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Abstract Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

Abstract In photonic crystal systems, topologically protected edge states and corner states can be achieved by breaking spatial inversion symmetry, which is expected to be applied to topologically protected lasers, optical communication and integrated photonics. However, designing ultrabroadband topological photonic crystals is still a challenge. In this work, we propose a valley photonic crystal composed of dendritic structures, which can realize valley transmission with a relative bandwidth up to 59.65%. Compared with the previously reported two-dimensional broadband photonic crystals with 32.02% bandwidth, the relative bandwidth of the proposed valley transmission is increased by almost 100%. Theoretical analysis, numerical simulation and experimental measurement all confirm flexible manipulation of electromagnetic wave propagation paths. Ultrabroadband topological waveguides with the zigzag and armchair interface are demonstrated, which can achieve experimentally 58.71% and 36.78% relative bandwidth, respectively. In addition, several topological channel intersections are designed. Finally, two types of corner states with valley switchability and selectivity are demonstrated.

This research developes an innovative thermodynamic coupling model for gas-bearing coal, improving temperature change simulations during coalbed methane desorption. The model distinctively integrates adsorption/desorption heat effects, free gas expansion, dynamic diffusion, the Klinkenberg effect, and moisture influence, offering a more comprehensive perspective of thermodynamic behavior. Comparisons with empirical data and previous models demonstrate that the predicted temperature changes closely match experimental results, indicating superior accuracy. The investigation finds a 23.51 % increase in desorption temperature as gas pressure rises from 0.4 MPa to 1.2 MPa, with temperature changes following the sequence CO2 > CH4 > N2, in the ratio ΔT(CO2): ΔT(CH4): ΔT(N2) = 1.76: 1.35: 1. Adsorbed gas desorption and free gas expansion are recognized as the primary drivers, especially near 0.5 MPa, where adsorbed gas contributes nearly 70 %. Sensitivity to variables such as gas pressure, adsorption heat, and permeability diminishes over time, with moisture exerting minimal impact. The study highlights a close thermodynamic connection between temperature changes and gas outbursts, proposing temperature variation as an reliable indicator for predicting and evaluating outburst risks. These findings enhance understanding of coalbed methane desorption and provide new theoretical foundations for efficient resource development and disaster prevention.

As the core component of China Fusion Engineering Test Reactor (CFETR), the forming and manufacturing of the first wall faces severe challenges due to the constraints of materials, service environment and geometric structure. The microstructure and mechanical properties of welded joints obtained by rolled and laser selective melted (SLMed) reduced activation ferritic/martensitic (RAFM) steel were investigated in depth. The microstructure analysis results showed that the weld metal (WM) was composed of coarse lath martensite and δ-ferrite, while the microstructure were mainly coarse grains in heat affected zone (HAZ) which was easy to break. The average grains size of SLMed RAFM steel (S-RAFMs) was smaller than that of rolled RAFM steel (R-RAFMs), since the rapid melting and solidification of laser in the additive manufacturing process prevented grains to grow. The microstructure of R-RAFMs joint was relatively more uniform and there was no obvious texture and preferred orientation, while the WM of S-RAFMs joint had a weak cubic texture. The results of mechanical properties showed that the S-RAFMs joints exhibited higher strength (UTS = 697.46 MPa) and the R-RAFMs joints exhibited better plasticity (EL = 13.49 %) under the same tensile conditions. The tensile and impact fracture morphologies showed that the fracture mechanism of two joints was ductile-brittle mixed fracture, and the dimples of R-RAFMs joints were finer and denser. It was clearly observed that the hardness of WM (∼390–430 HV0.3) was higher than that of the base metal (BM) (∼190–230 HV0.3) from the hardness distributions along the width directions. The average hardness of BM in R-RAFMs joint (227 HV0.3) was lower than S-RAFMs joint (197.3 HV0.3), which was mainly related to the fine grain strengthening effect during SLM forming. The above results may provide theoretical guidance for the high-performance manufacturing of the first wall and promote the application of SLM and EBW technology in the field of nuclear fusion.

Abstract Metasurfaces are 2D artificial nanostructures that exhibit fascinating optical phenomena and flexible capabilities. Multi-optical-parameter metasurfaces have advantages over single-function or single-dimensional metasurfaces, especially in practical applications like holography, sub-diffraction imaging, and vectorial fields. However, achieving multi-optical-parameter control is challenging due to a lack of design strategy, limited manipulation channels, and signal-to-noise ratio problems. Exceptional points (EPs) possess inherent polarization decoupling properties and allow for amplitude and wavelength modulation, opening up research prospects for multi-optical-parameter electromagnetic field modulation and developing compact integrated devices. Leveraging deep learning, we observe topological charge conservation and utilize the topologically protected optical parameter distribution around scattered EPs. Based on these, we introduce amplitude-phase multiplexing and wavelength division multiplexing devices. Our work allows rapid and precise discovery of EPs topology, offers a powerful tool for digging related physics, and provides a paradigm for multi-optical parametric manipulation with high performance and less crosstalk, which is critical for imaging, encryption, and information storage applications.

The development of the electrification of aircraft has prompted aviation hydraulic systems to shift from traditional centralized valve actuators (CVAs) to electro-hydrostatic actuators (EHAs). In this paper, aiming at the demand for a quantitative comparison of performance between CVAs and EHAs, CVA and EHA prototypes with the same power level and test platform were developed. Then, based on the power flow and dynamic models of the CVA and EHA, simulation and experimental comparative tests were conducted using different load spectrum test conditions and step response test conditions. The comparative test results showed that the efficiency of the EHA was better than that of the CVA, and the dynamic response of the CVA was better than that of the EHA. Finally, a power loss quantification and parameter sensitivity analysis were performed to reveal the impact of different parameters on the different power losses and to provide suggestions for improving the performance of CVAs and EHAs.

AimThis study aims to assess the association between sodium–glucose cotransporter type-2 inhibitor (SGLT-2i) treatment and muscle atrophy in patients with type 2 diabetes mellitus (T2DM).MethodsWe searched six databases from 1 January 2012 to 1 May 2023, without language restrictions. The primary outcome was muscle. Secondary outcomes were weight loss, weakness, malaise, or fatigue. Subgroup analyses were performed according to different definitions of muscle, treatment duration, and measurement methods. The quality of the studies was assessed using the Cochrane tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool.ResultsNineteen randomized controlled trials (RCTs) involving 1,482 participants were included. Compared with the control group, a meta-analysis showed that T2DM participants in the group treated with SGLT-2i demonstrated statistically significant reductions in lean body mass of 0.66 (95% confidence interval (CI), −1.05 to −0.27; p = 0.0009) and skeletal muscle mass of 0.35 (95% CI, −0.66 to −0.04; p = 0.03). No deaths or serious adverse events were reported. The quality of evidence in the included trials was low.ConclusionsSGLT-2i may lead to a reduction in muscle strength in the treatment of T2DM compared to the control group. However, there is still a lack of high-quality evidence to evaluate muscle atrophy caused by SGLT-2i.Systematic review registrationhttps://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.

Abstract Background Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen receptors gene. The major clinical manifestations of SBMA consist of weakness in the bulbar and limb muscles, fasciculations, tremors, cramps, sensory impairment, and gynecomastia. However, atypical SBMA cases may lead to misdiagnosis. Muscular fatigue and decremental responses to repetitive nerve stimulation (RNS), despite being observed in some SBMA patients, are usually occurred in MG patients, and patient with the symptom of mastication fatigue was rarely reported. In addition, cardiological investigations have been performed in SBMA patients and several ECG alterations were identified. Here we report an SBMA patient presenting with a rare onset symptom of mastication fatigue, who has been detected with a positive titin antibody in the serum and showed a WPW pattern electrocardiogram. Case presentation The patient showed mildly progressive fatigue in the muscles of mastication over 3 years. Neurological examination showed facial muscle weakness and a wasting tongue with fasciculations, but the weakness, wasting, or fasciculations were not obvious in the limbs. 3-Hz RNS showed a decremental response in bilateral orbicularis oculi. The test of titin antibody was positive in the serum, and the electrocardiogram showed a WPW pattern ECG. Genetic analysis revealed an increased number (39 repeats) of tandem CAG repeats in the AR gene, which confirmed the diagnosis of SBMA. The fatigue symptom was significantly improved after oral pyridostigmine bromide treatment. Conclusion This case calls for more attention to muscular fatigue as the onset symptoms of Kennedy’s disease. ECG screening is of importance in SBMA patients and further studies are needed to investigate the titin antibody in SBMA patients as well as other neurogenic disorders.

The increasing proportion of night consumption in the total daily consumption means the night economy has become an indispensable part of national economic development. However, early social science research on alcohol in the night economy and social science research on the night leisure industry dominated our understanding of the night city. Few researchers have built effective mathematical statistical models to explore the spatio-temporal distribution and regional interactions of the night economy. This paper presents a method to analyze the spatial and temporal distribution pattern of the night economy based on multi-source data. Firstly, K-Means++ and DBSCAN were used to cluster OD points to identify the gathering areas of night activities. Then, the local L-function in “flow space” was used to extract the aggregated flow of each aggregation area and analyze the regional interactions. Finally, the correlation between night activity and night service facilities was calculated by using geographic detector, and night activity and lighting were coupled by the profit and loss value. The research shows that this method can identify the main areas of night activity, dig out the interrelationships at the community level, and find the new night activity gathering points and night economic growth areas in the future. This study extends the current situation that the night economy is limited to theoretical research and research in central urban areas, provides the temporal and spatial distribution of night activities and night lighting supplies from the perspective of big data, and provides a basis for future night economy research, urban planning, and relevant policy issuance.

There are high demands for the early and reliable detection of metal components used in safety-critical structures. Nondestructive testing (NDT) is a pivotal technique used across industries to assess a material’s integrity without causing damage and has been used in early crack detection of metals, mainly based on changes in the crystal structure and magnetic properties of metals. This review provides an overview of internal and external detection technology based on nondestructive testing methods such as ultrasonic, electromagnetic, ray, magnetic particle, etc. Especially, the integration of advanced methodologies such as machine learning and artificial intelligence deserves a place in NDT methods. Furthermore, the multifactorial detection method is promoted to enhance the sensitivity and detection range due to advantage integration but still has emerging challenges for safer equipment and applications. The review aims to compare these methods and outline the future challenges of NDT technologies for metal crack detection.

Abstract As a unique two-dimensional atomic material, graphene offers excellent mechanical properties, dynamically tunable surface conductivity, ultra-high carrier mobility, and optical transparency, making it great potential for novel electromagnetic devices. However, dynamic manipulation of microwave polarization has not been experimentally realized in a graphene-assisted metasurface. In this paper, we present a general strategy for designing graphene-based active meta-device for achieving dynamic polarization control at microwave frequencies. When illuminated by a linear-polarized incident wave, the polarization angle of the reflected wave can be dynamically controlled by shifting the bias voltage applied to graphene. The simulated and measured results reveal that the proposed graphene-based meta-device offers a novel approach to the manipulation of microwave polarization and has potential applications in antenna, sensing, and communications.

Abstract Background Varicella zoster virus (VZV) can remain lifelong in the latent state in ganglionic neurons and adrenal glands after the initial infection. However, it can be reactivated anytime and can trigger several severe neurological manifestations such as encephalitis, meningitis, Ramsay-Hunt syndrome, cerebellitis, myelitis, and stroke. In addition, due to the diversity of clinical manifestations, clinical diagnosis of VZV can be difficult, especially in the absence of varicella. Here, we describe the case of a 52-year-old male who presented with symptoms of acute myelitis as well as polycranial neuritis, and was finally diagnosed with VZV infection through metagenomic next-generation sequencing (mNGS). Case presentation A 52-year-old male came to our hospital with complaint of headache, fever, weakness of right lower limb, abdominal distension, and hearing loss. T2-weighted MRI revealed a hyperintense lesion in the spinal cord extending from T8 to T11. In addition, enhanced MRI showed small patches and strips hyperintensities in both the spinal cord and meninges. Plain abdominal radiographs and abdominal computed tomography (CT) scan displayed air-fluid levels and incomplete bowel obstruction. Moreover, electrophysiological evaluation of the peripheral neuropathy in the extremities was found to be normal. Finally, by using metagenomic next-generation sequencing (mNGS) we found that the copy number of VZV DNA in cerebrospinal fluid (CSF) was significantly increased and IgG antibody against VZV in CSF was also noted to be positive. Hence, VZV infection was identified in patient’s central neuron system. Finally, after a few days of low dose steroid treatment, the patient's symptoms were found to be significantly improved. Conclusions The findings indicate that we should pay proper attention to the various symptoms caused by VZV infection due to the clinical heterogeneity, especially in the absence of cutaneous lesions.

To solve the ghosting artifacts problem in dynamic scene multi-scale exposure fusion, an improved multi-exposure fusion method has been proposed without ghosting based on the exposure fusion framework and the color dissimilarity feature of this study. This fusion method can be further applied to power system monitoring and unmanned aerial vehicle monitoring. In this study, first, an improved exposure fusion framework based on the camera response model was applied to preprocess the input image sequence. Second, the initial weight map was estimated by multiplying four weight items. In removing the ghosting weight term, an improved color dissimilarity feature was used to detect the object motion features in dynamic scenes. Finally, the improved pyramid model as adopted to retain detailed information about the poor exposure areas. Experimental results indicated that the proposed method improves the performance of images in terms of sharpness, detail processing, and ghosting artifacts removal and is superior to the five existing multi-exposure image fusion (MEF) methods in quality evaluation.

Reduced activation ferritic/martensitic (RAFM) steels are considered the main candidate material for the water-cooled ceramic breeder (WCCB) in a fusion reactor. High-energy density welding approaches, such as electron beam welding (EBW) and laser beam welding (LBW), are frequently utilized in the welding of RAFM steels. During the welding process, cracks and other defects are prone to appear. In this paper, EBW was selected for the welding of RAFM steels. Those with and without pre-heat and post-heat treatment by electron beams are studied by finite element simulation and trials. The results show that the experimental results are consistent with the simulation. In particular, in the case of similar deformation, the residual stress after electron beam heat treatment is far less than that without heat treatment. Without heat treatment, the residual stress near the weld is more than 400 MPa, while the residual stress after heat treatment is about 350 MPa. As the reduction of residual stress is essential to prevent the occurrence of cracks and other defects after welding, pre-heat and post-heat treatment by the electron beam is deemed as an effective way to greatly improve the welding quality in RAFM steel welding.

Assembled T-shaped aluminum alloy components represent a new type of structural member in aluminum alloy structures with broad application prospects. In this study, axial compression tests were carried out on 32 aluminum alloy components, considering parameters such as the cross-sectional type and slenderness ratio of the components, to obtain the ultimate bearing capacity and failure mode of the members. The test results show that, for the equilateral assembled T-shaped aluminum alloy components with obvious strong and weak axes, bending instability was most common, and local buckling of the plate occurred when the slenderness ratio of the component was relatively small. For the unequal T-shaped aluminum alloy structures without an obvious strong or weak axis, torsional buckling instability occurred, accompanied by local deformation of the connecting limbs due to mutual compression. A verified finite element model was also established. Based on this model, a parametric analysis was conducted to study the influence of parameters such as initial defects, slenderness ratio, and cross-sectional type on the axial compressive bearing capacity of the assembled T-shaped aluminum alloy components. The experimental and numerical results were then compared with Chinese and European standards, revealing that the standard calculation methods tend to be unsafe. Finally, the calculation parameters for component defects in Chinese and European standards were revised.

Steroid 5α-reductase 2 (SRD5A2), a testosterone metabolism enzyme, is implicated in human disease. Structural and biochemical analyses of PbSRD5A, a bacterial homolog, reveal SRD5A2 substrate binding pocket and provide framework for the design of new drugs targeting this enzyme.

Introduction: Propionic acidemia is an autosomal recessive metabolic disorder and the patients with adult onset are very rare.Methods: Two PCCB mutations were identified. Clinical data were collected from a patient, and metabolic screening and clinical exome sequencing analysis were performed.Results: Two novel mutations were identified in the PCCB gene: M1:c.404_406del:p.G135del and M2:c.632C>T:p.T211I.Conclusion: Late-onset propionic acidemia should be taken into account, and metabolic screening as well as gene analysis should be performed to make a definite diagnosis timely.

Oscillating electron beam welding (EBW) is necessary for the fabrication of pure niobium superconducting radiofrequency (SRF) cavities. Due to the negative effects that welding deformation and residual stress have on the performance of the SRF cavities, it is crucial to predict residual stress and welding distortion with high precision for the design of welding tooling and the optimization of welding parameters. However, the stress and distortion simulation of oscillating EBW received little attention in the previous research. In order to accurately predict the welding stress and distortion of niobium cavities with thin walls, a novel heat source with two reverse 2D Gaussian heat sources was used for the first time in the finite element method (FEM) simulation of EBW with beam oscillation. Additionally, a computational fluid dynamics (CFD) simulation of the molten pool was run as a guide for adjusting the parameters of the designed heat source. The FEM simulation with 2D Gaussian heat source was taken as a comparison. An EBW experiment of niobium sheets was performed to verify the simulation. The simulated molten pool of this model has a wider width, which is significantly closer to the actual measurement. Compared with the result estimated by 2D Gaussian heat source. The joint simulated with the designed heat source displays a smoother temperature gradient. The mechanical results suggest that the peak longitudinal stress in the weld center, the peak transverse stress in the weld center, the longitudinal contradiction, and the transverse contradiction estimated by the designed model deviate from the experimental results by only −4.88%, −4.03%, −9.32%, and −5.98%, respectively. The error of the simulation by the proposed method is dramatically smaller than the evaluation by the 2D Gaussian model. The designed heat source and the CFD validation provides a reliable simulation scheme for the oscillating EBW of thin sheets, and the oscillating EBW of thick plates will be simulated using the suggested method with the improvement of the heat source model in the future.

Avian pathogenic Escherichia coli (APEC) is one of the common extraintestinal infectious disease pathogens in chickens, geese, and other birds. It can cause a variety of infections, and even the death of poultry, causing enormous economic losses. However, the misuse and abuse of antibiotics in the poultry industry have led to the development of drug resistance in the gut microbes, posing a challenge for the treatment of APEC infections. It has been reported that the CpxRA two-component system has an effect on bacterial drug resistance, but the specific regulatory mechanism remains unclear. In this study, the regulatory mechanism of CpxRA on APEC biofilm formation and EmrKY efflux pump was investigated. The cpxRA knockout strain of E. coli APEC40 was constructed, and the molecular regulatory mechanism of CpxR on biofilms and efflux pump-coding genes were identified by biofilm formation assays, drug susceptibility test, real-time reverse transcription quantitative PCR, and electrophoretic mobility shift assay (EMSA). The results indicated that CpxR can directly bind to the promoter region of emrKY and negatively regulate the sensitivity of bacteria to ofloxacin and erythromycin. These results confirm the important regulatory role of the CpxRA two-component system under antibiotic stress in APEC.

Secret sharing is an advanced encryption method that distributes the secret information into multiple participants and only the predesigned subsets of authorized participants can recover the secret by gathering their independent subinformation. Herein, the security level of secret sharing using electromagnetic manners is further expanded and a simple platform for the realization and direct observation of secret sharing encryption using metasurface hologram is presented. As a proof of concept, a polarization‐assisted secret sharing phase encoding method by integrating visual secret sharing scheme with phase encoding technology using orthogonally polarization‐multiplexing metasurface is experimentally presented. The method achieves its encryption security and decryption simplicity by hiding the secret information into a pair of orthogonal polarization channels ensuring that the secret information is direct decryption as the two channels participate simultaneously while fully concealed in single channel. This scheme may pave a new route for future information encryption, hiding, and authentication.

As the most prevalent epi-transcriptional modification, m6A modifications play essential roles in regulating RNA fate. The molecular functions of YTH521-B homology (YTH) domain proteins, the most known READER proteins of m6A modifications, have been well-studied in animals. Although plants contain more YTH domain proteins than other eukaryotes, little is known about their biological importance. In dicot species Arabidopsis thaliana, the YTHDFA clade members ECT2/3/4 and CPSF30-L are well-studied and important for cell proliferation, plant organogenesis, and nitrate transport. More emphasis is needed on the biological functions of plant YTH proteins, especially monocot YTHs. Here we presented a detailed phylogenetic relationship of eukaryotic YTH proteins and clustered plant YTHDFC clade into three subclades. To determine the importance of monocot YTH proteins, YTH knockout mutants and RNAi-induced knockdown plants were constructed and used for phenotyping, transcriptomic analysis, and stress treatments. Knocking out or knocking down OsYTHs led to the downregulation of multicellular organismal regulation genes and resulted in growth defects. In addition, loss-of-function ythdfa mutants led to better salinity tolerance whereas ythdfc mutants were more sensitive to abiotic stress. Overall, our study establishes the functional relevance of rice YTH genes in plant growth regulation and stress response.

The electron beam welding of the tubes and the half-cells for our 1.3 GHz single-cell superconducting radiofrequency (SRF) cavities is complex due to the different thicknesses of the tubes and the half-cells in the iris region. However, the mechanical properties and microstructure of the iris welds in niobium SRF cavities have barely been explored in previous studies. For high-quality iris welds, welding experiments of niobium sheets of 2 mm and 2.8 mm were carried out under different oscillating conditions. The results show that welding with no oscillation or sinusoidal oscillation may not be applied in actual welding owing to the large misalignment of the bottom surface. The weld grains were not significantly refined through beam oscillation. The joints with infinity oscillation had a higher elongation than circular oscillation, which exhibited a brittle fracture in the tensile tests at 77 K. Nevertheless, the texture of the weld with infinity oscillation implies poor formability, so the feasibility of infinity oscillation in actual welding needs verification in future study.

The water-cooled ceramic breeder (WCCB) blanket is a component of the China Fusion Engineering Test Reactor (CFETR). The Reduced Activation Ferrite/Martensite (RAFM) steels are the preferred structural materials for WCCB blanket. As a kind of RAFM steels, China low activation martensitic (CLAM) steel was welded by electron beam welding (EBW), and then quenched-tempered treatment was carried out. The results show that at the welding state, the welding seam was composed of large martensite and δ ferrite and the organization of the heat-affected zone (HAZ) was changed slightly with the different heat input. Moreover, the hardness of welded joints was higher than that of base material (BM), but the impact toughness was very low. After quenched-tempered treatment, the δ ferrite in the weld was eliminated, the residual stress of the test plate decreased as a whole, and the mechanical properties were improved significantly.

Amyotrophic lateral sclerosis (ALS) is a disease of which the underlying etiology and pathogenesis are unknown. Numerous data indicate an important role of the immune system and mitochondrial function in the disease. Primary biliary cirrhosis (PBC) is an autoimmune liver disease resulting from a combination of genetic and environmental risk factors. Patients with PBC develop innate and adaptive immune reactions against mitochondrial antigens. Therefore, common mechanisms could exist in both diseases. We present two cases of ALS with PBC to explore the relationship between the two diseases from the immunological and mitochondrial aspects. Further attention should be given to immune-modulating therapy in ALS patients.

Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.

The modulation recognition technology for acoustic signals holds significant research importance in signal demodulation and communication signal reconnaissance, serving as a crucial component and key aspect. This paper investigates the modulation recognition technology for acoustic signals (< 20 kHz) from the perspectives of signal preprocessing and feature extraction. Firstly, it selects seven modulation signals 2ASK, 4ASK, 2FSK, 4FSK, 2PSK, 4PSK, and OFDM as recognition targets and systematically compares the effectiveness of four different endpoint detection algorithms in modulation signal recognition. To further enhance the performance of the short-time energy entropy ratio algorithm, this study introduces three different noise reduction algorithms for optimization. Finally, to accurately identify and distinguish between 2 and 4FSK signals, this study optimizes the related algorithms of the cyclic spectrum by using the kurtosis coefficient value Kur of the cyclic spectrum parameter matrix when the cyclic frequency α = 0 to differentiate between these two signals. The results show that at SNR of 4 dB, the proposed modulation recognition algorithm can effectively distinguish between these two signals, achieving a recognition accuracy of over 99%., (© 2024. The Author(s).)

Objective: This study aimed to investigate whether the spread pattern affects functional staging in amyotrophic lateral sclerosis (ALS). We examined the spreading patterns of disease following symptom onset and the affected regions in ALS using electromyography. Methods: This study reviewed the medical records of 103 patients with sporadic ALS in the Second Hospital of Hebei Medical University from 2012 to 2017. According to the clinical manifestation and the distribution of the affected regions on electromyography, spread patterns were classified as discontiguous or contiguous. The patients were graded according to the ALS-Milano-Torino staging (MITOS) system. Results: The clinical spread patterns were contiguous in 91.5% of patients and discontiguous in 8.5% of patients. The electrophysiological spread patterns were contiguous in 87.4% of patients and discontiguous in 12.6% of patients. Sex, age, or delay in diagnosis did not affect the clinical or electrophysiological spread patterns. No significant correlation was observed between the clinical classification and the ALS-MITOS grade, but the electrophysiological spread was significantly correlated with the ALS-MITOS. Conclusion: This study provides evidence that not all ALS patients show contiguous clinical or electrophysiological spread patterns. The electrophysiological spread pattern can affect the functional staging in ALS patients.