Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA.

Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in multiple diseases, PC has been regarded as a potential therapeutic target for obesity, diabetes, and cancer. Albeit acetyl-CoA has been recognized as the allosteric regulator of PC for over 60 years, the underlying mechanism of how acetyl-CoA induces PC activation remains enigmatic. Herein, by using time-resolved cryo-electron microscopy, we have captured the snapshots of PC transitional states during its catalytic cycle. These structures and the biochemical studies reveal that acetyl-CoA stabilizes PC in a catalytically competent conformation, which triggers a cascade of events, including ATP hydrolysis and the long-distance communication between the two reactive centers. These findings provide an integrated picture for PC catalysis and unveil the unique allosteric mechanism of acetyl-CoA in an essential biochemical reaction in all kingdoms of life.

Structural basis of nucleosome recognition and modification by MLL methyltransferases.

Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development1-6. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities7-9. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown10-12. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification.

Effects of early-life gut microbiota on the neurodevelopmental outcomes of preterm infants: a multi-center, longitudinal observational study in China.

To prospectively investigate associations between the features of gut microbiota at the fourth week after birth in preterm infants and neurodevelopment from 1 month of corrected age to 6 months of corrected age (MCA). Seventy-seven preterm infants were recruited from three NICUs of three tertiary hospitals between Apr 2021 to Sep 2022. Stool samples were collected during the fourth week after birth. Illumina MiSeq high-throughput sequencing technology was used to detect the composition and diversity of gut microbiota. Neurodevelopment assessments of preterm infants were conducted at 1, 3, and 6 MCA using the Ages and Stages Questionnaire, the third edition (ASQ-3). Spearman correlation, a generalized linear mixed model (GLMM), and permutational multivariate analysis of variance (PERMANOVA) analysis were used to horizontally and prospectively explore the associations between gut microbial and ASQ-3 dimension scores at each time point. The GLMM showed no significant associations between the alpha diversity and neurodevelopmental trajectory from 1 to 6 MCA. The beta diversity was significantly associated with gross motor scores at 1, 3, and 6 MCA (R2 = 0.067, p = 0.001; R2 = 0.039, p = 0.020; R2 = 0.031, p = 0.047); communication scores at 3 MCA (R2 = 0.030, p = 0.040); and fine motor scores at 6 MCA (R2 = 0.035, p = 0.022). After adjusting for covariates, the GLMM showed that the relative abundance of Klebsiella was negatively associated with gross motor score trajectory from 1 to 6 MCA (ß = - 1.449; 95% CI, - 2.275 to - 0.572; p = 0.001), while the relative abundance of Lactobacillus displayed a positive association (ß = 1.421; 95% CI, 0.139 to 2.702; p = 0.030). Moreover, the relative abundance of Streptococcus was negatively associated with fine motor trajectory from 1 to 6 MCA (ß = - 1.669; 95% CI, - 3.305 to - 0.033; p = 0.046). CONCLUSION: Our results suggest a possible association between the neonatal gut microbial diversity; the relative abundance of Klebsiella, Streptococcus, and Lactobacillus; and neurodevelopment from 1 to 6 MCA. In the future, clinical staff can focus on the window period of gut microbiota colonization, and implement probiotics targeted at the dominant genera to improve the neurodevelopment of preterm infants. WHAT IS KNOWN: • In the fields of biology and medicine, current studies suggest that gut microbiota may play an important role in the critical window period of neurodevelopment through the gut-brain axis pathway. • Extensive preclinical research has implied the vital role of the initial gut colonization in the long-term neurodevelopment of children. WHAT IS NEW: • The early-life gut microbiota was associated with neurodevelopment in preterm infants within 6 months of corrected age (MCA).

Morphological Aesthetics Assessment of the Predicted 3D Simulation Results and the Actual Results of Breast Augmentation.

BACKGROUND: Although three-dimensional (3D) simulations are becoming more common in preoperative breast augmentation planning, this does not necessarily imply that the simulated results are highly accurate. OBJECTIVES: We aimed to evaluate the accuracy of the 3D simulation technique by comparing the differences in breast morphology between the 3D prediction model and the actual results. METHODS: The simulation and actual postoperative results of 103 patients who underwent breast augmentation were analyzed retrospectively. Therefore, a 3D model was created, and the parameters of line spacing, nipple position, breast projection, surface area, and volume were evaluated. Furthermore, consider the difference in chest circumferences and breast volume. RESULTS: In comparison with the simulation results, the actual results had a mean increase in the nipple to the inframammary fold (N-IMF) of 0.3 cm (P < 0.05) and a mean increase in basal breast width (BW) of 0.3 cm (P < 0.001), a difference that was not statistically significant in patients with larger breast volumes. There was a significant difference in the mean upper and lower breast volume distribution between simulated and actual breasts (upper pole 52.9% vs. 49.2%, P < 0.05, and lower pole 47.1% vs. 50.8%, P < 0.001). However, it was not statistically significant in patients with larger chest circumferences. CONCLUSIONS: Our study shows that 3D simulation has uncertainties related to the patient's chest circumference and breast volume. Therefore, these two critical factors must be considered when using simulation assessment in preoperative planning. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical Relevance of the Variability of the Infraorbital Arterial Anatomy Evaluated by Three-Dimensional Computed Tomography.

BACKGROUND: Knowledge of the anatomy of the infraorbital artery (IOA) is crucial for the rejuvenation of the anterior medial aspect of the midface; however, studies adequately describing the anatomy of the IOA branches are lacking, and their connection with the ophthalmic artery branches remains unclear. OBJECTIVES: This study aims to elucidate the anatomical characteristics of the IOA in its deployment within the lower eyelid using three-dimensional (3D) technology, thereby offering an anatomical foundation for clinical surgical procedures. METHODS: An analysis was conducted on computed tomography scans of 132 cadaveric head sides post-contrast injection, utilizing the Mimics software for reconstruction. The study focused on examining the anastomosis of the IOA, its principal branches, and the branches emanating from the ophthalmic artery. RESULTS: The prevalence of type I IOA was observed at 38.6% (51/132), while Type II IOA was found in 61.4% (81/132) of cases. A 7.6% incidence (10/132) of IOA directly anastomosing with the angular artery was noted. The presence of palpebral branches (PIOA) was identified in 57.6% (76/132) of instances. In the lower eyelid, four distinct distribution patterns of IOA were discerned: The likelihood of Type I PIOA was 5.3%, whereas for Types IIA, IIB, and IIC PIOA, the probabilities were 8.3%, 32.6%, and 11.4%, respectively. The occurrence of the orbital branch of IOA was recorded at 41.7% (55/132). CONCLUSIONS: 3D technology can map IOA variants and identify the deployment patterns of IOA branches in the lower eyelid vascular vesicles at high resolution as a guide in clinical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Safety of Injections in the Infraorbital Region.

BACKGROUND:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications. OBJECTIVE:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection. METHODS:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution. RESULTS:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%). CONCLUSION:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exploring Effect of Postdischarge Developmental Support Program on Preterm Infant Neurodevelopment and BDNF Gene DNA Methylation.

BACKGROUND: Although developmental supportive care is an effective approach to improve the long-term psychomotor and/or neurobehavioral function of preterm infants, very limited studies have focused on the impact of after-discharge developmental support. The underlying epigenetic changes are unclear. PURPOSE: This study aimed to explore the preliminary effect of an evidence-based Postdischarge Developmental Support Program (PDSP) on preterm infant neurodevelopment and underlying epigenetic changes, including brain-derived neurotrophic factor (BDNF) gene-related DNA methylation and expression. METHODS: In this randomized controlled pilot trial, the preterm infant-parent dyads were randomized into either the intervention group/PDSP group (n = 22) or the control group/usual care group (n = 22). The neurodevelopmental outcomes of preterm infants were measured by Ages & Stages Questionnaires. Urine BDNF concentration level was tested by the enzyme-linked immunosorbent assay. Infant saliva specimens were collected to analyze the methylation level of BDNF gene promoter I at pre- and postintervention test. RESULTS: After PDSP intervention, the total neurodevelopmental and the 5 domain scores of the PDSP group were all significantly higher than those of the control group ( P < .05). The BDNF levels decreased significantly only within control group ( P = .01). The difference in BDNF concentration and methylation levels between groups was not statistically significant. IMPLICATIONS FOR PRACTICE AND RESEARCH: Postdischarge Developmental Support Program may promote the neurodevelopment of preterm infants but has no effect on BDNF's expression and gene methylation level at 3 months of corrected age. The epigenetic mechanism of PDSP needs further study using a larger sample and longer follow-up.

The relationship between NICU stress and neurodevelopmental outcomes of preterm infants: A multi-center prospective cohort study in China.

PURPOSE: To examine the relationship between NICU stress exposure and the neurodevelopmental outcomes of preterm infants. DESIGN AND METHODS: A multicenter, prospective cohort study was conducted between May 2021 and June 2022. Preterm infant participants (28-34 weeks gestational age) were recruited at birth from three NICUs of three tertiary hospitals by convenience sampling. The NICU stress includes acute NICU stress and chronic NICU stress which were measured over the total NICU hospitalization for each infant using the Neonatal Infant Stressor Scale (NISS). Neurodevelopmental outcomes of preterm infants were assessed at 3 months corrected age (CA) using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: Of one hundred and thirty preterm infant participants, 108 preterm infants were included into analysis. Results showed that acute NICU stress exposure significantly predicted the neurodevelopmental abnormalities in communication function (RR: 1.001, 95%CI: 1.000-1.001, p = .011), while chronic NICU stress exposure was significantly associated with the problem-solving function (RR: 1.003, 95%CI: 1.001-1.005, p = .002) at 3 months CA. No significant associations were found between NICU stress exposure and other dimensions of neurodevelopmental outcomes, including gross motor, fine motor, and personal-social functions. CONCLUSION: NICU stress exposure demonstrated a significant predicting relationship with abnormalities in communication and problem-solving functions of preterm infants at 3 months CA. PRACTICE IMPLICATIONS: During the NICU hospitalization, neonatal health caregivers should systematically monitor the NICU stress exposure to prevent neurodevelopmental problems in preterm infants.

Cardiovascular-specific PSEN1 deletion leads to abnormalities in calcium homeostasis.

Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia-induced failing hearts. Functionally, cardiovascular specific PSEN1 deletion led to spontaneous death of the mice due to cardiomyopathy. At the age of 11 months, the ratio of the heart weight/body weight was slightly lower in the Sm22a-PSEN1-KO mice compared with that of the WT mice. Echocardiography showed that the percentage of ejection fraction and fractional shortening was significantly reduced in the Sm22a-PSEN1-KO group compared with the percent of these measures in the WT group, indicating that PSEN1-KO resulted in heart failure. The abnormally regulated genes resulted from PSEN1-KO were detected to be enriched in muscle development and dilated cardiomyopathy. Among them, several genes encode Ca2+ ion channels, promoting us to investigate the effects of PSEN1 KO on regulation of Ca2+ in isolated adult cardiomyocytes. Consistently, in isolated adult cardiomyocytes, PSEN1-KO increased the concentration of cytosolic Ca2+ and reduced Ca2+ concentration inside the sarcoplasmic reticulum (SR) lumen at the resting stage. Additionally, SR Ca2+ was decreased in the failing hearts of WT mice, but with the lowest levels observed in the failing hearts of PSEN1 knockout mice. These results indicate that the process of Ca2+ release from SR into cytoplasm was affected by PSEN1 KO. Therefore, the abnormalities in Ca2+ homeostasis resulted from downregulation of PSEN1 in failing hearts might contribute to aging-related cardiomyopathy, which might had important implications for the treatment of aging-related heart diseases.

Isolation of Peptide Inhibiting SGC-7901 Cell Proliferation from Aspongopus chinensis Dallas.

Aspongopus chinensis Dallas is used as a traditional Chinese medicine as well as an edible insect. Although its anti-tumor effects have been observed, the anti-tumor active component(s) in the hemolymph of A. chinensis remains unknown. In this study, a combination usage of ultrafiltration, gel filtration chromatography, FPLC and RP-HPLC to separate and purify active peptides was performed based on the proliferation of the human gastric cancer SGC-7901 cell line treated with candidates. One peptide (MW = 2853.3 Da) was isolated from the hemolymph of A. chinensis. A total of 24 amino acid residues were continuously determined for the active peptide: N'-ECGYCAEKGIRCDDIHCCTGLKKK-C'. In conclusion, a peptide that can inhibit the proliferation of gastric cancer SGC-7901 cells in the hemolymph of A. chinensis was purified in this study, which is homologous to members of the spider toxin protein family. These results should facilitate further works for this peptide, such as the cloning of genes, expression in vitro by prokaryotic or eukaryotic systems, more specific tests of anti-tumor activity, and so on.

[Analysis of three patients with KBG syndrome and epileptic seizures due to variants of ANKRD11 gene].

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION: Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.

hCINAP is potentially a direct target gene of HIF-1 and is required for hypoxia-induced EMT and apoptosis in cervical cancer cells.

The early metastasis of cervical cancer is a multistep process requiring the cancer cells to adapt to the signal input from different tissue environments, including hypoxia. Hypoxia-induced epithelial-to-mesenchymal transition (EMT) plays a critical role in the ability to invade surrounding tissues. However, the molecular mechanisms underlying EMT in cervical cancer remain to be elucidated. Herein, we show that hypoxia-inducible factor-1alpha (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT) are recruited to the human coilin-interacting nuclear ATPase protein (hCINAP) promoter and initiate hCINAP expression in hypoxia. Ablation of hCINAP decreased the migratory capacity and EMT of cervical cancer cells under hypoxic conditions. Furthermore, hCINAP regulated EMT through the Akt-mTOR signaling pathway, and inhibits hypoxia-induced p53-dependent apoptosis. Our data collectively show that hCINAP may have essential roles in the metastasis of cervical cancer and could be a potential target for curing cervical cancer.

Knowledge, Attitudes and Practices of COVID-19 Among Urban and Rural Residents in China: A Cross-sectional Study.

This study aims to understand the knowledge, attitudes and practices of COVID-19 in the Chinese context and to provide insights for developing targeted outbreak prevention and control measures among the general public. We conducted an online survey of urban and rural residents in Henan Province. A total of 517 valid questionnaires were collected via the online platform. The mean scores for knowledge and practice were 5.57/9 and 2.04/3, respectively. More than 90% of the participants believed COVID-19 was serious and preventable, were concerned about the disease process, and actively engaged in learning related knowledge. Our results showed that the COVID-19 knowledge level was significantly different among groups with different ages, genders, education levels and marital statuses; COVID-19 practice was significantly different among different regions. Multiple linear regression analysis showed that education level, female sex, unmarried status, and health care worker status had a significant impact on COVID-19 knowledge; urban area was associated with a higher practice score; COVID-19 knowledge was significantly associated with residents' attitude toward preventive measures that can prevent COVID-19 infection; urban area was significantly related to the willingness to go to a fever clinic to check for suspected infection. We found that Chinese urban and rural residents held a moderate level of COVID-19 knowledge and practice and showed a positive attitude toward the disease. It is necessary to develop relevant education programs targeting the general population in China to improve COVID-19-related knowledge, attitudes and practices, particularly for rural and undereducated residents.

[New variants in FLNA gene cause periventricular nodular heterotopia and epileptic seizure in three cases].

OBJECTIVE: To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure. METHODS: The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants. RESULTS: In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively. CONCLUSION: The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.

Conditionally targeted deletion of PSEN1 leads to diastolic heart dysfunction.

Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established four types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology. PSEN1 null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. PSEN1 knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes. Cardiovascular loss of function of PSEN1 induced by Sm22a-Cre or Myh6-Cre/ER/tamoxifen also resulted in severe ultrastructural abnormalities, such as relaxed gap junctions between neighboring cardiomyocytes. Functionally, cardiovascular deletion of PSEN1 caused spontaneous mortality from birth to adulthood and led to diastolic heart dysfunction, including decreased volume of the left ventricle at the end-systolic and end-diastolic stages. Additionally, in a myocardial ischemia model, deletion of PSEN1 in the cardiovascular system first protected mice by inducing adaptive hypertrophy but ultimately resulted in severe heart failure. Furthermore, a collection of genes was abnormally expressed in the hearts of cardiac-specific PSEN1 knockout mice. They were enriched in cell proliferation, calcium regulation, and so on. Taken together, dynamic regulation and abnormal function of PSEN1 underlie the pathogenesis of cardiovascular diseases due to ultrastructural abnormality of cardiomyocytes.

Tunable assembly of amyloid-forming peptides into nanosheets as a retrovirus carrier.

Using and engineering amyloid as nanomaterials are blossoming trends in bionanotechnology. Here, we show our discovery of an amyloid structure, termed "amyloid-like nanosheet," formed by a key amyloid-forming segment of Alzheimer's Aß. Combining multiple biophysical and computational approaches, we proposed a structural model for the nanosheet that is formed by stacking the amyloid fibril spines perpendicular to the fibril axis. We further used the nanosheet for laboratorial retroviral transduction enhancement and directly visualized the presence of virus on the nanosheet surface by electron microscopy. Furthermore, based on our structural model, we designed nanosheet-forming peptides with different functionalities, elucidating the potential of rational design for amyloid-based materials with novel architecture and function.

Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis.

Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) family, comprising SMS1, SMS2 and SMS-related (SMSr) members. Although SMS1 and SMS2 exhibit SMS activity, SMSr possesses ceramide phosphoethanolamine synthase activity. Here we determined the cryo-electron microscopic structures of human SMSr in complexes with ceramide, diacylglycerol/phosphoethanolamine and ceramide/phosphoethanolamine (CPE). The structures revealed a hexameric arrangement with a reaction chamber located between the transmembrane helices. Within this structure, a catalytic pentad E-H/D-H-D was identified, situated at the interface between the lipophilic and hydrophilic segments of the reaction chamber. Additionally, the study unveiled the two-step synthesis process catalyzed by SMSr, involving PE-PLC (phosphatidylethanolamine-phospholipase C) hydrolysis and the subsequent transfer of the phosphoethanolamine moiety to ceramide. This research provides insights into the catalytic mechanism of SMSr and expands our understanding of sphingolipid metabolism.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Relationship between workplace bullying, spirituality, and job burnout in paediatric nurses: A cross-sectional study.

AIMS: To investigate the relationships and pathways between workplace bullying, workplace spirituality, and job burnout in Chinese paediatric nurses. DESIGN: A cross-sectional descriptive survey was conducted with paediatric nurses from six tertiary hospitals in Hubei Province, China. METHODS: The study consisted of 402 paediatric nurses. The data were collected using a sociodemographic data questionnaire, Negative Acts Questionnaire-Revised, Maslach Burnout Inventory-General Survey and Workplace Spirituality Scale. The model was tested using path analysis techniques within structural equation modelling. RESULTS: Workplace bullying had positive and direct effects on the job burnout of paediatric nurses. Workplace spirituality partially mediated the relationship between workplace bullying and burnout. PATIENT OR PUBLIC CONTRIBUTION: Workplace spirituality may reduce the incidence of work bullying and job burnout in paediatric nurses. Nursing managers need to consider and cultivate the workplace spirituality of paediatric nurses, with the aim of creating a healthy working environment and ensuring the stability of the nursing team.

Testing the effectiveness of motivation-based teaching in Nursing English course: A quasi-experimental study.

BACKGROUND: Motivation is a crucial factor in determining the student-learning process. Integrating the Attention, Relevance, Confidence, and Satisfaction (ARCS) motivation model into the Nursing English course has the potential to motivate nursing students and improve their learning outcomes. OBJECTIVES: To apply motivational tactics to the Nursing English course and explore the effects on the learning motivation, engagement, and performance of vocational college nursing students. DESIGN: A quasi-experimental study. SETTING: The study was conducted at a vocational college in XXXX. PARTICIPANTS: A total of 229 sophomore nursing students (experimental group = 114; comparison group = 115) participated. METHODS: Motivation-based teaching was applied to the experimental group, while traditional lecture-based teaching was used with the comparison group. The Course Interest Survey (CIS) was used to measure student learning motivation; the Utrecht Work Engagement Scale-Student (UWES-S) was used to assess student learning engagement (both pre- and posttest). Midterm and final examination scores were used to compare the learning performance between both groups. RESULTS: There were no significant differences between both groups at the pretest in the CIS, UWES-S, and midterm examination scores. Significant group ∗ time interactions were found for CIS, UWES-S, and examination scores. The simple effect analysis showed that the experimental group's CIS, UWES-S, and examination scores were significantly higher than the comparison group at the posttest. Furthermore, the motivation-based teaching led to significant improvements in the CIS scores (from 3.12 [0.43] to 3.66 [0.34], p < 0.001), UWES-S scores (from 3.72 [0.53] to 4.05 [0.69], p < 0.001) and the CIS and UWES-S sub-scale scores of the experimental group. No changes were observed in the comparison group. The experimental group showed more remarkable improvement than the comparison group in examination scores. CONCLUSIONS: Motivation-based teaching effectively improved learning motivation, learning engagement, and learning performance of students in the Nursing English course.