Prucalopride and Bowel Function Post Gastrointestinal Surgery: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Prolonged postoperative ileus (PPOI) contributes to morbidity and prolonged hospitalization. Prucalopride, a selective 5-hydroxytryptamine receptor agonist, may enhance bowel motility. This review assesses whether the perioperative use of prucalopride compared to placebo is associated with accelerated return of bowel function post gastrointestinal (GI) surgery. METHODS: OVID, CENTRAL, and EMBASE were searched as of January 2024 to identify randomized controlled trials (RCTs) comparing prucalopride and placebo for prevention of PPOI in adult patients undergoing GI surgery. The primary outcomes were time to stool, time to flatus, and time to oral tolerance. The secondary outcomes were incidence of PPOI, length of stay (LOS), postoperative complications, adverse events, and overall costs. The Cochrane risk of bias tool for randomized trials and the Grading of Recommendations, Assessment, Development, and Evaluations framework were used. An inverse variance random effects model was used. RESULTS: From 174 citations, 3 RCTs with 139 patients in each treatment group were included. Patients underwent a variety of GI surgeries. Patients treated with prucalopride had a decreased time to stool (mean difference 36.82 hours, 95% CI 59.4 to 14.24 hours lower, I2 = 62%, low certainty evidence). Other outcomes were not statistically significantly different (very low certainty evidence). Postoperative complications and adverse events could not be meta-analyzed due to heterogeneity; yet individual studies suggested no significant differences (very low certainty evidence). DISCUSSION: Current RCT evidence suggests that prucalopride may enhance postoperative return of bowel function. Larger RCTs assessing patient important outcomes and associated costs are needed before routine use of this agent.

Concurrent Use of Statins in Patients Undergoing Curative Intent Treatment for Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis.

Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC. Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to June 2022. Studies were included if they compared patients with TNBC receiving and not receiving statin therapy concurrently with oncologic treatment for curative intent in terms of recurrence and survival in a non-metastatic setting. The primary outcomes were 5-year disease-free survival (DFS) and 5-year overall survival (OS). A pairwise meta-analyses was performed using inverse variance random effects. Risk of bias was assessed with the ROBINS-I and the GRADE approach was conducted to assess quality of evidence. From 4014 citations, 5 studies with 625 patients on statin therapy and 2707 patients not on statin therapy were included. There was a significant increase in 5-year DFS for patients on statin therapy compared to patients not on statin therapy (OR 1.44, 95% CI 1.04-1.98, P = .03). No significant difference was noted in 5-year OS between the 2 groups (OR 1.12, 95% CI 0.86-1.47, P = .40). Included studies were at moderate-to-high risk of bias. The GRADE quality of evidence was very low. This review presents very low-quality evidence that concurrent use of statins with oncologic treatment may potentially improve long-term DFS for patients with TNBC undergoing curative intent therapy. Future research by way of large, prospective study is required to further clarify the clinical utility of statins on patients undergoing treatment for TNBC.

circUBE3C modulates myoblast development by binding to miR-191 and upregulating the expression of p27.

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.

Fragility of Statistically Significant Outcomes in Colonic Diverticular Disease Randomized Trials: A Systematic Review.

BACKGROUND: The p value has been criticized as an oversimplified determination of whether a treatment effect exists. One alternative is the fragility index. It is a representation of the minimum number of nonevents that would need to be converted to events to increase the p value above 0.05. OBJECTIVE: To determine the fragility index of randomized controlled trials assessing the efficacy of interventions for patients with diverticular disease since 2010 to assess the robustness of current evidence. DESIGN: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to August 2022. SETTINGS: Articles were eligible for inclusion if they were randomized trials conducted between 2010 and 2022 with parallel, superiority designs evaluating interventions in patients with diverticular disease. Only randomized trials with dichotomous primary outcomes with an associated p value of <0.05 were considered for inclusion. PARTICIPANTS: Any surgical or medical intervention for patients with diverticular disease. MAIN OUTCOME MEASURES: The fragility index was determined by adding events and subtracting nonevents from the groups with the smaller number of events. Events were added until the p value exceeded 0.05. The smallest number of events required was considered the fragility index. RESULTS: After screening 1271 citations, 15 randomized trials met the inclusion criteria. Nine of the studies evaluated surgical interventions and 6 evaluated medical interventions. The mean number of patients randomly assigned and lost to follow-up per randomized controlled trial was 92 (SD 35.3) and 9 (SD 11.4), respectively. The median fragility index was 1 (range, 0-5). The fragility indices for the included studies did not correlate significantly with any study characteristics. LIMITATIONS: Small sample, heterogeneity, and lack of inclusion of studies with continuous outcomes. CONCLUSIONS: The randomized trials evaluating surgical and medical interventions for diverticular disease are not robust. Changing a single-outcome event in most studies was sufficient to make a statistically significant study finding not significant. See Video Abstract . FRAGILIDAD DE LOS RESULTADOS ESTADSTICAMENTE SIGNIFICATIVOS EN ENSAYOS ALEATORIOS DE ENFERMEDAD DIVERTICULAR DEL COLON UNA REVISIN SISTEMTICA: ANTECEDENTES:El valor p ha sido criticado por una determinación demasiado simplificada de si existe un efecto del tratamiento. Una alternativa es el Índice de Fragilidad. Es una representación del número mínimo de no eventos que deberían convertirse en eventos para aumentar el valor p por encima de 0,05.OBJETIVO:Determinar el IF de ensayos controlados aleatorios que evalúan la eficacia de las intervenciones para pacientes con enfermedad diverticular desde 2010 para evaluar la solidez de la evidencia actual.FUENTES DE DATOS:Se realizaron búsquedas en MEDLINE, Embase y CENTRAL desde el inicio hasta agosto de 2022.SELECCIÓN DE ESTUDIOS:Los artículos eran elegibles para su inclusión si eran ensayos aleatorizados realizados entre 2010 y 2022 con diseños paralelos de superioridad que evaluaran intervenciones en pacientes con enfermedad diverticular. Sólo se consideraron para su inclusión los ensayos aleatorizados con resultados primarios dicotómicos con un valor de p asociado menor que 0,05.INTERVENCIÓNES:Cualquier intervención quirúrgica o médica para pacientes con enfermedad diverticular.PRINCIPALES MEDIDAS DE VALORACIÓN:El índice de fragilidad se determinó sumando eventos y restando no eventos de los grupos con el menor número de eventos. Se agregaron eventos hasta que el valor p superó 0,05. El menor número de eventos requeridos se consideró índice de fragilidad.RESULTADOS:Después de examinar 1271 citas, 15 ensayos aleatorios cumplieron los criterios de inclusión. Nueve de los estudios evaluaron intervenciones quirúrgicas y seis evaluaron intervenciones médicas. El número medio de pacientes aleatorizados y perdidos durante el seguimiento por ECA fue 92 (DE 35,3) y 9 (DE 11,4), respectivamente. La mediana del índice de fragilidad fue 1 (rango: 0-5). Los índices de fragilidad de los estudios incluidos no se correlacionaron significativamente con ninguna característica del estudio.LIMITACIONES:Muestra pequeña, heterogeneidad y falta de inclusión de estudios con resultados continuos.CONCLUSIONES:Los ensayos aleatorios que evalúan las intervenciones quirúrgicas y médicas para la enfermedad diverticular no son sólidos. Cambiar un solo evento de resultado en la mayoría de los estudios fue suficiente para que un hallazgo estadísticamente significativo del estudio no fuera significativo. (Traducción- Dr. Ingrid Melo ).

Avoidance of added salt for 6-12-month-old infants: A narrative review.

Most nutrition guidelines recommend avoiding foods with added salt for infants aged 6-12 months. However, the reason for no added salt lacks enough and reliable evidence. We re-searched and re-studied the relevant evidence. We searched PubMed and the Cochrane database for English-language studies published from 1904 through 2021. We also searched the databases of the websites of different national institutions. Randomized clinical trials (RCTs), systematic reviews, observational studies, and dietary guidelines were included in this review. The kidneys of infants aged 6-12 months have adequate sodium excretion capacity. There is insufficient evidence that high salt (sodium) intake early in life might lead to hypertension or salty diet preference in adults. Infants aged 6-12 months might be at risk of low sodium intake of only 150-300 mg of sodium/day, which may not meet the body's needs, if their supplementary food is not adequately salted.

Magnetic molecularly imprinted polymer based on dynamically established metal-mediated binding sites for the determination of trace captopril in rat plasma.

Therapeutic drug monitoring of captopril, which is a commonly used antihypertensive agent in clinical practice, is necessary. However, matrix effect-induced pretreatment is the bottleneck for determination. Metal-mediated molecularly imprinted polymers, an essential branch of molecularly imprinted polymers with better specificity and selectivity, have been used to separate/enrich analytes from complex matrices. In this work, Cu2+ was introduced to dynamically establish the binding sites of metal-mediated molecularly imprinted polymer towards captopril. All evidence demonstrated that the metal-mediated molecularly imprinted polymer based on Cu2+ coordination obtained a higher adsorption capacity (81.23 mg/g), faster adsorption rate (adsorption equilibrium within 50 min), and better selectivity (with the unrecognized analog). Subsequently, the Cu2+ -mediated molecularly imprinted polymer was used as dispersive molecularly imprinted solid-phase extraction to successfully establish an analytical platform for the determination of trace captopril in rat plasma. The enrichment factor was up to 20, the detection limit was as low as 0.16 µg/ml, and the average recovery was in the range of 87.51%-98.28% with a relative standard deviation of less than 3.29%. This study provides a promising reference for the preparation of selective adsorbents to improve pretreatment.

Changes in energy, macronutrient, and food consumption in 47 countries over the last 70 years (1950-2019): a systematic review and meta-analysis.

OBJECTIVES: We aimed to systematically examine trends in dietary energy, macronutrient, and food consumption in different geographic regions. METHODS: We searched Medline, Embase, CINAHL, and organizations for studies and reports using individual-level dietary assessments from 1950 to 2019 (PROSPERO CRD42022302843) and quantified changes using multivariable linear mixed-effects models. RESULTS: We identified 109 articles and reports from 47 countries, including Europe and Australasia (47% of studies), Asia (30%), Latin America (13%), the Middle East (6%), and North America (4%). In Southeast and East Asia, carbohydrate intake decreased, whereas fat consumption increased; the opposite pattern occurred in North America; and fat decreased while carbohydrate intake remained stable in Europe and Australasia. Consumption of carbohydrate and fat were stable in South Asia, Latin America, and the Middle East, but data were limited in these regions. A greater increase in national gross domestic product over time was associated with decreased carbohydrate and increased fat and protein intake. Dietary saturated fatty acid intake decreased in Northern and Eastern Europe and was stable in other regions. Changes in food varied by region; East and Southeast Asia increased meat, fish, dairy, egg, fruit, and vegetable consumption and decreased intake of grains, roots and tubers, legumes, whereas North America decreased dairy and red meat but increased eggs, nuts, poultry, and vegetable oil intake. Intakes of fruits, nuts, legumes, and roots and tubers were below recommendations in most regions. CONCLUSIONS: Our findings indicate regional variations in dietary trends and identify countries that would benefit from nutritional policies aimed at decreasing lower-quality carbohydrate foods and increasing consumption of fruits, vegetables, nuts, legumes, and dairy.

Copy number variation of bovine S100A7 as a positional candidate affected body measurements.

Beef production is closely related to the national economy and the attention has been paid to the improvement of beef cattle by molecular markers associated. Copy number variations (CNVs) recently have been gained many researches and recognized as an important source of genetic variation. Extensive studies have indicated that CNVs have effects on a large range of economic traits by a wide range of gene copy number alteration. S100A7 is a member of S100 family which is a famous family of Ca2+-binding proteins. S100A7 plays a crucial role in many important phenotypes (progress) including inflammatory diseases, psoriasis, obesity, etc. The aim of our study was to explore the phenotypic effects of CNV located in the S100A7 gene of bovine chromosome 3. We detected S100A7 CNV by qPCR in different cattle breeds, including Qinchuan cattle, Yunling cattle, Xianan cattle and a crossbred group Pinan. The copy number was identified as gain, normal and loss type, our results showed that the gain type was the main type in three types of S100A7 CNV of the whole tested breeds. After CNV detection, association analysis between S100A7 CNV and growth traits was carried out in four cattle breeds. We found significant effects of the CNV on cattle growth traits with differently preferred CNV types such as gain type with better chest depth (p = 0.043) in QC, loss type with better body length (p = 0.008) and rump width (p = 0.014) in YL, normal with better chest girth (p = 0.001), gain with better waist width (p = 0.001) and rump width (p = 0.044) in PN. These results suggested that the S100A7 CNV could affect the phenotypic traits and be used as a promising genetic marker for cattle molecular breeding.

Association analysis of indels in the VISFATIN gene with five cattle breeds and their growth traits.

VISFATIN is an adipose cytokine that has been proved to correlate with growth and development traits. In a previous study from our lab, two insertion/deletions (indels; including a 35-bp insertion at its intron 4 and a 6-bp deletion in intron 5) were identified within the VISFATIN gene. To validate these indels and evaluate their association with growth traits in Chinese cattle, a total of 413 samples from four Chinese indigenous breeds and 217 samples from Chinese breeds were detected. Three genotypes (WW, WI and II) at intron 4 were detected based on the 35-bp insertion (allele I) or deletion (allele W) and showed moderate polymorphism in all samples. Two genotypes (WW and WD) at intron 5 were detected based on the 6-bp deletion (allele D) or insertion (allele W) in Xianan (XN) cattle and Jinnan (JN) cattle population but showed poor polymorphisms. Association analysis illustrated that the indel at intron 4 is significantly associated with chest girth, rump length and body weight in Ji'an (JA) cattle and the indel at intron 5 can cause a significant difference in rump length in JN cattle. To our knowledge, it is the first time it has been shown that indels within the VISFATIN gene are associated with growth traits in the two Chinese indigenous cattle breeds. These findings suggest that the VISFATIN gene can be used as a molecular marker for JN and JA cattle breeding.

Enhancing erythritol production from crude glycerol in a wild-type Yarrowia lipolytica by metabolic engineering.

Background: Erythritol is a zero-calorie sweetener that is widely used in the food, pharmaceutical, and medical industries. Crude glycerol is the main by-product of biodiesel, and the effective utilization of crude glycerol will help to improve biodiesel viability. Previous studies on the production of erythritol from Y. lipolytica using crude glycerol as a carbon source have focused on optimizing the fermentation process of the mutant Y. lipolytica Wratislavia K1, while metabolic engineering has not been successfully applied. Results: To this end, we engineered the yeast Y. lipolytica to increase the productivity of this strain. Wild strains tolerant to high concentrations of crude glycerol were screened and identified. A series of rational metabolic approaches were employed to improve erythritol production. Among them, the engineered strain Y-04, obtained by tandem overexpression of GUT1 and GUT2, significantly increased glycerol assimilation by 33.3%, which was consistent with the results of RT-qPCR analysis. The effects of tandem overexpression of GUT1, GUT2, TKL1, and TAL1 on erythritol synthesis were also evaluated. The best results were obtained using a mutant that overexpressed GUT1, GUT2, and TKL1 and knocked out EYD1. The final Y-11 strain produced 150 g/l erythritol in a 5-L bioreactor with a yield and productivity of 0.62 g/g and 1.25 g/l/h, respectively. To the best of our knowledge, this is the highest erythritol yield and productivity from crude glycerol ever reported in Y. lipolytica. Conclusion: This work demonstrated that overexpression of GUT1, GUT2, and TKL1 and knockdown of EYD1 could be used to improve crude glycerol utilization and erythritol synthesis in Y. lipolytica. The process parameters such as erythritol yield and productivity were significantly elevated, which is valuable for industrial applications. Crude glycerol, as a carbon source, could efficiently restrict the synthesis of by-products while enhancing the generation of erythritol, compared to glucose. This indicates considerable potential for synthesizing value-added products from crude glycerol by Y. lipolytica.

Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss.

Background: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL. Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify abnormalities. Surface preparation and hair cell-specific marker Myo VIIa were employed to evaluated cochlear hair cell losses. Scanning electron microscopy (SEM) was to observe the microstructure of the organ of Corti (OC). The expression of related proteins in the RIPK1/RIPK3/MLKL pathway in cochlear tissue was detected by immunofluorescence. Results: In old mice (15 months), the ABR threshold increased significantly compared with the young mice. After 50 mg/kg RSV intervention, the hearing threshold of the old mice was significantly reduced at 8 kHz and 12 kHz as well as click. 100 mg/kg RSV led to a statistically significant reduction in hearing threshold only at clicks, whereas 300 mg/kg RSV showed no difference at all frequencies tested. In terms of cochlear hair cell loss, the damage of OHC and IHC was severe in old mice, but the damage was evidently reduced in RSV 50 mg/kg group. Notably, in the RSV 300 mg/kg group, the loss and disorientation of both the OHCs and IHCs were aggravated. Under SEM, a large number of OHCs were lost in the old group, but increased significantly in the RSV 50 mg/kg group, and even the OHCs were more seriously damaged in the RSV 300 mg/kg group. Furthermore, immunofluorescence showed that 50 mg/kg RSV significantly reduced the expression of RIPK3, RIPK1, and MLKL in the cochlea during aging, especially in necroptosis-sensitive regions OCs and SGN. Conclusion: Low-dose RSV inhibited RIPK3-mediated necroptosis in aging cochlea and delayed the onset of ARHL, which was a promising therapeutic strategy for ARHL.

Deletions in GSN gene associated with growth traits of four Chinese cattle breeds.

The aim of this study was to assess the potential of 21 bp mutation in the second intron of the GSN gene as a molecular marker-assisted by exploring the effect of 21 bp mutation on growth traits in four beef cattle breeds. Gelsolin (GSN), a member of the superfamily of gel proteins, is involved in the regulation of a variety of cellular activities in the organism and plays an important function in cell motility, apoptosis, signal transduction and inflammatory responses. Gelatin can not only negatively regulate the pro-apoptotic effect of P53 protein, but also promote apoptosis by blocking the interaction between actin and deoxyribonuclease, so, the GSN gene was selected as a candidate gene in this study. In this study, a 21 bp mutation on the second intron to the GSN gene was verified in 573 individuals of Yunling (YL, n = 220), Jiaxian (JX, n = 140), Xianan (XN, n = 114) and Qinchuan (QC, n = 97) cattle breeds using Once PCR and agarose gel electrophoresis. The association analysis of polymorphisms in the GSN gene with growth traits in four breeds was revealed: in YL cattle, the heart girth and forehead size of heterozygous ID genotype were significantly higher than II genotype (P < 0.05). In JX cattle, the withers height, body length and heart girth of II and ID genotype were significantly highest than DD genotype (P < 0.01); the height at hip cross and height at sacrum of II genotype was significantly highest than DD genotype (P < 0.01), but ID genotype was significantly higher than DD genotype. In XN cattle, the abdominal girth and circumference of the cannon bone of II genotype were significantly higher than ID genotype (P < 0.05). In QC cattle, the hucklebone width of ID genotype was significantly the highest than II genotype (P < 0.01). The results suggest that GSN may be an important candidate gene and that a 21 bp mutation on the second intron to the GSN gene can be used for molecular marker-assisted selection of four beef cattle breeds.

Comparisons of Hematological and Biochemical Profiles in Brahman and Yunling Cattle.

Brahman cattle are tolerant to parasite challenges and heat stress. Yunling cattle are three-way hybrids that are half Brahman cattle, a fourth Murray Grey cattle and a fourth Yunnan Yellow cattle, with good beef performance. The hematological and biochemical parameters can reflect the physiology and metabolic conditions of cattle, and there are valuable indicators of production performance and adaptability that can be found by studying the cattle. To assess the health status and differences, we compared 55 hematological and biochemical parameters of 28 Brahman cattle and 65 Yunling cattle using an automatic biochemical analyzer. Our results showed that 27 hematological and biochemical indices of Brahman cattle were lower than those of Yunling cattle, whereas the other parameters were higher. There are 20 indices with significant differences that were detected between Brahman and Yunling cattle (with p ≤ 0.01 or 0.01 ≤ p ≤ 0.05, respectively), and no significant differences were found for other indices (p > 0.05). Based on these results, Yunling cattle may have a better physical condition than Brahman cattle, may be better at adapting to local environments, and can maintain a good production and reproduction performance. As a new breed that is half Brahman, the abilities of Yunling cattle, including adaptability, stress resistance and tolerance to crude feed, were better than Brahman cattle under the same management conditions.

The Inclusion of Patients' Reported Outcomes to Inform Treatment Effectiveness Measures in Opioid Use Disorder. A Systematic Review.

Introduction: Patient centred care is needed now more than ever in the treatment of opioid use disorder. Trials, policy makers, and service providers have most often used treatment retention and opioid urine screens as measures of treatment effectiveness. However, patients receiving medication for opioid use disorder treatment (MOUD) may prioritise the use of different ways to assess treatment success. Objective: The aim of this review is to synthesize literature examining the self-reported goals patients would like to achieve in MOUD for opioid use disorder. Methods: We searched MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception until April 30th, 2021. No restrictions were placed on language, age, or type of MOUD. A qualitative synthesis is presented given that a meta-analysis was not possible. Results: The search yielded a total of 21,082 records from which 8 met criteria for inclusion in the qualitative synthesis. We identified a total of 43 patient-reported treatment goals from the 8 studies. Twelve domains were created from the 43 goals reported. These domains cover a range of important areas for patients' goals related to living a normal life, physical health, mental health, treatment, and substance use specific areas. Conclusion: This review highlights several patient goals that they would like to achieve during treatment for opioid use disorder that are not commonly considered as markers of treatment effectiveness. Goals related to health, living a normal life, and overall substance use concerns by patients should be taken into consideration by clinical trialists, researchers, policy makers, service providers, patients, and communities engaged in developing and tailoring treatment plans for opioid use disorder. Systematic Review Registration: PROSPERO CRD42018095553.

circMEF2D Negatively Regulated by HNRNPA1 Inhibits Proliferation and Differentiation of Myoblasts via miR-486-PI3K/AKT Axis.

Circular RNA (circRNA) is a form of endogenous RNA that can regulate gene expression and participate in the regulation of myogenesis. However, the molecular mechanisms and potential roles of circRNAs in bovine muscle development remain largely unknown. Nevertheless, the RNA splicing factors regulating the biogenesis of bovine circRNA have not yet been characterized. In this study, we identified a novel circRNA, circMEF2D, formed by back-splicing of constitutive exons (exons 5-7) of the bovine MEF2D gene. Functional assays showed that circMEF2D inhibited the proliferation and differentiation of bovine myoblasts. Importantly, we showed that circMEF2D regulated the PI3K-AKT signaling pathway through direct and competitive binding to miR-486. Furthermore, to explore the formation mechanism of circMEF2D, we explored the MEF2D gene alternative splicing progress. Four alternative linear variants of MEF2D were found. Due to its role in alternative splicing, the RNA-binding protein HNRNPA1 was selected for further study and the modulation of HNRNPA1 levels showed that it negatively regulated both back-splicing and linear splicing of MEF2D gene. Overall, in addition to the characterization of bovine circRNAs, these findings revealed the crucial role of HNRNPA1 in MEF2D gene alternative splicing and demonstrated a regulatory circMEF2D-miR-486-PI3K-AKT axis.

Alterations in the conformation and function of human serum albumin induced by the binding of methyl hydrogen phthalate.

Phthalate esters (PAEs) are widely used as plasticizer components in production. Methyl hydrogen phthalate (MHP) is a metabolite of dimethyl phthalate (DMP, a kind of PAEs), and its toxic residues accumulate in the nature and can enter the human body. Here, the interaction between MHP and human serum albumin (HSA) was probed by using multi-spectral, computer simulations, and biochemical techniques. The results showed that MHP was spontaneously embedded in site I of HSA to form a complex by H-bonds and van der Waals forces (ΔH < 0, ΔS < 0). The binding constant (Ka) of the HSA-MHP system was 1.136 ± 0.026 × 104 M-1 (298 K). The combination of MHP produced conformational variations of HSA, as shown by the 3D fluorescence spectrum, CD spectra, and molecular dynamics simulation. Additionally, molecular docking indicated that MHP was surrounded by multiple residues, such as Lys199, Leu203, Phe206, and Trp214. Specifically, Lys199 and Trp214 exerted a crucial effect on the interaction of HSA and MHP. The residues with important energy contribution were mostly located in site I. The ASA values of the aromatic amino acids of HSA changed after combining with MHP. The Rg and SASA values of HSA increased after adding MHP, suggesting that the structure of HSA was less compact. Moreover, the esterase-like activity of HSA increased after adding MHP to HSA, indicating that MHP may disturb the normal physiological activities in the human body. This study was helpful to understand the biological function of MHP and provided some insights for its side effect in the human body.

The flavonoid corylin exhibits lifespan extension properties in mouse.

In the long history of traditional Chinese medicine, single herbs and complex formulas have been suggested to increase lifespan. However, the identification of single molecules responsible for lifespan extension has been challenging. Here, we collected a list of traditional Chinese medicines with potential longevity properties from pharmacopeias. By utilizing the mother enrichment program, we systematically screened these traditional Chinese medicines and identified a single herb, Psoralea corylifolia, that increases lifespan in Saccharomyces cerevisiae. Next, twenty-two pure compounds were isolated from Psoralea corylifolia. One of the compounds, corylin, was found to extend the replicative lifespan in yeast by targeting the Gtr1 protein. In human umbilical vein endothelial cells, RNA sequencing data showed that corylin ameliorates cellular senescence. We also examined an in vivo mammalian model, and found that corylin extends lifespan in mice fed a high-fat diet. Taken together, these findings suggest that corylin may promote longevity.

Circular RNA ACTA1 Acts as a Sponge for miR-199a-5p and miR-433 to Regulate Bovine Myoblast Development through the MAP3K11/MAP2K7/JNK Pathway.

Circular RNAs (circRNAs) are a special class of noncoding RNA molecules that regulate many different biological processes. Myogenesis, a complex process, is primarily regulated by myogenic regulatory factors (MRFs) and various noncoding RNAs. However, the functions and regulatory mechanisms of circRNAs in myoblast development are unclear. In this study, we analyzed circRNA sequencing data of bovine myocyte tissues and identified circACTA1. Functional assays showed that circACTA1 could inhibit bovine myocyte proliferation and promote cell apoptosis and cytodifferentiation. In addition, circACTA1 could promote muscle repair in vivo. Mechanistically, luciferase assay and RNA immunoprecipitation were used to examine the interaction between circACTA1, miR-199a-5p, miR-433, and the target genes MAP3K11 and MAPK8. Meanwhile, we found that miR-199a-5p and miR-433 could suppress the expression of MAP3K11 and MAPK8, respectively. However, circACTA1 could mitigate this effect and activate the JNK signaling pathway. In conclusion, our results suggest that circACTA1 regulates the multiplication, apoptosis, and cytodifferentiation of bovine myocytes by competitively combining with miR-199a-5p and miR-433 to activate the mitogen-activated protein kinase kinase kinase 11 (MAP3K11)/mitogen-activated protein kinase kinase 7 (MAP2K7)/JNK signaling pathway.

Distribution of Copy Number Variation in SYT11 Gene and Its Association with Growth Conformation Traits in Chinese Cattle.

Currently, studies of the SYT11 gene mainly focus on neurological diseases such as schizophrenia and Parkinson's disease. However, some studies have shown that the C2B domain of SYT11 can interact with RISC components and affect the gene regulation of miRNA, which is important for cell differentiation, proliferation, and apoptosis, and therefore has an impact on muscle growth and development in animals. The whole-genome resequencing data detected a CNV in the SYT11 gene, and this may affect cattle growth traits. In this study, CNV distribution of 672 individuals from four cattle breeds, Yunling, Pinan, Xianan, and Qinchuan, were detected by qPCR. The relationship between CNV, gene expression and growth traits was further investigated. The results showed that the proportion of multiple copy types was the largest in all cattle breeds, but there were some differences among different breeds. The normal type had higher gene expression than the abnormal copy type. The CNVs of the SYT11 gene were significantly correlated with body length, cannon circumference, chest depth, rump length, and forehead size of Yunling cattle, and was significantly correlated with the bodyweight of Xianan cattle, respectively. These data improve our understanding of the effects of CNV on cattle growth traits. Our results suggest that the CNV of SYT11 gene is a protentional molecular marker, which may be used to improve growth traits in Chinese cattle.