Fusarium graminearum is a destructive wheat pathogen. No fully resistant cultivars are available. Knowledge concerning the molecular weapons of F. graminearum to achieve infection remains limited. ...Here, we report that deletion of the putative secondary metabolite biosynthesis gene cluster fg3_54 compromises the pathogen's ability to infect wheat through cell-to-cell penetration. Ectopic expression of fgm4, a pathway-specific bANK-like regulatory gene, activates the transcription of the fg3_54 cluster in vitro. We identify a linear, C- terminally reduced and D-amino acid residue-rich octapeptide, fusaoctaxin A, as the product of the two nonribosomal peptide synthetases encoded by fg3_54. Chemically-synthesized fusaoctaxin A restores cell-to-cell invasiveness in fg3_54-deleted F. graminearum, and enables colonization of wheat coleoptiles by two Fusarium strains that lack the fg3_54 homolog and are nonpathogenic to wheat. In conclusion, our results identify fusaoctaxin A as a virulence factor required for cell-to-cell invasion of wheat by F. graminearum.
Highlights • The first study to summarize the global trends in incidence and mortality of NPC. • Decreased NPC incidence with maximum AAPCs of −5.4% in males and −4.1% in females. • Declines in NPC ...mortality rates worldwide with AAPCs varying from −0.8% to −6.5%.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Glucose metabolism plays an important role in cell energy supply, and quantitative detection of the intracellular glucose level is particularly important for understanding many physiological ...processes. Glucose electrochemical sensors are widely used for blood and extracellular glucose detection. However, intracellular glucose detection cannot be achieved by these sensors owing to their large size and consequent low spatial resolution. Herein, we developed a single nanowire glucose sensor for electrochemical detection of intracellular glucose by depositing Pt nanoparticles (Pt NPs) on a SiC@C nanowire and further immobilizing glucose oxidase (GOD) thereon. Glucose was converted by GOD to an electroactive product H
2
O
2
which was further electro-catalyzed by Pt NPs. The glucose nanowire sensor is endowed with a high sensitivity, high spatial-temporal resolution and enzyme specificity due to its nanoscale size and enzymatic reaction. This allows the real-time monitoring of the intracellular glucose level, and the increase of the intracellular glucose level induced by a novel potential hypoglycemic agent, reinforcing its potential application in lowering the blood glucose level. This work provides a versatile method for the construction of enzyme-modified nanosensors to electrochemically detect intracellular non-electroactive molecules, which is of great benefit for physiological and pathological studies.
We report for the first time the development of a single nanowire electrochemical sensor for the detection of intracellular glucose levels.
Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in ...patients with NPC.
This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as AGR = ALB/(total serum protein--ALB). Survival analysis was used to evaluate the predictive value of AGR.
Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P = 0.029) and DMFS (P = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P = 0.033), high neutrophil count (P = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).
The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID‐19 patients, but the characteristics of symptomatic VTE in general COVID‐19 patients have not ...been described.
Objectives
To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID‐19 patients.
Methods/Results
This retrospective study enrolled all COVID‐19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID‐19. In comparison to 23,434 non‐COVID‐19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non‐severe hospitalized COVID‐19 patients were 5.94 (95% confidence interval CI 3.91–10.09) and 2.79 (95% CI 1.43–5.60), respectively. When 104 VTE cases and 208 non‐VTE cases were compared, pulmonary embolism cases had a higher rate for in‐hospital death (OR 6.74, 95% CI 2.18–20.81). VTE developed at a median of 21 days (interquartile range 13.25–31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D‐dimer on admission, and D‐dimer increment (DI) ≥1.5‐fold; of these, DI ≥1.5‐fold had the most significant association (OR 14.18, 95% CI 6.25–32.18, p = 2.23 × 10−10). A novel model consisting of three simple coagulation variables (fibrinogen and D‐dimer levels on admission, and DI ≥1.5‐fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822–0.907, sensitivity 0.930, specificity 0.710).
Conclusions
There is an excess risk of VTE in hospitalized COVID‐19 patients. This novel model can aid early identification of patients who are at high risk for VTE.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Quantitative measurements of intravesicular glutamate (Glu) and of transient exocytotic release contents directly from individual living neurons are highly desired for understanding the mechanisms ...(full or sub‐quantal release?) of synaptic transmission and plasticity. However, this could not be achieved so far due to the lack of adequate experimental strategies relying on selective and sensitive Glu nanosensors. Herein, we introduce a novel electrochemical Glu nanobiosensor based on a single SiC nanowire that can selectively measure in real‐time Glu fluxes released via exocytosis by large Glu vesicles (ca. 125 nm diameter) present in single hippocampal axonal varicosities as well as their intravesicular content before exocytosis. These measurements revealed a sub‐quantal release mode in living hippocampal neurons, viz., only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. Importantly, this fraction remained practically the same when hippocampal neurons were pretreated with L‐Glu‐precursor L‐glutamine, while it significantly increased after zinc treatment, although in both cases the intravesicular contents were drastically affected.
A nanowire electrochemical biosensor for the quantitative measurement of the intravesicular glutamate (Glu) content inside living neurons and its released fractions was developed. It is shown that only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. The sensor opens new possibilities for exploring the regulatory mechanisms of glutamatergic neurotransmission and plasticity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Reconstruction of sparsely sampled seismic data is critical for maintaining the quality of seismic images when significant numbers of shots and receivers are missing. We present a reconstruction ...method in the shot-receiver-time (SRT) domain based on a residual U-Net machine learning architecture, for seismic data acquired in a sparse 2-D acquisition and name it SRT2D-ResU-Net. The SRT domain retains a high level of seismic signal connectivity, which is likely the main data feature that the reconstructing algorithms rely on. We develop an " in situ training and prediction" workflow by dividing the acquisition area into two nonoverlapping subareas: a training subarea for establishing the network model using regularly sampled data and a testing subarea for reconstructing the sparsely sampled data using the trained model. To establish a reference base for analyzing the changes in data features over the study area, and quantifying the reconstructed seismic data, we devise a baseline reference using a tiny portion of the field data. The baselines are properly spaced and excluded from the training and reconstruction processes. The results on a field marine data set show that the SRT2D-ResU-Net can effectively learn the features of seismic data in the training process, and the average correlation between the reconstructed missing traces and the true answers is over 85%.
Accumulating evidence supports the hypothesis that white matter (WM) abnormalities are involved in the pathophysiology of bulimia nervosa (BN); however, findings from in vivo neuroimaging studies ...have been inconsistent. We aimed to investigate the possible brain WM alterations, including WM volume and microstructure, in patients with BN. We recruited 43 BN patients and 31 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging. Differences in WM volume and microstructure were evaluated using voxel‐based morphometry, tract‐based spatial statistics, and automated fibre quantification analysis. Compared with HCs, BN patients showed significantly decreased fractional anisotropy in the middle part of the corpus callosum (nodes 31–32) and increased mean diffusivity in the right cranial nerve V (CN V) (nodes 27–33 and nodes 55–88) and vertical occipital fasciculus (VOF) (nodes 58–85). Moreover, we found decreased axial diffusivity in the right inferior fronto‐occipital fasciculus (node 67) and increased radial diffusivity in the CN V (nodes 22–34 and nodes 52–89) and left VOF (nodes 60–66 and nodes 81–85). Meanwhile, WM microstructural changes were correlated with patients' clinical manifestations. We did not find any significant differences in WM volume and the main WM fibre bundle properties between BN patients and HCs. Taken together, these findings provide that BN shows significant brain WM reorganization, but primarily in microstructure (part of WM fibre bundle), which is not sufficient to cause changes in WM volume. The automated fibre quantification analysis could be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.
We combined voxel‐based morphometry, tract‐based spatial statistics, and automated fibre quantification (AFQ) to analyse the whole brain white matter (WM) reorganization of BN patients. Bulimia nervosa (BN) could result in significantly abnormal WM alterations but mainly located in the WM microstructure, rather than WM volume and principal WM fibre bundles. The AFQ analysis may be more sensitive to detect the subtle pathological changes in a point or segment of the WM fibre bundle.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons and low level of dopamine (DA) in the midbrain. Recent studies suggested ...that some natural products can protect neurons against injury, but their role on neurotransmitter release and the underlying mechanisms remained unknown. In this work, nanoelectrode electrochemistry was used for the first time to quantify DA release inside single DAergic synapses. Our results unambiguously demonstrated that harpagide, a natural product, effectively enhances synaptic DA release and restores DA release at normal levels from injured neurons in PD model. These important protective and curative effects are shown to result from the fact that harpagide efficiently inhibits the phosphorylation and aggregation of α-synuclein by alleviating the intracellular reactive oxygen level, being beneficial for vesicle loading and recycling. This establishes that harpagide offers promising avenues for preventive or therapeutic interventions against PD and other neurodegenerative disorders.
Nanoelectrode amperometry was used to monitor DA release inside single DAergic synapses, and demonstrated that harpagide effectively enhances synaptic DA release by reducing intracellular ROS generation and inhibiting α-Syn phosphorylation.
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IJS, KILJ, NUK, UL, UM, UPUK
The interplay of host‐guest interactions and controlled modulation of spin‐crossover (SCO) behavior is one of the most exploited topics regarding data storage, molecular sensing, and optical ...technologies. This study examines the effect of solvents on the spin‐crossover (SCO) behavior of manganese(III) complexes Mn(sal‐N‐1,5,8,12)I•S (S=CH3OH, C2H5OH, CH3CN) (1) and Mn(sal‐N‐1,5,8,12)I3 (2), where (sal‐N‐1,5,8,12)2− is 2,2′‐((1E,13E)‐2,6,9,13‐tetraazatetradeca‐1,13‐diene‐1,14‐diyl)diphenol synthesized by salicylaldehyde and 1,2‐bis(3‐aminopropylamino)ethane. The complexes, crystallizing in orthorhombic or monoclinic systems, exhibit similar supramolecular arrangements with one‐dimensional cationic chains at low temperatures. Magnetic studies reveal that solvent inclusion sharpens the SCO transition and lowers the transition temperature. Specifically, 1⋅CH3OH shows a 13 K thermal hysteresis due to methanol‘s mobility through the channels in the cationic framework. Although the solvent‐free compound was not obtained, compound 2 with a linear I3− anion was synthesized, displaying extensive cation‐anion contacts and a distinct 13 K thermal hysteresis upon heating due to altered intermolecular cooperativity. This emphasizes the significant role of solvent introduction and variation in crystal packing and their impact on the SCO properties.
Three new solvent adducts Mn(sal‐N‐1,5,8,12)I⋅CH3OH, Mn(sal‐N‐1,5,8,12)I⋅C2H5OH and Mn(sal‐N‐1,5,8,12)I⋅CH3CN, as well as a rare compound, Mn(sal‐N‐1,5,8,12)I3 are synthesized. Surprisingly, the solvent in compound Mn(sal‐N‐1,5,8,12)I⋅CH3OH easily escapes, and with a slight increase in temperature, the crystal collapses, eventually turning into a powdered state. The magnetic properties undergo significant changes accompanying the loss of the solvent.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
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