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Aims Coagulase (Coa), a crucial virulence factor of Staphylococcus aureus (S. aureus), is considered a vital target for anti-virulence strategies. The research aimed to discover a natural compound capable of inhibiting S. aureus infection by targeting the virulence factor Coa. Methods and results The study showed that sinensetin at a concentration of 128 μg mL−1 effectively inhibited both Coa-induced coagulation and biofilm formation in S. aureus. However, western blot results indicated that sinensetin did not impact the expression of Coa protein, suggesting that sinensetin may directly target Coa to counteract the virulence of S. aureus. Thermal shift assay results demonstrated that sinensetin enhanced the thermal stability of Coa, supporting the theory of direct binding. Molecular docking and point mutation experiments identified two key binding sites for sinensetin to Coa as R73A-Coa and R204A-Coa. In vivo studies on mice revealed that sinensetin not only reduced lung tissue damage caused by S. aureus infection, but also decreased inflammatory factors in the lung lavage fluid. Furthermore, combining sinensetin with oxacillin improved the survival rates of the Galleria mellonella and mice. Conclusions Sinensetin is a promising natural compound that acts as a direct inhibitor of Coa against S. aureus infections. [ABSTRACT FROM AUTHOR]

The accurate assessment of hydraulic transmissivity in rock fractures filled with particles is not only a scientific challenge but also a critical need for various industrial applications. However, the intricate dynamics of particle erosion and pore clogging that govern transmissivity evolution remain largely unexplored. In this study, we experimentally examine the fluid‐driven particle migration behavior in filled fractures and its consequent impact on fracture transmissivity under various hydraulic gradients, normal stresses, and fracture apertures. We find that escalating hydraulic gradients not only intensify particle erosion through amplified fluid drag forces and hydro‐mechanical coupling effects but also lead to an increase in the size of migrating particles, thereby augmenting pore clogging. The dynamics of erosion and clogging define four distinct migration phases within the filled fractures. Variations in normal stress and initial fracture aperture significantly alter the particle arrangement and the soil structure stability within the fractures, thereby modulating the progress of particle migration in response to hydraulic gradients. The pattern of particle migration in filled fractures dictates the development of the internal pore structure and normal deformation, ultimately affecting fracture transmissivity. We propose an empirical expression to encapsulate the comprehensive evolution of fracture transmissivity across different particle migration patterns. Our research advances the understanding of fluid‐driven particle migration within filled fractures and provides a practical tool for the precise determination of hydraulic properties of fractured rocks amidst complex geological settings. Plain Language Summary: Filled fractures in rock masses, serving as dominant flow channels and potential failure planes, are typically perceived to exhibit constant hydraulic transmissivity. However, this perspective oversimplifies the dynamic nature of filled fractures, where fluid flow can greatly change the hydraulic characteristics by either eroding or accumulating the internal particles. Understanding how these filling particles respond to water flow and affect fracture transmissivity is vital for many geological processes and human activities. Here, we experimentally uncover four distinct phases of particle migration within a filled fracture, instigated by the dynamics of erosion and clogging under elevated hydraulic gradients. Variations in normal stress and fracture aperture significantly influence the particle arrangement and the soil structure stability within fractures, thereby affecting particle migration characteristics across phases. On this basis, we delve into how the patterns of particle migration impact the geometric structure of the filled fracture and, thus, the fracture transmissivity. Finally, we quantitatively portray the evolution in fracture transmissivity across various particle migration scenarios using an empirical model. Our findings enhance the understanding of fluid‐driven particle migration in filled fractures and provide a path forward for accurately assessing the hydraulic properties of fractured rocks in complex geological environments. Key Points: Erosion and clogging dynamics, modulated by hydraulic gradients, define four particle migration phases in stressed‐filled fracturesParticle migration patterns dictate pore structure and normal deformation, impacting fracture transmissivityAn empirical model encapsulates fracture transmissivity evolution across different particle migration patterns [ABSTRACT FROM AUTHOR]

Polyimide (PI) aerogels, renowned for their nano-porous structure and exceptional performance across a spectrum of applications, often encounter significant challenges during fabrication, primarily due to severe shrinkage. In this study, we innovatively incorporated ceramic fibers of varying diameters into the PI aerogel matrix to enhance the shape stability against shrinkage. The structure of the resulting ceramic fiber-reinforced PI (CF-PI) aerogel composites as well as their performance in thermal decomposition, thermal insulation, and compression resistance were characterized. The results revealed that the CF-PI aerogel composites dried by supercritical ethanol achieved greatly reduced shrinkage as low as 5.0 vol.% and low thermal conductivity ranging from 31.2 mW·m−1·K−1 to 35.3 mW·m−1·K−1, showcasing their excellent performance in shape stability and thermal insulation. These composites also inherited the superior residue-forming ability of ceramic fibers and the robust mechanical attributes of PI, thereby exhibiting enhanced thermal stability and compression resistance. Besides, the effects of different drying conditions on the structure and properties of CF-PI aerogels were also discussed. The coupling use of supercritical ethanol drying with the addition of ceramic fibers is preferred. This preferred condition gives birth to low-shrinkage CF-PI aerogel composites, which also stand out for their integrated advantages include high thermal stability, low thermal conductivity, and high mechanical strength. These advantages attribute to CF-PI aerogel composites substantial potential for a wide range of applications, particularly as high-performance thermal insulation materials for extreme conditions. [ABSTRACT FROM AUTHOR]

Background: The hippocampus consists of histologically and functionally distinct subfields, which shows differential vulnerabilities to Alzheimer's disease (AD)-associated pathological changes. Objective: To investigate the atrophy patterns of the main hippocampal subfields in patients with mild cognitive impairment (MCI) and AD and the relationships among the hippocampal subfield volumes, plasma biomarkers and cognitive performance. Methods: This cross-sectional study included 119 patients stratified into three categories: normal cognition (CN; N = 40), MCI (N = 39), and AD (N = 40). AD-related plasma biomarkers were measured, including amyloid-β (Aβ)42, Aβ40, Aβ42/Aβ40 ratio, p-tau181, and p-tau217, and the hippocampal subfield volumes were calculated using automated segmentation and volumetric procedures implemented in FreeSurfer. Results: The subiculum body, cornu ammonis (CA) 1-head, CA1-body, CA4-body, molecular_layer_HP-head, molecular_layer_HP-body, and GC-ML-DG-body volumes were smaller in the MCI group than in the CN group. The subiculum body and CA1-body volumes accurately distinguished MCI from CN (area under the curve [AUC] = 0.647–0.657). The subiculum-body, GC-ML-DG-body, CA4-body, and molecular_layer_HP-body volumes accurately distinguished AD from MCI (AUC = 0.822–0.833) and AD from CN (AUC = 0.903–0.905). The p-tau 217 level served as the best plasma indicator of AD and correlated with broader hippocampal subfield volumes. Moreover, mediation analysis demonstrated that the subiculum-body volume mediated the associations between the p-tau217 and p-tau181 levels, and the Montreal Cognitive Assessment and Auditory Verbal Learning Test recognition scores. Conclusions: Hippocampal subfields with distinctive atrophy patterns may mediate the effects of tau pathology on cognitive function. The subiculum-body may be the most clinically meaningful hippocampal subfield, which could be an effective target region for assessing disease progression. [ABSTRACT FROM AUTHOR]

Water is a limited and highly valuable resource. In many parts of the world, water agencies allocate water according to agreed entitlement systems. The allocations are largely based on water already available in storages and rivers. Water agencies may also issue seasonal water allocation outlooks by anticipating future inflows to the storages and rivers. These outlooks are meant to assist water entitlement holders to plan for their crop planting, irrigation, and participation in water markets. Currently, these outlooks are generally based on historical inflow observations (climatology) and are often determined for a small selection of possible climatic scenarios (e.g., extreme dry, dry, average, and wet). These outlooks have large uncertainties, which require users to manage high risks themselves, leading to inefficient water use. In this study, we investigate the use of ensemble seasonal inflow forecasts to improve the production of seasonal water allocation outlooks through a case study of the Goulburn system in central Victoria, Australia. This is a complex system with active water trade both within the region and outside with the larger connected southern Murray-Darling Basin. In this case study, we integrate Australian Bureau of Meteorology's seasonal streamflow forecasts with Goulburn-Murray Water's water allocation to produce fully probabilistic water allocation outlooks. We evaluate the outlooks for three irrigation seasons from 2017 to 2020. We compare these outlooks with those produced from using inflows based on climatology only, an approach akin to the current practice of Goulburn-Murray Water. Using seasonal streamflow forecasts resulted in outlooks up to 60% (average 20%) closer to actual determinations, with uncertainty reduced by up to 65% (average 19%) Improvements were most obvious for short lead times and later in the irrigation season. This is a clear demonstration of how integration of streamflow forecasts can improve end-user products, which can lead to more efficient water use and water market participation. This paper demonstrates how skillful forecasts of streamflow can be used to produce meaningful products for end users. Specifically, improvements are made to outlooks of water that will be made available to irrigators in dry years. The new outlooks are up to 60% closer, with up to 65% less uncertainty. These improved outlooks allow entitlement holders to more confidently plan for the irrigation season, leading in turn to more efficient water use. The method presented here should provide benefits for any water management systems where skillful streamflow forecasts are available. Beyond its use for high-reliability water share outlooks, it could easily be adapted for other water manager applications such as outlooks of low-reliability water shares in very dry years, or risk of spill (insufficient storage capacity) in wet years. [ABSTRACT FROM AUTHOR]

Background: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in the formation of amyloid-β (Aβ) protein. Increasing evidence suggests that BACE1 concentration is a potential biomarker for Alzheimer's disease (AD). Objective: To evaluate the correlations between plasma BACE1 concentration, cognition, and hippocampal volume at different stages of the AD continuum. Methods: Plasma BACE1 concentrations were measured in 32 patients with probable dementia due to AD (ADD), 48 patients with mild cognitive impairment (MCI) due to AD, and 40 cognitively unimpaired (CU) individuals. Memory function was evaluated using the auditory verbal learning test (AVLT), and voxel-based morphometry was used to analyze bilateral hippocampal volumes. Correlation and mediation analyses were performed to investigate the associations between plasma BACE1 concentration, cognition, and hippocampal atrophy. Results: The MCI and ADD groups exhibited elevated BACE1 concentrations compared with the CU group after adjusting for age, sex, and apolipoprotein E (APOE) genotype. Increased BACE1 concentration was found in AD continuum patients who were APOE ɛ4 carriers (p < 0.05). BACE1 concentration was negatively associated with the scores of the subitems of the AVLT and hippocampal volume (p < 0.05, false discovery rate correction) in the MCI group. Moreover, bilateral hippocampal volume mediated the relationship between BACE1 concentration and recognition in the MCI group. Conclusion: BACE1 expression increased in the AD continuum, and bilateral hippocampal volume mediated the effect of BACE1 concentration on memory function in patients with MCI. Research has indicated that the plasma BACE1 concentration might be a biomarker at the early stage of AD. [ABSTRACT FROM AUTHOR]

Background: The primary manifestations of Alzheimer's disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear. Objective: To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition. Methods: In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants' brain GMV. Partial correlation and mediation analyses were conducted in AD group. Results: Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified. Conclusion: The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). Methods: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non‐T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. Results: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta‐analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = −0.72, 95% confidence interval (CI; −1.12, −0.33)], liver fat [SMD = −0.78, 95% CI (−1.24, −0.32)] and body mass index [weighted mean difference = −1.44, 95% CI (−1.95, −0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = −0.74, 95% CI (−1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. Conclusions: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured. [ABSTRACT FROM AUTHOR]

We demonstrate broadband mid-infrared supercontinuum generation in a piece of indium fluoride fiber pumped by an ultralow repetition rate noise-like pulse mode-locked fiber laser. This figure-9 mode-locked Tm-doped fiber laser has a long laser cavity by inserting a piece of standard single mode fiber and a piece of dispersion compensation fiber, which delivers mode-locked noise-like pulse with a repetition rate of ∼190 kHz. The mode-locked noise-like pulse train has a low pulse duty cycle of 4.38 × 10−4. With only one Tm-doped fiber amplifier, the ultra-low repetition rate noise-like pulse is amplified to ∼3 W. The pulse energy is boosted to ∼15 μJ with a peak power of ∼6.5 kW. Pumping a piece of highly nonlinear indium fluoride fiber with the amplified noise-like pulse, a flat mid-infrared supercontinuum with a covering range from ∼1500 nm to ∼4100 nm can be achieved. Due to the low operational power, no cooling installations are required to control the temperature of the supercontinuum laser system. This all-fiber mid-infrared SC laser source has a relatively simple architecture and low cost. This study demonstrates the great advantages of this type of ultra-low repetition rate noise-like pulses in mid-infrared supercontinuum generation. [ABSTRACT FROM AUTHOR]

In order to study the applicability of Z-type perfluoropolyether ( PFPE-Z) lubricant in high temperature and atmospheric environment, the evaporation loss test, maximum operating temperature test and corrosion test of PFPE-Z lubricant were carried out in high temperature and atmospheric environment respectively to determine the maximum operating temperature of PFPE-Z lubricant. Ultrafine depth of field digital microscopic system, energy disperse spectroscopy (EDS) and fourier transform infrared spectrophotometer (FTIR) were used for microscopic observation and component analysis for the bearing materials and PFPE-Z lubricating oi, and the corrosion rate of PFPE-Z lubricating oil to different bearing materials and the degradation rate of PFPE-Z lubricating oil were obtained. The results show that in high temperature and atmospheric environment, the maximum operating temperature of PFPE-Z grease (PTFE thickened) is 290 T, the maximum operating temperature of PFPE-Z lubricating oil is 310 T. PFPE-Z lubricating oil is corrosive to common metal materials of bearings, but the corrosion rate of different metal materials is different. [ABSTRACT FROM AUTHOR]

Reference crop evapotranspiration (ETo) is calculated using a standard formula with temperature, vapor pressure, solar radiation, and wind speed as input variables. ETo forecasts can be produced when forecasts of these input variables from numerical weather prediction (NWP) models are available. As raw ETo forecasts are often subject to systematic errors, statistical calibration is needed for improving forecast quality. The most straightforward and widely used approach is to directly calibrate raw ETo forecasts constructed with the raw forecasts of input variables. However, the predictable signal in ETo forecasts may not be fully implemented by this approach, which does not deal with error propagation from input variables to ETo forecasts. We hypothesize that correcting errors in input variables as a precursor to forecast calibration will lead to more skillful ETo forecasts. To test this hypothesis, we evaluate two calibration strategies that construct raw ETo forecasts with the raw (strategy i) or bias-corrected (strategy ii) input variables in ETo forecast calibration across Australia. Calibrated ETo forecasts based on bias-corrected input variables (strategy ii) demonstrate lower biases, higher correlation coefficients, and higher skills than forecasts produced by the calibration using raw input variables (strategy i). This investigation indicates that improving raw forecasts of input variables could effectively reduce error propagation and enhance ETo forecast calibration. We anticipate that future NWP-based ETo forecasting will benefit from adopting the calibration strategy developed in this study to produce more skillful ETo forecasts. [ABSTRACT FROM AUTHOR]

Reference crop evapotranspiration (ETo) is calculated using a standard formula with temperature, vapor pressure, solar radiation, and wind speed as input variables. ETo forecasts can be produced when forecasts of these input variables from numerical weather prediction (NWP) models are available. As raw ETo forecasts are often subjective to systematic errors, calibration is necessary for improving forecast quality. The most straightforward and widely used approach is to directly calibrate raw ETo forecasts constructed with the raw forecasts of input variables. However, the potential predictability of ETo may not be fully explored by this approach, which ignores the non-linear interactions of input variables in constructing ETo forecasts. We hypothesize that reducing errors in individual inputs as a precursor to ETo forecast calibration will lead to more skillful ETo forecasts. To test this hypothesis, we evaluate two calibration strategies, including (i) calibration directly applied to raw ETo forecasts constructed with raw forecasts of input variables, and (ii) bias-correcting input variables first, and then calibrating the ETo forecasts constructed with bias-corrected input variables. We calibrate ETo forecasts based on weather forecasts of the Australian Community Climate and Earth System Simulator G2 version (ACCESS-G2). Calibrated ETo forecasts with bias-corrected input variables (strategy ii) demonstrate lower bias, higher correlation coefficient, and higher skills than the calibration based on raw input variables (strategy i). This investigation indicates that improving raw forecasts of input variables could enhance ETo forecast calibration and produce more skillful ETo forecasts. This calibration strategy is expected to enhance future NWP-based ETo forecasting. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the long-term changes of corneal endothelial cells (EC) in anterior chamber intraocular lens- (AC-IOL-) implanted eyes. Methods. Retrospective study. We included 37 eyes (25 patients) that received AC-IOL implantation previously in the Eye and ENT Hospital of Fudan University between 1995 and 2016. Follow-up outcomes included the best-corrected visual acuity (BCVA), endothelial cell density, hexagonality, coefficient of variance, and central corneal thickness. Results. In total, 23 eyes (62.16%) with phakic and 14 eyes (37.84%) with aphakic AC-IOLs were included. Among these, 3 eyes (8.11%) were angle-supported AC-IOLs and 34 eyes (91.89%) were Artisan iris-fixated AC-IOLs. The mean age of patients was 41.40 ± 17.17 years, and the mean follow-up time was 12.12 ± 4.71 years in our study. At the follow-up time, corneal decompensation existed in 3 angle-supported AC-IOL eyes with a rate of 100% and 15 iris-fixated AC-IOL eyes with a rate of 44.12%. AC-IOL displacement occurred in 14 (41.18%) iris-fixated AC-IOL eyes. In the 19 iris-fixated AC-IOL eyes without corneal decompensation, significant changes also took place in corneal endothelial cells. The endothelial cell density decreased from 2843.26 ± 300.76 to 2015.58 ± 567.99 cells/mm2 (29.1% loss, P < 0.001) and hexagonality decreased from 51.21 ± 7.83 to 42.53 ± 9.17 (%) (16.9% loss, P < 0.001). The Kaplan–Meier survival curve also demonstrated the accumulated expectation rates of corneal endothelial cell decomposition for AC-IOLs with a median survival time of 12 years. Conclusion. We reported a significant chronic loss and long-term decompensation destiny of corneal endothelial cells in AC-IOL eyes. Semiannual or annual follow-up and evaluation of endothelial cells should be conducted in AC-IOL-implanted patients. [ABSTRACT FROM AUTHOR]

Electrochemical and chemical interfacial reaction mechanisms between LiNi0.5Co0.2Mn0.3O2 (NMC532) and poly(propylene carbonate) solid polymer electrolyte (PPC‐SPE) are studied. Ni3+ and Co4+ species which are electrochemically oxidized from Ni2+ and Co3+ during the charging process will induce the decomposition of PPC. Fourier transform infrared spectroscopy (FT‐IR) and 1H nuclear magnetic resonance (NMR) analysis confirm that the decomposition products of PPC contains ether, which might produce through condensation reaction of alcohol compounds. To retard this side reaction, graphene oxide is applied to coat commercial LiNi0.5Co0.2Mn0.3O2 particles via a facile chemical approach. Compared with pristine cathode, the coated sample displays higher initial capacity, better cycle stability and lower interfacial resistance after cycled. After 300 cycles, the capacity retention is 69.2% at 0.3 C and the resistance is only 25 Ω after 180 cycles. This is due to the graphene layer facilitates the interfacial charge‐transfer process and slows the cathode/electrolyte interfacial side reaction. Consequently, the study illuminated the interface issues of PPC based solid‐state lithium batteries. [ABSTRACT FROM AUTHOR]