CERS6-derived ceramides aggravate kidney fibrosis by inhibiting PINK1-mediated mitophagy in diabetic kidney disease.

During diabetic kidney disease (DKD), ectopic ceramide (CER) accumulation in renal tubular epithelial cells (RTECs) is associated with interstitial fibrosis and albuminuria. As RTECs are primarily responsible for renal energy metabolism, their function is intimately linked to mitochondrial quality control. The role of CER synthesis in the progression of diabetic renal fibrosis has not been thoroughly investigated. In this study, we observed a significant upregulation of ceramide synthase 6 (Cers6) expression in the renal cortex of db/db mice, coinciding with increased production of CER (d18:1/14:0) and CER (d18:1/16:0) by Cer6. Concurrently, the number of damaged mitochondria in RTECs rose. Cers6 deficiency reduced the abnormal accumulation of CER (d18:1/14:0) and CER (d18:1/16:0) in the kidney cortex, restoring the PTEN-induced kinase 1 (PINK1)-mediated mitophagy in RTECs, and resulting in a decrease in damaged mitochondria and attenuation of interstitial fibrosis in DKD. Automated docking analysis suggested that both CER (d18:1/14:0) and CER (d18:1/16:0) could bind to the PINK1 protein. Furthermore, inhibiting PINK1 expression in CERS6 knockdown HK-2 cells diminished the therapeutic effect of CERS6 deficiency on DKD. In summary, CERS6-derived CER (d18:1/14:0) and CER (d18:1/16:0) inhibit PINK1-regulated mitophagy by possibly binding to the PINK1 protein, thereby exacerbating the progression of renal interstitial fibrosis in DKD.NEW & NOTEWORTHY This article addresses the roles of ceramide synthase 6 (CERS6) and CERS6-derived ceramides in renal tubular epithelial cells of diabetic kidney disease (DKD) associated interstitial fibrosis. Results from knockdown of CERS6 adjusted the ceramide pool in kidney cortex and markedly protected from diabetic-induced kidney fibrosis in vivo and in vitro. Mechanically, CERS6-derived ceramides might interact with PINK1 to inhibit PINK1/Parkin-mediated mitophagy and aggravate renal interstitial fibrosis in DKD.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

Intracardiac thrombosis after congenital heart disease surgeries in neonates: a report of two cases.

BACKGROUND: Intracardiac thrombosis (ICT) is a rare complication after the cardiopulmonary surgery for interrupted aortic arch (IAA) or total anomalous pulmonary venous connection (TAPVC) without previous records. There are still no general guidelines regarding as the mechanism or management of postoperative ICT in neonates and younger infants. CASE PRESENTATION: We reported the conservative and surgical therapies in two neonates with intra-ventricular and intra-atrial thrombosis after the anatomical repair for IAA and TAPVC, respectively. There were no risk factors for ICT in both patients, except for the use of blood product and prothrombin complex concentrate. The surgery was indicated after TAPVC correction due to the worsening respiratory status and rapidly decreased mixed venous saturation. Anticoagulation combined with antiplatelet therapies was adopted in another patient. These two were both finally recovered, and three-month, six-month, and one-year follow-up echocardiography revealed no abnormality. CONCLUSIONS: ICT is uncommon in pediatric population after the surgery for congenital heart disease. Single ventricle palliation, heart transplantation, longer central line use, post-extracorporeal membrane oxygenation, and massive blood product use are major risk factors for postcardiotomy thrombosis. The causes of postoperative ICT are multifactorial, and the immaturity of thrombolytic and fibrinolytic system in neonates may serve as a prothrombotic factor. However, no consensus reached regarding as the therapies for postoperative ICT, and the large-scale prospective cohort study or randomized clinical trial is needed.

Perceived knowledge, attitudes and practices regarding the medical consortium among medical staff in Sichuan, China: a cross-sectional survey.

BACKGROUND: In China, fragmented and inefficient health care systems are common while quality resources are limited. To promote an organized, efficient system, the government launched a medical consortium policy to vertically integrate health care through the collaboration of different levels of medical care. Logically, medical staff's knowledge, attitudes and practices (KAP) regarding the consortium are critical for its development. The objective of this study was to explore the KAP regarding the medical consortium among medical staff in a medical consortium in Sichuan Province, China. METHODS: A cross-sectional survey was conducted. In total, 690 medical staff members in 3 cities of Sichuan Province, China, were interviewed from November 2018 to December 2018. The questionnaire consisted of 18 items, including 4 items related to perceived knowledge, 4 items related to attitudes and 2 items related to practices, and was rated on a 5-point Likert scale (one = strongly disagree/do not know, five = strongly agree/know). RESULTS: The effective response sample was 640 copies of the questionnaire, and most medical staff members (92.50%) knew about the cooperation with other hospitals in the medical consortium. Medical staff scored differently on each item in the questionnaire, with the highest score being the item 'agreeing with the ward rounds and clinical teaching and training organized by the leading hospital' (4.54 ± 0.76), and the lowest score being the item 'frequency in participating in ward rounds and clinical teaching organized by the leading hospital' (2.83 ± 1.36). In addition, the effect of demographic characteristics on KAP was evaluated by stepwise multiple regression analysis, and a significant positive correlation was found between all the studied variables by Spearman's correlation (p < 0.05). CONCLUSIONS: This study showed that the attitudes toward and knowledge of the medical consortium significantly contribute to practices, satisfaction with the support work performed by the leading hospital and agreement of improvement after joining the medical consortium. Thus, to improve medical staff's KAP and satisfaction, publicity and educational programs in medical consortia are necessary, and the leading hospital should attach importance to the informatization construction and demand of different medical staff members. CLINICAL TRIAL REGISTRATION: There are no clinical trials in this study.

Elucidating the Role of Surface Ce4+ and Oxygen Vacancies of CeO2 in the Direct Synthesis of Dimethyl Carbonate from CO2 and Methanol.

Cerium dioxide (CeO2) was pretreated with reduction and reoxidation under different conditions in order to elucidate the role of surface Ce4+ and oxygen vacancies in the catalytic activity for direct synthesis of dimethyl carbonate (DMC) from CO2 and methanol. The corresponding catalysts were comprehensively characterized using N2 physisorption, XRD, TEM, XPS, TPD, and CO2-FTIR. The results indicated that reduction treatment promotes the conversion of Ce4+ to Ce3+ and improves the concentration of surface oxygen vacancies, while reoxidation treatment facilitates the conversion of Ce3+ to Ce4+ and decreases the concentration of surface oxygen vacancies. The catalytic activity was linear with the number of moderate acidic/basic sites. The surface Ce4+ rather than oxygen vacancies, as Lewis acid sites, promoted the adsorption of CO2 and the formation of active bidentate carbonates. The number of moderate basic sites and the catalytic activity were positively correlated with the surface concentration of Ce4+ but negatively correlated with the surface concentration of oxygen vacancies. The surface Ce4+ and lattice oxygen were active Lewis acid and base sites respectively for CeO2 catalyst, while surface oxygen vacancy and lattice oxygen were active Lewis acid and base sites, respectively, for metal-doped CeO2 catalysts. This may result from the different natures of oxygen vacancies in CeO2 and metal-doped CeO2 catalysts.

Tanshinol inhibits trophoblast cell migration and invasion by regulating Gadd45a in preeclampsia.

OBJECTIVE: Tanshinol is an active constituent of Salvia miltiorrhiza that possesses anti-inflammatory, antioxidant, and antibacterial activities. Therefore, this study attempted to detect whether it has a role in the treatment of preeclampsia (PE). METHODS: In this study, we explored the effect of tanshinol on the development of PE at the cellular level. The effect of tanshinol on cell proliferation was measured by colony formation and EdU assays. The migration, invasion, and in vitro angiogenesis of HTR-8/SVneo cells were detected by wound-healing, transwell, and tube formation assays, respectively. In addition, a PE cell model was established by overexpression of Gadd45a, and this cell model was assessed with the optimal concentration of tanshinol. RESULTS: The results show that tanshinol enhanced proliferation, migration, invasion, and tube formation of HTR-8/SVneo cells in vitro. Furthermore, the reduction in proliferation, migration, invasion, and tube formation of cells by Gadd45a overexpression was partially reversed by tanshinol treatment. Tanshinol also inhibited the apoptosis of HTR-8/SVneo cells transfected with Gadd45a. CONCLUSIONS: In summary, tanshinol promoted proliferation, migration, invasion, and tube formation and inhibited the apoptosis of HTR-8/SVneo cells. It may be a novel therapeutic compound to attenuate the development of PE.

Traditional Chinese medicine has maintained the health of people in Asia for thousands of years and is increasingly used worldwide. Tanshinol has been found to be useful in the treatment and prevention of many diseases. Through experiments, we found that tanshinol is a novel therapeutic compound that promotes the proliferation, migration, invasion and tubular formation of HTR-8/SVneo cells. In addition, tanshinol also inhibited the apoptosis rate of preeclampsia cell models. Follow-up experiments will further validate the results of this study.

Tubular epithelial cell-derived extracellular vesicles induce macrophage glycolysis by stabilizing HIF-1α in diabetic kidney disease.

BACKGROUND: Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. METHODS: Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. RESULTS: Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. CONCLUSION: Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria.

Thinopyrum intermedium TiAP1 interacts with a chitin deacetylase from Blumeria graminis f. sp. tritici and increases the resistance to Bgt in wheat.

The biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) is a crucial factor causing reduction in global wheat production. Wild wheat relatives, for example Thinopyrum intermedium, is one of the wild-used parents in wheat disease-resistant breeding. From T. intermedium line, we identified the aspartic protease gene, TiAP1, which is involved in resistance against Bgt. TiAP1 is a secreted protein that accumulates in large amounts at the infection sites of Bgt and extends to the intercellular space. Yeast two-hybrid, luciferase complementation imaging and bimolecular florescent complimentary analysis showed that TiAP1 interacted with the chitin deacetylase (BgtCDA1) of Bgt. The yeast expression, purification and in vitro test confirmed the chitin deacetylase activity of BgtCDA1. The bombardment and VIGS-mediated host-induced gene silencing showed that BgtCDA1 promotes the invasion of Bgt. Transcriptome analysis showed the cell wall xylan metabolism, lignin biosynthesis-related and defence genes involved in the signal transduction were up-regulated in the transgenic TiAP1 wheat induced by Bgt. The TiAP1 in wheat may inactivate the deacetylation function of BgtCDA1, cause chitin oligomers expose to wheat chitin receptor, then trigger the wheat immune response to inhibit the growth and penetration of Bgt, and thereby enhance the resistance of wheat to pathogens.

The HDAC2/SP1/miR-205 feedback loop contributes to tubular epithelial cell extracellular matrix production in diabetic kidney disease.

Extracellular matrix (ECM) accumulation is considered an important pathological feature of diabetic kidney disease (DKD). Histone deacetylase (HDAC) inhibitors protect against kidney injury. However, the potential mechanisms of HDACs in DKD are still largely unknown. Here, we describe a novel feedback loop composed of HDAC2 and miR-205 that regulates ECM production in tubular epithelial cells in individuals with DKD. We found that HDAC2 mRNA expression in peripheral blood was markedly higher in patients with DKD than in patients with diabetes. Nuclear HDAC2 protein expression was increased in TGFß1-stimulated tubular epithelial cells and db/db mice. We also found that miR-205 was regulated by HDAC2 and down-regulated in TGFß1-treated HK2 cells and db/db mice. In addition, HDAC2 reduced histone H3K9 acetylation in the miR-205 promoter region to inhibit its promoter activity and subsequently suppressed miR-205 expression through an SP1-mediated pathway. Furthermore, miR-205 directly targeted HDAC2 and inhibited HDAC2 expression. Intriguingly, miR-205 also regulated its own transcription by inhibiting HDAC2 and increasing histone H3K9 acetylation in its promoter, forming a feedback regulatory loop. Additionally, the miR-205 agonist attenuated ECM production in HK2 cells and renal interstitial fibrosis in db/db mice. In conclusion, the HDAC2/SP1/miR-205 feedback loop may be crucial for the pathogenesis of DKD.

Comparative genomic analysis of carboxylesterase genes in Tenebrio molitor and other four tenebrionids.

Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The α-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm.

How effective is the health promotion policy in Sichuan, China: based on the PMC-Index model and field evaluation.

BACKGROUND: Many countries around the world highlight the health in all policies (HiAP). However, most of the related research focused on the influential factors and implementation strategies, with less concern on the evaluation of HiAP. In response to HiAP's call, the Chinese government has proposed health promotion policies (HPPs) in counties or districts, the evaluation of HPPs in sample counties or districts of Sichuan province in China is an essential basis for optimizing policy content, improving policy implementation, and ensuring health promotion's continuous and efficient operation. METHODS: This paper established an evaluation system for HPPs based on the PMC-Index model and then quantitatively analyzed 37 representative HPPs from the pilot areas in Sichuan province. In addition, a team of experts conducted a field assessment. RESULTS: The results showed that the average PMC index of 37 HPPs was 7.091, and correlation analysis showed that there was a significant correlation between the PMC index and expert score. CONCLUSIONS: This study indicates that the overall consistency of HPPs was good and proves a connection between the formulation and implementation of HPPs.

Silencing lncRNA-DGCR5 increased trophoblast cell migration, invasion and tube formation, and inhibited cell apoptosis via targeting miR-454-3p/GADD45A axis.

Long noncoding RNA (lncRNA)-DGCR5 has been recognized as a potential tumor progression regulator, while its expression and specific functions in preeclampsia (PE) development remain unveiled. The expressions of miR-454-3p, lncRNA-DiGeorge syndrome critical region gene 5 (DGCR5) and growth arrest and DNA damage protein-inducible 45A (GADD45A) in placental tissues from PE patients or HTR-8/SVneo cells were assessed by Western blot or qRT-PCR. Dual-luciferase reporter assay determined the binding relations between miR-454-3p and GADD45A and between miR-454-3p and lncRNA-DGCR5. The viability, apoptosis, migration, invasiveness and tube formation of HTR-8/SVneo cell were evaluated using cell counting kit (CCK)-8, Annexin-V/Propidium iodide staining, wound healing, transwell and tube formation assays, respectively. miR-454-3p was low-expressed in PE tissue, and upregulation of miR-454-3p increased viability and promoted migration, invasion and tube formation in HTR-8/SVneo cells while inhibiting apoptosis. Then, miR-454-3p was found to directly target GADD45A which was high-expressed in PE tissues. Overexpressing GADD45A decreased the viability and inhibited the migration, invasion and tube formation of HTR-8/SVneo cells while enhancing apoptosis, and it neutralized the effect of miR-454-3p upregulation. In turn, miR-454-3p upregulation reversed the effect of GADD45A overexpression. Meanwhile, miR-454-3p could also target lncRNA-DGCR5. Silencing lncRNA-DGCR5 increased miR-454-3p expression and cell viability and promoted migration, invasion and tube formation in HTR-8/SVneo cells while inhibiting apoptosis, and it counteracted the effect of miR-454-3p downregulation. As usual, miR-454-3p downregulation reversed the effect of lncRNA-DGCR5 silencing. To conclude, silencing lncRNA-DGCR5 increased viability, promoted migration, invasion and tube formation, and inhibited apoptosis in HTR-8/SVneo cells by rescuing the inhibition of GADD45A expression caused by miR-454-3p.

Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial.

BACKGROUND: Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. METHODS: In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 µg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. RESULTS: Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. CONCLUSIONS: The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

Genome-wide identification and expression analysis of the TaYUCCA gene family in wheat.

Auxin is an important endogenous hormone in plants. The YUCCA gene encodes a flavin monooxygenase, which is an important rate-limiting enzyme in the auxin synthesis pathway and involved in the regulation of plant growth and development. In the study, we identified 63 wheat TaYUCCA genes; among them, some genes appeared in clusters. By constructing phylogenetic trees, we found that the TaYUCCA genes could be divided into six groups. In the WheatExp database, there were 22 differential expressed TaYUCCA genes, among which the TaYUCCA10 gene was abundantly expressed in the endosperm and medium milk stage, the TaYUCCA2 gene was abundantly expressed in the roots of three leaves and meiosis and transfer cells at 20 days post anthesis and the others 16 TaYUCCA genes had different expression level at different developmental stages in wheat, and there were 15 TaYUCCA genes induced by drought and heat stress, among which the TaYUCCA2-D, TaYUCCA3-B, and TaYUCCA9-D might be upregulated induced by drought stress, TaYUCCA10.1 might be upregulated induced drought and heat stress, TaYUCCA6-A was upregulated induced both drought and heat stress and the others 9 TaYUCCA genes were downregulated induced by drought and heat stress. Transcriptome and qRT-PCR analysis showed that TaYUCCA7-A was upregulated significantly after induced by powdery mildew. The comprehensive annotation and expression profiling of the TaYUCCA genes in this study enhanced our understanding of TaYUCCA family gene expression in wheat growth and development and laid the foundation for the further study of TaYUCCA gene mechanism.

Seed-specific expression of TaYUC10 significantly increases auxin and protein content in wheat seeds.

KEY MESSAGE: Present study revealed that specific expression of TaYUC10.3 in wheat young seeds could increase the content of auxin, and protein. Auxin is a vital endogenous hormone in plants, which is involved in the regulation of various physiological and biochemical processes in plants. The flavin-containing monooxygenase encoded by the YUCCA gene is a rate-limiting enzyme in the tryptophan-dependent pathway of auxin synthesis. TaYUC10.3 was identified, cloned and found that it was abundantly expressed in wheat young seeds. In this study, a seed-specific expression vector of TaYUC10.3 was constructed with the promoter of 1Bx17 glutenin subunit gene and transformed wheat using the particle bombardment method. The quantitative RT-PCR showed that TaYUC10.3 was expressed in a large amount in young seeds of the transgenic lines. Plant hormone-targeted metabolomics showed that the auxin content of the transgenic lines was significantly increased compared with controls. The GC / MS non-targeted metabolite multiple statistical analyses showed that the variable importance in projection (VIP) of tryptophan reduced in the transgenic lines. Simultaneously, the VIP of indole acetic acid increased. The precursor amino acids for synthesizing some proteins and carbohydrates were upregulated in the transgenic lines. Subsequently, it was found that the protein content of the seeds of the transgenic TaYUC10.3 wheat was significantly higher than that of the control. The wet gluten content and sedimentation value of the transgenic TaYUC10.3 wheat were also high. This result indicated that TaYUC10.3 might participate in auxin synthesis and affects the protein content of wheat seeds.

A gap existed between physicians' perceptions and performance of pain, agitation-sedation and delirium assessments in Chinese intensive care units.

BACKGROUND: Pain, agitation-sedation and delirium management are crucial elements in the care of critically ill patients. In the present study, we aimed to present the current practice of pain, agitation-sedation and delirium assessments in Chinese intensive care units (ICUs) and investigate the gap between physicians' perception and actual clinical performance. METHODS: We sent invitations to the 33 members of the Neuro-Critical Care Committee affiliated with the Chinese Association of Critical Care Physicians. Finally, 24 ICUs (14 general-, 5 neuroscience-, 3 surgical-, and 2 emergency-ICUs) from 20 hospitals participated in this one-day point prevalence study combined with an on-site questionnaire survey. We enrolled adult ICU admitted patients with a length of stay ≥24 h, who were divided into the brain-injured group or non-brain-injured group. The hospital records and nursing records during the 24-h period prior to enrollment were reviewed. Actual evaluations of pain, agitation-sedation and delirium were documented. We invited physicians on-duty during the 24 h prior to the patients' enrollment to complete a survey questionnaire, which contained attitude for importance of pain, agitation-sedation and delirium assessments. RESULTS: We enrolled 387 patients including 261 (67.4%) brain-injured and 126 (32.6%) non-brain-injured patients. There were 19.9% (95% confidence interval [CI]: 15.9-23.9%) and 25.6% (95% CI: 21.2-29.9%) patients receiving the pain and agitation-sedation scale assessment, respectively. The rates of these two types of assessments were significantly lower in brain-injured patients than non-brain-injured patients (p = 0.003 and < 0.001). Delirium assessment was only performed in three patients (0.8, 95% CI: 0.1-1.7%). In questionnaires collected from 91 physicians, 70.3% (95% CI: 60.8-79.9%) and 82.4% (95% CI: 74.4-90.4%) reported routine use of pain and agitation-sedation scale assessments, respectively. More than half of the physicians (52.7, 95% CI: 42.3-63.2%) reported daily screening for delirium using an assessment scale. CONCLUSIONS: The actual prevalence of pain, agitation-sedation and delirium assessment, especially delirium screening, was suboptimal in Chinese ICUs. There is a gap between physicians' perceptions and actual clinical practice in pain, agitation-sedation and delirium assessments. Our results will prompt further quality improvement projects to optimize the practice of pain, agitation-sedation and delirium management in China. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03975751 . Retrospectively registered on 2 June 2019.

Comparison of User-Oriented Information Services on the Websites of Large Hospitals in China and the United States: Cross-sectional Study.

BACKGROUND: Many people use the internet to access health care information to support health care decisions, and hospital websites can be the first point of contact to provide health care information services for consumers. However, little is known about the current information services provided by the websites of large Chinese hospitals. OBJECTIVE: The aim of this study is to evaluate and compare the information services of the websites of large hospitals in China and the United States. We hope that our findings will benefit hospital managers worldwide in providing service information on the web. METHODS: This study adopted a cross-sectional analytical approach to evaluate the websites of large hospitals in China and the United States in 2020. A total of 300 large hospitals were randomly selected, of which half were in China and half were in the United States. Based on the 7Ps marketing mix, we identified 39 items that represent typical hospital website information services, covering the following seven dimensions: product, price, place, propagation, people, process, and physical evidence. RESULTS: Most of the items (34/39, 87%) related to information services offered by hospital websites were less covered in China than in the United States; however, 5 items (appointments by a third-party platform, mobile payment, hospital value, hospital environment display, and physicians' profiles) had higher coverage in China. The average scores for hospital websites in China and the United States were 13.25 (SD 2.99) points and 23.16 (SD 2.76) points, respectively. Generally, high scores were given to the south areas of China and north areas of the United States. CONCLUSIONS: Hospital websites in China lagged behind those in the United States with regard to information services offered. We recommend that hospital managers in China place more emphasis on the people, product, and propagation dimensions of the 7Ps marketing mix in the construction of information services on hospital websites. Through the comparison of the websites of large hospitals in China and the United States, our study findings can provide suggestions for forming standard hospital website construction guidelines worldwide.

Non-obstructed supracardiac total anomalous pulmonary venous connection with giant superior vena cava aneurysm.

BACKGROUND: Giant superior vena cava (SVC) aneurysm in non-obstructed supracardiac total anomalous pulmonary venous connection (TAPVC) is even more rare than in obstructed one, and this combination has not been reported. CASE PRESENTATION: Here we reported a 29-year-old young lady with non-obstructed TAPVC complicated with a giant SVC aneurysm. Routine TAPVC correction and tricuspid valve repair were done. Additionally, venoctomy was carried out to seek for its histological etiology and to avoid potential complications. CONCLUSIONS: If confirmed by further and larger experiences, for patients with non-obstructed supracardiac TAPVC with giant SVC aneurysm, surgical treatment of SVC aneurysm could be more aggressive to prevent cardiovascular complications.

Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia-mesenchymal transition during pancreatic carcinogenesis.

OBJECTIVE: SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. DESIGN: TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (PdxcreSetd2flox/flox) together with KrasG12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism. RESULTS: SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelia-mesenchymal transition (EMT) through impaired epigenetic regulation of Ctnna1. In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis. CONCLUSION: Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.

Genome-wide identification of the aspartic protease gene family and their response under powdery mildew stress in wheat.

Aspartic proteases (APs) are one of the four main protease super families. In plants, they are involved in many biological processes, such as biotic and abiotic stress resistance, protein processing and degradation, senescence, and programmed cell death. By performing a database (TGACv1) search and domain prediction, we identified 263 wheat AP (TaAP) proteins and observed 38 TaAP genes exhibiting alternative splicing. Moreover, by constructing a phylogenetic tree, we found that the TaAP proteins can be divided into three families and have a certain close evolutionary relationship to Arabidopsis thaliana and rice AP proteins. Transcriptome analysis showed that 29 genes in the TaAP family were up-regulated after being induced by powdery mildew. The expression of TaAP224 showed the most significant difference in transcriptome and qRT-PCR analyses. Subsequently, the promoters of these 29 genes were analysed, and we found that they contained multiple disease resistance and hormone elements, such as WRKY71OS, a common disease resistance element that is also involved in the GA signalling pathway and inhibits starch hydrolysis. The comprehensive annotation and expression profiling performed in this study increased our understanding of the TaAP family genes in wheat growth and development, and the results can be used as a basis for further study of candidate TaAP genes involved in powdery mildew resistance mechanisms.