Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Final year dental students' self-assessed confidence in general dentistry.

BACKGROUND: Self-assessment is an important introspective skill that dental professionals will utilise throughout their professional career. Its value lies in its ability to help individuals identify areas of strengths and weakness, and subsequently seek further development of professional skills where needed. The aim of this study was to investigate the correlation between self-assessed confidence and the assessment grade of final year dental students based on the professional attributes and competencies of newly qualified dentists outlined by the Australian Dental Council (ADC). METHODS: Ethical approval was obtained prior to distribution of a questionnaire with 45 statements to final year dental students. The survey was created based on the learning outcomes of the ADC guidelines in the domains of "scientific and clinical knowledge" and "patient care." Participants indicated their level of self-assessed confidence by marking "X" on a visual analogue scale (VAS) from zero ("No Confidence") to 10 cm ("Very Confident"). The assessment grade was based on OSCE, viva voce, case report and written paper. RESULTS: A total of 58 (71.6%) dental students participated in the survey. The reported self-assessed confidence over two domains were under "patient care": clinical information gathering 8.92 ± 1.07 cm (range =3.94-10.0 cm: n = 58; 100%), clinical diagnosis and management planning 8.26 ± 1.34 cm (range =0.50-9.95 cm: n = 55; 94.8%), clinical treatment and evaluation, 6.07 ± 1.69 cm (range =0-10.00 cm: n = 55; 94.8%), and "scientific and clinical knowledge": 6.98 ± 1.58 cm (range =0-10.00 cm: n = 58; 100.0%). Within these categories, high confidence was reported for routine dental care (caries management and preventive care) whilst lower confidence was reported for the management of oral medicine and pathologies, dental emergencies, trauma, paediatric dentistry and prosthodontics. Correlation between the assessment grade and the overall score of self-assessed confidence is low positive (r = .225) and not statistically significant (n = 46; P = .132, Spearman'sρ). CONCLUSIONS: The final year dental students appear to have good overall self-assessed confidence in core areas of general dentistry. However, confidence seems to be over-estimated when compared with summative assessment.

Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures.

The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.

Temperature fluctuation promotes the thermal adaptation of soil microbial respiration.

The magnitude of the feedback between soil microbial respiration and increased mean temperature may decrease (a process called thermal adaptation) or increase over time, and accurately representing this feedback in models improves predictions of soil carbon loss rates. However, climate change entails changes not only in mean temperature but also in temperature fluctuation, and how this fluctuation regulates the thermal response of microbial respiration has never been systematically evaluated. By analysing subtropical forest soils from a 2,000 km transect across China, we showed that although a positive relationship between soil microbial biomass-specific respiration and temperature was observed under increased constant incubation temperature, an increasing temperature fluctuation had a stronger negative effect. Our results further indicated that changes in bacterial community composition and reduced activities of carbon degradation enzymes promoted the effect of temperature fluctuation. This adaptive response of soil microbial respiration suggests that climate warming may have a lesser exacerbating effect on atmospheric CO2 concentrations than predicted.

Influence of polluted SY River on child growth and sex hormones.

OBJECTIVE: To investigate the influence of the polluted SY River on children's growth and sex hormones, and provide scientific data for assessment of the polluted status of the SY River. METHODS: The study areas were selected randomly from the SY River Basin. Lead (Pb), mercury (Hg), arsenic (As), phthalates (DEP, DBP, DMP, DEHP), and bisphenol A (BPA) were measured both in the river water and in the drinking water. School children were selected by cluster sampling (n=154). Physical development indexes (height, weight, bust-circumference, and skinfold thickness) and sex hormones [testosterone (T) and estradiol (E2)] were measured for all the children. RESULTS: The contents of Pb and Hg exceeded Class V standards of surface water quality in each section of the river and other indicators exceeded Class III. Compared to the control area, the concentrations of Pb, Hg, As, BPA, DEP, and DBP in the drinking water were significantly higher than in the polluted area (P<0.05). Children from the control area had significantly lower E2 and T than children from the polluted area (P<0.05). Among anthropometric results, only skinfold thickness had statistically significant difference between the two groups (P<0.05), while the other indexes showed no significant differences between the two groups (P>0.05). CONCLUSION: The drinking water has been polluted by the SY River and affected serum sex hormone levels of children living in the polluted area.

Advances in the clinical application of oxycodone in the perioperative period.

To review the research progress of pure opioid receptor agonist oxycodone. The research progress of oxycodone in terms of pharmacokinetics, pharmacodynamics, adverse reactions, clinical application, combined medication and new progress in clinical application was summarized by referring to the literature. Oxycodone is a semi-synthetic thebaine derivative of opioid alkaloids, and is a pure opioid µ and κ receptor agonist. The main action sites are the central nervous system and visceral smooth muscle. Due to its advantages of low adverse reactions, good analgesic effects, and a wide range of safe doses, the drug has been widely used in the control of acute and chronic postoperative pain, as well as malignant and non-malignant pain. Since the end of the 20th century, researchers have begun to formulate antipyretic analgesics, opioid receptor agonists, opioid receptor antagonists, dopamine receptor antagonists and other drugs with oxycodone in different proportions to enhance the analgesic effect. At the same time, it can reduce the dosage of oxycodone and reduce its adverse reactions, so as to achieve the purpose of limiting opioid abuse. With the continuous research on the efficacy and safety of oxycodone in the perioperative period at home and abroad, oxycodone has become the only dual-opioid potent analgesic that can be used in clinical work.

Experimental comparative study of the effect of fractional CO2 laser combined with pulsed dye laser versus each laser alone on the treatment of hypertrophic scar of rabbit ears.

BACKGROUND AND OBJECTIVE: The use of fractional CO2  laser and pulsed dye laser (PDL) therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. The objective of this study was to directly compare the efficacy of PDL, fractional CO2 , and PDL and fractional CO2  laser therapy in immature red hypertrophic scars in a standardized animal model. METHODS: Ten New Zealand big-eared rabbits were used to make rabbit ear hypertrophic scar models. A total of 80 hypertrophic scar models were obtained and randomly divided into groups: control (Group A), Fractional CO2  laser (Group B), pulse dye laser (Group C), combined (Group D), 20 in each group. Wound sites were treated with PDL, Fractional CO2  laser, or both at 28 days post-grafting. Grafts receiving no laser therapy served as controls. Hypertrophic scar appearance, morphology, size, and erythema were assessed, and punch biopsies were collected. At days 7 and 28, additional tissue was collected for biomechanical analyses and markers for HE staining, Masson staining, immunohistochemical method to determine the CD31 content in the scar; Western blot to detect the expression of VEGF protein in scars. After the day 7 and 28, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining. The expression of CD31, VEGF protein, and the cell apoptosis rate was detected by immunohistochemical method. RESULTS: (i) In morphological observation, HE staining and Masson staining, both the number of fibroblasts and amount of collagen fibrils in the experimental group were significantly reduced compared with those in control group. (ii) Micro-vessel Density (MVD) value can be found much smaller in the experimental groups than the control (p < 0.05). Among the four experimental groups, there was a significant difference among 14d, 21d, and 28d groups (p < 0.05). (iii) On days 7 and 28 after treatment, expression of VEGF could be regulated in experimental group (p < 0.05). Among the three experimental groups, the decrease of VEGF in the combined group was significantly stronger than that of the other two. CONCLUSION: The effect of Fractional CO2  laser combined with pulsed dye laser treatment was shown to be better than that of Fractional CO2  laser or pulsed dye laser alone and inhibits the early hypertrophic scar in rabbit ears.

[Concentration, Source, and Health Risk Assessment of PM1 Heavy Metals in Typical Pollution Processes in Zhengzhou].

Heavy metal elements in particulate matter can cause adverse effects on human health, and the smaller the particle size, the greater the harm. A total of 16 heavy metal elements (Al, Si, K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Ba, Pb, and Cd) in PM1 were continuously determined by an online heavy metal observation instrument in Zhengzhou city from January 7 to 25, 2021. The results showed that ρ(K) concentration was the highest during the observation period (0.62 µg·m-3). According to pollutant concentration and meteorological characteristics, the observation period was divided into clean days, dust days, and haze days. The contribution of heavy metal pollution characteristics and health risk assessment in atmospheric PM1 was different under different pollution processes. The US EPA health risk assessment method was used to assess the health risks of heavy metals, and the enrichment factor method and positive matrix factorization (PMF) were used to analyze the sources of heavy metals. The influence of the transmission was evaluated by using the concentration-weighted trajectory (CWT) method and the backward trajectory method. The results show that the enrichment factors of Zn, As, Se, Pb, and Cd were more than 100 under different pollution processes, which were greatly affected by human activities. During the sampling period, the main sources of heavy metals were industrial sources, coal/biomass sources, motor vehicle sources, and dust sources. The results of the health risk assessment were substituted into PMF analysis, and it was found that industrial sources were the main contributing sources of carcinogenic and non-carcinogenic health risks during cleaning days, dust days, and haze days, and the carcinogenic risk of heavy metal elements in PM1 in this region for adults exceeded that for children. CWT and backward trajectory methods revealed that regional transmission was one of the main factors affecting local health risks.

[Pollution Characterization, Source Identification, and Health Risks of Atmospheric Particle-Bound Heavy Metals in PM2.5 in Zhengzhou City: Based on High-resolution Data].

In order to study the pollution characteristics and sources of heavy metals in urban atmospheric PM2.5, 21 elements in atmospheric PM2.5 in Zhengzhou City were detected using an online metal analyzer during July and October 2017 and January and April 2018, and the changes in heavy metal concentrations were analyzed. Heavy metals were traced by enrichment factors, principal component analysis, and potential source function. The US EPA risk assessment model was used to assess their health risks. The results showed that:the concentrations of K, Zn, Mn, Pb, Cu, As, Cr, and Se increased with the increase in pollution level. The results of enrichment factors and principal component analysis showed that the main sources of heavy metals were crust, mixed combustion, industry, and motor vehicles. The characteristic radar charts showed that the pollution dominated by crustal sources mainly occurred in spring and winter, whereas the pollution dominated by mixed combustion sources mainly occurred in winter. Pb, As, and Ni were greatly affected by the transport of a fen nutrient-laden plain, Beijing-Tianjin-Hebei, and southern Henan, whereas Cd was greatly affected by the northwest region of the sampling site. As presented a significant carcinogenic risk in both adults and children, whereas Pb and Sb presented a significant non-carcinogenic risk in children.

[Characteristics of Plant Diversity and Heavy Metal Enrichment and Migration Under Different Ecological Restoration Modes in Abandoned Mining Areas].

In order to select plant materials suitable for the ecological restoration of abandoned mining land, ecological restoration experiments were set up in landfills. The effects of different ecological restoration measures on plant diversity and heavy metal enrichment and migration characteristics were studied. The results showed that under different ecological restoration measures, a total of eight families and 10 species of surviving plants appeared, most of which were herbs. The restoration effect of the arbor shrub and grass plots was the best; the plant coverage reached 100%, and the survival rate was over 69%. The diversity index of the plant community was as follows:arbor shrub grass > shrub grass > joe grass > grass. The dominant plants under different ecological restoration measures were Pinus elliottii, Ligustrum lucidum, Boehmeria nivea, Lagerstroemia indica, and Plantago asiatica. The contents of most heavy metals in plants were higher than the normal values. Among them, the enrichment and transfer coefficients of the leaf stems of P. elliottii and L. indica were close to or greater than 1, showing a strong ability of enrichment and transfer to Cd; these two plants belong to Cd-enrichment type plants. The roots of L. lucidum Ait and P. asiatica, which are root-hoarding plants, had a high retention rate of heavy metals. Boehmeria nivea was a heavy metal-avoidance plant with a low content of heavy metals in each part and had the ability to fix and repair potential soil heavy metal pollution. Considering the diversity of plants and the ability of plant enrichment and migration, the combination of trees, shrubs, and grasses was the best restoration mode. Pinus elliottii, L. indica, and P. asiatica can be the target plants for ecological restoration in the abandoned land of mining areas.

Anesthetic technique for awake artery malformation clipping with motor evoked potential and somatosensory evoked potential: A case report.

BACKGROUND: Awake craniotomy has been widely used for tumor resection, epilepsy surgery, deep brain stimulation, and carotid endarterectomy. The report on awake artery malformation clipping is rare, especially for anesthesia management. CASE SUMMARY: A 62-year-old female diagnosed with malformation of anterior cerebral artery at the right side. We clipped the artery malformation with intraoperative neuromonitoring (IONM) in awake craniotomy. Spontaneous respiration was maintained throughout the procedure by nasopharyngeal airway during the surgery successfully. CONCLUSION: The technique of monitoring anesthesia care can be performed successfully for the patient with IONM.

Anesthetic management of a child with double outlet right ventricle and severe polycythemia: A case report.

BACKGROUND: Double outlet right ventricle (DORV) is a rare and complex congenital heart defect, and the surgical repairs vary with type and pathophysiology consequences. Due to prolonged progressive hypoxemia, severe polycythemia is common in patients with DORV, which ultimately leads to coagulation dysfunction and increases the risk of thrombosis and infarction. Consequently, the anesthetic management is challenging and how to manage severe polycythemia and avoid hypoxia-related complications in such patients is of great significance. CASE SUMMARY: Herein, we report the anesthetic management of a 10-year-old female patient with a DORV. She lived in the low-oxygen Qinghai-Tibet Plateau, and presented with severe polycythemia (hemoglobin, 24.8 g/dL; hematocrit, 75%). She underwent a modified Fontan surgery, which was satisfactory and without any perioperative complications. Our anesthetic management highlights the importance of perioperative hemodilution in decreasing the risk of thromboembolism and the importance of correcting coagulopathy in preventing hemorrhage. CONCLUSION: Anesthetic management is challenging in rare cyanotic congenital heart disease patients with severe polycythemia. It is important to adopt perioperative hemodilution and correction of coagulopathy in preventing thrombosis and hemorrhage.

Dental implant surface treatments may modulate cytokine secretion in Porphyromonas gingivalis-stimulated human gingival fibroblasts: a comparative study.

Peri-implantitis is an inflammation that affects dental implants and can lead to implant loss. The aim of this study was to analyze the in vitro effect of different implant surface treatments on cytokine production by human gingival fibroblasts (HGFs) stimulated or not with Porphyromonas gingivalis lipopolysaccharide (PgLPS). Six different titanium implants were tested: turned, sandblasted, anodized, acid-etched, TiO2-blasted/acid-etched, and grit-blasted/acid-etched. HGFs were seeded with each implant in a 6-well plate and assayed before LPS treatment (-LPS) or after 36 h of LPS (+LPS) treatment. Protein concentrations were measured using a Pierce bicinchoninic acid (BCA) assay and cytokine secretions were analyzed using a multiplex cytokine array. Scanning electron microscopy was performed for sterile implants and after cell attachment. Protein levels were consistent across all implants indicating that cell growth was uniform (p > 0.05). Sandblasted and turned surfaces significantly increased the secretion of interleukin (IL)-6, -8, -10, MCP-1 and VEGF (p < 0.05) when compared with the other surfaces. PgLPS stimulus increased cytokine secretion in all tested surfaces. In conclusion, different implant surfaces had various effects on HGFs' cytokine secretion. The findings may provide insights into the progression of peri-implantitis.