Genome-Scale Analysis of the Grapevine KCS Genes Reveals Its Potential Role in Male Sterility.

Very long-chain fatty acid (VLCFA) synthesis in plants, is primarily rate-limited by the enzyme 3-ketoacyl CoA synthase (KCS), which also controls the rate and carbon chain length of VLCFA synthesis. Disruption of VLCFA during pollen development, may affect the pollen wall formation and ultimately lead to male sterility. Our study identified 24 grapevine KCS (VvKCS) genes and provided new names based on their relative chromosome distribution. Based on sequence alignment and phylogenetic investigation, these genes were grouped into seven subgroups, members of the same subgroup having similar motif structures. Synteny analysis of VvKCS genes, showed that the segmental duplication events played an important role in expanding this gene family. Expression profiles obtained from the transcriptome data showed different expression patterns of VvKCS genes in different tissues. Comparison of transcriptome and RT-qPCR data of the male sterile grape 'Y-14' and its fertile parent 'Shine Muscat', revealed that 10 VvKCS genes were significantly differentially expressed at the meiosis stage, which is a critical period of pollen wall formation. Further, joint analysis by weighted gene co-expression network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed that five of these VvKCS (VvKCS6/15/19/20/24) genes were involved in the fatty acid elongation pathway, which may ultimately affect the structural integrity of the pollen wall in 'Y-14'. This systematic analysis provided a foundation for further functional characterization of VvKCS genes, with the aim of grapevine precision breeding improvement.

Diagnosis and treatment of traumatic duodenal rupture in children.

BACKGROUND: The purpose of this study was to investigate the diagnosis and treatment experience of traumatic duodenal ruptures in children. METHODS: Clinical data were collected from four children suffering from a traumatic duodenal rupture who were admitted to and treated by our hospital from January 2012 to December 2020. The early diagnosis and treatment, surgical plan, postoperative management, complications, and prognosis of each child were analyzed. The key points and difficulties of the diagnosis and treatment for this type of injury are summarized. RESULTS: One child had an extreme infection caused by drug-resistant bacteria, which resulted in severe complications, including wound infection, dehiscence, and an intestinal fistula. One child developed an anastomotic stenosis after the duodenostomy, which improved following an endoscopic balloon dilatation. The other two children had no relevant complications after their operations. All four patients were cured and discharged from hospital. The average hospital stay was 48.25 ± 26.89 days. The follow-up period was 0.5 to 1 year. No other complications occurred, and all children had a positive prognosis. CONCLUSIONS: The early identification of a duodenal rupture is essential, and surgical exploration should be carried out proactively. The principles of damage-control surgery should be followed as much as possible during the operation. Multidisciplinary cooperation and management are both important to reduce the occurrence of postoperative complications and improve cure rates.

A Standardized Extubation Schedule Reduces Respiratory Events After Extubation Following Mandibular Distraction in Infants.

PURPOSE: The rational time for intubation during early mandibular distraction osteogenesis (MDO) in infants is unknown. To investigate the differences in clinical outcomes following MDO before and after a standardized extubation protocol implementation in infants. METHODS: A retrospective cohort study was performed for infant patients under 1 year old undergoing MDO. The study population was composed of all patients presenting for evaluation and management who underwent MDO between November 2016 and February 2021. We divided them into 2 groups: the pre-protocol group and the protocol group. The inpatient charts of infants were assessed. The primary outcome was respiratory events after extubation. The secondary outcomes were duration of mechanical ventilation (MV), postoperative length of stay (LOS), and success rate of the first extubation. Other variables included age, sex, weight, height, and information related to diagnosis, distraction, anesthesia, and operation. The logistic regression model and linear regression model were used to calculate unadjusted and adjusted relative risk (RR) and mean difference (MD) for associations between 2 groups and the primary and secondary outcomes. RESULTS: There were 142 infants in the pre-protocol group and 135 infants in the protocol group. The patients in the protocol group were heavier in weight than those in the pre-protocol group (P<.05). The Cormack-Lehane grade and the duration of operation and anesthesia were higher and longer in the pre-protocol group than in the protocol group (P<.05). Respiratory events after extubation were significantly more common in the pre-protocol group than in the protocol group [21.1 vs. 9.6%, adjusted relative risk 0.46 (95% CI 0.22-0.89), P <.01]. CONCLUSIONS: Among infants undergoing MDO, the standardization of extubation practices can reduce respiratory events after extubation compared with traditional management.

Combined non-intubated anaesthesia and paravertebral nerve block in comparison with intubated anaesthesia in children undergoing video-assisted thoracic surgery.

BACKGROUND: This study is to investigate if non-intubated anaesthesia combined with paravertebral nerve block (PVNB) can enhance recovery in children undergoing video-assisted thoracic surgery (VATS). METHODS: A randomized controlled trial including 60 patients aged 3 to 8 years old who underwent elective VATS was performed. They were randomly assigned to receive non-intubated anaesthesia combined with PVNB or general anaesthesia with tracheal intubation (1:1 ratio). The primary outcome was the length of postoperative in-hospital stay. The secondary outcomes included emergence time, the incidence of emergence delirium, time to first feeding, time to first out-of-bed activity, pain score and in-hospital complications. RESULTS: The non-intubated group had shorter postoperative in-hospital stay than the control group (4 days [IQR, 4-6] vs 5 days [IQR, 5-8], 95% CI 0-2; P = .013). When compared to the control group, the incidence of emergence delirium (odds ratio [OR] 3.39, 95% CI 1.01-11.41; P = .043), emergence time, duration in the PACU, time to first eating food, first out-of-bed activity, pain score and consumption of sufentanil (at 6 and 12 hours after surgery) were decreased in the intervention group. In contrast, the incidence of airway complications was higher in the control than the intervention group (27.6% vs 6.9%, P = .037). There was no statistical significance in the occurrence of PONV, pneumothorax and other complications between the two groups. CONCLUSIONS: Non-intubated anaesthesia combined with PVNB enhances recovery in paediatric patients for video-assisted thoracic surgery although further multi-centre study is needed.

Influence of pyrolysis temperature on the properties and environmental safety of heavy metals in chicken manure-derived biochars.

Animal manures usually contain high contents of heavy metals (HMs) and thus pose a considerable threat to human health and environment when applied to soil. In this study, the effect of pyrolysis temperature (300 °C, 400 °C, 500 °C, 600 °C, and 700 °C) on the properties of biochar produced from chicken manure was studied. In addition, the response of speciation, bioavailability, leachability, and environmental risk of HMs in biochar to different pyrolysis temperature was investigated. The results showed that biochars pyrolyzed at high temperatures generally had high pH, ash content, surface area, and stability. As the pyrolysis temperature increased, the total concentrations of Cu, Zn, Cr, and Ni continually increased, whereas those of Pb and Cd initially increased and then decreased. Moreover, the transformation of the bioavailable fractions of HMs into stable fractions obviously increased with increasing pyrolysis temperature. Thus, pyrolysis at high temperature led to a further decrease in the bioavailability, leachability, and environmental risk of six HMs, as shown by DTPA, TCLP, and the potential ecological risk index. Overall, it is convincing that that 700 °C is the optimal temperature when considering the quality and environmental safety of biochar derived from chicken manure.

Soil properties and species composition under different grazing intensity in an alpine meadow on the eastern Tibetan Plateau, China.

As the main form of land use and human disturbance of grassland, livestock grazing has great influences on the soil resources and plant communities. This study observed the variation of soil properties and community characteristics of four treatments of different grazing intensity (no grazing, UG; light grazing, LG; moderate grazing, MG; and heavy grazing, HG) in an alpine meadow of Sichuan Province on the northeastern margin of the Tibetan Plateau. The results showed that grazing increased the pH, soil bulk density (BD), and contents of total carbon (TC) and total nitrogen (TN), and the BD increased while the others decreased with the grazing intensity. At the community level, with the increase of the grazing intensity, the vegetation coverage (R 2 = 0.61, P < 0.001), mean height of community (R 2 = 0.37, P < 0.001), aboveground biomass (R 2 = 0.54, P < 0.001), litter biomass (R 2 = 0.84, P < 0.001), and percentage of aboveground biomass of palatable grasses to total biomass (R 2 = 0.74, P < 0.001) significantly decreased, while the belowground biomass (R 2 = 0.72, P < 0.001) and the root/shoot (R/S) ratio (R 2 = 0.65, P < 0.001) increased. The species richness was the greatest at LG and the total biomass at UG. With grazing, the dominant species of the plant community shifted from palatable grasses (Gramineae and Cyperaceae) to unpalatable grasses (Compositae and Ranunculaceae). Based on the results, LG may be the optimal grassland management mode to be used in the long time in the alpine meadow of the Tibetan Plateau.

[ED50 of dexmedetomidine nasal drip in induction of hypnosis in children during computed tomography].

OBJECTIVE: To explore the 50% effective dose (ED50) of dexmedetomidine nasal drip in the induction of hypnosis in children during computed tomography (CT). METHODS: A total of 34 American Society of Anesthesiologists (ASA)I-IIautistic children scheduled for brain CT examination were studied. The induction was made by dexmedetomidine nasal drip and the ED50 of dexmedetomidine determined by up-and down sequential experiment.When eyelash reflex became lost or Ramsay score was ≥ 4 in 1 hour after dosing, hypnosis was achieved. The study ended after 8 crossovers (successive "accept" and "refuse"). RESULTS: Among them, the ED50 of dexmedetomidine was 1.76 µg/kg (95% confident interval:1.64-1.88 µg/kg). CONCLUSION: The ED50 of dexmedetomidine nasal drip is 1.76 µg/kg in the induction of hypnosis in children.

Fibroblast growth factor 3 contributes to neuropathic pain through Akt/mTOR signaling in mouse primary sensory neurons.

Neuropathic pain (NP), a severe chronic pain condition, remains a substantial clinical challenge due to its complex pathophysiology and limited effective treatments. An association between the members of the Fibroblast Growth Factors (FGFs), particularly Fgf3, and the development of NP has become evident. In this study, utilizing a mouse model of NP, we observed a time-dependent increase in Fgf3 expression at both mRNA and protein levels within the dorsal root ganglia (DRG). Functional studies revealed that blocking Fgf3 expression mitigated nerve injury induced nociceptive hypersensitivity, suggesting its pivotal role in pain modulation. Moreover, our findings elucidate that Fgf3 contributes to pain hypersensitivity through the activation of the Akt/mTOR signaling in injured DRG neurons. These results not only shed light on the involvement of Fgf3 in nerve injury-induced NP but also highlight its potential as a promising therapeutic target for pain management. This study thereby advances our understanding of the molecular mechanisms underlying NP and opens new avenues for the development of effective treatment strategies.

Purification effect and microbial community structure of bio filter on rural dispersed sewage.

Taking rural dispersed sewage for research objects, the treatment effect and microbial community structure characteristics of a bio filter (BF) reactor was studied. At fixed time and location, the removal efficiencies of common pollutants were investigated. By using high-throughput sequencing method, the heterogeneities of microbial community structure in fillers and plant roots were analyzed. The results showed that the average annual removal rates of CODCr, NH3-N, TN, and TP by the BF were 83.10 %, 65.67 %, 60.25 %, and 80.32 % respectively, and the effluent could reach the first grade of the water pollutant discharge standard of rural sewage treatment facility (DB51/2626-2019). During the sewage treatment process, Scindapsus could effectively establish complex and stable microbial communities, and could better degrade pollutants, especially nitrogen removal. The dominant microbial communities were more than 11 phyla and 19 classes. At the genus level, the dominant bacteria included Nitrospira, Arthrobacter, Rhodoplanes, etc.

Gene polymorphisms of METTL5 and METTL16 are related to epithelial ovarian cancer risk in South China: A three-center case-control study.

Background: The potential relation of methyltransferase-like gene polymorphisms and epithelial ovarian cancer (EOC) remains unclear. Methods: Five SNPs (METTL5 rs3769767 A>G, METTL16 rs1056321 T>C, METTL5 rs10190853 G>A, METTL5 rs3769768 G>A and METTL16 rs11869256 A>G) of methyltransferase-like genes was selected trough NCBI dbSNP database. Two hundred and eighty-eight cases and 361 controls were enrolled from three hospitals in South China to conduct the case-control study. Genomic DNA was abstracted from peripheral blood and genotyped through a TapMan assay. Stratified analysis was conducted to explore the association of rs10190853, rs3769768, rs11869256 genotype and EOC susceptibility. The combination analysis was adopted to evaluate the relation between inferred haplotypes of the METTL5, METTL16 genes and EOC risk. Multifactor dimensionality reduction (MDR) analysis was performed to verify the interaction of SNPs. Results: Among the five analyzed SNPs, METTL5 rs3769768 AA exhibited a significant association with increased EOC risk, while METTL5 rs10190853 GA, METTL16 rs11869256 GA was certified to decrease the susceptibility of EOC. The stratified analysis further revealed the harmful effect of METTL5 rs3769768 AA in EOC patients. On the contrary, METTL16 rs11869256 AG/GG and METTL5 rs10190853 AA showed the reduced risk of EOC in patients of specific subgroups. Combination analysis identified that haplotypes AAA highly connected with reduced risk of EOC. MDR analysis revealed that these SNPs existed no specific interactions. Conclusion: METTL5 rs3769768 was related to increased risk of EOC. METTL5 rs10190853 and METTL16 rs11869256 decreased the susceptibility in EOC. METTL5 and METTL16 could be potential target of molecular therapy and prognosis markers.

METTL3-Mediated LINC00475 Alternative Splicing Promotes Glioma Progression by Inducing Mitochondrial Fission.

Mitochondrial fission promotes glioma progression. The function and regulation mechanisms of lncRNAs in glioma mitochondrial fission are unclear. The expression of LINC00475 and its correlation with clinical parameters in glioma were analyzed using bioinformatics. Then, in vitro and in vivo assays were performed to explore the function of spliced variant LINC00475 (LINC00475-S) in gliomas. To explore the mechanisms, RNA-seq, MeRIP, RIP, pulldown-IP, dCas9-ALKBH5 editing system, LC/MS, and Western blotting were utilized. LINC00475 was confirmed to be overexpressed and with higher frequencies of AS events in gliomas compared to normal brain tissue and was associated with worse prognosis. In vitro and animal tumor formation experiments demonstrated that the effect of LINC00475-S on proliferation, metastasis, autophagy, and mitochondrial fission of glioma cells was significantly stronger than that of LINC00475. Mechanistically, METTL3 induced the generation of LINC00475-S by splicing LINC00475 through m6A modification and subsequently promotes mitochondrial fission in glioma cells by inhibiting the expression of MIF. Pull-down combined LC/MS and RIP assays identified that the m6A recognition protein HNRNPH1 bound to LINC00475 within GYR and GY domains and promoted LINC00475 splicing. METTL3 facilitated HNRNPH1 binding to LINC00475 in an m6A-dependent manner, thereby inducing generation of LINC00475-S. METTL3 facilitated HNRNPH1-mediated AS of LINC00475, which promoted glioma progression by inducing mitochondrial fission. Targeting AS of LINC00475 and m6A editing could serve as a therapeutic strategy against gliomas.

Risk factors of intraoperative blood loss and transfusion for pediatric patients undergoing brain tumor removal: a retrospective cohort study.

OBJECTIVE: Intraoperative blood loss is a major challenge in pediatric brain tumor removal. Several clinical and surgical factors may influence the occurrence of intraoperative blood loss and blood transfusion. This study aimed to identify the risk factors of intraoperative blood loss and intraoperative red blood cell (RBC) transfusion for pediatric patients undergoing brain tumor removal. METHODS: A total of 297 pediatric patients undergoing brain tumor removal were selected in this retrospective, singlecenter study. Demographic data, laboratory data, imaging data, and surgical records were collected, and then independent risk factors for intraoperative blood loss and transfusion were identified using multivariate stepwise regression analysis. RESULTS: The median intraoperative blood loss in our cohort was 23.1 ml/kg (IQR 10.0-60.0 ml/kg). In total, 284 (95.6%) patients received intraoperative RBC transfusion, with a median amount of 0.2 U/kg (IQR 0.0-2.6 U/kg). Age (ß = -0.189; 95% CI [-1.359, -0.473]; p < 0.001); preoperative hemoglobin level (ß = -0.141; 95% CI [-1.528, -0.332]; p = 0.003); anesthesia time (ß = 0.189; 95% CI [0.098, 0.302]; p < 0.001); unclear tumor boundary (ß = 0.100; 95% CI [2.067, 41.053]; p = 0.031); tumor size (ß = 0.390; 95% CI [14.706, 24.342]; p < 0.001); and intraoperative continuous infusion of vasopressor (ß = 0.155; 95% CI [13.364, 52.400]; p = 0.001) were independent predictors of intraoperative blood loss. Independent predictors of the need for RBC transfusion included age (ß = -0.268; 95% CI [-0.007, -0.004]; p < 0.001); preoperative hemoglobin level (ß = -0.117; 95% CI [-0.005, -0.001]; p = 0.003); anesthesia time (ß = 0.221; 95% CI [0.001, 0.001]; p < 0.001); unclear tumor boundary (ß = 0.110; 95% CI [0.024, 0.167]; p = 0.010); tumor size (ß = 0.370; 95% CI [0.056, 0.092]; p < 0.001); intraoperative continuous infusion of vasopressor (ß = 0.157; 95% CI [0.062, 0.205]; p < 0.001); and tumor grade (ß = 0.107; 95% CI [0.007, 0.062]; p = 0.014). CONCLUSIONS: Overall, age, preoperative hemoglobin, tumor size, anesthesia time, continuous infusion of vasopressors, and unclear tumor boundary were the main determinants for intraoperative blood loss and RBC transfusion in pediatric patients undergoing brain tumor removal. Clinical trial registration no.: ChiCTR1900024803 (ChiCTR.org).

Optimization pilot scale study on ammonia nitrogen removal by bio filter.

In order to obtain the optimal conditions for ammonia nitrogen (AN) wastewater treatment by bio filter (BF), the effects of ratio of carbon to nitrogen (C/N), pH, and hydraulic load (HL) on the AN degradation were studied by Response Surface Methodology (RSM). Central Composite Design (CCD) experiments were conducted, and the response of the AN removal rates were fitted to a second-order polynomial model. The analysis of variance showed that the model was accurate and reliable. Through model fitting, the optimal condition for AN removal was: C/N of 18.95, pH of 7.78, and HL of 1.04 d-1. The maximum AN removal rate predicted by the model was 91.90%, accorded with the experimental verification value of 91.37% under the optimal condition. The research provided valuable demonstration for optimizing process parameters on AN removal in BF.

Comparison of the postoperative in-hospital versus at-home recovery quality and circadian rhythm status in preschool kids after adenotonsillectomy: a cohort and observational study.

Background: At present, minimally invasive surgery is often used in paediatric patients as a day surgery to promote rapid post-operative recovery. Obstructive Sleep Apnea Syndrome (OSAS) Patients recovery in the hospital or at home after surgery may differ in terms of recovery quality and circadian rhythm status because of sleep disruption; however, this remains unknown. Pediatric patients usually unable to explain their feelings effectively, and objective indicators to measure recovery situation in different environments are promising. This study was conducted to compare the impact of in-hospital and at-home postoperative recovery quality (primary outcome) and circadian rhythm (as measured via the salivary melatonin level) (secondary outcome) in preschool-age patients. Methods: This was a cohort, non-randomized and exploratory observational study. A total of 61 children aged 4 to 6 years who were scheduled to receive adenotonsillectomy were recruited and assigned to recover either in the hospital (Hospital group) or at home (Home group) after surgery. There were no differences in the patient characteristics and perioperative variables between the Hospital and Home groups at baseline. They received the treatment and anesthesia in the same way. The patients' preoperative and up to 28 days post-surgery OSA-18 questionnaires were harvested. Moreover, their pre- and post-surgery salivary melatonin concentrations, body temperature, three-night postoperative sleep diaries, pain scales, emergence agitation, and other adverse effects were recorded. Results: There were no significant differences in the postoperative recovery quality, as assessed by the OSA-18 questionnaire, body temperature, sleep quality, pain scales, and other adverse events (such as respiratory depression, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea, and vomiting) between the two groups. The preoperative morning saliva melatonin secretion was decreased in both groups on the first postoperative morning (P<0.05), while a significantly greater decrease was found in the Home group on postoperative day 1 (P<0.05) and day 2 (P<0.05). Conclusions: The postoperative recovery quality of preschool kids in the hospital is as good as at home based on OSA-18 evaluation scale. However, the clinical importance of the significant decrease in morning saliva melatonin levels with at-home postoperative recovery remains unknown and warrants further study.

The Role of the miR-548au-3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations.

Background: Literature has identified differentially expressed miRNAs in congenital pulmonary airway malformation (CPAM). However, the functional role of these miRNAs in CPAM remains unclear. Methods: We obtained diseased lung tissues as well as adjacent normal lung tissue from CPAM patients attending the centre. Hematoxylin and eosin (H&E) and Alcian blue staining were performed. Differentially expressed mRNA expression profile was CPAM tissue, and matched normal tissue specimens were examined by high-throughput RNA sequencing. CCK-8 assay, EdU staining, TUNEL staining, flow cytometry, and the Transwell assay were performed to investigate the effect of miR-548au-3p/CA12 axis on proliferation, apoptosis, and chondrogenic differentiation in rat tracheal chondrocytes. mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and western blot analysis, respectively. The relationship between miR-548au-3p and CA12 was evaluated using the luciferase reporter assay. Results: The expression level of miR-548au-3p was significantly increased in diseased tissues compared with normal adjacent tissues from patients with CPAM. Our results indicate that miR-548au-3p functions as a positive regulator in rat tracheal chondrocyte proliferation and chondrogenic differentiation. At molecular level, miR-548au-3p promoted N-cadherin, MMP13, and ADAMTS4 expressions and reduced E-cadherin, aggrecan, and Col2A1 expressions. CA12 has been previously reported as a predicted target of miR-548au-3p, and here, we show that overexpression of CA12 in rat tracheal chondrocyte mimics the effects of inhibition of miR-548au-3p. On the other hand, CA12 knockdown reversed the effects of miR-548au-3p on cell proliferation, apoptosis, and chondrogenic differentiation. Conclusions: In conclusion, the miR-548au-3p/CA12 axis plays a role in the pathogenesis of CPAM and may lead to identification of new approaches for CPAM treatment.

Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma.

Background: Mitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored. Methods: MAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes. Results: We compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors. Conclusions: Collectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.

Metformin interacts with AMPK through binding to γ subunit.

Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.

[Effect of dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing cleft lip and palate repair].

OBJECTIVE: To explore the effect of different doses of dexmedetomidine on the sedation of recovery period and the postoperative early pain scores in pediatric patients undergoing cleft lip and palate repair. METHODS: A total of 100 American Society of Anesthesiologists (ASA) I-II pediatric patients undergoing cleft lip and palate repair were randomly divided into 5 groups (D1, D2, D3, D4 and C, n = 20 each). Groups D1-D4 received a continuous pump infusion of dexmedetomidine at 0.25, 0.5, 0.75, 1.0 µg × kg(-1)× h(-1) respectively for 1 h before the completion of operation. Then an intravenous injection of 1 µg/kg was prescribed over 10 min as a loading dose. Group C, taken as control, received an equal volume of normal saline. Propofol 2 mg/kg was added for the occurrence of emergence agitation. Mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), partial pressure of end-tidal carbon dioxide (P(ET)CO(2)), Riker sedation-agitation scale, times of additional propofol requirements, times of additional artificial ventilation, extubation time, discharge time, side effects and face, legs, activity, cry and consolability (FLACC) scale were observed and recorded. RESULTS: The Riker sedation-agitation scale were 5.3 ± 0.9, 4.3 ± 0.8, 3.5 ± 0.8, 2.6 ± 0.6 and 6.1 ± 0.7, times of additional propofol requirements were 4.7 ± 1.7, 2.5 ± 1.4, 0.8 ± 0.9, 0.1 ± 0.4 and 5.7 ± 0.7 in groups D1, D2, D3, D4 and C respectively. In short, group D4 ≈ group D3 < group D2 < group D1 < group C (P < 0.05). As compared with group D4, the extubation time and discharge time significantly increased in groups D1, D2, D3 and C (P < 0.05). The FLACC scales in groups D2, D3 and D4 were lower than those in groups D1 and C. Side effects: 2 cases developed sinus bradycardia in group D4 and heart rate returned to normal after treatment. CONCLUSION: At a load dosage of 1 µg/kg and a maintenance dosage of 0.75 µg × kg(-1)× h(-1), dexmedetomidine shows excellent effects on the recovery period of cleft lip and palate repairing in pediatric patients. The FLACC scale decreases with fewer side effects, but extubation time and discharge time increase.

Electron Transfer Flavoprotein (ETF) α Controls Blood Vessel Development by Regulating Endothelial Mitochondrial Bioenergetics and Oxygen Consumption.

While impairment of vascular homeostasis induced by hypercholesterolemia is the first step of cardiovascular diseases, the molecular mechanism behind such impairment is not well known. Here, we reported that high-cholesterol diet (HCD) induced defective vessel sprouting in zebrafish larvae. Electron transfer flavoprotein subunit α (ETFα) (encoded by the ETFA gene), a protein that mediates transfer of electrons from a series of mitochondrial flavoenzymes to the respiratory chain, was downregulated in HCD-fed zebrafish and in endothelial cells treated with oxidized low-density lipoprotein. Knockdown of ETFα with morpholino antisense oligonucleotides reproduced vascular sprouting defects in zebrafish larvae, while replenishing with exogeneous ETFA mRNA could successfully rescue these defects. ETFA knockdown in endothelial cells reduces cell migration, proliferation, and tube formation in vitro. Finally, knockdown of ETFA in endothelial cells also reduced fatty acid oxidation, oxygen consumption rate, and hypoxia-inducible factor-1α (HIF1α) protein levels. Taken together, we demonstrate that downregulation of ETFα is involved in hypercholesterolemia-induced defective vessel sprouting in zebrafish larvae via inhibition of endothelial proliferation and migration. The molecular mechanism behind this phenomenon is the decrease of HIF1α induced by downregulation of ETFα in endothelial cells. This work suggests that disturbance of ETFα-mediated oxygen homeostasis is one of the mechanisms behind hypercholesterolemia-induced vascular dysfunction.

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1.

Diabetic cardiomyopathy (DCM) is initially characterized by early diastolic dysfunction, left ventricular remodeling, hypertrophy, and myocardial fibrosis, and it is eventually characterized by clinical heart failure. MicroRNAs (miRNAs), endogenous small noncoding RNAs, play significant roles in diabetes mellitus (DM). However, it is still largely unknown about the mechanism that links miRNAs and the development of DCM. Here, we aimed to elucidate the mechanism underlying the potential role of microRNA-340-5p in DCM in db/db mouse, which is a commonly used model of type 2 DM and diabetic complications that lead to heart failure. We first demonstrated that miR-340-5p expression was dramatically increased in heart tissues of mice and cardiomyocytes under diabetic conditions. Overexpression of miR-340-5p exacerbated DCM, which was reflected by extensive myocardial fibrosis and more serious dysfunction in db/db mice as represented by increased apoptotic cardiomyocytes, elevated ROS production, and impaired mitochondrial function. Inhibition of miR-340-5p by a tough decoy (TUD) vector was beneficial for preventing ROS production and apoptosis, thus rescuing diabetic cardiomyopathy. We identified myeloid cell leukemia 1 (Mcl-1) as a major target gene for miR-340-5p and showed that the inhibition of Mcl-1 was responsible for increased functional loss of mitochondria, oxidative stress, and cardiomyocyte apoptosis, thereby caused cardiac dysfunction in diabetic mice. In conclusion, our results showed that miR-340-5p plays a crucial role in the development of DCM and can be targeted for therapeutic intervention.