Molecular tuning of CO2-to-ethylene conversion.

The electrocatalytic reduction of carbon dioxide, powered by renewable electricity, to produce valuable fuels and feedstocks provides a sustainable and carbon-neutral approach to the storage of energy produced by intermittent renewable sources1. However, the highly selective generation of economically desirable products such as ethylene from the carbon dioxide reduction reaction (CO2RR) remains a challenge2. Tuning the stabilities of intermediates to favour a desired reaction pathway can improve selectivity3-5, and this has recently been explored for the reaction on copper by controlling morphology6, grain boundaries7, facets8, oxidation state9 and dopants10. Unfortunately, the Faradaic efficiency for ethylene is still low in neutral media (60 per cent at a partial current density of 7 milliamperes per square centimetre in the best catalyst reported so far9), resulting in a low energy efficiency. Here we present a molecular tuning strategy-the functionalization of the surface of electrocatalysts with organic molecules-that stabilizes intermediates for more selective CO2RR to ethylene. Using electrochemical, operando/in situ spectroscopic and computational studies, we investigate the influence of a library of molecules, derived by electro-dimerization of arylpyridiniums11, adsorbed on copper. We find that the adhered molecules improve the stabilization of an 'atop-bound' CO intermediate (that is, an intermediate bound to a single copper atom), thereby favouring further reduction to ethylene. As a result of this strategy, we report the CO2RR to ethylene with a Faradaic efficiency of 72 per cent at a partial current density of 230 milliamperes per square centimetre in a liquid-electrolyte flow cell in a neutral medium. We report stable ethylene electrosynthesis for 190 hours in a system based on a membrane-electrode assembly that provides a full-cell energy efficiency of 20 per cent. We anticipate that this may be generalized to enable molecular strategies to complement heterogeneous catalysts by stabilizing intermediates through local molecular tuning.

ZmPTOX1, a plastid terminal oxidase, contributes to redox homeostasis during seed development and germination.

Maize plastid terminal oxidase1 (ZmPTOX1) plays a pivotal role in seed development by upholding redox balance within seed plastids. This study focuses on characterizing the white kernel mutant 3735 (wk3735) mutant, which yields pale-yellow seeds characterized by heightened protein but reduced carotenoid levels, along with delayed germination compared to wild-type (WT) seeds. We successfully cloned and identified the target gene ZmPTOX1, responsible for encoding maize PTOX-a versatile plastoquinol oxidase and redox sensor located in plastid membranes. While PTOX's established role involves regulating redox states and participating in carotenoid metabolism in Arabidopsis leaves and tomato fruits, our investigation marks the first exploration of its function in storage organs lacking a photosynthetic system. Through our research, we validated the existence of plastid-localized ZmPTOX1, existing as a homomultimer, and established its interaction with ferredoxin-NADP+ oxidoreductase 1 (ZmFNR1), a crucial component of the electron transport chain (ETC). This interaction contributes to the maintenance of redox equilibrium within plastids. Our findings indicate a propensity for excessive accumulation of reactive oxygen species (ROS) in wk3735 seeds. Beyond its known role in carotenoids' antioxidant properties, ZmPTOX1 also impacts ROS homeostasis owing to its oxidizing function. Altogether, our results underscore the critical involvement of ZmPTOX1 in governing seed development and germination by preserving redox balance within the seed plastids.

Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain.

Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through 13C-enriched diets. A 13C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient 13C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.

Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.

Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.

Accelerated 3D metabolite T1 mapping of the brain using variable-flip-angle SPICE.

PURPOSE: To develop a practical method to enable 3D T1 mapping of brain metabolites. THEORY AND METHODS: Due to the high dimensionality of the imaging problem underlying metabolite T1 mapping, measurement of metabolite T1 values has been currently limited to a single voxel or slice. This work achieved 3D metabolite T1 mapping by leveraging a recent ultrafast MRSI technique called SPICE (spectroscopic imaging by exploiting spatiospectral correlation). The Ernst-angle FID MRSI data acquisition used in SPICE was extended to variable flip angles, with variable-density sparse sampling for efficient encoding of metabolite T1 information. In data processing, a novel generalized series model was used to remove water and subcutaneous lipid signals; a low-rank tensor model with prelearned subspaces was used to reconstruct the variable-flip-angle metabolite signals jointly from the noisy data. RESULTS: The proposed method was evaluated using both phantom and healthy subject data. Phantom experimental results demonstrated that high-quality 3D metabolite T1 maps could be obtained and used for correction of T1 saturation effects. In vivo experimental results showed metabolite T1 maps with a large spatial coverage of 240 × 240 × 72 mm3 and good reproducibility coefficients (< 11%) in a 14.5-min scan. The metabolite T1 times obtained ranged from 0.99 to 1.44 s in gray matter and from 1.00 to 1.35 s in white matter. CONCLUSION: We successfully demonstrated the feasibility of 3D metabolite T1 mapping within a clinically acceptable scan time. The proposed method may prove useful for both T1 mapping of brain metabolites and correcting the T1-weighting effects in quantitative metabolic imaging.

Optimization of 3D dynamic speech MRI: Poisson-disc undersampling and locally higher-rank reconstruction through partial separability model with regional optimized temporal basis.

PURPOSE: To improve the spatiotemporal qualities of images and dynamics of speech MRI through an improved data sampling and image reconstruction approach. METHODS: For data acquisition, we used a Poisson-disc random under sampling scheme that reduced the undersampling coherence. For image reconstruction, we proposed a novel locally higher-rank partial separability model. This reconstruction model represented the oral and static regions using separate low-rank subspaces, therefore, preserving their distinct temporal signal characteristics. Regional optimized temporal basis was determined from the regional-optimized virtual coil approach. Overall, we achieved a better spatiotemporal image reconstruction quality with the potential of reducing total acquisition time by 50%. RESULTS: The proposed method was demonstrated through several 2-mm isotropic, 64 mm total thickness, dynamic acquisitions with 40 frames per second and compared to the previous approach using a global subspace model along with other k-space sampling patterns. Individual timeframe images and temporal profiles of speech samples were shown to illustrate the ability of the Poisson-disc under sampling pattern in reducing total acquisition time. Temporal information of sagittal and coronal directions was also shown to illustrate the effectiveness of the locally higher-rank operator and regional optimized temporal basis. To compare the reconstruction qualities of different regions, voxel-wise temporal SNR analysis were performed. CONCLUSION: Poisson-disc sampling combined with a locally higher-rank model and a regional-optimized temporal basis can drastically improve the spatiotemporal image quality and provide a 50% reduction in overall acquisition time.

Simultaneous high-resolution whole-brain MR spectroscopy and [18F]FDG PET for temporal lobe epilepsy.

PURPOSE: Precise lateralizing the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy (mTLE) remains challenging, particularly when routine MRI scans are inconclusive (MRI-negative). This study aimed to investigate the synergy of fast, high-resolution, whole-brain MRSI in conjunction with simultaneous [18F]FDG PET for the lateralization of mTLE. METHODS: Forty-eight drug-resistant mTLE patients (M/F 31/17, age 12-58) underwent MRSI and [18F]FDG PET on a hybrid PET/MR scanner. Lateralization of mTLE was evaluated by visual inspection and statistical classifiers of metabolic mappings against routine MRI. Additionally, this study explored how disease status influences the associations between altered N-acetyl aspartate (NAA) and FDG uptake using hierarchical moderated multiple regression. RESULTS: The high-resolution whole-brain MRSI data offers metabolite maps at comparable resolution to [18F]FDG PET. Visual examinations of combined MRSI and [18F]FDG PET showed an mTLE lateralization accuracy rate of 91.7% in a 48-patient cohort, surpassing routine MRI (52.1%). Notably, out of 23 MRI-negative mTLE, combined MRSI and [18F]FDG PET helped detect 19 cases. Logistical regression models combining hippocampal NAA level and FDG uptake improved lateralization performance (AUC=0.856), while further incorporating extrahippocampal regions such as amygdala, thalamus, and superior temporal gyrus increased the AUC to 0.939. Concurrent MRSI/PET revealed a moderating influence of disease duration and hippocampal atrophy on the association between hippocampal NAA and glucose uptake, providing significant new insights into the disease's trajectory. CONCLUSION: This paper reports the first metabolic imaging study using simultaneous high-resolution MRSI and [18F]FDG PET, which help visualize MRI-unidentifiable lesions and may thus advance diagnostic tools and management strategies for drug-resistant mTLE.

Identification and diagnostic potential of hsa_circ_101303 in colorectal cancer: unraveling a regulatory network.

BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.

PAGEANT: personal access to genome and analysis of natural traits.

GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed PAGEANT (Personal Access to Genome & Analysis of Natural Traits), usable through Graphical User Interface or command line-based version, aiming to serve as a protocol and prototype that guides the overarching design of genetic reporting tools. PAGEANT is structured across five core modules, summarized by five Qs: (i) quality assurance of the genetic data; (ii) qualitative assessment of genetic characteristics; (iii) quantitative assessment of health risk susceptibility based on polygenic risk scores and population reference; (iv) query of third-party variant databases (e.g. ClinVAR and PharmGKB) and (v) quick Response code of genetic variants of interest. Literature review was conducted to compare PAGEANT with academic and industry tools. For 2504 genomes made publicly available through the 1000 Genomes Project, we derived their genomic characteristics for a suite of qualitative and quantitative traits. One exemplary trait is susceptibility to COVID-19, based on the most up-to-date scientific findings reported.

Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway.

BACKGROUND: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. METHODS: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. RESULTS: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. CONCLUSION: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.

ortho-Methoxycarbonylethynylphenyl Thioglycosides (MCEPTs): Versatile Glycosyl Donors Enabled by Electron-Withdrawing Substituents and Catalyzed by Gold(I) or Cu(II) Complexes.

With easily accessible and operator-friendly reagents, shelf-stable ortho-methoxycarbonylethynylphenyl thioglycosides were efficiently prepared. Based on these MCEPT glycoside donors, a novel glycosylation protocol featuring mild and catalytic promotion conditions with Au(I) or Cu(II) complexes, expanded substrate scope encompassing challenging donors and acceptors and clinically used pharmaceuticals, and versatility in various strategies for highly efficient synthesis of glycosides has been established. The practicality of the MCEPT glycosylation protocol was fully exhibited by highly efficient and scalable synthesis of surface polysaccharide subunits of Acinetobacter baumannii via latent-active, reagent-controlled divergent orthogonal one-pot and orthogonal one-pot strategies. The underlying reaction mechanism was investigated systematically through control reactions, leading to the isolation and characterization of the vital catalyst species in MCEPT glycosylation, the benzothiophen-3-yl-gold(I) complex. Based on the results obtained both from control reactions and from studies leading to the glycosylation protocol establishment, an operative mechanism was proposed and the effect of the vital catalyst species reactivity on the results of metal-catalyzed alkyne-containing donor-involved glycosylation was disclosed. Moreover, the mechanism for C-glycosylation side product formation from ortho-(substituted)ethynylphenyl thioglycoside donors with electron-donating substituents was also illuminated.

JSENSE-Pro: Joint sensitivity estimation and image reconstruction in parallel imaging using pre-learned subspaces of coil sensitivity functions.

PURPOSE: To improve calibrationless parallel imaging using pre-learned subspaces of coil sensitivity functions. THEORY AND METHODS: A subspace-based joint sensitivity estimation and image reconstruction method was developed for improved parallel imaging with no calibration data. Specifically, we proposed to use a probabilistic subspace model to capture prior information of the coil sensitivity functions from previous scans acquired using the same receiver system. Both the subspace basis and coefficient distributions were learned from a small set of training data. The learned subspace model was then incorporated into the regularized reconstruction formalism that includes a sparsity prior. The nonlinear optimization problem was solved using alternating minimization algorithm. Public fastMRI brain dataset was retrospectively undersampled by different schemes for performance evaluation of the proposed method. RESULTS: With no calibration data, the proposed method consistently produced the most accurate coil sensitivity estimation and highest quality image reconstructions at all acceleration factors tested in comparison with state-of-the-art methods including JSENSE, DeepSENSE, P-LORAKS, and Sparse BLIP. Our results are comparable to or even better than those from SparseSENSE, which used calibration data for sensitivity estimation. The work also demonstrated that the probabilistic subspace model learned from T2 w data can be generalized to aiding the reconstruction of FLAIR data acquired from the same receiver system. CONCLUSION: A subspace-based method named JSENSE-Pro has been proposed for accelerated parallel imaging without the acquisition of companion calibration data. The method is expected to further enhance the practical utility of parallel imaging, especially in applications where calibration data acquisition is not desirable or limited.

Enhancing linguistic research through 2-mm isotropic 3D dynamic speech MRI optimized by sparse temporal sampling and low-rank reconstruction.

PURPOSE: To enable a more comprehensive view of articulations during speech through near-isotropic 3D dynamic MRI with high spatiotemporal resolution and large vocal-tract coverage. METHODS: Using partial separability model-based low-rank reconstruction coupled with a sparse acquisition of both spatial and temporal models, we are able to achieve near-isotropic resolution 3D imaging with a high frame rate. The total acquisition time of the speech acquisition is shortened by introducing a sparse temporal sampling that interleaves one temporal navigator with four randomized phase and slice-encoded imaging samples. Memory and computation time are improved through compressing coils based on the region of interest for low-rank constrained reconstruction with an edge-preserving spatial penalty. RESULTS: The proposed method has been evaluated through experiments on several speech samples, including a standard reading passage. A near-isotropic 1.875 × 1.875 × 2 mm3 spatial resolution, 64-mm through-plane coverage, and a 35.6-fps temporal resolution are achieved. Investigations and analysis on specific speech samples support novel insights into nonsymmetric tongue movement, velum raising, and coarticulation events with adequate visualization of rapid articulatory movements. CONCLUSION: Three-dimensional dynamic images of the vocal tract structures during speech with high spatiotemporal resolution and axial coverage is capable of enhancing linguistic research, enabling visualization of soft tissue motions that are not possible with other modalities.

B1 mapping using pre-learned subspaces for quantitative brain imaging.

PURPOSE: To develop a machine learning-based method for estimation of both transmitter and receiver B1 fields desired for correction of the B1 inhomogeneity effects in quantitative brain imaging. THEORY AND METHODS: A subspace model-based machine learning method was proposed for estimation of B1t and B1r fields. Probabilistic subspace models were used to capture scan-dependent variations in the B1 fields; the subspace basis and coefficient distributions were learned from pre-scanned training data. Estimation of the B1 fields for new experimental data was achieved by solving a linear optimization problem with prior distribution constraints. We evaluated the performance of the proposed method for B1 inhomogeneity correction in quantitative brain imaging scenarios, including T1 and proton density (PD) mapping from variable-flip-angle spoiled gradient-echo (SPGR) data as well as neurometabolic mapping from MRSI data, using phantom, healthy subject and brain tumor patient data. RESULTS: In both phantom and healthy subject data, the proposed method produced high-quality B1 maps. B1 correction on SPGR data using the estimated B1 maps produced significantly improved T1 and PD maps. In brain tumor patients, the proposed method produced more accurate and robust B1 estimation and correction results than conventional methods. The B1 maps were also applied to MRSI data from tumor patients and produced improved neurometabolite maps, with better separation between pathological and normal tissues. CONCLUSION: This work presents a novel method to estimate B1 variations using probabilistic subspace models and machine learning. The proposed method may make correction of B1 inhomogeneity effects more robust in practical applications.

Engineered Sucrose Metabolism Improves the Smut Disease Suppression Potency of Pseudomonas sp. ST4.

Sporisorium scitamineum and Ustilago maydis are two fungal pathogens causing severe sugarcane and maize diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We showed recently that in the presence of exogenous glucose, the Pseudomonas sp. strain ST4 could block the fungal mating and display a strong disease suppression potency on S. scitamineum. With the aim of conferring strain ST4 the ability to metabolize sucrose in plants for glucose production, we identified a strong native promoter pSsrA in strain ST4 and additional promoter elements to facilitate translation and peptide translocation for the construction of a fusion gene encoding sucrose metabolism. The cscA gene encoding sucrose hydrolase from Pseudomonas protegens Pf-5 was fused to the promoter pSsrA, a translational coupler bicistronic design and a Tat signal peptide, which was then cloned into mini-Tn7 transposon. This synthetic gene cassette was integrated into the chromosome of strain ST4, and the resultant engineered strain ST4E was able to hydrolyze sucrose with high efficiency and displayed elevated inhibitory activity on the mating and virulence of S. scitamineum and U. maydis. The findings from this study provide a valuable device and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens. IMPORTANCE Sporisorium scitamineum and Ustilago maydis are typical dimorphic fungi causing severe sugarcane and maize smut diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We previously demonstrated that the biocontrol strain Pseudomonas sp. ST4 could block the fungal mating and displays a strong suppression potency on smut diseases, while it was unable to utilize the host-sourced sucrose for glucose production critical for antifungus efficiency. In this study, we constructed a high-expression gene cassette for minitransposon-mediated genome integration and sucrose hydrolysis in the bacterial periplasmic space. The resultant engineered strain ST4E was able to hydrolyze sucrose and inhibit the mating and hyphal growth of S. scitamineum and U. maydis. These findings provide a valuable tool and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens.

Study of electronic and optical properties of CdI2 modulated by electric field: a first-principles study.

We found that an out-of-plane vertical electric field of 1.0 V/Ang helps to maintain the thermodynamic and kinetic stability of monolayer CdI2.The results indicated that the electric field modulates monolayer CdI2 to produce the Mexican-hat electronic state and the giant Stark effect of the vertical electric field on monolayer CdI2 originates from electric field lifting its conduction band. The results based on HSE06 + SOC calculations show that electric field induces strong spin polarization, leading to significant energy level splitting and spin flipping in the valence band. Based on GW0 + BSE, the electric field broadens effective optical response range of monolayer CdI2, the new peak in the optical absorption spectrum under electric field indicates that electric field helps to diminish excitonic effect of monolayer CdI2.

Ampelopsin attenuates Staphylococcus aureus Alpha-Toxin-Induced Lung Injury.

Staphylococcus aureus is a prevalent cause of lung infections in hospitals and communities, and can cause a wide spectrum of human infections. Due to the bottleneck caused by antibiotic resistance and substantial increases in morbidity and mortality, targeting the virulence factors released by S. aureus as an alternative prevention and treatment method has become a promising approach. Ampelopsin, a component of vine tea, has promising potential for treating S. aureus-induced acute lung injury. In this study, the effects of ampelopsin were investigated on a mouse model of acute lung injury established using S. aureus 8325-4 and the α-hemolysin (hla) silent strain DU1090. The hla silent strain did not cause mortality in mice, whereas lethal and sublethal concentrations of S. aureus 8325-4 caused high mortality. Notably, ampelopsin treatment protected against mortality stemming from S. aureus infection. Ampelopsin yielded enhancements in lung barrier function, decreased total protein leakage in the alveolar lavage fluid, and modulated inflammatory signaling pathway-related proteins, thereby reducing the release of pro-inflammatory factors and improving respiratory dysfunction. Moreover, ampelopsin prevented the upregulation of ADAM10 activity, leading to E-cadherin mucin cleavage. In conclusion, our findings establish the key role of alpha -toxin in infectious lung injury in S. aureus and provide support for ampelopsin as an effective therapeutic approach to improve lung injury.

Birefringent, low loss, and broadband semi-tube anti-resonant hollow-core fiber.

We report on the design, fabrication, and characterization of a low-loss birefringent semi-tube anti-resonant hollow-core fiber (AR-HCF). By optimizing the structure design and the stack-and-draw fabrication technique, a transmission loss of 4.8 dB/km at 1522 nm, a <10 dB/km bandwidth of 154 nm, and a phase birefringence of 1.8 × 10-5 are demonstrated. This achieved loss is more than one order of magnitude lower than the previously reported birefringent AR-HCF and the bandwidth is one order of magnitude broader than the reported birefringent photonic bandgap hollow-core fiber (PBG-HCF) with the same loss level. The polarization extinction ratio (PER) reaches the ∼20 dB level in a 90 m-long fiber under >25 cm bending radius. Combined with the single mode and low dispersion features, the developed semi-tube AR-HCF may find a variety of applications in frequency metrology, interferometric fiber gyroscopes, and long-baseline stellar interferometry.

Accurate modeling and measurement of pressure-induced group velocity dispersion variations in anti-resonant hollow-core fibers.

Precise control of group velocity dispersion (GVD) by pressure in a gas-filled hollow-core fiber (HCF) is of essential importance for many gas-based nonlinear optical applications. To accurately calculate the pressure-induced dispersion variations (∂ß2/∂p) in anti-resonant types of HCF, an analytical model combining the contribution of the gas material, capillary waveguide, and cladding resonances is developed, with an insightful physical picture. Broadband (∼1000 nm) GVD measurements in a single-shot manner realize accuracy and precision as low as 0.1 ps2/km and 2 × 10-3 ps2/km, respectively, and validate our model. Consistent with our model, a pronounced negative ∂ß2/∂p is observed experimentally for the first time, to our knowledge. Our model can also be extended to other HCFs with cladding resonances in predicting ∂ß2/∂p, such as in photonic bandgap types of HCF.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

BACKGROUND: Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. PURPOSE: To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24 hours) hyperacute stroke groups. STUDY TYPE: Cross-sectional cohort. POPULATION: A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. FIELD STRENGTH/SEQUENCE: A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. ASSESSMENT: Patients were divided into hyperacute (0-24 hours), acute (24 hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. STATISTICAL TESTS: Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. RESULTS: Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = -0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = -0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). DATA CONCLUSION: High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.