survival in HCC at the single-cell level. We assessed this subset at the tissue level and found that the prognostic significance of CD274 is dependent on CD8A expression in HCC. Subsequently, we identified a unique high-risk subpopulation that showed high CD8A expression coupled with intense CD274 expression in multiple HCC cohorts. CD8AHighCD274High* subgroup was correlated with malignant indexes and remained an independent prognostic factor when considering the influence of these indexes. Molecular characteristic analyses showed that the CD8AHighCD274High* subgroup harbored more mutations, had higher immune response activity and presented enrichment of cancer-related biological processes. Moreover, this high-risk subpopulation in HCC was characterized by high immune cell infiltration, low tumor purity, and enrichment of cancer-related signatures. Finally, cases with this phenotype demonstrated higher immunomodulator and IC levels and greater sensitivity to IC inhibitors. Conclusion: Our findings illustrate that some HCC patients may have a poor prognosis despite high CD8+ T-cell infiltration. These patients would probably benefit from IC inhibitor-based combination treatment.

Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment.

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.

PEG-GNPs aggravate MCD-induced steatohepatitic injury and liver fibrosis in mice through excessive lipid accumulation-mediated hepatic inflammatory damage.

Rapid development of gold nanoparticles (GNPs) in delivering pharmaceutics and therapeutics approaches still linger the concerns of their toxic effects. Nonalcoholic steatohepatitis (NASH) is characterized by excessive lipid accumulation and overt hepatic inflammatory damage, and is the leading cause of chronic liver disease worldwide. This study aimed to assess the potential hepatic effects of GNPs on NASH phenotype and progression in mice. Mice were fed a MCD diet for 8 weeks to elicit NASH and then intravenously injected with PEG-GNPs at a single dose of 1, 5, and 25 mg/kg-bw. After 24 h and 1 week of administration, the levels of plasma ALT and AST, and the number of lipid droplets, the degree of lobular inflammation and the contents of triglycerides and cholesterols in the livers of the NASH mice significantly increased compared with the untreated NASH mice, indicating that the severity of MCD diet-induced NASH-like symptoms in mice increased after PEG-GNP administration. Moreover, the aggravated hepatic steatosis in a manner involving altered expression of the genes related to hepatic de novo lipogenesis, lipolysis, and fatty acid oxidation was observed after PEG-GNP administration. Additionally, the RNA levels of biomarkers of hepatic pro-inflammatory responses, endoplasmic reticulum stress, apoptosis, and autophagy in MCD-fed mice increased compared with the untreated NASH group. Moreover, PEG-GNP-treated NASH mice displayed an increase in MCD diet-induced hepatic fibrosis, revealed by massive deposition of collagen fiber in the liver and increased expression of fibrogenic genes. Collectively, these results suggest that hepatic GNP deposition after PEG-GNP administration increase the severity of MCD-induced NASH phenotype in mice, which is attributable to, in large part, increased steatohepatitic injury and liver fibrosis in mice.

Therapeutic m6A Eraser ALKBH5 mRNA-Loaded Exosome-Liposome Hybrid Nanoparticles Inhibit Progression of Colorectal Cancer in Preclinical Tumor Models.

Although therapeutic targets have been developed for colorectal cancer (CRC) therapy, the therapeutic effects are not ideal and the survival rate for CRC patients remains poor. Therefore, it is crucial to recognize a specific target and develop an efficacious delivery system for CRC therapy. Herein, we demonstrate that reduced ALKBH5 mediates aberrant m6A modification and tumor progression in CRC. Mechanically, histone deacetylase 2-mediated H3K27 deacetylation inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development. Further, METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. Moreover, ALKBH5 mRNA-loaded folic acid-modified exosome-liposome hybrid nanoparticles were synthesized and significantly inhibit the progression of CRC in preclinical tumor models by modulating the ALKBH5/JMJD8/PKM2 axis and inhibiting glycolysis. Overall, our research confirms the crucial function of ALKBH5 in regulating the m6A status in CRC and provides a direct preclinical approach for using ALKBH5 mRNA nanotherapeutics for CRC.

Classifying Heart-Sound Signals Based on CNN Trained on MelSpectrum and Log-MelSpectrum Features.

The intelligent classification of heart-sound signals can assist clinicians in the rapid diagnosis of cardiovascular diseases. Mel-frequency cepstral coefficients (MelSpectrums) and log Mel-frequency cepstral coefficients (Log-MelSpectrums) based on a short-time Fourier transform (STFT) can represent the temporal and spectral structures of original heart-sound signals. Recently, various systems based on convolutional neural networks (CNNs) trained on the MelSpectrum and Log-MelSpectrum of segmental heart-sound frames that outperform systems using handcrafted features have been presented and classified heart-sound signals accurately. However, there is no a priori evidence of the best input representation for classifying heart sounds when using CNN models. Therefore, in this study, the MelSpectrum and Log-MelSpectrum features of heart-sound signals combined with a mathematical model of cardiac-sound acquisition were analysed theoretically. Both the experimental results and theoretical analysis demonstrated that the Log-MelSpectrum features can reduce the classification difference between domains and improve the performance of CNNs for heart-sound classification.