Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.

Rationality is a fundamental pillar of Economics. It is however unclear if this assumption holds when decisions are made under stress. To answer this question, we design two laboratory experiments where we exogenously induce physiological stress in participants and test the consistency of their choices with economic rationality. In both experiments we induce stress with the Cold Pressor test and measure economic rationality by the consistency of participants’ choices with the Generalized Axiom of Revealed Preference (GARP). In the first experiment, participants delay the decision-making task for 20 min until the cortisol level peaks. We find significant differences in cortisol levels between the stressed group and the placebo group which, however, do not affect the consistency of choices with GARP. In a second experiment, we study the immediate effect of the stressor on rationality. Overall, results from the second experiment confirm that rationality is not impaired by the stressor. If anything, we observe that compared to the placebo group, participants are more consistent with rationality immediately after the stressor. Our findings provide strong empirical support for the robustness of the economic rationality assumption under physiological stress.

During the investigation of parasitic pathogens of Mytilus coruscus, infection of a Perkinsus-like protozoan parasite was detected by alternative Ray's Fluid Thioglycolate Medium (ARFTM). The diameter of hypnospores or prezoosporangia was 8–27 (15.6 ± 4.0, n = 111) μm. The prevalence of the Perkinsus-like species in M. coruscus was 25 and 12.5% using ARFTM and PCR, respectively. The ITS1-5.8S-ITS2 fragments amplified by PCR assay had 100% homology to that of P. beihaiensis, suggesting that the protozoan parasite was P. beihaisensis and M. coruscus was its new host in East China Sea (ECS). Histological analysis showed the presence of trophozoites of P. beihaiensis in gill, mantle and visceral mass, and the schizonts only found in visceral mass. Perkinsus beihaiensis infection led to inflammatory reaction of hemocyte and the destruction of digestive tubules in visceral mass, which had negative effect on health of the farmed M. coruscus and it deserves more attention.

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.

With the in-depth study of thin-film structures, nonuniform thin films with rigid elements have been applied in the aerospace and flexible electronics industries. For thin-film structures with rigid elements, there is an interaction force between the rigid element and the thin film; therefore, the wrinkling mode of the thin film changes under the influence of the interaction force. In this study, a wrinkle model was developed to predict the wrinkle morphology of thin-film structures with rigid elements on the diagonal. First, the wrinkle patterns of the rigid elements were observed at different positions using tensile experiments. Then, the relationship between the tilt of the rigid element and the wrinkle wavelength was investigated using a finite-element eigenvalue buckling analysis. Finally, local wrinkling caused by the perturbed stress of the rigid element was introduced, and a wrinkling model of a square thin film with rigid elements on the diagonal under tension was established. The theoretical analysis results were compared with simulation and experimental results, demonstrating that the model can accurately describe the wrinkle patterns of thin-film structures containing rigid elements on the diagonal under tension.

Recently released Moderate-Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) collection 6.1 (C6.1) products are useful for understanding ice–atmosphere interactions over East Antarctica, but their accuracy should be known prior to application. This study assessed Level 2 and Level 3 MODIS C6.1 LST products (MxD11_L2 and MxD11C1) in comparison with the radiance-derived in situ LSTs from 12 weather stations. Significant cloud-related issues were identified in both LST products. By utilizing a stricter filter based on automatic weather station cloud data, despite losing 29.4% of the data, accuracy of MODIS LST was greatly improved. The cloud-screened MODIS LST exhibited cold biases (−5.18 to −0.07°C, and root mean square errors from 2.37 to 6.28°C) than in situ LSTs at most stations, with smaller cold biases at inland stations, but larger ones at coastal regions and the edge of plateau. The accuracy was notably higher during warm periods (October–March) than during cold periods (April–September). The cloud-screened MODIS C6.1 LST did not show significant improvements over C5 (Collection 5) version across East Antarctica. Ice-crystal precipitation occurring during temperature inversions at the surface (Tair-Tsurface) played a crucial role in MODIS LST accuracy on inland plateau. In coastal regions, larger MODIS LST biases were observed when the original measurements were lower.

The chemistry of Al transformation has been well documented, though little is known about the mechanisms of structural perturbation of Al precipitates by carbonates at a molecular level. The purpose of the present study was to investigate the structural perturbation of Al precipitates formed under the influence of carbonates. Initial carbonate/Al molar ratios (MRs) used were 0, 0.1, and 0.5 after aging for 32 days, then the samples were analyzed by X-ray absorption near edge structure spectroscopy (XANES), X-ray diffraction (XRD), Fourier-transform infrared absorption spectroscopy (FTIR), and chemical analysis. The XRD data were in accord with the FTIR results, which revealed that as the carbonate/Al MR was increased from 0 to 0.1, carbonate preferentially retarded the formation of gibbsite and had relatively little effect on the formation of bayerite. As the carbonate/Al MR was increased to 0.5, however, the crystallization of both gibbsite and bayerite was completely inhibited. The impact of carbonate on the nature of Al precipitates was also evident in the increase of adsorbed water and inorganic C contents with increasing carbonate/Al MR. The Al K- and L- edge XANES data provide the first evidence illustrating the change in the coordination number of Al from 6-fold to mixed 6- and 4-fold coordination in the structural network of short-range ordered (SRO) Al precipitates formed under the increasing perturbation of carbonate. The fluorescence yield spectra of the O K-edge show that the intensity of the peak at 534.5 eV assigned to σ* transitions of Al-O and O-H bonding decreased with increasing carbonate/Al MR. The XANES data, along with the evidence from XRD, FTIR, and chemical analysis showed clearly that carbonate caused the alteration of the coordination nature of the Al-O bonding through perturbation of the atomic bonding and structural configuration of Al hydroxides by complexation with Al in the SRO network of Al precipitates. The surface reactivity of an Al-O bond is related to its covalency and coordination geometry. The present findings were, therefore, of fundamental significance in understanding the low-temperature geochemistry of Al and its impacts on the transformation, transport, and fate of nutrients and pollutants in the ecosystem.

The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

Planting patterns have significant effects on rice growth. Nonetheless, little is known about differences in annual crop yield and resource utilization among mechanized rice planting patterns in a rice–wheat cropping system. Field experiments were conducted from 2014 to 2017 using three treatments: pot seedling transplanting for rice and row sowing for wheat (PST-RS), carpet seedling transplanting for rice and row sowing for wheat (CST-RS) and row sowing for both crops (RS-RS). The results showed that, compared with RS-RS, PST-RS and CST-RS prolonged annual crop growth duration by 25–26 and 13–15 days, increased effective accumulated temperature by 399 and 212°C days and increased cumulative solar radiation by 454 and 228 MJ/m2 because of the earlier sowing of rice by 28 and 16 days in PST-RS and CST-RS, respectively. Compared with RS-RS, the annual crop yield of PST-RS and CST-RS increased by 3.1–3.8 and 2.0–2.6 t/ha, respectively, because of the increase in the number of spikelets/kernels per hectare, aboveground biomass, mean leaf area index and grain–leaf ratio. In addition, temperature production efficiency, solar radiation production efficiency and solar radiation use efficiency were higher in PST-RS, followed by CST-RS and RS-RS. These results suggest that mechanized rice planting patterns such as PST-RS increase annual crop production in rice–wheat cropping systems by increasing yield and solar energy utilization.

We describe a new low-frequency wideband radio survey of the southern sky. Observations covering 72–231 MHz and Declinations south of $+30^\circ$ have been performed with the Murchison Widefield Array “extended” Phase II configuration over 2018–2020 and will be processed to form data products including continuum and polarisation images and mosaics, multi-frequency catalogues, transient search data, and ionospheric measurements. From a pilot field described in this work, we publish an initial data release covering 1,447$\mathrm{deg}^2$ over $4\,\mathrm{h}\leq \mathrm{RA}\leq 13\,\mathrm{h}$, $-32.7^\circ \leq \mathrm{Dec} \leq -20.7^\circ$. We process twenty frequency bands sampling 72–231 MHz, with a resolution of 2′–45′′, and produce a wideband source-finding image across 170–231 MHz with a root mean square noise of $1.27\pm0.15\,\mathrm{mJy\,beam}^{-1}$. Source-finding yields 78,967 components, of which 71,320 are fitted spectrally. The catalogue has a completeness of 98% at ${{\sim}}50\,\mathrm{mJy}$, and a reliability of 98.2% at $5\sigma$ rising to 99.7% at $7\sigma$. A catalogue is available from Vizier; images are made available via the PASA datastore, AAO Data Central, and SkyView. This is the first in a series of data releases from the GLEAM-X survey.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

The apple buprestid, Agrilus mali Matsumura, that was widespread in north-eastern China, was accidently introduced to the wild apple forest ecosystem in mountainous areas of Xinjiang, China. This invasive beetle feeds on domesticated apples and many species of Malus and presents a serious threat to ancestral apple germplasm sources and apple production worldwide. Estimating the potential area at risk of colonization by A. mali is crucial for instigating appropriate preventative management strategies, especially under global warming. We developed a CLIMEX model of A. mali to project this pest's potential distribution under current and future climatic scenarios in 2100 using CSIRO-Mk 3.0 GCM running the SRES A1B emissions scenario. Under current climate, A. mali could potentially invade neighbouring central Asia and eventually the mid-latitude temperate zone, and some subtropical areas and Pampas Steppe in the Southern Hemisphere. This potential distribution encompasses wild apples species, the ancestral germplasm for domesticated apples. With global warming, the potential distribution shifts to higher latitudes, with the potential range expanding slightly, though the overall suitability could decline in both hemispheres. In 2100, the length of the growing season of this pest in the mid-latitude temperature zone could increase by 1–2 weeks, with higher growth rates in most sites compared with current climate in mid-latitudes, at least in China. Our work highlights the need for strategies to prevent the spread of this pest, managing the threats to wild apples in Tian Shan Mountain forests in Central Asia, and commercial apple production globally. We discuss practical management tactics to reduce the spread of this pest and mitigate its impacts.

Glutamine synthetase (GS) and glutamate synthase (GOGAT) play a central role in plant nitrogen (N) metabolism. In order to study the effect of powdery mildew (Blumeria graminis f. sp. tritici, Bgt) on N metabolism, field experiments were carried out to evaluate GS and GOGAT activity, GS expression and grain protein content (GPC) in susceptible (Xi'nong 979) and resistant (Zhengmai 103) wheat cultivars under three treatments. The three treatments were no inoculation (CK), inoculated once with Bgt (MP) and inoculated nine times with Bgt (HP). For Xi'nong 979, the activities of GS and GOGAT in grains as well as GS activity in flag leaves increased at 10–15 days after anthesis (DAA), and decreased significantly at 15 or 20–30 DAA in HP and MP. However, GS activity in grains decreased from 20 DAA, which was later than that of flag leaves (15 DAA). At the same time, GS expression in grains was up-regulated at early stage, with GS1 at 10 DAA and GS2 at 15 DAA, followed by a continuous down-regulation. This result indicated that GS and GOGAT activity as well as GS expression were inhibited by powdery mildew, indicating that N metabolism in grains was inhibited at 20–30 DAA. The current study also found out that the yield of the susceptible cultivar decreased significantly, while its GPC increased obviously in HP. It was shown that the increase of GPC was not due to the enhancement of N metabolism, but due to the passive increase caused by yield reduction.

We have extended our previous work to use the Murchison widefield array (MWA) as a non-coherent passive radar system in the FM frequency band, using terrestrial FM transmitters to illuminate objects in low Earth orbit (LEO) and the MWA as the sensitive receiving element for the radar return. We have implemented a blind detection algorithm that searches for these reflected signals in difference images constructed using standard interferometric imaging techniques. From a large-scale survey using 20 h of archived MWA observations, we detect 74 unique objects over multiple passes, demonstrating the MWA to be a valuable addition to the global Space Domain Awareness network. We detected objects with ranges up to 977 km and as small as $0.03$ ${\rm m}^2$ radar cross section. We found that 30 objects were either non-operational satellites or upper-stage rocket body debris. Additionally, we also detected FM reflections from Geminid meteors and aircraft flying over the MWA. Most of the detections of objects in LEO were found to lie within the parameter space predicted by previous feasibility studies, verifying the performance of the MWA for this application. We have also used our survey to characterise these reflected signals from LEO objects as a source of radio frequency interference (RFI) that corrupts astronomical observations. This has allowed us to undertake an initial analysis of the impact of this RFI on the MWA and the future square kilometer array (SKA). As part of this analysis, we show that the standard MWA RFI flagging strategy misses most of this RFI and that this should be a careful consideration for the SKA.