Desminopathy is a rare heritable cardiac and skeletal muscle disease caused by variants in the DES gene, which encodes the primary muscle-specific intermediate filament protein, known as desmin. Childhood-onset is commonly associated with severe early-onset myopathy and early death. Here, we reported an 11-year-old Chinese girl presenting with complete atrioventricular block and cardiomyopathy, without skeletal muscle involvement. Genetic analysis identified a de novo variant (c.152C > T/p.Ser51Phe) in the DES gene.

The flexible delivery of single-frequency lasers is far more challenging than that of conventional lasers due to the onset of stimulated Brillouin scattering (SBS). Here we present the successful delivery of 100 W single-frequency laser power through 100 m of anti-resonant hollow-core fiber (AR-HCF) in an all-fiber configuration, with the absence of SBS. By employing a custom-designed AR-HCF with a mode-field diameter matching that of a large-mode-area panda fiber, the system achieves high coupling efficiency without the need for free-space components or fiber post-processing. The AR-HCF attains a transmission efficiency of 92%, delivering an output power of 100.3 W with a beam quality factor (M2) of 1.22. The absence of SBS is confirmed through monitoring backward light, which shows no increase in intensity. This all-fiber architecture ensures high stability, compactness and efficiency, potentially expanding the application scope of single-frequency lasers in high-precision metrology, optical communication, light detection and ranging systems, gravitational wave detection and other advanced applications.

External seeded free-electron lasers (FELs) have exhibited substantial progress in diverse applications over the last decade. However, the frequency up-conversion efficiency in single-stage seeded FELs, particularly in high-gain harmonic generation (HGHG), remains constrained to a modest level. This limitation restricts its capability to conduct experiments within the ‘water window’. This paper presents a novel method for generating coherent X-ray FEL pulses in the water window region based on the HGHG scheme with multi-stage harmonic cascade. Without any additional modifications to the HGHG configuration, simulation results demonstrate the generation of intense 3 nm coherent FEL radiation using an external ultraviolet seed laser. This indicates an increase of the harmonic conversion number to approximately 90. A preliminary experiment is performed to evaluate the feasibility of this method. The proposed approach could potentially serve as an efficient method to broaden the wavelength coverage accessible to both existing and planned seeded X-ray FEL facilities.

The reactive Navier–Stokes equations with adaptive mesh refinement and a detailed chemical reactive mechanism (11 species, 27 steps) were adopted to investigate a detonation engine considering the injection and supersonic mixing processes. Flame acceleration and deflagration-to-detonation transition (DDT) in a premixed/inhomogeneous supersonic hydrogen–air mixture with and without transverse jet obstacles were addressed. Results demonstrate the difficulty in undergoing DDT in the premixed/inhomogeneous supersonic mixture within a smooth chamber. By contrast, multiple transverse jets injected into the chamber aid detonation transition by introducing perturbed vortices, shock waves and a suitable blockage ratio. Increasing distance between the leading shock and the flame tip impedes detonation transition due to an insufficient blockage ratio. The extremely perturbed distributions of fuel-lean and fuel-rich mixtures lead to more complicated flame structures. Also, a larger flame thickness appears in the inhomogeneous mixture compared with the premixed mixture, resulting in a lower combustion temperature. The key findings are that the DDT, detonation quenching and reinitiation are generated in the inhomogeneous supersonic mixture, but both DDT mechanisms are ascribed to a strong Mach stem with the Zel'dovich gradient mechanism. Additionally, the obtained results demonstrate that an intensely fuel-lean mixture (equivalence ratio = 0.15) results in a partially decoupled flame front. However, detonation reinitiation and subsequent self-sustained detonation occur when a fierce shock wave propagates through a highly sensitive mixture, even within a smaller and elongated area. Moreover, the inhomogeneous mixture also augments the propagation speed and detonation cell structure instabilities and delays the sonic point resulting from the extending non-equilibrium reaction.

We present a practical verification method for safety analysis of the autonomous driving system (ADS). The main idea is to build a surrogate model that quantitatively depicts the behavior of an ADS in the specified traffic scenario. The safety properties proved in the resulting surrogate model apply to the original ADS with a probabilistic guarantee. Given the complexity of a traffic scenario in autonomous driving, our approach further partitions the parameter space of a traffic scenario for the ADS into safe sub-spaces with varying levels of guarantees and unsafe sub-spaces with confirmed counter-examples. Innovatively, the partitioning is based on a branching algorithm that features explainable AI methods. We demonstrate the utility of the proposed approach by evaluating safety properties on the state-of-the-art ADS Interfuser, with a variety of simulated traffic scenarios, and we show that our approach and existing ADS testing work complement each other. We certify five safe scenarios from the verification results and find out three sneaky behavior discrepancies in Interfuser which can hardly be detected by safety testing approaches.

With the increase in egg production rate and the coming of peak laying period, some metabolic disorders usually emerge in layers. The current study was conducted to compare the physiological difference between the early laying stage (around 30% laying rate) and peak laying stage (more than 95% laying rate) of laying hens based on hepatic transcriptome, serum metabolomics and caecal microbiota. The results showed that the egg weight and yolk weight were significantly higher in peak laying hens. Further, serum malondialdehyde and total bile acid concentrations were higher, but total anti-oxidant capacity, total bilirubin and low-density lipoprotein cholesterol (LDL-c) concentrations were significantly lower in peak laying hens. Hepatic transcriptome analysis identified 540 up-regulated and 269 down-regulated genes. Consistently, fatty acid biosynthesis, PPAR and insulin signalling pathways were significantly enriched. Subsequently, the result of serum metabolomics identified 74 up- and 77 down-regulated metabolites. Among down-regulated metabolites, hesperetin, apigenin and betaine related to anti-oxidant function were down-regulated. In addition, western blotting result showed BCL2 and p53 proteins expressions were decreased in the peak laying period, whereas hepatic CEBPα protein level was increased. On the other hand, gut microbiota analysis revealed that Chao index was decreased in peak laying hens. And the LEfSe analysis showed the dominant microflora including Ruminococcus, Oxalobacter, Paracoccus and so on was found in peak laying hens. These findings indicated that the hepatic lipid metabolism of peak laying hens is enhanced and the decline in anti-oxidant performance of hens also implies its importance during the early stage of egg production.

We report a high-power ultra-narrow fiber-coupled diode laser using a Faraday anomalous dispersion optical filter (FADOF) as an external cavity element. An external cavity suitable for both the fiber-coupled package and FADOF configuration has been proposed. Using a 87Rb-based FADOF as the frequency-selective element, we realized a 103 W continuous laser output with a uniform circular beam. The center wavelength was precisely locked at the D2 line of the Rb resonance, and the bandwidth was narrowed from 1.8 nm (free-running, full width at half maximum (FWHM)) to 0.013 nm (6.9 GHz, FWHM). The side mode suppression ratio reached 31 dB. Such diode lasers with precise wavelength and high spectral brightness have critical applications in many fields, such as high-energy gas laser pumping, spin-exchange optical pumping, Raman spectroscopy and nonlinear optics.

Glycosylation modifications of proteins and glycan hydrolysis are critical for protein function in biological processes. Aberrations in glycosylation enzymes are linked to lysosomal storage disorders (LSDs), immune interactions, congenital disorders and tumour progression. Mannosidase alpha class 2B member 1 (MAN2B1) is a lysosomal hydrolase from the α-mannosidase family. Dysfunction of MAN2B1 has been implicated as causative factors in mannosidosis, a lysosomal storage disorder characterised by cognitive impairment, hearing loss and immune system and skeletal anomalies. Despite decades of research, its role in pathogenic infections, autoimmune conditions, cancers and neurodegenerative pathologies is highly ambiguous. Future studies are required to shed more light on the intricate functioning of MAN2B1. To this end, we review the biological functions, expression patterns, enzymatic roles and potential implications of MAN2B1 across various cell types and disease contexts. Additionally, the novel insights presented in this review may aid in understanding the role of MAN2B1 in immune cells, thereby paving the way for targeted therapeutic interventions in immune-related disorders.

We demonstrated a method to improve the output performance of a Ti:sapphire laser in the long-wavelength low-gain region with an efficient stimulated Raman scattering process. By shifting the wavelength of the high-gain-band Ti:sapphire laser to the long-wavelength low-gain region, high-performance Stokes operation was achieved in the original long-wavelength low-gain region of the Ti:sapphire laser. With the fundamental wavelength tuning from 870 to 930 nm, first-order Stokes output exceeding 2.5 W was obtained at 930–1000 nm, which was significantly higher than that directly generated by the Ti:sapphire laser, accompanied by better beam quality, shorter pulse duration and narrower linewidth. Under the pump power of 42.1 W, a maximum first-order Stokes power of 3.24 W was obtained at 960 nm, with a conversion efficiency of 7.7%. Furthermore, self-mode-locked modulations of first- and second-order Stokes generation were observed in Ti:sapphire intracavity solid Raman lasers for the first time.

We consider linear-fractional branching processes (one-type and two-type) with immigration in varying environments. For $n\ge0$, let $Z_n$ count the number of individuals of the nth generation, which excludes the immigrant who enters the system at time n. We call n a regeneration time if $Z_n=0$. For both the one-type and two-type cases, we give criteria for the finiteness or infiniteness of the number of regeneration times. We then construct some concrete examples to exhibit the strange phenomena caused by the so-called varying environments. For example, it may happen that the process is extinct, but there are only finitely many regeneration times. We also study the asymptotics of the number of regeneration times of the model in the example.

Exercise-based cardiac rehabilitation is effective in improving cardiovascular disease risk factor management, cardiopulmonary function, and quality of life. However, the precise mechanisms underlying exercise-induced cardioprotection remain elusive. Recent studies have shed light on the beneficial functions of noncoding RNAs in either exercise or illness models, but only a limited number of noncoding RNAs have been studied in both contexts. Hence, the present study aimed to elucidate the pathophysiological implications and molecular mechanisms underlying the association among exercise, noncoding RNAs, and cardiovascular diseases. Additionally, the present study analysed the most effective and personalized exercise prescription, serving as a valuable reference for guiding the clinical implementation of cardiac rehabilitation in patients with cardiovascular diseases.

Reducing drag under high turbulence is a critical but challenging issue that has engendered great concern. This study utilizes hydrophilic tips in superhydrophobic (SHP) grooves to enhance the stability of plastron, which results in a considerable drag reduction ($DR$) up to 62 %, at Reynolds number ($Re$) reaching $2.79 \times 10^{4}$. The effect of the spacing width $w$ of the microgrooves on both $DR$ and flow structures is investigated. Experimental results demonstrate that $DR$ increases as either microgroove spacing $w$ or $Re$ increases. The velocity fields obtained using particle image velocimetry indicate that the air-filled SHP grooves induce a considerable wall slip. This slip significantly weakens the intensity of Taylor rolls, reduces local momentum transport, and consequently lowers drag. This phenomenon becomes more pronounced with increasing $w$. Furthermore, to quantify the multiscale relationship between global response and geometrical as well as driving parameters, $DR\sim (w, \phi _s, Re)$, a theoretical model is established based on angular momentum defect theory and magnitude estimate. It is demonstrated that a decrease in the surface solid fraction can reduce wall shear, and an increase in the groove width can weaken turbulence kinetic energy production, rendering enhanced slip and drag reduction. This research has implications for designing and optimizing turbulent-drag-reducing surfaces in various engineering applications, such as transportation and marine engineering.

Growing evidence indicates a link between diet and depression risk. We aimed to examine the association between an inflammatory diet index and depression utilising extensive data from UK biobank cohort. The energy-adjusted dietary inflammation index (E-DII) was calculated to quantify the potential of daily diet, with twenty-seven food parameters utilised. The E-DII scores were classified into two categories (low v. high) based on median value. To mitigate bias and ensure comparability of participant characteristics, propensity score matching was employed. To ascertain the robustness of these associations, sensitivity analyses were conducted. Subgroup analyses were performed to evaluate the consistency of these associations within different subpopulations. Totally, 152 853 participants entered the primary analyses with a mean age of 56·11 (sd 7·98) years. Employing both univariate and multivariate logistic regression models, adjustments were made for varying degrees of confounding factors (socio-demographics, lifestyle factors, common chronic medical conditions including type 2 diabetes and hypertension). Results consistently revealed a noteworthy positive correlation between E-DII and depression. In the context of propensity score matching, participants displaying higher E-DII scores exhibited an increased likelihood of experiencing incident depression (OR = 1·12, 95 % CI: 1·05, 1·19; P = 0·000316). Subgroup analysis results demonstrated variations in these associations across diverse subpopulations. The E-value for the point-estimate OR calculated from the propensity score matching dataset was 1·48. Excluding individuals diagnosed with type 2 diabetes or hypertension, the findings consistently aligned with the positive association in the primary analysis. These findings suggested that consumption of a diet with higher pro-inflammatory potential might associated with an increase of future depression risk.