Characterizing the safety profile of vagus nerve stimulation devices for epilepsy from 21,448 manufacturer and user reports.

OBJECTIVE: This study summarizes medical device reports (MDRs) associated with adverse events for vagus nerve stimulation (VNS) devices indicated for epilepsy as reported by the Manufacturer and User Facility Device Experience (MAUDE) database of the US Food and Drug Administration. METHODS: The MAUDE database was surveyed for MDRs from November 2013 to September 2022 regarding VNS devices for epilepsy. Event descriptions, device problems, correlated patient consequences, and device models were grouped and analyzed in Python. Based on event description, revision surgeries and other unique events were identified. Revenue from VNS device sales was used to approximate growth in their use over time. RESULTS: A total of 21,448 MDRs met the inclusion criteria. High VNS impedance, the most prevalent device malfunction overall (17.0% of MDRs), was the most common factor for 18 of the 102 encountered patient problems and led to 1001 revision surgeries (3371 total revisions). Included in those 18 device malfunctions were 3 of the top 6 occurring patient problems: seizure recurrence (9.9% associated with high impedance; encompassed focal, absence, and grand mal subtypes), death (1.3%), and generalized pain (7.9%). The next 4 top cited device malfunctions-lead fracture (13.7% of MDRs), operational issue (6.6%), battery problem holding charge (4.2%), and premature end-of-life indicator (2.9%)-differed widely in their percentage of cases that did not impact patients (77.4%, 57.3%, 48.9%, and 92.2%, respectively), highlighting differing malfunction severities. Seizure recurrence, the most prevalent patient impact, was the outcome most associated with 32 of the 68 encountered device problems, including high impedance (12.8%), lead fracture (12.2%), operational issue (18.4%), battery problem holding charge (31.2%), and premature end-of-life indicator (8.9%), which comprised the top 5 occurring device problems. In general, MDRs spanned a diverse range including device age, hardware, software, and surgeon or manufacturer error. Trends were seen over time with declining annual MDRs coupled with a rise in the use of VNS devices as gauged by revenue growth. Shifting device and patient problem profiles were also seen in successive models, reflecting engineering updates. CONCLUSIONS: This study characterizes the most common and consequential side effects of VNS devices for epilepsy while clarifying likely causes. In addition, the outcomes of 68 distinct device malfunctions were identified, including many not ubiquitously present in literature, lending critical perspective to clinical practice.

Research on the metabolic regulation mechanism of Yangyin Qingfei decoction plus in severe pneumonia caused by Mycoplasma pneumoniae in mice.

Introduction: With amazing clinical efficacy, Yangyin Qingfei Decoction Plus (YQDP), a well-known and age-old Chinese compound made of ten Chinese botanical drugs, is utilized in clinical settings to treat a range of respiratory conditions. This study examines the impact of Yangyin Qingfei Decoction (YQDP) on lung tissue metabolic products in severe Mycoplasma pneumoniae pneumonia (SMPP) model mice and examines the mechanism of YQDP in treating MP infection using UPLC-MS/MS technology. Methods: YQDP's chemical composition was ascertained by the use of Agilent 1260 Ⅱ high-performance liquid chromatography. By using a nasal drip of 1010 CCU/mL MP bacterial solution, an SMPP mouse model was created. The lung index, pathology and ultrastructural observation of lung tissue were utilized to assess the therapeutic effect of YQDP in SMPP mice. Lung tissue metabolites were found in the normal group, model group, and YQDP group using UPLC-MS/MS technology. Using an enzyme-linked immunosorbent test (ELISA), the amount of serum inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), was found. Additionally, the protein expression of PI3K, P-PI3K, AKT, P-AKT, NF-κB, and P-NF-κB was found using Western blot. Results: The contents of chlorogenic acid, paeoniflorin, forsythrin A, forsythrin, and paeonol in YQDP were 3.480 ± 0.051, 3.255 ± 0.040, 3.612 ± 0.017, 1.757 ± 0.031, and 1.080 ± 0.007 mg/g respectively. YQDP can considerably lower the SMPP mice's lung index (p < 0.05). In the lung tissue of YQDP groups, there has been a decrease (p < 0.05) in the infiltration of inflammatory cells at varying concentrations in the alveoli compared with the model group. A total of 47 distinct metabolites, including choline phosphate, glutamyl lysine, L-tyrosine, 6-thioinosine, Glu Trp, 5-hydroxydecanoate, etc., were linked to the regulation of YQDP, according to metabolomics study. By controlling the metabolism of porphyrins, pyrimidines, cholines, fatty acids, sphingolipids, glycerophospholipids, ferroptosis, steroid hormone biosynthesis, and unsaturated fatty acid biosynthesis, enrichment analysis suggested that YQDP may be used to treat SMPP. YQDP can lower the amount of TNF-α and IL-6 in model group mice as well as downregulate P-PI3K, P-AKT, and P-NF-κB expression (p < 0.05). Conclusion: A specific intervention effect of YQDP is observed in SMPP model mice. Through the PI3K/Akt/NF-κB signaling pathways, YQDP may have therapeutic benefits by regulating the body's metabolism of α-Linoleic acid, sphingolipids, glycerophospholipids, arachidonic acid, and the production of unsaturated fatty acids.

High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein.

BACKGROUND: The reproductive performance of chickens mainly depends on the development of follicles. Abnormal follicle development can lead to decreased reproductive performance and even ovarian disease among chickens. Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer. In recent years, the involvement of circRNAs in follicle development and atresia regulation has been confirmed. RESULTS: In the present study, we used healthy and atretic chicken follicles for circRNA RNC-seq. The results showed differential expression of circRALGPS2. It was then confirmed that circRALGPS2 can translate into a protein, named circRALGPS2-212aa, which has IRES activity. Next, we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1. CONCLUSIONS: Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

Circular RNA circRPS19 promotes chicken granulosa cell proliferation and steroid hormone synthesis by interrupting the miR-218-5p/INHBB axis.

Ovarian follicle development is an important physiological activity for females and makes great significance in maintaining female health and reproduction performance. The development of ovarian follicle is mainly affected by the granulosa cells (GCs), whose growth is regulated by a variety of factors. Here, we identified a novel circular RNA (circRNA) derived from the Ribosomal protein S19 (RPS19) gene, named circRPS19, which is differentially expressed during chicken ovarian follicle development. Further explorations identified that circRPS19 promotes GCs proliferation and steroid hormone synthesis. Furthermore, circRPS19 was found to target and regulate miR-218-5p through a competitive manner with endogenous RNA (ceRNA). Functionals investigation revealed that miR-218-5p attenuates GCs proliferation and steroidogenesis, which is opposite to that of circRPS19. In addition, we also confirmed that circRPS19 upregulates the expression of Inhibin beta B subunit (INHBB) by binding with miR-218-5p to facilitate GCs proliferation and steroidogenesis. Overall, this study revealed that circRPS19 regulates GCs development by releasing the repression of miR-218-5p on INHBB, which suggests a novel mechanism in respect to circRNA and miRNA regulation in ovarian follicle development.

Transcriptome profiling reveals SLC5A5 regulates chicken ovarian follicle granulosa cell proliferation, apoptosis, and steroid hormone synthesis.

The egg-laying performance of hens holds significant economic importance within the poultry industry. Broody inheritance of the parent stock of chickens can result in poor options for the improvement of egg production, and is a phenomenon influenced by multiple genetic factors. However, few studies have been conducted to delineate the molecular mechanism of ovarian regression in brooding chickens. Here, we explored the pivotal genes responsible for the regulation of ovarian follicles in laying hens, using RNA-sequencing analysis on the small ovarian follicles from broody and laying chickens. Sequencing data analysis revealed the differential expression of 200 genes, with a predominant enrichment in biological processes related to cell activation and metabolism. Among these genes, we focused on solute carrier family 5 member 5 (SLC5A5), which exhibited markedly higher RNA expression levels in follicles from laying compared with broody chickens. Subsequent cellular function studies with knockdown of SLC5A5 in chicken ovarian follicle granulosa cells (GCs) led to the down-regulation of genes associated with cell proliferation and steroid hormone synthesis, and concurrent promotion of gene expression linked to apoptosis. These findings indicated that SLC5A5 deficiency led to the inhibition of proliferation, steroid hormone synthesis and secretion, and promotion of apoptosis in chicken GCs. Our study demonstrated a pivotal role for SLC5A5 in the development and function of chicken GCs, shedding light on its potential significance in the broader context of chicken ovarian follicle development, and providing a prospective target to improve the egg-laying performance of chickens via molecular marker-assisted breeding technology.

Atraumatic Polycompartment Syndrome Secondary to Cardiogenic Shock: A Case Report.

We report the case of a 53-year-old male who developed polycompartment syndrome (PCS) secondary to cardiogenic shock. After suffering a cardiac arrest, a self-perpetuating cycle of intra-abdominal hypertension (IAH) and vital organ damage led to abdominal compartment syndrome (AbCS), which then contributed to the precipitation of extremity compartment syndrome (CS) in bilateral thighs, legs, forearms, and hands. This report is followed by a review of the literature regarding the pathophysiology of this rare sequela of cardiogenic shock. While the progression from cardiogenic shock to AbCS and ultimately to PCS has been hypothesized, no prior case reports demonstrate this. Furthermore, this case suggests more generally that IAH may be a risk factor for extremity CS. Future studies should examine the potential interplay between IAH and extremity CS in patients at risk, such as polytrauma patients with tibial fractures.

Evolutionary conserved circular MEF2A RNAs regulate myogenic differentiation and skeletal muscle development.

Circular RNAs (circRNAs) have been recognized as critical regulators of skeletal muscle development. Myocyte enhancer factor 2A (MEF2A) is an evolutionarily conserved transcriptional factor that regulates myogenesis. However, it remains unclear whether MEF2A produces functional circRNAs. In this study, we identified two evolutionarily conserved circular MEF2A RNAs (circMEF2As), namely circMEF2A1 and circMEF2A2, in chicken and mouse muscle stem cells. Our findings revealed that circMEF2A1 promotes myogenesis by regulating the miR-30a-3p/PPP3CA/NFATC1 axis, whereas circMEF2A2 facilitates myogenic differentiation by targeting the miR-148a-5p/SLIT3/ROBO2/ß-catenin signaling pathway. Furthermore, in vivo experiments demonstrated that circMEF2As both promote skeletal muscle growth. We also discovered that the linear MEF2A mRNA-derived MEF2A protein binds to its own promoter region, accelerating the transcription of MEF2A and upregulating the expression of both linear MEF2A and circMEF2As, forming a MEF2A autoregulated positive feedback loop. Moreover, circMEF2As positively regulate the expression of linear MEF2A by adsorbing miR-30a-3p and miR-148a-5p, which directly contribute to the MEF2A autoregulated feedback loop. Importantly, we found that mouse circMEF2As are essential for the myogenic differentiation of C2C12 cells. Collectively, our results demonstrated the evolution, function, and underlying mechanisms of circMEF2As in animal myogenesis, which may provide novel insight for both the farm animal meat industry and human medicine.

CircLRRFIP1 promotes the proliferation and differentiation of chicken skeletal muscle satellite cells by sponging the miR-15 family via activating AKT3-mTOR/p70S6K signaling pathway.

Skeletal muscle is important for animal meat production, regulating movements, and maintaining homeostasis. Circular RNAs (circRNAs) have been founded to play vital role in myogenesis. However, the effects of the numerous circRNAs on growth and development of the skeletal muscle are yet to be uncovered. Herein, we identified circLRRFIP1, which is a novel circular RNA that is preferentially expressed in the skeletal muscle. To study the role of circLRRFIP1 in the skeletal muscle, the skeletal muscle satellite cells (SMSCs) was used to silenced or overexpressed circLRRFIP1. The results obtained in this study showed that circLRRFIP1 play a positive role in the proliferation and differentiation of SMSCs. The SMSCs were generated with stable knockdown and overexpression of circLRRFIP1, and the results showed that circLRRFIP1 exerts a stimulatory effect on the proliferation and differentiation of SMSCs. We further generated SMSCs with stable knockdown and overexpression of circLRRFIP1, and the results revealed that circLRRFIP1 exerts a stimulatory effect on the proliferation and differentiation of SMSCs. Mechanistically, circLRRFIP1 targets the myogenic inhibitory factor-miR-15 family to release the suppression of the miR-15 family to AKT3. The knockdown of AKT inhibits SMSC differentiation through the mTOR/p70S6K pathway. Taken together, the results obtained in this present study revealed the important role and the regulatory mechanisms of circLRRFIP1 in the development of chicken skeletal muscle. Therefore, this study provides an attractive target for molecular breeding to enhance meat production in the chicken industry.

What Factors Are Associated With Arterial Line-Related Limb Ischemia in Patients on Extracorporeal Membrane Oxygenation? A Single-Center Retrospective Cohort Study.

OBJECTIVES: The primary purpose of this study was to identify factors associated with the development of arterial line-related limb ischemia in patients on extracorporeal membrane oxygenation (ECMO). The authors also sought to characterize and report the outcomes of patients who developed arterial line-related limb ischemia. DESIGN: Retrospective cohort study. SETTING: A single academic tertiary referral ECMO center. PARTICIPANTS: Consecutive patients who were treated with ECMO over 6 years. INTERVENTIONS: Use of arterial line. MEASUREMENTS AND MAIN RESULTS: A total of 278 consecutive ECMO patients were included, with 19 (7%) patients developing arterial line-related limb ischemia during the ECMO run. Postcannulation Sequential Organ Failure Assessment (SOFA) (adjusted odds ratio [aOR] 1.20, 95% CI 1.08-1.32), Acute Physiology and Chronic Health Evaluation-II (aOR 0.84, 95% CI 0.74-0.95), and adjusted Vasopressor Dose Equivalence (aOR 1.03, 95% CI 1.01-1.05) scores were independently associated with the development of arterial line-associated limb ischemia. A SOFA score of ≥17 at the time of ECMO cannulation had an 80% sensitivity and 87% specificity for predicting arterial line-related limb ischemia. CONCLUSIONS: Arterial line-related limb ischemia is much more common in ECMO patients than in the typical intensive care unit setting. The SOFA score may be useful in identifying which patients may be at risk for arterial line-related limb ischemia. As this was a single-center retrospective study, these results are inherently exploratory, and prospective multicenter studies are necessary to validate these results.

Rates of Internal Hiring of Ophthalmology Faculty from their Institution of Training at Top Academic Medical Centers: A Cross-Sectional Study.

Background Throughout graduate and postgraduate education, trainees need to gauge the impact of training location on future institutions of practice. Objective We assessed rates of internal hiring of ophthalmology faculty at academic institutions from their same institution of training. Methods This was a cross-sectional study. We included 1,246 clinical ophthalmology faculty at the 13 top-ranked institutions listed in the 2021 U.S. News and World Report. Primary, emeritus, adjunct, and affiliate faculty were included. Publicly available information was collected from institutional websites and other online sources. Statistical analyses were conducted using t -tests or Mann-Whitney tests, chi-squared or Fisher's exact tests, and multivariate logistic regression. The main outcome measured was internal hires, defined as faculty who had completed residency and/or fellowship training at their current institution. Results In total, 47.3% of faculty were internal hires who completed residency or fellowship at the same institution. Among externally trained faculty, 27.7% completed residency and 56.0% completed fellowship at another top 13 programs. Internal hires were more frequently fellowship-trained, had a greater number of publications, and practiced in smaller departments ( p < 0.001, p < 0.001, and p = 0.002, respectively). A greater proportion of internal hires held leadership positions ( p = 0.012). Faculty practicing in the Midwest or West and with more years since residency graduation were less likely (odds ratio [OR], 0.29, 95% confidence interval [CI], 0.18-0.48; OR, 0.49, 95% CI, 0.31-0.78; OR, 0.98, 95% CI, 0.97-0.99, respectively) to be internal hires. Faculty with non-R01 National Institutes of Health funding were more likely to be internal hires (OR, 1.82, 95% CI: 1.12-2.96). Conclusions Training institution is key to determining the institution of practice. These results may be beneficial for trainees to consider when selecting a training program.

Pearls and pitfalls of ChatGPT in medical oncology.

Recently, ChatGPT has drawn attention to the potential uses of artificial intelligence (AI) in academia. Here, we discuss how ChatGPT can be of value to medicine and medical oncology and the potential pitfalls that may be encountered.

Sex-based differences in safety and efficacy of catheter ablation for atrial fibrillation.

BACKGROUND: Studies have identified significant sex-based differences and disparities in the clinical presentation and treatment of atrial fibrillation (AF). Studies have shown women are less likely to be referred for catheter ablation, are older at the time of ablation, and are more likely to have recurrence after ablation. However, in most studies investigating AF ablation outcomes, the female cohorts were relatively small. The impact of sex on the outcome and safety of ablation procedures is still unclear. OBJECTIVE: To investigate sex-based differences in outcomes and complications after AF catheter ablation, with a significant female cohort METHOD: In this retrospective study, patients undergoing AF ablation from January 1, 2014, to March 31, 2021, were included. We investigated clinical characteristics, duration and progression of AF, number of EP appointments from diagnosis to ablation, procedural data, and procedure complications. RESULTS: Total of 1346 patients underwent first catheter ablation for AF during this period, including 896 (66.5%) male and 450 (33.4%) female patients. Female patients were older at the time of ablation (66.2 vs. 62.4 years; p < .001). Women had higher CHA2 DS2 -VASc (congestive heart failure, hypertension, age, diabetes, stroke, vascular disease, sex category) scores (3 vs. 2; p < .001) than men, expectedly, as the female sex warrants an additional point. 25.3% female patients had PersAF at the time of diagnosis versus 35.3% male patients (p < .001). At the time of ablation, 31.8% female patients had PersAF as compared to 43.1% male patients (p < .001), indicating progression of PAF to PersAF in both sexes. Women tried more AADs than men before ablation (1.13 vs. 0.98; p = .002). Male and female patients had no statistically significant difference in (a) arrhythmia recurrence at 1-year post ablation (27.7% vs. 30%; p = .38) or (b) procedural complication rate (1.8% vs. 3.1%; p = .56). CONCLUSION: Female patients were older and had higher CHA2 DS2 -VASc scores compared to males at the time of AF ablation. Women tried more AADs than men before ablation. One-year arrhythmia recurrence rates and procedural complications were similar in both sexes. No sex-based differences were observed in safety and efficacy of ablation.

Magnetic CoFe2O4 and NiFe2O4 Induced Self-Assembled Graphene Nanoribbon Framework with Excellent Properties for Li-Ion Battery.

A magnetically induced self-assembled graphene nanoribbons (GNRs) method is reported to synthesize MFe2O4/GNRs (M = Co,Ni). It is found that MFe2O4 compounds not only locate on the surface of GNRs but anchor on the interlayers of GNRs in the diameter of less than 5 nm as well. The in situ growth of MFe2O4 and magnetic aggregation at the joints of GNRs act as crosslinking agents to solder GNRs to build a nest structure. Additionally, combining GNRs with MFe2O4 helps to improve the magnetism of the MFe2O4. As an anode material for Li+ ion batteries, MFe2O4/GNRs can provide high reversible capacity and cyclic stability (1432 mAh g-1 for CoFe2O4/GNRs and 1058 mAh g-1 for NiFe2O4 at 0.1 A g-1 over 80 cycles).

Most Common Ophthalmic Diagnoses in Eye Emergency Departments: A Multicenter Study.

PURPOSE: To characterize the most common ophthalmic conditions seen in the emergency department (ED) DESIGN: Cross-sectional study METHODS: This is a multicenter study of 64,988 patients who visited the Bascom Palmer Eye Institute, Massachusetts Eye and Ear, Wills Eye Hospital, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1, 2019, until December 31, 2019. Demographic and primary diagnosis data were extracted including gender, age, race, ethnicity, insurance type, and ophthalmology consult status. Descriptive statistics were performed on all data using STATA IC 14 (64-bit). RESULTS: A total of 64,988 patients with primary ocular diagnoses were seen across all 4 EDs. The majority of patients were White (63.1%), non-Hispanic/Latino (64.8%), and female (52.3%). The most frequently seen age group was 50-64 years (28.6%). The most common diagnoses across all institutions were conjunctivitis (7.91%), corneal abrasions (5.61%), dry eye (4.49%), posterior vitreous detachments (4.15%), chalazions (3.71%), corneal ulcers (3.01%), subconjunctival hemorrhages (2.96%), corneal foreign bodies (2.94%), retinal detachments (2.51%), and glaucoma (2.12%). Specifically, viral conjunctivitis (2283 of 5139, 44.4%) and primary open-angle glaucoma (382 of 1379, 27.7%) were the most frequently seen subtypes of conjunctivitis and glaucoma. CONCLUSIONS: The most regularly treated ophthalmic conditions in high-volume EDs tend to be lower acuity diagnoses. To combat ED overcrowding and rising health care costs in the United States, we suggest diverting eye-related ED visits to a specialized eye ED service or same-day eye clinic appointment in addition to expanding education for patients and primary care clinicians.

Bamboo Nanocellulose/Montmorillonite Nanosheets/Polyethyleneimine Gel Adsorbent for Methylene Blue and Cu(II) Removal from Aqueous Solutions.

In recent years, the scarcity of pure water resources has received a lot of attention from society because of the increasing amount of pollution from industrial waste. It is very important to use low-cost adsorbents with high-adsorption performance to reduce water pollution. In this work, a gel adsorbent with a high-adsorption performance on methylene blue (MB) and Cu(II) was prepared from bamboo nanocellulose (BCNF) (derived from waste bamboo paper) and montmorillonite nanosheet (MMTNS) cross-linked by polyethyleneimine (PEI). The resulting gel adsorbent was characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS), etc. The results indicated that the MB and Cu(II) adsorption capacities of the resulting gel adsorbent increased with the solution pH, contact time, initial concentration, and temperature before equilibrium. The adsorption processes of MB and Cu(II) fitted well with the fractal-like pseudo-second-order model. The maximal adsorption capacities on MB and Cu(II) calculated by the Sips model were 361.9 and 254.6 mg/g, respectively. The removal of MB and Cu(II) from aqueous solutions mainly included electrostatic attraction, ion exchange, hydrogen bonding interaction, etc. These results suggest that the resulting gel adsorbent is an ideal material for the removal of MB and Cu(II) from aqueous solutions.

MiR-34a-5p promotes autophagy and apoptosis of ovarian granulosa cells via the Hippo-YAP signaling pathway by targeting LEF1 in chicken.

Follicular atresia is a natural physiological phenomenon in poultry reproduction. It is well known that follicular atresia is caused by both autophagy and apoptosis of granulosa cells. In current experiment, we evaluated the function of miR-34a-5p on autophagy and apoptosis in chicken follicular atresia. First, the follicular atresia model of chicken was successfully constructed by subcutaneous injection of tamoxifen (TMX), and found the expression of miR-34a-5p in the atresia follicles obviously increased. Then, we confirmed that miR-34a-5p accelerates autophagy and apoptosis of chicken granulose cells in vitro, and miR-34a-5p could induce apoptosis by mediating autophagy. Mechanistically, lymphoid enhancer binding factor 1 (LEF1) was deemed as a target gene for miR-34a-5p. On the contrary, LEF1 overexpression attenuated the autophagy and apoptosis of chicken granular cells. In addition, it was confirmed that the miR-34a-5p/LEF1 axis plays a regulatory role in chicken granulosa cells by mediating the Hippo-YAP signaling pathway. Taken together, this study demonstrated that miR-34a-5p contributes to autophagy and apoptosis of chicken follicular granulosa cells by targeting LEF1 to mediate the Hippo-YAP signaling pathway.

Effects of Small Peptide Supplementation on Growth Performance, Intestinal Barrier of Laying Hens During the Brooding and Growing Periods.

The growing period is a critical period for growth and development in laying hens. During this period, chicks grow rapidly, but are accompanied by unstable digestive function, incomplete organ development, and high mortality. Small peptide, a feed additive, which has been proved to promote intestinal development and immunity in poultry. In order to elucidate the effects of small peptides on growth performance, immunity, antioxidant capacity, and intestinal health of growing laying hens, a total of 900 Tianfu green shell laying hens (1-day-old) were randomly divided into 5 treatments with 6 replicates of 30 birds each in this 18-week trial. Dietary treatments included a corn-soybean meal-based diet supplemented with 0 g/kg, 1.5 g/kg, 3.0 g/kg, 4.5 g/kg and 6.0 g/kg small peptide, respectively. The results showed that the supplementation of small peptides significantly increased growth rate (P<0.05) in laying hens, as well as elevated the serum immunoglobulins (P<0.05) and antioxidant indices (P<0.05), however, it decreased inflammation parameters (P<0.05). The supplementation of small peptides enhanced the intestinal function by promoting gut development (P<0.05) and improving gut integrity (P<0.05), barrier function (P<0.05) and the diversity of gut microbiota (P<0.05) in the growing hens. The best performance was recorded among the hens fed 4.5 g/kg level of small peptide. Taken together, these results showed that small peptide supplementation could improve the economic value of growing hens by promoting growth rate, disease resistance, and the optimal amount of addition for Tianfu green shell laying hens was 4.5 g/kg.

CircCCDC91 regulates chicken skeletal muscle development by sponging miR-15 family via activating IGF1-PI3K/AKT signaling pathway.

Circular RNAs (circRNAs) has been reported in various tissues of animals and associated with multiple biological processes. From our previous sequencing data, we found a novel circRNA, circCCDC91 which was generated from exon 2 to 8 of the CCDC91 gene. We observed that circCCDC91 was differentially expressed in the chicken breast muscle among 4 different embryonic developmental time points (embryonic day 10 [E10], E13, E16, and E19). Therefore, we assumed that circCCDC91 have a potential function in chicken skeletal muscle development. In this study, we firstly verify the annular structure and expression pattern of circCCDC91, and further investigate on whether circCCDC91 could promote chicken skeletal development. Mechanistically, circCCDC91 could absorb miR-15a, miR-15b-5p, and miR-15c-5p to modulate the expression of Insulin receptor substrate1 (IRS1), as well as activate insulin-1ike growth factor 1-phosphatidylinositol 3-kinase/AKT (IGF1-PI3K/AKT) signaling pathway. In addition, circCCDC91 could rescue skeletal muscle atrophy by activating IGF1-PI3K/AKT pathway. Taken together, the findings in this study revealed that the newly identified circCCDC91 promotes myoblasts proliferation and differentiation, and alleviates skeletal muscle atrophy by directly binding to miR-15 family via activating IGF1-PI3K/AKT signaling pathway in chicken.

Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy.

FilaminC (Flnc) is a member of the actin binding protein family, which is preferentially expressed in the cardiac and skeletal muscle tissues. Although it is known to interact with proteins associated with myofibrillar myopathy, its unique role in skeletal muscle remains largely unknown. In this study, we identify the biological functions of Flnc in vitro and in vivo using chicken primary myoblast cells and animal models, respectively. From the results, we observe that the growth rate and mass of the skeletal muscle of fast-growing chickens (broilers) were significantly higher than those in slow-growing chickens (layers). Furthermore, we find that the expression of Flnc in the skeletal muscle of broilers was higher than that in the layers. Our results indicated that Flnc was highly expressed in the skeletal muscle, especially in the skeletal muscle of broilers than in layers. This suggests that Flnc plays a positive regulatory role in myoblast development. Flnc knockdown resulted in muscle atrophy, whereas the overexpression of Flnc promotes muscle hypertrophy in vivo in an animal model. We also found that Flnc interacted with dishevelled-2 (Dvl2), activated the wnt/ß-catenin signaling pathway, and controlled skeletal muscle development. Flnc also antagonized the LC3-mediated autophagy system by decreasing Dvl2 ubiquitination. Moreover, Flnc knockdown activated and significantly increased mitophagy. In summary, these results indicate that the absence of Flnc induces autophagy or mitophagy and regulates muscle atrophy.

Circular RNA circFNDC3AL Upregulates BCL9 Expression to Promote Chicken Skeletal Muscle Satellite Cells Proliferation and Differentiation by Binding to miR-204.

Skeletal muscle is a heterogeneous tissue that is essential for initiating movement and maintaining homeostasis. The genesis of skeletal muscle is an integrative process that lasts from embryonic development to postnatal stages, which is carried out under the modulation of many factors. Recent studies have shown that circular RNAs (circRNAs), a class of non-coding RNAs, are involved in myogenesis. However, more circRNAs and their mechanisms that may regulate skeletal muscle development remain to be explored. Through in-depth analysis of our previous RNA-Seq data, circFNDC3AL was found to be a potentially functional circRNA highly expressed during embryonic development of chicken skeletal muscle. Therefore, in this study, we investigated the effect of circFNDC3AL on skeletal muscle development in chickens and found that circFNDC3AL promoted chicken skeletal muscle satellite cell (SMSC) proliferation and differentiation. To gain a thorough understanding of the exact modulatory mechanisms of circFNDC3AL in chicken skeletal muscle development, we performed target miRNA analysis of circFNDC3AL and found that circFNDC3AL has a binding site for miR-204. Subsequently, we demonstrated that miR-204 inhibited chicken SMSC proliferation and differentiation, which showed the opposite functions of circFNDC3AL. Furthermore, we identified the miR-204 target gene B-cell CLL/lymphoma 9 (BCL9) and validated that miR-204 had an inhibitory effect on BCL9, while the negative effect could be relieved by circFNDC3AL. In addition, we verified that BCL9 performed the same positive functions on chicken SMSC proliferation and differentiation as circFNDC3AL, as opposed to miR-204. In conclusion, our study identified a circRNA circFNDC3AL that upregulates BCL9 expression to promote the proliferation and differentiation of chicken SMSCs by binding to miR-204.