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The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on ß-catenin regulates the patterning of dorsoventral, anteroposterior, and left-right axes. Non-canonical Wnt signaling that is independent of ß-catenin modulates cytoskeletal organization to coordinate cell polarity changes and asymmetric cell movements. It is now well documented that components of these Wnt pathways biochemically and functionally interact to mediate cell-cell communications and instruct cellular polarization in breaking the embryonic symmetry. The dysfunction of Wnt signaling disrupts embryonic axis specification and proper tissue morphogenesis, and mutations of Wnt pathway genes are associated with birth defects in humans. This review discusses the regulatory roles of Wnt pathway components in embryonic axis formation by focusing on vertebrate models. It highlights current progress in decoding conserved mechanisms underlying the establishment of asymmetry along the three primary body axes. By providing an in-depth analysis of canonical and non-canonical pathways in regulating cell fates and cellular behaviors, this work offers insights into the intricate processes that contribute to setting up the basic body plan in vertebrate embryos.

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The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants, called germ plasm, confer germline fate in the early embryo. Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development. RNA-binding proteins, acting in concert with other germ plasm components, play essential roles in the organization of the germ plasm and the specification, migration, maintenance, and differentiation of primordial germ cells. The loss of their functions impairs germ cell formation and causes sterility or sexual conversion. Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells. However, the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification. Because failure to control the developmental outcome of germ cells disrupts the formation of gametes, it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage. This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.

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PURPOSE: To analyze the influence of propranolol (Prop) plus methimazole (MMI) on curative efficacy and thyroid function (TF) of patients with hyperthyroidism (HT). METHODS: In this retrospective study, 107 cases of HT presented between August 2019 and August 2021 were grouped according to different therapeutic regimens: a control group (the Con) with 53 cases treated with MMI, and a research group (the Res) with 54 cases treated with Prop + MMI. Inter-group comparisons were performed in terms of the following domains: heart rate (HR), efficacy, adverse reactions (ARs), TF parameters (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH), hepatic function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST), and quality of life (Short-Form 36 Item Health Survey, SF-36). Finally, multivariate analysis was performed by Logistic regression to determine the risk factors leading to the ineffectiveness of treatment. RESULTS: The analysis showed an obviously higher total effective rate and an evidently lower AR rate in the Res compared with the Con group. Besides, the Res group had notably lower FT3, FT4, ALT and AST and statistically higher TSH after treatment compared with the baseline (before treatment) and the Con group. Higher SF-36 scores were also determined in the Res group. Finally, the results of Logistic regression analysis revealed that AST was an independent risk factor for ineffective treatment. CONCLUSIONS: Prop plus MMI is effective in the treatment of HT, which can effectively improve the HR, thyroid hormone levels, hepatic function, and quality of life of patients, with a lower incidence of ARs.

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The post-transcriptional regulation of gene expression plays an important role in heart development and disease. Cardiac-specific alternative splicing, mediated by RNA-binding proteins, orchestrates the isoform switching of proteins that are essential for cardiomyocyte organization and contraction. Dysfunctions of RNA-binding proteins impair heart development and cause the main types of cardiomyopathies, which represent a heterogenous group of abnormalities that severely affect heart structure and function. In particular, mutations of RBM20 and RBFOX2 are associated with dilated cardiomyopathy, hypertrophic cardiomyopathy, or hypoplastic left heart syndrome. Functional analyses in different animal models also suggest possible roles for other RNA-binding proteins in cardiomyopathies because of their involvement in organizing cardiac gene programming. Recent studies have provided significant insights into the causal relationship between RNA-binding proteins and cardiovascular diseases. They also show the potential of correcting pathogenic mutations in RNA-binding proteins to rescue cardiomyopathy or promote cardiac regeneration. Therefore, RNA-binding proteins have emerged as promising targets for therapeutic interventions for cardiovascular dysfunction. The challenge remains to decipher how they coordinately regulate the temporal and spatial expression of target genes to ensure heart function and homeostasis. This review discusses recent advances in understanding the implications of several well-characterized RNA-binding proteins in cardiomyopathies, with the aim of identifying research gaps to promote further investigation in this field.

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Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

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Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.

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Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations.

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The effects of different cooking methods (steaming, boiling, air frying, and oven baking) and cooking times (0, 5, 10, 15, and 20 min) on the bioactive components (total phenol, total flavonoid, crude polysaccharides, and eritadenine), color, texture, microstructure, and volatiles in shiitake mushrooms were investigated in this study. Steaming, boiling, and air frying for 5-20 min could decrease the contents of all the four bioactive components in the shiitake mushroom. However, oven baking for 5 min and 10 min showed the highest contents of total phenolics and total flavonoids, respectively. Moreover, the lowest losses of crude polysaccharides and eritadenine were observed for oven baking for 5 min and 15 min, respectively. The lightness of shiitake mushrooms was decreased by all treatments; however, steaming could keep a higher brightness compared with other methods. The microstructure was damaged by all cooking methods, especially air frying for 20 min. Meanwhile, steaming for 20 min decreased the hardness mostly, and there was no significant difference with air frying for 20 min. All cooking treatments decreased the complexity of the flavors and the relative contents of volatile compounds; the lowest contents were found when boiling for 5 min. From these results it can be seen that the physical, histological, and chemical features in shiitake mushroom were influenced by cooking methods and times. In addition, our results provide valuable information for the cooking and processing of shiitake mushrooms and other fungi.

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BACKGROUND: Laparoscopic-assisted colorectal surgery is an effective surgery to treat colorectal cancer. During the laparoscopic-assisted colorectal surgery, a midline incision and several trocar insertions are required during the surgery. OBJECTIVE: To observe whether the rectus sheath block based on the locations of the surgical incision and trocars can significantly reduce the pain score on the first day after surgery. DESIGN: This study was a prospective, double-blinded, randomized controlled trial approved by the Ethics Committee of First Affiliated Hospital of Anhui Medical University (registration number: ChiCTR2100044684). SETTINGS: All patients were recruited from 1 hospital. PATIENTS: Forty-six patients aged 18 to 75 years undergoing elective laparoscopic-assisted colorectal surgery were successfully recruited, and 44 patients completed the trial. INTERVENTIONS: Patients in the experimental group received rectus sheath block, with 0.4% ropivacaine 40 to 50 mL, whereas the control group received an equal volume of normal saline. MAIN OUTCOME MEASURES: The primary outcome was pain score on postoperative day 1. Secondary outcomes included patient-controlled analgesia use at 24 and 48 hours after surgery and pain score at 6, 12, and 48 hours after surgery. RESULTS: Pain scores at rest and during activity at 6, 12, 24, and 48 hours after surgery and patient-controlled analgesia consumption of patients on the first day after surgery were significantly lower in the experimental group than those in the control group (all p < 0.05). LIMITATIONS: We did not separate pain into visceral and somatic pain because patients often had difficulty differentiating the source of pain. CONCLUSIONS: Our research indicates that in the context of multimodal analgesia, the rectus sheath block according to the midline incision and the positions of the trocars can reduce the pain scores and consumption of analgesic drugs on the first day after surgery for patients undergoing laparoscopic-assisted colorectal surgery. LA EFICIENCIA DEL BLOQUEO DE LA VAINA DEL RECTO DE VARIOS PUNTOS SEGN LA UBICACIN DE LA INCISIN EN LA CIRUGA COLORRECTAL ASISTIDA POR LAPAROSCOPIA UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La cirugía colorrectal asistida por laparoscopia es una cirugía eficaz para tratar el cáncer colorrectal. Durante la cirugía colorrectal asistida por laparoscopia, se requiere una incisión en la línea media y varias inserciones de trócaresOBJETIVO:El propósito de nuestro estudio fue observar si el bloqueo de la vaina del recto basado en las ubicaciones de la incisión quirúrgica y los trocares puede reducir significativamente la puntuación del dolor en el primer día después de la cirugía.DISEÑO:Este estudio fue un ensayo controlado aleatorio prospectivo, doble ciego, aprobado por el Comité de Ética del Primer Hospital Afiliado de la Universidad Médica de Anhui (número de registro: ChiCTR2100044684).ESCENARIO:Todos los pacientes fueron reclutados en un hospital.PACIENTES:Cuarenta y seis pacientes de 18 a 75 años de edad que se sometieron a cirugía colorrectal electiva asistida por laparoscopía fueron reclutados con éxito y cuarenta y cuatro pacientes completaron el ensayo.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueo de la vaina del recto con 40-50 ml de ropivacaína al 0.4%, mientras que el grupo de control recibió el mismo volumen de solución salina normal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la puntuación del dolor en el día 1 postoperatorio. Los resultados secundarios incluyeron el uso de analgesia controlada por el paciente a las 24 y 48 horas después de la cirugía y la puntuación del dolor a las 6, 12, y 48 horas después de la cirugía.RESULTADOS:Las puntuaciones de dolor en reposo y durante la actividad a las 6, 12, 24, y 48 horas después de la cirugía, y el consumo de PCA de los pacientes el primer día después de la cirugía fueron significativamente más bajos en el grupo experimental que en el grupo control (todos p < 0.05).LIMITACIONES:No separamos el dolor en dolor visceral y somático porque los pacientes a menudo tenían dificultades para diferenciar la fuente del dolor.CONCLUSIONES:Nuestra investigación indica que, en el contexto de la analgesia multimodal, el bloqueo de la vaina del recto de acuerdo con la incisión de la línea media y las posiciones de los trócares pueden reducir los puntajes de dolor y el consumo de analgésicos en el primer día después de la cirugía para pacientes sometidos a cirugía colorrectal laparoscópica. (Traducción-Dr. Jorge Silva Velazco ).

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The carbon source, an essential factor for submerged culture, affects fungal polysaccharides production, structures, and activities. This study investigated the impact of carbon sources, including glucose, fructose, sucrose, and mannose, on mycelial biomass and the production, structural characterization, and bioactivities of intracellular polysaccharides (IPS) produced by submerged culture of Auricularia auricula-judae. Results showed that mycelial biomass and IPS production varied with different carbon sources, where using glucose as the carbon source produced the highest mycelial biomass (17.22 ± 0.29 g/L) and IPS (1.62 ± 0.04 g/L). Additionally, carbon sources were found to affect the molecular weight (Mw) distributions, monosaccharide compositions, structural characterization, and activities of IPSs. IPS produced with glucose as the carbon source exhibited the best in vitro antioxidant activities and had the strongest protection against alloxan-damaged islet cells. Correlation analysis revealed that Mw correlated positively with mycelial biomass (r = 0.97) and IPS yield (r = 1.00), while IPS antioxidant activities correlated positively with Mw and negatively with mannose content; the protective activity of IPS was positively related to its reducing power. These findings indicate a critical structure-function relationship for IPS and lay the foundation for utilizing liquid-fermented A. aruicula-judae mycelia and the IPS in functional food production.

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Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it becomes upregulated after cardiac injury. Both gain- and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N6-methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair.

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The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.HighlightsCircRRAS2 expression is higher in DM cells than in GM cells.CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.

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OBJECTIVE: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors. METHODS: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes. RESULTS: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts. CONCLUSIONS: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients.

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Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one of the most abundant components of exosomes, exosomal proteins have been revealed to participate in the development of many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune responses, cardiovascular diseases, and infection. Thus, understanding the functions and mechanisms of exosomal proteins potentially assists clinical diagnosis and targeted delivery of therapies. However, current knowledge about the function and application of exosomal proteins is still limited. In this review, we summarize the classification of exosomal proteins, and the roles of exosomal proteins in exosome biogenesis and disease development, as well as in the clinical applications.

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BACKGROUND: Profound trauma from laparoscopic-assisted gastrectomy (LAG) requires medication with a large number of opioids. The purpose of our study was to observe whether an incision-based rectus sheath block (IBRSB) based on the locations of the surgical incision could significantly reduce the consumption of remifentanil during LAG. METHODS: A total of 76 patients were included. The patients were prospectively randomized into two groups. Patients in group IBRSB (n = 38) received ultrasound-guided IBRSB, and the patients received 0.4% ropivacaine 40-50 mL. Patients in group C (n = 38) received the same IBRSB with 40-50 mL normal saline. The following were recorded: the consumption of remifentanil and sufentanil during surgery, pain scores at rest and during conscious activity in the post-anesthesia care unit (PACU) and at 6, 12, 24, and 48 h after surgery, and use of the patient-controlled analgesia (PCA) at 24 and 48 h after surgery. RESULTS: A total of 60 participants completed the trial. The consumption of remifentanil and sufentanil in group IBRSB were significantly lower than that in group C (p < 0.001). Pain scores at rest and during conscious activity in the PACU and at 6, 12, 24, and 48 h after surgery and patients' PCA consumption within 48 h of surgery were significantly lower in group IBRSB than in group C (all p < 0.05). CONCLUSIONS: IBRSB based on incision multimodal anesthesia can effectively reduce the consumption of opioids during LAG, improving the postoperative analgesic effect and increasing patients' satisfaction.

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The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six "core" proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization. In vertebrates, all these pathways are essential for tissue and organ morphogenesis, such as neural tube closure, left-right symmetry breaking, heart and gut morphogenesis, lung and kidney branching, stereociliary bundle orientation, and proximal-distal limb elongation. Mutations in planar polarity genes are closely linked to various congenital diseases. Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing organs and the maintenance of tissue homeostasis. The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification. Interdisciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation. This review outlines current advances on planar polarity regulators in asymmetric organ formation, with the aim to identify questions that deserve further investigation.

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Postoperative delirium (POD) is common in the elderly and is associated with poor clinical outcomes. Reactive oxygen species (ROS) and blood-brain barrier (BBB) damage have been implicated in the development of POD, but the association between these two factors and the potential mechanism is not clear. Cyclophilin A (CypA) is a specifically chemotactic leukocyte factor that can be secreted in response to ROS, which activates matrix metalloproteinase 9 (MMP9) and mediates BBB breakdown. We, therefore, hypothesized that ROS may contribute to anesthesia/surgery-induced BBB damage and delirium-like behavior via the CypA/MMP9 pathway. To test these hypotheses, 16-month-old mice were subjected to laparotomy under 3% sevoflurane anesthesia (anesthesia/surgery) for 3 h. ROS scavenger (N-acetyl-cysteine) and CypA inhibitor (Cyclosporin A) were used 0.5 h before anesthesia/surgery. A battery of behavior tests (buried food test, open field test, and Y maze test) was employed to evaluate behavioral changes at 24 h before and after surgery in the mice. Levels of tight junction proteins, CypA, MMP9, postsynaptic density protein (PSD)-95, and synaptophysin in the prefrontal cortex were assessed by western blotting. The amounts of ROS and IgG in the cortex of mice were observed by fluorescent staining. The concentration of S100ß in the serum was detected by ELISA. ROS scavenger prevented the reduction in TJ proteins and restored the permeability of BBB as well as reduced the levels of CypA/MMP9, and further alleviated delirium-like behavior induced by anesthesia/surgery. Furthermore, the CypA inhibitor abolished the increased levels of CypA/MMP, which reversed BBB damage and ameliorated delirium-like behavior caused by ROS accumulation. Our findings demonstrated that ROS may participate in regulating BBB permeability in aged mice with POD via the CypA/MMP9 pathway, suggesting that CypA may be a potential molecular target for preventing POD.

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Gastrulation and neurulation are successive morphogenetic processes that play key roles in shaping the basic embryonic body plan. Importantly, they operate through common cellular and molecular mechanisms to set up the three spatially organized germ layers and to close the neural tube. During gastrulation and neurulation, convergent extension movements driven by cell intercalation and oriented cell division generate major forces to narrow the germ layers along the mediolateral axis and elongate the embryo in the anteroposterior direction. Apical constriction also makes an important contribution to promote the formation of the blastopore and the bending of the neural plate. Planar cell polarity proteins are major regulators of asymmetric cell behaviors and critically involved in a wide variety of developmental processes, from gastrulation and neurulation to organogenesis. Mutations of planar cell polarity genes can lead to general defects in the morphogenesis of different organs and the co-existence of distinct congenital diseases, such as spina bifida, hearing deficits, kidney diseases, and limb elongation defects. This review outlines our current understanding of non-canonical Wnt signaling, commonly known as Wnt/planar cell polarity signaling, in regulating morphogenetic movements of gastrulation and neural tube closure during development and disease. It also attempts to identify unanswered questions that deserve further investigations.

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RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level. They play major roles in the tissue- and stage-specific expression of protein isoforms as well as in the maintenance of protein homeostasis. The inner ear is a bi-functional organ, with the cochlea and the vestibular system required for hearing and for maintaining balance, respectively. It is relatively well documented that transcription factors and signaling pathways are critically involved in the formation of inner ear structures and in the development of hair cells. Accumulating evidence highlights emerging functions of RBPs in the post-transcriptional regulation of inner ear development and hair cell function. Importantly, mutations of splicing factors of the RBP family and defective alternative splicing, which result in inappropriate expression of protein isoforms, lead to deafness in both animal models and humans. Because RBPs are critical regulators of cell proliferation and differentiation, they present the potential to promote hair cell regeneration following noise- or ototoxin-induced damage through mitotic and non-mitotic mechanisms. Therefore, deciphering RBP-regulated events during inner ear development and hair cell regeneration can help define therapeutic strategies for treatment of hearing loss. In this review, we outline our evolving understanding of the implications of RBPs in hair cell formation and hearing disease with the aim of promoting future research in this field.

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