Identification and validation of tryptophan metabolism-related lncRNAs in lung adenocarcinoma prognosis and immune response.

BACKGROUND: Tryptophan (Trp) is an essential amino acid. Increasing evidence suggests that tryptophan metabolism plays a complex role in immune escape from Lung adenocarcinoma (LUAD). However, the role of long non-coding RNAs (lncRNAs) in tryptophan metabolism remains to be investigated. METHODS: This study uses The Cancer Genome Atlas (TCGA)-LUAD dataset as the training cohort, and several datasets from the Gene Expression Omnibus (GEO) database are merged into the validation cohort. Genes related to tryptophan metabolism were identified from the Molecular Signatures Database (MSigDB) database and further screened for lncRNAs with Trp-related expression. Subsequently, a prognostic signature of lncRNAs related to tryptophan metabolism was constructed using Cox regression analysis, (Least absolute shrinkage and selection operator regression) and LASSO analysis. The predictive performance of this risk score was validated by Kaplan-Meier (KM) survival analysis, (receiver operating characteristic) ROC curves, and nomograms. We also explored the differences in immune cell infiltration, immune cell function, tumor mutational load (TMB), tumor immune dysfunction and exclusion (TIDE), and anticancer drug sensitivity between high- and low-risk groups. Finally, we used real-time fluorescence quantitative PCR, CCK-8, colony formation, wound healing, transwell, flow cytometry, and nude mouse xenotransplantation models to elucidate the role of ZNF8-ERVK3-1 in LUAD. RESULTS: We constructed 16 tryptophan metabolism-associated lncRNA prognostic models in LUAD patients. The risk score could be used as an independent prognostic indicator for the prognosis of LUAD patients. Kaplan-Meier survival analysis, ROC curves, and risk maps validated the prognostic value of the risk score. The high-risk and low-risk groups showed significant differences in phenotypes, such as the percentage of immune cell infiltration, immune cell function, gene mutation frequency, and anticancer drug sensitivity. In addition, patients with high-risk scores had higher TMB and TIDE scores compared to patients with low-risk scores. Finally, we found that ZNF8-ERVK3-1 was highly expressed in LUAD tissues and cell lines. A series of in vitro experiments showed that knockdown of ZNF8-ERVK3-1 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. In vivo experiments with xenografts have shown that knocking down ZNF8-ERVK3-1 can significantly inhibit tumor size and tumor proliferation. CONCLUSION: We constructed a new prognostic model for tryptophan metabolism-related lncRNA. The risk score was closely associated with common clinical features such as immune cell infiltration, immune-related function, TMB, and anticancer drug sensitivity. Knockdown of ZNF8-ERVK3-1 inhibited LUAD cell proliferation, migration, invasion, and G0/G1 phase blockade and promoted apoptosis.

Mechanistic and biophysical characterization of polymyxin resistance response regulator PmrA in Acinetobacter baumannii.

Introduction: Acinetobacter baumannii PmrAB is a crucial two-component regulatory system (TCS) that plays a vital role in conferring resistance to polymyxin. PmrA, a response regulator belonging to the OmpR/PhoB family, is composed of a C-terminal DNA-binding effector domain and an N-terminal receiver domain. The receiver domain can be phosphorylated by PmrB, a transmembrane sensor histidine kinase that interacts with PmrA. Once phosphorylated, PmrA undergoes a conformational change, resulting in the formation of a symmetric dimer in the receiver domain. This conformational change facilitates the recognition of promoter DNA by the DNA-binding domain of PmrA, leading to the activation of adaptive responses. Methods: X-ray crystallography was carried out to solve the structure of PmrA receiver domain. Electrophoretic mobility shift assay and Isothermal titration calorimetry were recruited to validate the interaction between the recombinant PmrA protein and target DNA. Field-emission scanning electron microscopy (FE-SEM) was employed to characterize the surface morphology of A. baumannii in both the PmrA knockout and mutation strains. Results: The receiver domain of PmrA follows the canonical α5ß5 response regulator assembly, which undergoes dimerization upon phosphorylation and activation. Beryllium trifluoride is utilized as an aspartate phosphorylation mimic in this process. Mutations involved in phosphorylation and dimerization significantly affected the expression of downstream pmrC and naxD genes. This impact resulted in an enhanced cell surface smoothness with fewer modifications, ultimately contributing to a decrease in colistin (polymyxin E) and polymyxin B resistance. Additionally, a conservative direct-repeat DNA PmrA binding sequence TTTAAGNNNNNTTTAAG was identified at the promoter region of the pmrC and naxD gene. These findings provide structural insights into the PmrA receiver domain and reveal the mechanism of polymyxin resistance, suggesting that PmrA could be a potential drug target to reverse polymyxin resistance in Acinetobacter baumannii.

The Functional Study of Response Regulator ArlR Mutants in Staphylococcus Aureus.

Staphylococcus aureus is a major cause of hospital-associated infections worldwide. The organism's ability to form biofilms has led to resistance against current treatment options such as beta-lactams, glycopeptides, and daptomycin. The ArlRS two-component system is a crucial regulatory system necessary for S. aureus autolysis, biofilm formation, capsule synthesis, and virulence. This study aims to investigate the role of the arlR deletion mutant in the detection and activation of S. aureus. We created an arlR deleted mutant and complementary strains and characterized their impact on the strains using partial growth measurement. The quantitative real-time PCR was performed to determine the expression of icaA, and the microscopic images of adherent cells were captured at the optical density of 600 to determine the primary bacterial adhesion. The biofilm formation assay was utilized to investigate the number of adherent cells using crystal violet staining. Eventually, the Triton X-100 autolysis assay was used to determine the influence of arlR on the cell autolytic activities. Our findings indicate that the deletion of arlR reduced the transcriptional expression of icaA but not icaR in the ica operon, leading to decrease in polysaccharide intercellular adhesin (PIA) synthesis. Compared to the wild-type and the complementary mutants, the arlR mutant exhibited decreased in biofilm production but increased autolysis. It concluded that the S. aureus response regulatory ArlR influences biofilm formation, agglutination, and autolysis. This work has significantly expanded our knowledge of the ArlRS two-component regulatory system and could aid in the development of novel antimicrobial strategies against S. aureus.

Combining fecal microbiome and metabolomics reveals diagnostic biomarkers for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Chewing difficulties mediated association between edentulism and depressive symptoms among middle aged and older population.

BACKGROUND: Depression is a major health condition among the aging population. Previous studies indicated that edentulism was a risk factor for depression. The link between edentulism and depression has not been fully clarified. OBJECTIVES: This study aimed to estimate whether chewing difficulties play a mediating role in the association between edentulism and depression among middle-aged and older populations with national cross-sectional data. METHODS: Data were obtained from the latest fourth wave of the China Health and Retirement Longitudinal Study (CHARLS). The outcome variable was set as depression, which was measured by the Center for Epidemiologic Studies Depression Scale (CES-D-10). Independent and mediated variables were separately set as self-assessed edentulism and chewing difficulties. The nearest neighbour propensity score matching (PSM) method was used to construct a matching group to balance the basic characteristics of individuals with and without edentulism with minimised bias in the estimation. Causal mediation analysis was performed to estimate the degree of contribution of chewing difficulties to the association between edentulism and depression. Several sensitivity analyses were performed to evaluate the robustness of the primary result. RESULTS: A total of 15 853 individuals remained for analysis. After PSM, 809 individuals with edentulism and 2628 without edentulism remained for analysis. Among the matched individuals, the mean age was 66.3 ± 9.2 years, 58.5% were female, 78.8% lived in rural areas, 23.5% had edentulism, 51.1% had depressive symptoms, and 50.1% had chewing difficulties. Logistic regression results showed that a higher incidence of edentulism was associated with a higher rate of depression (OR: 1.39, 95% CI: 1.19-1.63) in the matching group. Causal mediation analysis results indicated that the average mediation effect of chewing difficulties on the association between edentulism and depression was 0.010 (95% CI: 0.005-0.015), and the average direct effect was 0.072 (95% CI: 0.036-0.11). The mediation proportion of chewing difficulties was 11.7% (95% CI: 0.079-0.21). CONCLUSION: A higher prevalence of edentulism was associated with a higher rate of depression among middle-aged and elderly populations. Chewing difficulties moderately mediated the association between edentulism and depression. Fundamental oral function should not be neglected to improve mental health among the aging population.

The coupling coordination and spatiotemporal evolution of industrial water-energy-CO2 in the Yellow River Basin.

The Yellow River Basin (YRB) is an important energy, chemical, raw material, and basic industrial base in China. With economic growth, water and energy consumption in industrial industries increasing dramatically, huge pressure for CO2 emission reduction has generated. This paper constructed an industrial water-energy-CO2 (WEC) evaluation index system, analyzed the comprehensive evaluation level, coupling status and coupling coordination status, by using the comprehensive evaluation method, coupling degree model and coupling coordination degree model and used the spatial autocorrelation analysis to study the spatiotemporal evolution from 1999 to 2019 in the YRB. The results demonstrated that the integrated development level of the basin's industrial WEC system and subsystems had been improving. The basin was at a high coupling and the level of coupling had been increasing as a whole, and the industrial energy-CO2 coupling degree was bigger than the industrial water-energy and industrial water-CO2 coupling degrees in the YRB. The coupling coordination status had transitioned from forced coordination to good coordination. Spatially, the coupling coordination didn't appear a significant correlation and showed a random distribution. Accordingly, the suggestions were made to improve the level of industrial development in the basin, strengthen integrated resource management, and enhance intra-basin cooperation.

Management of cavernous sinus meningiomas: Clinical features, treatment strategies, and long-term outcomes.

OBJECTIVES: The purpose of this research was to summarize the clinical and prognostic features of cavernous sinus meningiomas (CSM), evaluate the treatment strategies and long-term prognosis of CSM, and improve the management of CSM and the treatment effect for patients. METHODS: We retrospectively studied the data of 54 patients who received initial surgical resection and 45 patients who received initial gamma knife radiosurgery (GKRS) for CSM at West China Hospital of Sichuan University from 2009 to 2021. Progression-free survival (PFS), Karnofsky Performance Scale (KPS) scores and neurological function recovery were adopted to assess a comprehensive management strategy for CSM. RESULTS: Gross total resection (GTR) was performed in 51.9 % of cases with 3.7 % surgical mortality. The average follow-up time was 48.7 months, with a progression rate of 29.3 %. The overall improvement rate for cranial nerve function deficits was 50.0 %. By survival analysis, the extent of resection and the histological grade were significantly related to the prognosis. The role of postoperative GKRS is uncertain. For patients who received initial GKRS, the progression rate was 17.8 %, and the overall improvement rate for cranial nerve function deficits was 61.1 %. Primary treatment with GKRS showed better long-term tumor control in patients with CSM (P = 0.046). CONCLUSIONS: Maximum safe resection of CSM can improve the neurological function and quality of life of patients, but aggressive resection will cause high perioperative mortality and complication rates. For CSM patients who are suitable for initial gamma knife treatment, choosing GKRS can achieve better long-term tumor control and neurological outcomes.

Robotic Frameless Stereotactic Aspiration with Thrombolysis for Primary Pontine Hemorrhage: A Therapeutic Evaluation of a Retrospective Cohort Study.

INTRODUCTION: It remains controversial whether primary pontine hemorrhage (PPH) should be managed conservatively or treated promptly via surgical evacuation of the hematoma. The purpose of this study was to assess the therapeutic effect of robotic frameless stereotactic aspiration with thrombolysis in the treatment of PPH. METHODS: A total of 39 patients with PPH between January 2012 and November 2016 were included in the study. Sixteen patients with frameless stereotactic surgical treatment (ST group) and twenty-three patients with conservative treatment (CT group). Clinical and radiological parameters were assessed, and patient outcomes were analyzed over a 6-month follow-up period. RESULTS: Surgical treatment did not result in any intracranial infections, or complications. Baseline characteristics did not significantly differ between the two groups. At discharge, the average Glasgow Coma Scale (GCS) score and the overall Glasgow Outcome Scale (GOS) score were significantly higher in the ST group compared to the CT group (P < 0.05). The mortality rate (GOS score 1) was significantly lower in the ST group (18.75%, 3/16) than in the CT group (52.17%, 12/23). For patients with hematoma volumes of 5-10 ml or GCS scores of 6-8, following treatment, the ST group exhibited markedly higher Glasgow Outcome Scale (GOS) scores in comparison to the CT group. CONCLUSION: In conclusion, our study suggests that robotic frameless stereotactic aspiration with thrombolysis is a safe and efficient method for the treatment of PPH. Patients with hematomas of 5-10 ml or GCS scores of 6-8 could benefit from surgery.

Hematoma-like dynamic hydrogelation through natural glycopeptide molecular recognition for infected bone fracture repair.

Infected bone fractures remain a major clinical challenge for orthopedic surgeons. From a tissue regeneration perspective, biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired, while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research. Hematoma, the gel-like blood coagulum, plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing. In light of this, we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study. The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin (Van) and its target dipeptide D-Ala-D-Ala (AA), which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide (OGP). In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria, improve bone regeneration and restore the local inflammatory microenvironment. Together, findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.

Rational multivalency construction enables bactericidal effect amplification and dynamic biomaterial design.

The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix (ECM)-mimicking biomaterials. However, designing controllable multivalency construction strategies is still challenging. Herein, we synthesized a series of well-defined multivalent antimicrobial peptide polymers (mAMPs) by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization. The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding, leading to amplification of the bactericidal effect. In addition to multivalency-enhanced antibacterial activity, mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure. The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds. The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Structure and assembly of type VI secretion system cargo delivery vehicle.

Type VI secretion system is widely used in Gram-negative bacteria for injecting toxic effectors into neighboring prokaryotic or eukaryotic cells. Various effectors can be loaded onto the T6SS delivery tube via its core components: Hcp, VgrG, or PAAR. Here, we report 2.8-Å resolution cryo-EM structure of intact T6SS Hcp5-VgrG-PAAR cargo delivery system and crystal structure of unbound Hcp5 from B. fragilis NCTC 9343. Loading of Hcp5 hexameric ring onto VgrG causes expansion of its inner cavity and external surface, explaining how structural changes could be propagated to regulate co-polymerization and surrounding contractile sheath. High-affinity binding between Hcp and VgrG causes entropically unfavorable structuring of long loops. Furthermore, interactions between VgrG trimer and Hcp hexamer are asymmetric, with three of the six Hcp monomers exhibiting a major loop flip. Our study provides insights into the assembly, loading, and firing of T6SS nanomachine that contributes to bacterial inter-species competition and host interactions.

Mechanistic and structural insights into the bifunctional enzyme PaaY from Acinetobacter baumannii.

PaaY is a thioesterase that enables toxic metabolites to be degraded through the bacterial phenylacetic acid (PA) pathway. The Acinetobacter baumannii gene FQU82_01591 encodes PaaY, which we demonstrate to possess γ-carbonic anhydrase activity in addition to thioesterase activity. The crystal structure of AbPaaY in complex with bicarbonate reveals a homotrimer with a canonical γ-carbonic anhydrase active site. Thioesterase activity assays demonstrate a preference for lauroyl-CoA as a substrate. The AbPaaY trimer structure shows a unique domain-swapped C-termini, which increases the stability of the enzyme in vitro and decreases its susceptibility to proteolysis in vivo. The domain-swapped C-termini impact thioesterase substrate specificity and enzyme efficacy without affecting carbonic anhydrase activity. AbPaaY knockout reduced the growth of Acinetobacter in media containing PA, decreased biofilm formation, and impaired hydrogen peroxide resistance. Collectively, AbPaaY is a bifunctional enzyme that plays a key role in the metabolism, growth, and stress response mechanisms of A. baumannii.

Introducing value-based healthcare perspectives into hospital performance assessment: A scoping review.

OBJECTIVE: Value-based healthcare (VBHC) puts patient outcomes at the center of the healthcare process while optimizing the use of hospital resources across multiple stakeholders. This scoping review was conducted to summarize how VBHC had been represented in theory and in practice, how it had been applied to assess hospital performance, and how well it had been ultimately implemented. METHODS: For this review, we followed the PRISMA-ScR protocol and searched five major online databases for articles published between January 2006 and July 2022. We included original articles that used the concept of VBHC to conduct performance assessments of healthcare organizations. We extracted and analyzed key concepts and information on the dimensions of VBHC, specific strategies and methods for using VBHC in performance assessment, and the effectiveness of the assessment. RESULTS: We identified 48 eligible studies from 7866 articles. Nineteen nonempirical studies focused on the development of a VBHC performance assessment indicator system, and 29 empirical studies reported on the ways and points of introducing VBHC into performance assessment and its effectiveness. Ultimately, we summarized the key dimensions, processes, and effects of performance assessment after introducing VBHC. CONCLUSION: Current healthcare performance assessment has begun to focus on implementing VBHC as an integrated strategy, and future work should further clarify the reliability of metrics and their association with evaluation outcomes and consider the effective integration of clinical outcomes and patient-reported outcomes.

Pulmonary Artery Denervation Inhibits Left Stellate Ganglion Stimulation-Induced Ventricular Arrhythmias Originating From the RVOT.

BACKGROUND: Electrical stimulation of the left stellate ganglion (LSG) can evoke ventricular arrhythmias (VAs) that originate from the right ventricular outflow tract (RVOT). The involvement of pulmonary artery innervation is unclear. OBJECTIVES: This study investigated the effects of selective pulmonary artery denervation (PADN) on blood pressure (BP), sympathetic activity, ventricular effective refractory period (ERP), and the incidence of VAs induced by LSG stimulation in canines. METHODS: Radiofrequency ablation with basic anesthetic monitoring was used to induce PADN in canines. In Protocol 1 (n = 11), heart rate variability, serum norepinephrine and angiotensin-II levels, BP changes and ventricular ERP in response to LSG stimulation were measured before and after PADN. In Protocol 2 (n = 8), the incidence of VAs induced by LSG stimulation was calculated before and after PADN in a canine model of complete atrioventricular block. In addition, sympathetic nerves in the excised pulmonary arteries were immunohistochemically stained with tyrosine hydroxylase. RESULTS: The low-frequency components of heart rate variability, serum norepinephrine and angiotensin-II levels were remarkably decreased post-PADN. Systolic BP elevation and RVOT ERP shortening induced by LSG stimulation were mitigated by PADN. The number of RVOT-premature ventricular contractions as well as RVOT tachycardia episodes and duration induced by LSG stimulation were significantly reduced after PADN. In addition, a large number of tyrosine hydroxylase-immunoreactive nerve fibers were located in the anterior wall of the pulmonary artery. CONCLUSIONS: PADN ameliorated RVOT ERP shortening, and RVOT-VAs induced by LSG stimulation by inhibiting cardiac sympathetic nerve activity.

Total tubeless percutaneous nephrolithotomy without artificial hydronephrosis in preschool children: Three case reports.

RATIONALE: Indwelling ureteral catheter, double J tube, or nephrostomy tube are routine procedures for percutaneous nephrolithotomy (PCNL) in children. There are a few cases in which PCNL has been performed in children without any additional instruments being left in place. PATIENT CONCERNS: In this study, 3 children were treated for hematuria and complicated with different degrees of urinary tract infection. All of them were diagnosed as upper urinary tract calculi by abdominal computed tomography. DIAGNOSIS: Three preschoolers were diagnosed with upper urinary tract calculi before surgery, one with no hydronephrosis and the other 2 with different degrees of hydronephrosis. INTERVENTIONS: After preoperative evaluation, all the children successfully completed PCNL without indwelling ureteral catheter, double J tube, or nephrostomy tube. OUTCOMES: The operation was successful and there were no residual stones observed during postoperative review. The operating times for the children were 33 minutes, 17 minutes, and 20 minutes, and the intraoperative bleeding volumes were 1 mL, 2 mL, and 2 mL. The catheter was removed on the second day after the operation, the postoperative review of the abdominal computed tomography or ultrasound did not indicate any stone residue, and there were no fever, bleeding, and other related complications after the operation. LESSONS: We believe that total tubeless PCNL without artificial hydronephrosis can be achieved in the preschool population.

Efficiency of the Brain Network Is Associated with the Mental Workload with Developed Mental Schema.

The study of mental workload has attracted much interest in neuroergonomics, a frontier field of research. However, there appears no consensus on how to measure mental workload effectively because the mental workload is not only regulated by task difficulty but also affected by individual skill level reflected as mental schema. In this study, we investigated the alterations in the functional brain network induced by a 10-day simulated piloting task with different difficulty levels. Topological features quantifying global and local information communication and network organization were analyzed. It was found that during different tests, the global efficiency did not change, but the gravity center of the local efficiency of the network moved from the frontal to the posterior area; the small-worldness of the functional brain network became stronger. These results demonstrate the reconfiguration of the brain network during the development of mental schema. Furthermore, for the first two tests, the global and local efficiency did not have a consistent change trend under different difficulty levels, but after forming the developed mental schema, both of them decreased with the increase in task difficulty, showing sensitivity to the increase in mental workload. Our results demonstrate brain network reconfiguration during the motor learning process and reveal the importance of the developed mental schema for the accurate assessment of mental workload. We concluded that the efficiency of the brain network was associated with mental workload with developed mental schema.

Screening and epitope characterization of diagnostic nanobody against total and activated Bacteroides fragilis toxin.

Enterotoxigenic Bacteroides fragilis (ETBF) can rapidly secrete an enterotoxin termed B. fragilis toxin (BFT), which is thought to be the only recognized virulence factor in ETBF. ETBF can cause acute diarrhea, inflammatory bowel disease (IBD), colorectal cancer, and breast cancer. BFT is divided into three subtypes, BFT1, BFT2, and BFT3. BFT1 is the most widely distributed in human B. fragilis isolates. BFT can be used as a biomarker for predicting the inflammation-cancer transformation of intestine and breast. Nanobodies have the advantages of small structure, complete antigen recognition capacity, rapid selection via phage display technology, and can be massively produced in microbial expression systems. Nanobodies have become a powerful tool for medical diagnosis and treatment. This study focuses on screening and structural characterization of nanobodies targeting full length and active BFT. By constructing prokaryotic expression systems to obtain recombinant BFT1 protein, high purity BFT1 protein was used to immunize alpacas. Phage display technology was used to construct a phage display library. The positive clones were selected by bio-panning, and the isothermal titration calorimetry was used to select high-affinity nanobodies. Then the three-dimensional structures of BFT1:Nb2.82 and BFT1:Nb3.27 were solved by crystal X-ray diffraction. We got two kinds of nanobodies, Nb2.82 targeting the BFT1 prodomain and Nb3.27 recognizing the BFT1 catalytic domain. This study provides a new strategy for the early diagnosis of ETBF and the possibility for BFT as a biomarker for diagnosing diseases.

Ecological security evaluation and early warning in the water source area of the Middle Route of South-to-North Water Diversion Project.

Ecological security has important influence on regional sustainable development. The ecological security of Nanyang, the water source area of the Middle Route of South-to-North Water Diversion Project, was threatened because of surface water pollution. The existing studies had not been able to comprehensively assess the ecological security and future trend of water source area. In order to promote the high-quality development of the follow-up projects of the South-to-North Water Diversion project, it is very important to probe into the current situation and predict the future trend of ecological security in the water source area. Therefore, this paper constructed an ecological security evaluation index system based on the Driving force, Pressure, State, Impact and Response (DPSIR) model, used the combination of Analytic Hierarchy Process and- entropy weighting method to evaluate the ecological security of each district and county in Nanyang from 2000 to 2020, and used the auto regressive integrated moving average (ARIMA) model to predict the ecological security of the water source area from 2021 to 2030. The results demonstrated that: (1) The ecological security of Nanyang had changed from a moderate warning to a general safety, and the ecological security index had improved. The ecological security level of Nanyang would improve continuously from 2021 to 2030. (2) The northwest area and the central area of Nanyang had better ecological security states, while the southeast area wasn't so. Based on the results, the countermeasures for improving ecological security were proposed.