Endoscopic Endonasal Reconstruction of Intraoperative Cerebrospinal Fluid Leak in Different Skull base Regions: Outcomes, Meningitis and Risk Factors.

OBJECTIVE: Various non-vascularized or vascularized techniques have been adopted in endoscopic endonasal surgery (EES) for repairing intraoperative cerebrospinal fluid (CSF) leaks after tumor resection. Vascularized nasoseptal flaps (VNSF), free nasoseptal grafts (FNSG), free turbinate grafts (FTG), fascia lata and mashed muscle (FLMM) are frequently used. Outcomes of those grafts applied in the defects of different regions need to be clarified. METHODS: The data from a series of 162 patients with skull base tumor who underwent EES that had intraoperative CSF leak between Jan 2012 and Jan 2021 were retrospectively analyzed. The regions included anterior skull base (ASB), sellar region, clivus and infratemporal fossa (ITF). Repair failure rate (RFR), meningitis rate and associated risk factors were assessed. RESULTS: In total, 172 reconstructions were performed in 162 patients for the four sites of the skull base. There were 7 cases (4.3%) that had postoperative CSF leaks, which required second repair. The RFR for ASB, sellar region, clivus, and ITF was 2.6%, 2.2%, 16.7%, and 0%, respectively. The clivus defect was an independent risk factor for repair failure (P<0.01). The postoperative meningitis rate was 5.6%. Repair failure was an independent risk factor for meningitis (P < 0.01). CONCLUSIONS: VNSF, FNSG, FTG, FLMM are reliable autologous materials for repairing the dural defects in different regions during EES. Clivus reconstruction remains a great challenge, which had a higher RFR and meningitis rate. Repair failure is significantly associated with postoperative meningitis.

In vivo determination of the bioavailability of folic acid through the utilization of the PBPK model in conjunction with UPLC.

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake.

miR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease.

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

Effect of a comprehensive geriatric assessment nursing intervention model on older patients with diabetes and hypertension.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) was introduced late in China and is primarily used for investigating and evaluating health problems in older adults in outpatient and community settings. However, there are few reports on its application in hospitalized patients, especially older patients with diabetes and hypertension. AIM: To explore the nursing effect of CGA in hospitalized older patients with diabetes and hypertension. METHODS: We performed a retrospective single-center analysis of patients with comorbid diabetes mellitus and hypertension who were hospitalized and treated in the Jiangyin Hospital of Traditional Chinese Medicine between September 2020 and June 2022. Among the 80 patients included, 40 received CGA nursing interventions (study group), while the remaining 40 received routine nursing care (control group). The study group's comprehensive approach included creating personalized CGA profiles, multidisciplinary assessments, and targeted interventions in areas, such as nutrition, medication adherence, exercise, and mental health. However, the control group received standard nursing care, including general and medical history collection, fall prevention measures, and regular patient monitoring. After 6 months of nursing care implementation, we evaluated the effectiveness of the interventions, including assessments of blood glucose levels fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin, type A1c (HbA1c); blood pressure indicators such as diastolic blood pressure (DBP) and systolic blood pressure (SBP); quality of life as measured by the 36-item Short Form Survey (SF-36) questionnaire; and treatment adherence. RESULTS: After 6 months, the nursing outcomes indicated that patients who underwent CGA nursing interventions experienced a significant decrease in blood glucose indicators, such as fasting blood glucose, 2-h postprandial blood glucose, and HbA1c, as well as blood pressure indicators, including DBP and SBP, compared with the control group (P < 0.05). Quality of life assessments, including physical health, emotion, physical function, overall health, and mental health, showed marked improvements compared to the control group (P < 0.05). In the study group, 38 patients adhered to the clinical treatment requirements, whereas only 32 in the control group adhered to the clinical treatment requirements. The probability of treatment adherence among patients receiving CGA nursing interventions was higher than that among patients receiving standard care (95% vs 80%, P < 0.05). CONCLUSION: The CGA nursing intervention significantly improved glycemic control, blood pressure management, and quality of life in hospitalized older patients with diabetes and hypertension, compared to routine care.

The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

DNA nanoassembly based turn-on amplification probe for sensitive colorimetric CRISPR/Cas12a-mediated detection of pathogen DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR) system has been explored as an efficient tool for nucleic acid diagnostics. However, it normally needs instrumentation or produces turn-off signals. Herein, a bulged Y-shape DNA (Y-DNA) nanoassembly was designed and synthesized as a novel turn-on probe. A CRISPR/Cas12a and Y-DNA probe mediated colorimetric assay (named as CYMCOA) strategy was developed for visual detection of pathogen DNA. Upon activating Cas12a with pathogen DNA, the Y-DNA bulge is catalytically trans-cleaved, releasing the G-quadruplex sequence embedded in the Y-DNA nanoassembly as a peroxidase-like DNAzyme. Visible signals with chromogen substrates are thus produced. The CYMCOA strategy was combined with recombinase polymerase amplification (RPA), an isothermal amplification technique, in detecting Helicobacter pylori (Hp) bacteria and SARS-CoV-2 N plasmids as two model pathogens. The bioassay has very excellent detection sensitivity and specificity, owing to the triple cascade amplification reactions and the very low mismatch tolerance. The lower limit of detection values were 0.16 cfu⋅mL-1, 1.5 copies⋅µL-1, and 0.17 copies⋅µL-1 for Hp bacteria, Hp plasmids, and SARS-CoV-2 N plasmids respectively. The detection is fast and accurate. The colorimetric bioassay strategy provides to be a simple, accurate, fast and instrumentation-free platform for nucleic acids detections in various settings, including crude and emergent situations.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.

Influence of meaningfulness of work and leadership characteristics on customer-directed counterproductive work behavior resulting from customer mistreatment.

This study explored the impact of customer mistreatment on counterproductive work behavior (CWB) and the moderating role of supervisor responses (self-sacrificial and self-serving leadership) to clarify why customer-directed CWB occurs and how it can be reduced. A sample of 392 customer-facing employees in the USA completed measures assessing the meaningfulness of work and self-sacrificial and self-serving leadership experiences. The meaningfulness of work moderated the relationship between customer mistreatment and employee anger, and a three-way interaction was found between employee anger and self-sacrificial and self-serving leadership on customer-directed CWB. Implications for managing customer mistreatment and fostering meaningful work to promote employee well-being are discussed.

Report on three cases of familial primary aldosteronism type IV.

Primary aldosteronism is the most common cause of secondary hypertension, which is caused by increased aldosterone secretion in the adrenal cortex and contains many subtypes, among which familial hyperaldosteronism is relatively rare. Familial hyperaldosteronism can be divided into four subtypes based on its clinical manifestations and mutated genes: FH-I, FH-II, FH-III, and FH-IV. This article reports on three patients with FH-IV: a mother and her two sons. They were diagnosed with hypertension in other hospitals, and hypokalemia was found during hospitalization in our department. Diltiazem and terazosin were used for elution for 1 month. Renin and aldosterone levels in standing or supine positions improved, and the aldosterone-to-renin ratio was positive. Primary aldosteronism was diagnosed based on improved saline and captopril inhibition tests. As the three patients were blood-related immediate family members, gene screening was performed, diagnosing them with FH-IV. This article reports the clinical characteristics of the three cases in combination with related literature to improve the understanding of FH-IV.

3.73 W all-solid-state dual-wavelength Nd:Lu2O3 crystal laser.

The laser output characteristics of N d:L u 2 O 3 crystals were investigated in detail to obtain a dual-wavelength all-solid-state laser. Using 806 nm LD end-face pumped N d:L u 2 O 3 crystals with lengths of 6 mm, a 1076 & 1080 nm laser outputs with a maximum output power of 3.73 W were obtained, with a slope efficiency of 30.4%, an optical-to-optical conversion efficiency of 28.5%, and a power stability of 0.41% for 4 h of continuous measurement. Furthermore, by suppressing the higher-order modes, a high beam quality laser output with beam quality factors of 2.092 and 1.589 in the x and y directions, respectively, and a maximum output power of 1.27 W were obtained. In addition, it was experimentally verified that both wavelengths of the output laser were elliptically polarized.

Microfluidic device reveals new insights into impairment of neutrophil transmigration in patients with sepsis.

Neutrophils need to migrate through tight tissue spaces to eliminate pathogens, but their movement is often hindered by their large and stiff nuclei. Neutrophil migration is impaired in sepsis patients, but it is unclear whether this defect is related to the deformability of their nuclei. Herein, we designed microfluidic devices with micron-scale narrow slits to simulate biological barriers. This setup allowed us to observe and record neutrophil movement and nuclear deformation in real-time. We also developed a method for morphological analysis to quantify nucleus deformation in numerous individual cells. Our studies showed that neutrophils from healthy individuals could adjust their nuclear shape to squeeze through these constrictions, whereas those from sepsis patients demonstrated less flexibility. Neutrophils with rigid nuclei struggled to pass through narrow gaps and were more likely to rupture under pressure. These findings suggest that the migration defects of neutrophils observed in sepsis may be attributed to the inability of neutrophils to deform their nuclei, highlighting the crucial role of microfluidic technologies in offering new insights into migration defects under pathological conditions.

Novel diacylglycerol oil-based nanostructured lipid carriers improves the stability and digestibility of lycopene.

Diacylglycerol (DAG) has garnered attention for its safe and nutritious qualities, and its utilization in emulsion systems to encapsulate hydrophobic bioactives is anticipated to enhance their bioaccessibility. Thus, this study aimed to evaluate the influence of DAG oil as a carrier on the stability and digestive characteristics of nanostructured lipid carriers (NLCs) containing lycopene (LYC). The results indicated that DAG oil demonstrated superior storage and heating stability in comparison to triacylglycerol (TAG) oil. Furthermore, NLCs formulated with DAG oil exhibited a faster rate of lipolysis (>76.3%) and higher loading capacity (1.48%), resulting in an approximate 11% enhancement in the bioaccessibility of LYC (reaching up to 31.4%). DAG oils show considerable potential for enhancing and prolonging the properties and bioactivity of NLC carriers, thereby boosting bioaccessibility. The incorporation of DAG oil in food systems holds promise for enriching their functionality over traditional TAG oil.

Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

[Radial growth response of Populus euphratica to climate change in the Cele desert oasis ecotone, China]. / ç­–å‹’æ²™æ¼ ç»¿æ´²è¿‡æ¸¡å¸¦èƒ¡æ¨å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Populus euphratica is an important tree species in the arid regions of Northwest China, which is sensitive to climate changes. Climate of the Northwest China is changing to be "warm and humid", but how it would affect the regional forest growth is not clear. In this study, the radial growth response of P. euphratica to major climatic factors and their temporal changes during 1984-2021 were analyzed by using dendrochronology method in the desert oasis ecotone of Cele in the southern Tarim basin. The results showed that tree-ring width index of P. euphratica had a significant negative correlation with temperature in September of the previous year, and in February and May of current year, had significant positive correlation with precipitation in September of previous year and March and May of current year, and had significant positive correlations with SPEI in February and May of current year. The relationships between tree-ring width index and combined month climatic factors were more obvious. The results of moving correlation analysis showed that the correlation between tree-ring width index and temperature in the growing season tended to be strengthened in recent years, while the correlation between tree-ring width index and precipitation, SPEI tended to be declined or remain stable. The variations of the relationships between tree-ring width index and combined month climatic factors were more obvious compared that with single month. Current regional climate is conducive to the growth and development, as well as the improvement of ecological shelter function of P. euphratica forest in the desert oasis ecotone of Cele.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling.

Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor ß (TGF-ß) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of activin A on NK cell migration. In vitro, activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, activin A increased Ca2+, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca2+ chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that activin A induces NK cell migration through AKT signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

circMIRIAF aggravates myocardial ischemia-reperfusion injury via targeting miR-544/WDR12 axis.

Exploring and discovering novel circRNAs is one of the ways to develop innovative drugs for the diagnosis and treatment of myocardial ischemia-reperfusion injury (MI/RI). In the work, some dysregulated circRNAs were found by microarray screening analysis in AC16 cells, and hsa_circRNA_104852 named circMIRIAF was screened, which was up-regulated in AC16 cells damaged by hypoxia-reoxygenation injury (H/RI). The comprehensive analysis of ceRNA network revealed the potential relationship of circMIRIAF/miR-544/WDR12. Then, the results of interaction research confirmed that circMIRIAF acted as sponge of miR-544 to positively regulate WDR12 protein expression. Further, the validation results indicate that miR-544 silencing increased the expression of WDR12, and WDR12 activated Notch1 signal to aggravate H/RI of AC16 cells and MI/RI of mice via regulating oxidative stress and inflammation. Furthermore, silencing circMIRIAF caused the decreased circMIRIAF levels and the increased miR-544 levels in cardiomyocytes, while excessive miR-544 inhibited WDR12 expression to alleviate the disorder. On the contrary, excessive circMIRIAF increased WDR12 expression by adsorbing miR-544 to exacerbate H/RI in AC16 cells. In addition, circMIRIAF siRNA reversed the aggravation of H/RI in cells caused by WDR12 overexpression. Overall, circMIRIAF can serve as a drug target or treating MI/RI, and circMIRIAF could sponge miR-544 and enhance WDR12 expression to aggravate MI/RI, which may provide a novel therapeutic strategy for MI/RI treatment.