Oesophago-pericardial fistula after catheter ablation of atrial fibrillation: a case report.

Background: Oesophageal fistula is a rare complication of catheter ablation of atrial fibrillation with most fistulas being atrio-oesophageal fistulas, but oesophageal-pericardial fistula can also happen in the absence of atrial perforation. Case summary: A 68-year-old male patient presented with chest pain 10 days after catheter ablation of paroxysmal atrial fibrillation. He was discharged after an initial negative workup that included a CT chest without contrast. He later presented again with severe chest pain and fever and was found to have an oesophageal-pericardial fistula. He underwent surgical and endoscopic treatment with good recovery. Discussion: Patients with oesophago-pericardial fistulas often have delayed presentation 1-4 weeks after the ablation procedure. Early diagnosis can be challenging. CT with oral and intravenous contrast is often used for diagnosis. Treatment often includes antibiotics, surgical or interventional drainage of infected spaces with oesophageal repair, clipping or stenting. In contrast to atrio-oesophageal fistulas that carry a high mortality rate, mortality for oesophago-pericardial fistulas appears to be much lower.

Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells.

AIM: To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects. METHODS: Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip. RESULTS: BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity. CONCLUSION: BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.

CuCo2O4/CuO Heterostructure with Oxygen Vacancies Induced by Plasma for Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction (NO3RR) to ammonia production is regarded as one of the potential alternatives for replacing the Haber-Bosch technology for realizing artificial ammonia synthesis. In this study, a CuCo2O4/CuO-Ar heterostructure in the shape of dandelion nanospheres formed by nanoarrays has been successfully constructed, demonstrating excellent NO3RR performance. Experimental results indicate that Ar plasma etching of CuCo2O4/CuO-Ar significantly increases the content of oxygen vacancies compared to the sample of CuCo2O4/CuO-Air etched by air plasma, resulting in improved NO3RR performance. Density functional theory calculations further confirm that the existence of more oxygen vacancies effectively decreases the energy barrier of nitrate adsorption, which is due to the generation of more oxygen vacancies facilitating nitrate adsorption and weakening the N-O bonds of nitrate after plasma treatment. As a result, CuCo2O4/CuO-Ar exhibits a high NH3 yield of 0.55 mmol h-1 cm-2 and a Faraday efficiency of 95.07% at the optimal potential of -0.9 V (vs RHE) in a neutral medium. Importantly, CuCo2O4/CuO-Ar also showcases excellent electrocatalytic stability. This study presents new views on the design and structure regulation of NO3RR electrocatalysts and their potential applications in the future.

Chronological Management of Adjuvant Effect for Optimized mRNA Vaccine Inspired by Natural Virus Infection.

The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely Precede, Coincide, and Follow. Follow, the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8+ T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.

Co-learning companionship benefits word learning in a new language: Evidence from a dual-brain EEG examination.

Companionship refers to one's being in the presence of another individual. For adults, acquiring a new language is a highly social activity that often involves learning in the context of companionship. However, the effects of companionship on new language learning have gone relatively underexplored, particularly with respect to word learning. Using a within-subject design, the current study employs electroencephalography to examine how two types of companionship (monitored and co-learning) affect word learning (semantic and lexical) in a new language. Dyads of Chinese speakers of English as a second language participated in a pseudo-word-learning task during which they were placed in monitored and co-learning companionship contexts. The results showed that exposure to co-learning companionship affected the early attention stage of word learning. Moreover, in this early stage, evidence of a higher representation similarity between co-learners showed additional support that co-learning companionship influenced attention. Observed increases in delta and theta interbrain synchronization further revealed that co-learning companionship facilitated semantic access. In all, the similar neural representations and interbrain synchronization between co-learners suggest that co-learning companionship offers important benefits for learning words in a new language.

Recent advances in CO2 reduction with renewable reductants under hydrothermal conditions: towards efficient and net carbon benefit CO2 conversion.

The ever-growing atmospheric CO2 concentration threatening the environmental sustainability of humankind makes the reduction of CO2 to chemicals or fuels an ideal solution. Two priorities are anticipated for the conversion technology, high efficiency and net carbon benefit, to ensure the mitigation of the CO2 problem both promptly and sustainably. Until now, catalytic hydrogenation or solar/electro-chemical CO2 conversion have achieved CO2 reduction promisingly while, to some extent, compromising to fulfill the two rules, and thus alternative approaches for CO2 reduction are necessary. Natural geochemical processes as abiotic CO2 reductions give hints for efficient CO2 reduction by building hydrothermal reaction systems, and this type of reaction atmosphere provides room for introducing renewable substances as reductants, which offers the possibility to achieve CO2 reduction with net carbon benefit. While the progress in CO2 reduction has been abundantly summarized, reviews on hydrothermal CO2 reduction are relatively scarce and, more importantly, few have focused on CO2 reduction with renewable reductants with the consideration of both scale of efficiency and sustainability. This review provides a fundamental and critical review of metal, biomass and polymer waste as reducing agents for hydrothermal CO2 reduction. Various products including formic acid, methanol, methane and multi-carbon chemicals can be formed, and effects of operational parameters such as temperature, batch holding time, pH value and water filing as well as detailed reaction mechanisms are illustrated. Particularly, the critical roles of high temperature and pressure water as reaction promotor and catalyst in hydrothermal CO2 conversion are discussed at the mechanistic level. More importantly, this review compares hydrothermal CO2 reduction with other methods such as catalytic hydrogenation and photo/electrocatalysis, evaluating their efficiency and potential for net carbon benefit. The aim of this review is to promote the understanding of CO2 activation under a hydrothermal environment and provide insights into the efficient and sustainable strategy of hydrothermal CO2 conversion for future fundamental research and industrial applications.

A portable europium complex-loaded fluorescent test paper combined with smartphone analysis for the on-site and visual detection of mancozeb in food samples.

The on-site detection of mancozeb in food samples holds immense value for food safety. A red-fluorescent europium complex (Eu-PYDC-Phen) has been prepared and employed as a fluorescence probe for mancozeb detection. The optimized probe suspension exhibits excellent detection performances, including a wide linear range (0-0.24 mM), low detection limit (65 nM), rapid response (2 mins) and high selectivity. Moreover, a portable detection platform was carefully designed, integrating the Eu-PYDC-Phen-based fluorescent test strips with smartphone color recognition software. This innovative platform enables visual and on-site detection of mancozeb in tomato, apple, and lettuce, achieving satisfactory recovery rates (90.34 to 106.50%). Furthermore, the integration of machine learning techniques based on hierarchical clustering algorithm has the potential to further improve the prediction and decision-making efficiency in mancozeb detection. This work provides an economical, convenient, and reliable strategy for on-site detection of pesticide in agricultural products, thereby making a meaningful contribution to food safety.

A Spatial-Spectral Relation-Guided Fusion Network for Multisource Optical RS Image Classification.

Multisource optical remote sensing (RS) image classification has obtained extensive research interest with demonstrated superiority. Existing approaches mainly improve classification performance by exploiting complementary information from multisource data. However, these approaches are insufficient in effectively extracting data features and utilizing correlations of multisource optical RS images. For this purpose, this article proposes a generalized spatial-spectral relation-guided fusion network ( S2 RGF-Net) for multisource optical RS image classification. First, we elaborate on spatial-and spectral-domain-specific feature encoders based on data characteristics to explore the rich feature information of optical RS data deeply. Subsequently, two relation-guided fusion strategies are proposed at the dual-level (intradomain and interdomain) to integrate multisource image information effectively. In the intradomain feature fusion, an adaptive de-redundancy fusion module (ADRF) is introduced to eliminate redundancy so that the spatial and spectral features are complete and compact, respectively. In interdomain feature fusion, we construct a spatial-spectral joint attention module (SSJA) based on interdomain relationships to sufficiently enhance the complementary features, so as to facilitate later fusion. Experiments on various multisource optical RS datasets demonstrate that S2 RGF-Net outperforms other state-of-the-art (SOTA) methods.

High bioavailable testosterone levels increase the incidence of isolated REM sleep behavior disorder: Results from multivariable and network Mendelian randomization analysis.

OBJECTIVES: To explore the causal relationships between sex hormone levels and incidence of isolated REM sleep behavior disorder (iRBD). METHODS: In our study, we utilized Genome-Wide Association Studies (GWAS) data for iRBD, including 9447 samples with 1061 cases of iRBD provided by the International RBD Study Group. Initially, we conducted a two-sample univariate MR analysis to explore the impact of sex hormone-related indicators on iRBD. This was followed by the application of multivariable MR methods to adjust for other hormone levels and potential confounders. Finally, we undertook a network MR analysis, employing brain structure Magnetic Resonance Imaging (MRI) characteristics as potential mediators, to examine whether sex hormones could indirectly influence the incidence of iRBD by affecting brain structure. RESULTS: Bioavailable testosterone (BioT) is an independent risk factor for iRBD (Odds Ratio [95 % Confidence Interval] = 2.437 [1.308, 4.539], P = 0.005, corrected-P = 0.020), a finding that remained consistent even after adjusting for other sex hormone levels and potential confounders. Additionally, BioT appears to indirectly increase the risk of iRBD by reducing axial diffusivity and increasing the orientation dispersion index in the left cingulum and cingulate gyrus. CONCLUSIONS: Our research reveals that elevated levels of BioT contribute to the development of iRBD. However, the specific impact of BioT on different sexes remains unclear. Furthermore, high BioT may indirectly lead to iRBD by impairing normal pathways in the left cingulum and cingulate gyrus and fostering abnormal pathway formation.

Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach.

Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.

Antibacterial effect of the metal nanocomposite on Escherichia coli.

Ag nanocomposites (NAs) have been found to induce irreversible harm to pathogenic bacteria, however, NAs tend to aggregate easily when used alone. These nanocomposites also show increased toxicity and their underlying antibacterial mechanism is still unknown. In short, practical applications of NA materials face the following obstacles: elucidating the mechanism of antibacterial action, reducing cytotoxicity to body cells, and enhancing antibacterial activity. This study synthesized a core-shell structured ZnFe2O4 @Cu-ZIF-8 @Ag (FUA) nanocomposite with high antibacterial activity and low cytotoxicity. The nanocomposites achieved a 99.99 % antibacterial rate against Escherichia coli (E. coli) and tetracycline-resistant E. coli (T - E. coli), in under 20 min at 100 µg/mL. The nanocomposites were able to inactivate E. coli due to the gradual release of Cu2+, Zn2+, and Ag+ ions, which synergistically form •OH from FUA in an aerobic environment. The presence of •OH has significant effects on the antibacterial activity. The released metal ions combine with •OH to cause damage to the bacterial cell wall, resulting in the leakage of electrolytes and ions. Moreover, in comparison to NA, the toxicity of FUA is considerably reduced. This study is expected to inspire the development of other silver-based nanocomposite materials for the inactivation of drug-resistant bacteria.

Prediction models for diagnosis and prognosis of the colonisation or infection of multidrug-resistant organisms in adults: A systematic review, critical appraisal, and meta-analysis.

BACKGROUND: Prediction models help target patients at risk of multidrug-resistant organism (MDRO) colonisation or infection and could serve as tools informing clinical practices to prevent MDRO transmission and inappropriate empiric antibiotic therapy. However, limited evidence identifies which among the available models are of low risk of bias and suitable for clinical application. OBJECTIVES: To identify, describe, appraise, and summarise the performance of all prognostic and diagnostic models developed or validated for predicting MDRO colonisation or infection. DATA SOURCES: Six electronic literature databases and clinical registration databases were searched until April 2022. STUDY ELIGIBILITY CRITERIA: Development and validation studies of any multivariable prognostic and diagnostic models to predict MDRO colonisation or infection in adults. ASSESSMENT OF RISK OF BIAS: The Prediction Model Risk of Bias Assessment Tool was used to assess risk of bias. Evidence certainty was assessed using the GRADE approach. METHODS OF DATA SYNTHESIS: Meta-analyses were conducted to summarise the discrimination and calibration of the models' external validations conducted in at least two non-overlapping datasets. RESULTS: We included 162 models (108 studies) developed for diagnosing (n=135) and predicting (n=27) MDRO colonisation or infection. Models exhibited a high risk of bias, especially in statistical analysis. High-frequency predictors were age, recent invasive procedures, antibiotic usage, and prior hospitalisation. Less than 25% of the models underwent external validations, with only seven by independent teams. Meta-analyses for one diagnostic and two prognostic models only produced very-low to low certainty of evidence. CONCLUSIONS: The review comprehensively described the models for identifying patients at risk of MDRO colonisation or infection. We cannot recommend which models are ready for application due to high risk of bias, limited validations, and low certainty of evidence from meta-analyses, indicating a clear need to improve the conducting and reporting of model development and external validation studies to facilitate clinical application.

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-ß signalling pathway.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Application of Emerging Teaching Models in Dental Education: A Systematic Review and Meta-Analysis.

INTRODUCTION AND AIMS: As an experimental teaching method, emerging learning methods including problem-based learning (PBL), case-based learning, team-based learning and flipped classroom (FC) have been widely applied in dental education. This study aims to evaluate the effect of these teaching methods on dental education performance compared to traditional lecture-based learning (LBL). METHODS: The search was carried out in April 2024 in PubMed, EMBASE, Web of Science, and Cochrane Library. All randomized controlled trials were included and the methodological quality assessment was based on the guidelines described in the Cochrane Handbook for Systematic Reviews, followed by a meta-analysis using Stata 14.0 software. Using standard mean deviation (SMD) and 95% confidence interval (95% CI) to determine the effectiveness of emerging teaching methods and LBL in all dental disciplines. Meta-regression was used to analyse sources of heterogeneity. Sensitivity analysis was performed to determine the stability, and Begg's analysis was used to determine whether there is publication bias. RESULTS: A total of 29 randomized controlled trials including 3502 students were included. The results indicate that emerging educational methods have a significantly positive effect on achieving higher scores (SMD = 0.48, 95% CI = 0.34-0.62, P < .001), whether it was theoretical scores (SMD = 0.52, 95% CI = 0.32-0.72, P < .001) or skill scores (SMD = 0.45, 95% CI = 0.15-0.76, P < .001). Compared to LBL, PBL (SMD = 0.33, 95% CI = 0.01-0.65, P = .045) and FC (SMD = 0.50, 95% CI = 0.31-0.69, P < .001) can both significantly improve students' academic performance. CONCLUSION: Compared to LBL, emerging educational methods (PBL, case-based learning, and FC) have significantly improved the learning effectiveness of dental students. These emerging educational methods can be advocated and popularized as routine teaching methods. CLINICAL RELEVANCE: This study is the first meta-analysis of the effects of emerging teaching methods in dental education which shows great impact of emerging teaching methods on students' development.

Effects of pay-for-performance based antimicrobial stewardship on antimicrobial consumption and expenditure: An interrupted time series analysis.

Objectives: To evaluate the impact of pay-for-performance on antimicrobial consumption and antimicrobial expenditure in a large teaching hospital in Guangzhou, China. Methods: We collected data from hospital information system from January 2018 through September 2022 in the inpatient wards. Antimicrobial consumption was evaluated using antibiotic use density (AUD) and antibiotic use rate (AUR). The economic impact of intervention was assessed by antimicrobial expenditure percentage. The data was analyzed using interrupted time series (ITS) analysis. Results: Following the implementation of the intervention, immediate decreases in the level of AUD were observed in Department of Hematology Unit 3 (ß = -66.93 DDDs/100PD, P = 0.002), Urology (ß = -32.80 DDDs/100PD, P < 0.001), Gastrointestinal Surgery Unit 3 (ß = -11.44 DDDs/100PD, P = 0.03), Cardiac Surgery (ß = -14.30 DDDs/100PD, P = 0.01), ICU, Unit 2 (ß = -81.91 DDDs/100PD, P = 0.02) and Cardiothoracic Surgery ICU (ß = -41.52 DDDs/100PD, P = 0.05). Long-term downward trends in AUD were also identified in Organ Transplant Unit (ß = -1.64 DDDs/100PD, P = 0.02). However, only Urology (ß = -6.56 DDDs/100PD, P = 0.02) and Gastrointestinal Surgery Unit 3 (ß = -8.50 %, P = 0.01) showed an immediate decrease in AUR, and long-term downward trends in AUR were observed in Pediatric ICU (ß = -1.88 %, P = 0.05) and ICU Unit 1 (ß = -0.55 %, P = 0.02). Conclusion: This study demonstrates that the adoption of pay-for-performance effectively reduces antibiotic consumption in specific departments of a hospital in Guangzhou in the short term. However, it is important to recognize that the long-term impact of such interventions is often limited. Additionally, it should be noted that the overall effectiveness of the intervention across the entire hospital was not significant.

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and sarcopenia.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

QTL mapping of downy mildew resistance in foxtail millet by SLAF­seq and BSR-seq analysis.

KEY MESSAGE: Key message Three major QTLs for resistance to downy mildew were located within an 0.78 Mb interval on chromosome 8 in foxtail millet. Downy mildew, a disease caused by Sclerospora graminicola, is a serious problem that jeopardizes the yield and quality of foxtail millet. Breeding resistant varieties represents one of the most economical and effective solutions, yet there is a lack of molecular markers related to the resistance. Here, a mapping population comprising of 158 F6:7 recombinant inbred lines (RILs) was constructed from the crossing of G1 and JG21. Based on the specific locus amplified fragment sequencing results, a high-density linkage map of foxtail millet with 1031 bin markers, spanning 1041.66 cM was constructed. Based on the high-density linkage map and the phenotype data in four environments, a total of nine quantitative trait loci (QTL) associated with resistance to downy mildew were identified. Further BSR-seq confirmed the genomic regions containing the potential candidate genes related to downy mildew resistance. Interestingly, a 0.78-Mb interval between C8M257 and C8M268 on chromosome 8 was highlighted because of its presence in three major QTL, qDM8_1, qDM8_2, and qDM8_4, which contains 10 NBS-LRR genes. Haplotype analysis in RILs and natural population suggest that 9 SNP loci on Seita8G.199800, Seita8G.195900, Seita8G.198300, and Seita.8G199300 genes were significantly correlated with disease resistance. Furthermore, we found that those genes were taxon-specific by collinearity analysis of pearl millet and foxtail millet genomes. The identification of these new resistance QTL and the prediction of resistance genes against downy mildew will be useful in breeding for resistant varieties and the study of genetic mechanisms of downy mildew disease resistance in foxtail millet.

Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate.

Bacteroidales (syn. Bacteroidetes) are prominent members of the human gastrointestinal ecosystem mainly due to their efficient glycan-degrading machinery, organized into gene clusters known as polysaccharide utilization loci (PULs). A single PUL was reported for catabolism of high-mannose (HM) N-glycan glyco-polypeptides in the gut symbiont Bacteroides thetaiotaomicron, encoding a surface endo-ß-N-acetylglucosaminidase (ENGase), BT3987. Here, we discover an ENGase from the GH18 family in B. thetaiotaomicron, BT1285, encoded in a distinct PUL with its own repertoire of proteins for catabolism of the same HM N-glycan substrate as that of BT3987. We employ X-ray crystallography, electron microscopy, mass spectrometry-based activity measurements, alanine scanning mutagenesis and a broad range of biophysical methods to comprehensively define the molecular mechanism by which BT1285 recognizes and hydrolyzes HM N-glycans, revealing that the stabilities and activities of BT1285 and BT3987 were optimal in markedly different conditions. BT1285 exhibits significantly higher affinity and faster hydrolysis of poorly accessible HM N-glycans than does BT3987. We also find that two HM-processing endoglycosidases from the human gut-resident Alistipes finegoldii display condition-specific functional properties. Altogether, our data suggest that human gut microbes employ evolutionary strategies to express distinct ENGases in order to optimally metabolize the same N-glycan substrate in the gastroinstestinal tract.

Abnormal Scanning Patterns Based on Eye Movement Entropy in Early Psychosis.

BACKGROUND: Restricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing upon gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were to process image stimuli. METHODS: Eighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy controls (HCs) completed an eye-tracking examination for freely viewing 35 static images (each presented 10s) and cognitive assessments. We compared the group differences in overall entropy score, as well as entropy scores under various conditions. Furthermore, we also investigated the correlation between entropy scores and symptoms along with cognitive function. RESULTS: Increased overall entropy scores were noted in FES and CHR groups relative to HCs, and these differences were already apparent within 0∼2.5s. In addition, the CHR group exhibited higher entropy when viewing low-meaning images compared to HCs. Moreover, the entropy within 0∼2.5s showed significant correlations with negative symptoms in the FES group, Attention/Vigilance scores in the CHR group, as well as Speed of processing and Attention/Vigilance scores across all three groups. CONCLUSIONS: The results indicate that FES and CHR individuals scan pictures more randomly and less strategically than HCs. These patterns also correlate with clinical symptoms and neurocognition. The present study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.