An Unexpected Decrease in Vibrational Entropy of Multicomponent Rutile Oxides.

High-entropy oxides (HEOs), featuring infinite chemical composition and exceptional physicochemical properties, are attracting much attention. The configurational entropy caused by a component disorder of HEOs is popularly believed to be the main driving force for thermal stability, while the role of vibrational entropy in the thermodynamic landscape has been neglected. In this study, we systematically investigated the vibrational entropy of multicomponent rutile oxides (including Fe0.5Ta0.5O2, Fe0.333Ti0.333Ta0.333O2, Fe0.25Ti0.25Ta0.25Sn0.25O2, and Fe0.21Ti0.21Ta0.21Sn0.21Ge0.16O2) by precise heat capacity measurements. It is found that vibrational entropy gradually decreases with increasing component disorder, beyond what one could expect from an equilibrium thermodynamics perspective. Moreover, all multicomponent rutile oxides exhibit a positive excess vibrational entropy at 298.15 K. Upon examinations of configuration disorder, size mismatch, phase transition, and polyhedral distortions, we demonstrate that the excess vibrational entropy plays a pivotal role in lowering the crystallization temperature of multicomponent rutile oxides. These findings represent the first experimental confirmation of the role of lattice vibrations in the thermodynamic landscape of rutile HEOs. In particular, vibrational entropy could serve as a novel descriptor to guide the predictive design of multicomponent oxide materials.

A comprehensive exploration of twist1 to identify a biomarker for tumor immunity and prognosis in pan-cancer.

Twist1 has been identified as a critical gene in tumor, but current study of this gene remains limitative. This study aims to investigate its roles and potential mechanisms across pan-cancer. The study used various databases and computational techniques to analyze twist's RNA expression, clinical data, gene mutations, tumor stemness, tumor microenvironment, immune regulation. Furthermore, the experimental method of fluorescence staining was carried out to identify twist1 expression in various tumor masses. After analyzing the protein-protein interaction of TWIST, enrichment analysis and predictive potential drugs were performed, and molecular docking was conducted to validate. We found that twist1 expression was significantly higher in various types of cancer and associated with tumor stage, grade, and poor prognosis in multiple cancers. Differential expression of twist1 was linked to gene mutation, RNA modifications, and tumor stemness. Additionally, twist1 expression was positively associated with tumor immunoregulation and immune checkpoint. Salinomycin, klugline, isocephaelince, manassantin B, and pimonidazole are predictive potential drugs targeting TWIST1. This study revealed that twist1 plays an important role in tumor, and might be a curial marker in tumor diagnose and prognosis. The study also highlighted twist1 as a promising therapeutic target for cancer treatment and provided a foundation for future research.

Ensuring that ingested fishbones that migrate to the neck are located, diagnosed, and removed early.

OBJECTIVES: The aim of this retrospective study was to explore the clinical characteristics of and diagnostic and therapeutic strategies for the removal of fish bones that migrate to the neck. METHODS: We reviewed the clinical data of 30 patients over the past 12 years who underwent neck surgery in our otorhinolaryngology department for the migration of fish bones from the throat. The location of fish bones and the positivity rate of different examination methods (neck CT and B-ultrasound) were evaluated statistically. The diagnosis and treatment strategy for fish bone migration to the neck was also summarized. RESULTS: A total of 24 patients had a history of foreign body ingestion. The duration from foreign body ingestion to the appearance of symptoms in the neck ranged from 26 to 151 days, with a median of 50 days (interquartile range, 32-86 days). Among the 24 patients with fish bones located in the front or side of the neck, 50% (12/24) and 100% (24/24) of whom had positive neck CT and B-ultrasound results, respectively. Additionally, for 6 patients with fish bones in the retropharyngeal space, the positive rate for neck CT was 100%, whereas neck B-ultrasound showed negative results due to the air and depth in the trachea and esophagus. A strong correlation was observed between the length of fish bones detected by B-ultrasound and CT and the actual length. Indeed, no significant difference was observed between the length of fish bone determined by B-ultrasound and the actual length. In patients with fish bones located in the anterior and lateral neck regions, the foreign bodies were successfully removed by a lateral cervical approach operation (23/24). For the 6 cases with fish bones located in the retropharyngeal space, all (6/6) were removed by incising the posterior pharyngeal wall with assistance from transoral endoscopy. CONCLUSIONS: The techniques of B-ultrasound and CT have advantages for the diagnosis of migratory foreign bodies in the neck. Although B-ultrasound is more accurate for estimating the length of migratory fish bones in the neck, a combination of both methods can improve the preoperative positive rate of diagnosis. Therefore, a variety of surgical approaches should be employed to manage the different locations of cervical foreign bodies.

Modulating Lattice Oxygen Activity of Iron-Based Triple-Conducting Nanoheterostructure Air Electrode via Sc-Substitution Strategy for Protonic Ceramic Cells.

Iron-based perovskite air electrodes for protonic ceramic cells (PCCs) offer broad application prospects owing to their reasonable thermomechanical compatibility and steam tolerance. However, their insufficient electrocatalytic activity has considerably limited further development. Herein, oxygen-vacancy-rich BaFe0.6 Ce0.2 Sc0.2 O3-δ (BFCS) perovskite is rationally designed by a facile Sc-substitution strategy for BaFe0.6 Ce0.4 O3-δ (BFC) as efficient and stable air electrode for PCCs. The BFCS electrode with an optimized Fe 3d-eg orbital occupancy and more oxygen vacancies exhibits a polarization resistance of ≈ 0.175 Ω cm2 at 600 °C, ≈ 1/3 of the BFC electrode (≈0.64 Ω cm2 ). Simultaneously, BFCS shows favorable proton uptake with a low proton defect formation enthalpy (- 81 kJ mol-1 ). By combining soft X-ray absorption spectroscopy and electrical conductivity relaxation studies, it is revealed that the enhancement of Fe4+ -O2- interactions in BFCS promotes the activation and mobility of lattice oxygen, triggering the activity of BFCS in both oxygen reduction and evolution reactions (ORR/OER). The single cell achieves encouraging output performance in both fuel cell (1.55 W cm-2 ) and electrolysis cell (-2.96 A cm-2 at 1.3 V) modes at 700 °C. These results highlight the importance of activating lattice oxygen in air electrodes of PCCs.

Artesunate inhibits macrophage-like phenotype switching of vascular smooth muscle cells and attenuates vascular inflammatory injury in atherosclerosis via NLRP3.

Inflammation is one of the main pathogenic factors of atherosclerosis (AS), and the phenotypic transformation of macrophages in human vascular smooth muscle cells (HVSMCs) contributes to the inflammatory injury of blood vessels and the formation of atherosclerotic plaques. Artesunate reportedly exerts anti-inflammatory activity against AS. Herein, we aimed to explore the artesunate-mediated anti-inflammatory and HVSMC phenotypic switch effects against AS and elucidate potential underlying mechanisms. In vitro, artesunate decreased expression of NLRP3, caspase-1, and interleukin (IL)- 1ß. Artesunate significantly inhibited low-density lipoprotein (LDL) expression in HVSMCs and macrophages. In vivo, artesunate reduced atherosclerotic plaque formation in high-fat diet (HFD)-fed ApoE-/- mice, as well as decreased NLRP3 and CD68 expression in atherosclerotic plaques. Artesunate decreased serum levels of triglycerides and increased high-density lipoprotein levels in HFD-med mice; however, serum levels of total cholesterol and LDL were unaltered. Treatment with artesunate substantially increased α-smooth muscle actin expression in aortic tissues while inhibiting expression levels of NLRP3, IL-1ß, heparinase, matrix metalloproteinase 9, and Krüppel-like factor 4 (KLF4). Collectively, our findings suggest that artesunate-mediated effects may involve inhibition of the ERK1/2/NF-κB/IL-1ß pathway in HVSMCs via the downregulation of NLRP3 expression. Thus, artesunate could serve as a novel strategy to treat AS by inhibiting AS plaque formation and suppressing macrophage-like phenotype switching of HVSMCs.

Clinical Characteristics and Risk Factors for Allergic Rhinitis in Children with Epistaxis.

Background: Epistaxis is frequently observed in children with allergic rhinitis. However, few studies have addressed the clinical characteristics and risk factors for allergic rhinitis in children with epistaxis. This study aimed to describe the factors associated with allergic rhinitis in children with epistaxis. Methods: In total, we recruited 80 children (aged 3-14 years) who presented with epistaxis at a tertiary hospital between January 2014 and January 2022. The follow-up duration was at least 3 months, and we performed a multivariate logistic regression analysis to identify the risk factors for allergic rhinitis. Results: Among the 80 children examined, 57 (71.25%) had allergic rhinitis. Epistaxis mainly occurred in autumn in children with allergic rhinitis; in contrast, it mostly occurred in summer in children without it (P = 0.029). Mites are common allergens for allergic rhinitis in children with epistaxis; the univariate analysis revealed significant differences between allergic-rhinitis group and nonallergic-rhinitis group in the number of allergens (P < 0.001) and total IgE (P < 0.001). The difference in severity of nasal symptoms between the two groups was statistically significant and included nasal obstruction (P < 0.001), rhinorrhea (P < 0.001), sneezing (P < 0.001), and nasal itching (P < 0.001). After adjusting for potential confounders, the severity of rhinorrhea symptoms was found to be associated with an increased risk of allergic rhinitis in children with epistaxis (odds ratio: 3.86; 95% confidence interval: 1.61-9.26; P = 0.003). Conclusions: Observing the onset season, number of allergens, total IgE, and nasal symptoms in cases of epistaxis could suggest the presence of associated allergic rhinitis and reduce the number of missed diagnoses; antiallergic drugs could help control epistaxis in these cases.

A novel approach to precipitation prediction using a coupled CEEMDAN-GRU-Transformer model with permutation entropy algorithm.

The accurate forecasting of precipitation in the upper reaches of the Yellow River is imperative for enhancing water resources in both the local and broader Yellow River basin in the present and future. While many models exist for predicting precipitation by analyzing historical data, few consider the impact of different frequency sequences on model accuracy. In this study, we propose a coupled monthly precipitation prediction model that leverages the adaptive noise complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), gated recurrent unit neural network (GRU), and attention mechanism-based transformer model. The permutation entropy (PE) algorithm is employed to partition the data processed by CEEMDAN into different frequencies, with different models utilized to predict different frequencies. The predicted results are subsequently combined to obtain the monthly precipitation prediction value. The model is applied to precipitation prediction in four regions in the upper reaches of the Yellow River and compared with other models. Evaluation results demonstrate that the CEEMDAN-GRU-Transformer model outperforms other models in predicting precipitation for these regions, with a coefficient of determination R2 greater than 0.8. These findings suggest that the proposed model provides a novel and effective method for improving the accuracy of regional medium and long-term precipitation prediction.

Gut microbiota and microbiota-derived metabolites in colorectal cancer: enemy or friend.

Colorectal cancer (CRC) is a highly prevalent gastrointestinal cancer worldwide. Recent research has shown that the gut microbiota plays a significant role in the development of CRC. There is mounting evidence supporting the crucial contributions of bacteria-derived toxins and metabolites to cancer-related inflammation, immune imbalances, and the response to therapy. Besides, some gut microbiota and microbiota-derived metabolites have protective effects against CRC. This review aims to summarize the current studies on the effects and mechanisms of gut microbiota and microbiota-produced metabolites in the initiation, progression, and drug sensitivity/resistance of CRC. Additionally, we explore the clinical implications and future prospects of utilizing gut microbiota as innovative approaches for preventing and treating CRC.

Why is tinnitus a problem? A large-scale qualitative evaluation of problems reported by tinnitus patients in mainland China.

Objectives: The lived experience of tinnitus has biopsychosocial characteristics which are influenced by sociocultural factors. The main purpose of this study is to investigate how tinnitus affects people in their everyday life in China. A deductive qualitative analysis examined whether an a priori Western-centric conceptual framework could extend to an Asian context.Design: A large-scale prospective survey collected patient-reported problems associated with tinnitus in 485 adults attending four major ENT clinics in Eastern and Southern mainland China.Results: The evidence suggests that patients in China express a narrower range of problem domains associated with the lived experience of tinnitus. While 13 tinnitus-related problem domains were confirmed, culture-specific adaptations included the addition uncomfortable (a novel concept not previously reported), and the potential exclusion of concepts such as intrusiveness, loss of control, loss of peace and loss of sense of self.Conclusions: The sociocultural context of patients across China plays an important role in defining the vocabulary used to describe the patient-centred impacts of tinnitus. Possible explanatory factors include cultural differences in the meaning and relevance of certain concepts relating to self and in help-seeking behaviour, low health literacy and a different lexicon in Chinese compared to English to describe tinnitus-related problems.

Analysis of Etiology, Diagnosis, and Treatment Strategy and Efficacy of Pulsatile Tinnitus Caused by Abnormal Vascular Anatomy.

OBJECTIVE: To investigate the etiology, clinical characteristics, diagnosis, and treatment strategies and efficacy of pulsatile tinnitus (PT) caused by vascular anatomy abnormality. METHODS: The clinical data of 45 patients with PT in our hospital from 2012 to 2019 were collected and retrospectively analyzed. RESULTS: All 45 patients had vascular anatomical abnormalities. The patients were divided into 10 categories according to the different locations of vascular abnormalities: sigmoid sinus diverticulum (SSD), sigmoid sinus wall dehiscence (SSWD), SSWD with high jugular bulb, pure dilated mastoid emissary vein, aberrant internal carotid artery (ICA) in the middle ear, transverse-sigmoid sinus (TSS) transition stenosis, TSS transition stenosis with SSD, persistent occipital sinus stenosis, petrous segment stenosis of ICA, and dural arteriovenous fistula. All patients complained of PT synchronous with heartbeat rhythm. Endovascular interventional therapy and extravascular open surgery were used according to the location of the vascular lesions. Tinnitus disappeared in 41 patients, was significantly relieved in 3 patients, and was unchanged in 1 patient postoperatively. Except for one patient with transient headache postoperatively, no obvious complications occurred. CONCLUSION: PT caused by vascular anatomy abnormalities can be identified by detailed medical history and physical and imaging examination. PT can be relieved or even completely alleviated after appropriate surgical treatments.

Infection of Diabetes Foot Caused by Carbapenem-Resistant Proteus penneri Mediated by a Novel Plasmid Containing blaNDM.

Objective: A strain of Proteus penneri with carbapenem resistance was found in a patient with a diabetic foot infection. We studied drug resistance, genome, and homology of P. penneri to support clinical prevention and treatment of infection caused by carbapenem-resistant P. penneri (CR-PPE). Methods: The strains were obtained through bacterial culture from purulence. VITEK 2 compact (GN13) and Kirby-Bauer (K-B) disk diffusion methods were used for antimicrobial susceptibility testing. Ceftriaxone, amikacin, gentamicin, ampicillin, aztreonam, ceftazidime, ciprofloxacin, levofloxacin, cefepime, trimethoprim-sulfamethoxazole, tobramycin, cefotetan, piperacillin-tazobactam, ampicillin-sulbactam, ertapenem, piperacillin, meropenem, cefuroxime, cefazolin, cefoperazone/sulbactam, cefoxitin, and imipenem were used for antimicrobial susceptibility testing. After bacterial genome extraction, sequencing, and sequence assembly, whole-genome sequencing (WGS) was performed to explore the CR-PPE genotype. Results: CR-PPE was resistant to two carbapenems (imipenem and ertapenem), ceftriaxone, and cefazolin, and was sensitive to aztreonam, piperacillin-tazobactam, and cefotetan. WGS results depict that the resistant phenotype of CR-PPE is consistent with the genotype, without common virulence genes of Enterobacteriaceae bacteria detected (virulence factor database). The carbapenem resistance gene blaNMD-1 is contained in a new plasmid, pWF127-NDM. The transposon Tn125 in pWF127-NDM carrying blaNMD-1 has almost the same structure as Tn125 in the reference plasmid pHFK418-NDM (Accession: MH491967). In addition, through phylogenetic analysis, CR-PPE depicts the closest evolutionary relationship with GCF 024129515.1, which was found in Gallus gallus in the Czech Republic in 2019 (downloaded from National Center for Biotechnology Information database). According to the evolutionary tree, CR-PPE has high homology with the two P. penneri strains found in China. Conclusion: CR-PPE exhibits strong drug resistance owing to the presence of multiple resistance genes. CR-PPE infection should receive more attention, especially in patients with underlying diseases, such as diabetes and weak immunity.

Efficacy of various surgical methods in the treatment of allergic rhinitis: A network meta-analysis.

OBJECTIVE: We often use surgery to treat allergic rhinitis (AR) patients who have failed drug treatment, but there is currently no clear gold standard for the treatment of allergic rhinitis. Using network meta-analysis, we evaluated the efficacy of different surgical methods in the treatment of AR. METHODS: PubMed, Embase, The Cochrane Library, Web of Science, CBM, Wan Fang Data, and CNKI databases were searched to collect clinical randomized controlled trials of AR with different surgical methods that met the inclusion criteria. After two investigators independently screened literature, extracted data, and assessed the risk of bias of included studies, R software was used to evaluate inconsistency using the node splitting method, and Stata15.1 was used to estimate the ranking probability of treatment. RESULTS: A total of 47 randomized control studies involving 17 surgical schemes and 4144 participants were included. The results showed that after excluding surgical methods that did not form a closed loop, in AR patients without chronic rhinosinusitis and nasal polyps, surgical efficiency and symptom score ranked the same, which were posterior nasal neurectomy (PNN), Vidian neurectomy (VN), anterior ethmoid neurectomy (AEN), nasal septal reconstruction (NSR), and bilateral inferior turbinoplasty (BIT). In AR patients with chronic rhinosinusitis with nasal polyps, the effective rate (OR = 5.06; 95% CI = 2.75-9.32) and symptom and sign scores (MD = -3.80; 95% CI = -6.50-1.09) of PNN + FESS (functional endoscopic sinusitis surgery) were higher than FESS, and there was a significant difference. CONCLUSION: Our findings suggest that PNN is the best single operation for patients with AR and without chronic rhinosinusitis and nasal polyps, and the combination of multiple procedures may be better than a single operation. FESS + PNN is more effectual in AR patients with chronic rhinosinusitis with nasal polyps.

Efficacy of various surgical methods in the treatment of allergic rhinitis: A network meta-analysis

Objective: We often use surgery to treat allergic rhinitis (AR) patients who have failed drug treatment, but there is currently no clear gold standard for the treatment of allergic rhinitis. Using network meta-analysis, we evaluated the efficacy of different surgical methods in the treatment of AR. Methods: PubMed, Embase, The Cochrane Library, Web of Science, CBM, Wan Fang Data, and CNKI databases were searched to collect clinical randomized controlled trials of AR with different surgical methods that met the inclusion criteria. After two investigators independently screened literature, extracted data, and assessed the risk of bias of included studies, R software was used to evaluate inconsistency using the node splitting method, and Stata15.1 was used to estimate the ranking probability of treatment. Results: A total of 47 randomized control studies involving 17 surgical schemes and 4144 participants were included. The results showed that after excluding surgical methods that did not form a closed loop, in AR patients without chronic rhinosinusitis and nasal polyps, surgical efficiency and symptom score ranked the same, which were posterior nasal neurectomy (PNN), Vidian neurectomy (VN), anterior ethmoid neurectomy (AEN), nasal septal reconstruction (NSR), and bilateral inferior turbinoplasty (BIT). In AR patients with chronic rhinosinusitis with nasal polyps, the effective rate (OR = 5.06; 95% CI = 2.75–9.32) and symptom and sign scores (MD = -3.80; 95% CI = -6.50–1.09) of PNN + FESS (functional endoscopic sinusitis surgery) were higher than FESS, and there was a significant difference. Conclusion: Our findings suggest that PNN is the best single operation for patients with AR and without chronic rhinosinusitis and nasal polyps, and the combination of multiple procedures may be better than a single operation. FESS + PNN is more effectual in AR patients with chronic rhinosinusitis with nasal polyps (AU)

A Rare Case of Pleomorphic Adenoma in the Internal Auditory Canal.

Pleomorphic adenoma is a common tumor of the salivary gland tumor, but it is rare in the ear. To the authors' knowledge, this patient is the first reported case of pleomorphic adenoma arising in the internal auditory canal. There have been few documents reporting the manifestations and the therapy strategy of this disease. This study clearly demonstrated the experience in treating pleomorphic adenoma, including the characteristics of the clinical manifestation, the key procedures of surgery, and key points of the diagnosis. The translabyrinthine approach under the microscope performed to remove this tumor is a good option for resecting this type of tumor.

Alkannin Inhibits the Development of Ovarian Cancer by Affecting miR-4461.

BACKGROUND: Previous studies have shown that alkannin has anticancer, anti-inflammatory, and antibacterial effects. However, the effect of alkannin in the development of ovarian cancer (OC) remains unknown. Therefore, this study aims to elucidate the function of alkannin in OC progression. METHODS: RT-qPCR and western blot analysis were used to measure mRNA and protein expression. Cell viability and metastasis were detected by the CCK-8 assay, flow cytometry analysis, and transwell assay. RESULTS: Alkannin had no cytotoxicity toward normal ovarian cells, but alkannin can inhibit cell proliferation and induce apoptosis in OC cells. In addition, alkannin inhibited cell migration and invasion and blocked EMT in OC. Besides, upregulation of miR-4461 was found in OC tissues and cells, which was regulated by alkannin. More importantly, miR-4461 can inverse the effects of alkannin on cell viability and metastasis in OC cells. CONCLUSION: Alkannin restrains cell viability, metastasis, and EMT in OC by downregulating miR-4461 expression.

Deubiquitinating enzyme USP30 negatively regulates mitophagy and accelerates myocardial cell senescence through antagonism of Parkin.

Cell senescence is associated with age-related pathological changes. Increasing evidence has revealed that mitophagy can selectively remove dysfunctional mitochondria. Overexpression of ubiquitin-specific protease 30 (USP30) has been documented to influence mitophagy and deubiquitination of mitochondrial Parkin substrates. This study was conducted to evaluate the roles of USP30 and Parkin in myocardial cell senescence and mitophagy. Initially, myocardial cells were isolated from neonatal SD rats and subjected to D-gal treatment to induce cell senescence, after which the effects of D-gal on mitochondria damage, ROS production, cell senescence, and mitophagy were assessed. The myocardial cells were infected with lentiviruses bearing overexpression plasmids or shRNA targeting Parkin or USP30 to elucidate the effects of Parkin and USP30 on D-gal-induced mitophagy damage and cell senescence. Finally, aging was induced in rats by subcutaneous injection of D-gal to determine the role of Parkin and USP30 on cell senescence in vivo. D-gal was found to trigger mitochondria damage, ROS production, and cell senescence in myocardial cells. The overexpression of Parkin or silencing of USP30 reduced D-gal-induced mitochondrial damage and relieved D-gal-induced myocardial cell senescence. Moreover, the in vivo experiments validated that either elevation of Parkin or silencing USP30 could alleviate D-gal-induced myocardial cell senescence in rats. Silencing USP30 alleviates D-gal-induced mitochondrial damage and consequently suppresses myocardial cell senescence by activating Parkin. Our study highlights the potential of USP30 as a novel target against myocardial cell senescence.

microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.

The current study aimed to investigate the mechanism by which miR-454 influences the progression of heart failure (HF) in relation to the neural precursor cell expressed, developmentally downregulated 4-2 (NEDD4-2)/tropomyosin receptor kinase A (TrkA)/cyclic adenosine 3',5'-monophosphate (cAMP) axis. Sprague-Dawley rats were used to establish a HF animal model via ligation of the left anterior descending branch of the coronary artery. The cardiomyocyte H9c2 cells were treated with H2 O2 to stimulate oxidative stress injury in vitro. RT-qPCR and Western blot assay were subsequently performed to determine the expression patterns of miR-454, NEDD4-2, TrkA, apoptosis-related proteins and cAMP pathway markers. Dual-luciferase reporter gene assay coupled with co-immunoprecipitation was performed to elucidate the relationship between miR-454, NEDD4-2 and TrkA. Gain- or loss-of-function experiments as well as rescue experiments were conducted via transient transfection (in vitro) and adenovirus infection (in vivo) to examine their respective functions on H9c2 cell apoptosis and myocardial damage. Our results suggested that miR-454 was aberrantly downregulated in the context of HF, while evidence was obtained suggesting that it targeted NEDD4-2 to downregulate NEDD4-2 in cardiomyocytes. miR-454 exerted anti-apoptotic and protective effects on cardiomyocytes through inhibition of NEDD4-2, while NEDD4-2 stimulated ubiquitination and degradation of TrkA protein. Furthermore, miR-454 activated the cAMP pathway via the NEDD4-2/TrkA axis, which ultimately suppressed cardiomyocyte apoptosis and attenuated myocardial damage. Taken together, the key findings of the current study highlight the cardioprotective role of miR-454, which is achieved through activation of the cAMP pathway by impairing NEDD4-2-induced TrkA ubiquitination.

In vitro and in vivo combinatorial anticancer effects of oxaliplatin- and resveratrol-loaded N,O-carboxymethyl chitosan nanoparticles against colorectal cancer.

BACKGROUND: Oxaliplatin (OXE) combined with other chemotherapy drugs against colorectal cancer had been reported in the literature before, however, the efficacy of oxaliplatin combined with natural compounds was elusive. In addition, the clinical bioactivity and therapeutic dose of antitumor drugs are severely limited due to poor targeting and side effects. NDDSs offers an excellent strategy to overcome the disadvantages of small molecule anticancer drugs. METHODS: Here, we have prepared N,O-carboxymethyl chitosan Oxaliplatin nanoparticles (CMCS-OXE NPs) and N,O-carboxymethyl chitosan Resveratrol nanoparticles (CMCS-Res NPs) were prepared by ion crosslinking and emulsification crosslinking, respectively. RESULTS: The results revealed that the CMCS-OXE NPs exhibited a high encapsulation efficiency (60%) with a size of approximately 190.0 nm, and the CMCS-Res NPs exhibited a high encapsulation efficiency (65%) with a size of approximately 164.2 nm. The treatment with both types of nanoparticles combined exhibited more significant anti-colon cancer activity than the free drugs or either type of nanoparticle alone. In the in vivo experiments, the inhibition efficiency of the combined nanoparticle treatment was much stronger than the free drugs or either type of nanoparticle alone. CONCLUSIONS: Overall, combination of oxaliplatin and resveratrol into a nanoparticle-drug delivery systems (NDDSs) appears to be a promising strategy for colorectal cancer (CRC) therapy.