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Abstract The sand cat swarm optimization (SCSO) is a recently proposed meta-heuristic algorithm. It inspires hunting behavior with sand cats based on hearing ability. However, in the later stage of SCSO, it is easy to fall into local optimality and cannot find a better position. In order to improve the search ability of SCSO and avoid falling into local optimal, an improved algorithm is proposed - Improved sand cat swarm optimization based on lens opposition-based learning and sparrow search algorithm (LSSCSO). A dynamic spiral search is introduced in the exploitation stage to make the algorithm search for better positions in the search space and improve the convergence accuracy of the algorithm. The lens opposition-based learning and the sparrow search algorithm are introduced in the later stages of the algorithm to make the algorithm jump out of the local optimum and improve the global search capability of the algorithm. To verify the effectiveness of LSSCSO in solving global optimization problems, CEC2005 and CEC2022 test functions are used to test the optimization performance of LSSCSO in different dimensions. The data results, convergence curve and Wilcoxon rank sum test are analyzed, and the results show that it has a strong optimization ability and can reach the optimal in most cases. Finally, LSSCSO is used to verify the effectiveness of the algorithm in solving engineering optimization problems.

In this study, a novel localized selective remelting technique was proposed to treat the welding interface regions on the top and bottom surfaces of the AZ31 friction stir welded joint. Compared with the untreated joint, the treated joint achieved a favorable combination of strength (ultimate tensile strength of 238 MPa) and ductility (elongation of 13.3%). Digital image correlation (DIC) characterization revealed that the high strain-hardening ability primarily stemmed from the substantial mitigation of strain localization, which was caused by a comprehensive factor, including reduced SF value fluctuation between weld micro-zones, low residual dislocation density, and numerous extension twinning activation in the nugget zone.

In this work, we report a counter-intuitive activation of abnormal grain growth (AGG) in randomly-oriented fine grains (FGs) in an L-PBF Al–Mg–Sc–Zr alloy, which is unlikely from perspectives of curvature-driven grain growth, crystallographic texture or strain-induced boundary migration. The observed spontaneous AGG is understood in light of the growth instability of an arbitrary grain in an evolving particle-pinned polycrystalline aggregation. A generalized criterion for AGG is hence proposed, which efficaciously explains the observed susceptibility of FGs to AGG, the presence of multiple AGG activation sites, and the asynchrony of AGG activation.

Abstract Underground wastewater treatment plants (U-WWTPs) have emerged as a novel paradigm for urban wastewater pollutants management, offering benefits such as alleviating the Not-in-my-backyard (NIMBY) effect and utilizing land resources efficiently. China stands at the forefront, witnessing swift advancements in U-WWTP technology and deployment. However, the absence of a thorough understanding of their geographical distribution and operational characteristics could lead to misaligned planning and construction, resulting in inefficient resource allocation and treatment capacities for urban wastewater treatment. This dataset provides an up-to-date overview of the spatial distribution, process selection, and discharge standards for all U-WWTPs in China (with a total number of 201) constructed since 1995. To enhance comparative analysis, the dataset has been supplemented with information on conventional aboveground wastewater treatment plants (A-WWTPs), comprising a total of 2464 records, which enriches a more comprehensive evaluation of different wastewater treatment approaches. Utilizing this dataset can provide essential data support for the strategic management of urban wastewater systems and serve as a valuable reference for the paradigmatic renovation of existing wastewater treatment plants.

Abstract T-cell therapies based on chimeric antigen receptor (CAR) targeting of a tumor-specific antigen offer hope for patients with relapsed or refractory cancers. CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage leukemia/lymphoma. By using nuclear Overhauser effect spectroscopy (NOESY), which detects even transiently occupied structural motifs, we observed otherwise elusive local structural elements amidst overall disorder in CD28H, including a conformational switch from a native β-strand to a 310-helix and polyproline II helix-like structure. These local structural motifs contribute to an overall loosely formed extended geometry that could be captured by NOESY data. All FDA-approved CARs use prolines in the hinge region, which we find in CD28, and previously in CD8α, isomerize to promote structural plasticity and dynamics. These local structural elements may function in recognition and signaling events and constrain the spacing between the transmembrane and antigen recognition domains. Our study thus demonstrates a method for detecting local and transient structure within intrinsically disordered systems and moreover, our CD28H findings may inform future CAR design.

Abstract. Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Frictional sliding creates distinct microstructural and chemical discontinuities between the subsurface layer and base materials, which dictate the friction and wear properties. Traditional methods for lowering friction and wear in metals primarily rely on strategies that lower the interfacial shear strength between the contacting discontinuities. Contrary to conventional wisdom, we propose an alternative strategy: introducing tribo-induced or pre-designed heterostructures to suppress tribo-induced strain localization, thus yielding superior tribological properties unachievable with their conventional homogeneous counterparts. Citing recent experimental examples, this review explores the multiscale heterogeneities contributing low friction and wear, by interlinking surface deformation mechanisms and applied tribological conditions.

Abstract Background Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson’s disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation. Methods We introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023. Results QSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples. Conclusion We introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) in vitro and in vivo, as well as in atherosclerotic patients’ arteries. Mechanistically, the histone chaperone ASF1A was first identified as a cofactor of P300, which precisely regulated the enrichment of H3K18la at the promoter of SNAI1, thereby activating SNAI1 transcription and promoting EndMT. We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction. Functional analysis based on ApoeKOAsf1aECKO mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endothelium-specific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development. Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la, SNAI1 transcription, and EndMT-induced atherosclerosis. This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis, which provides emerging therapies for atherosclerosis.

This study aimed to investigate the effects of curcumin on the expression of antioxidation-related genes in the liver and jejunum and caecum microorganisms of rabbits. A total of 160 IRA rabbits with similar body weight were randomised assigned to 4 groups. The control group received a basal diet, while the experimental groups were given diets supplemented with 50, 100, and 150 g/t curcumin, respectively. The pre-test period spanned 7 days, followed by a 21-day test period. Results revealed a significant upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) mRNA in the liver and jejunum due to curcumin (p

In recent years, a new class of metallic materials featuring heterogeneous structures has emerged. These materials consist of distinct soft and hard domains with significant differences in mechanical properties, allowing them to maintain high strength while offering superior ductility. Magnesium (Mg) alloys, renowned for their low density, high specific strength, exceptional vibration damping, and electromagnetic shielding properties, exhibit tremendous potential as lightweight and functional materials. Despite their advantageous properties, high-strength Mg alloys often suffer from limited ductility. However, the emergence of heterogeneous materials provides a fresh perspective for the development of Mg alloys with both high strength and ductility. This article provided a fundamental overview of heterostructured materials and systematically reviewed the recent research progress in the design of Mg alloys with strength-ductility balance based on heterostructure principles. The review encompassed various aspects, including preparation methods, formation mechanisms of diverse heterostructures, and mechanical properties, both within domestic and international contexts. On this basis, the article discussed the challenges encountered in the design and fabrication of heterostructured Mg alloys, as well as the urgent issues that require attention and resolution in the future.

Abstract Staircases are a frequently encountered obstacle in daily life, requiring individuals to navigate ascending and descending movements that place additional demands on the trunk and lower limbs compared to walking on level surfaces. Therefore, it is crucial to examine the biomechanical characteristics of the trunk and lower limbs in individuals with scoliosis during stair activity. The aim of this study was to investigate the biomechanical differences in trunk and lower limbs during daily stair activities between patients with scoliosis and a healthy population. Additionally, the study aimed to explore the relationship between trunk abnormalities and lower limb biomechanics, providing a clinical and objective assessment basis for scoliosis. The Qualisys system, based in Gothenburg, Sweden, was employed for data collection in this study, with a sampling frequency of 150 Hz. It captured the kinematics of the trunk and lower limbs, as well as the kinetics of the lower limbs during stair ascent and descent for both the 28 individuals with scoliosis and the 28 control participants. The results indicate that scoliosis patients demonstrated significantly higher asymmetry compared to the control group in various measures during ascent and decent. These include different parts of kinematics and kinetics. Scoliosis patients demonstrate noticeable variations in their movement patterns compared to the healthy population when engaging in stair activities. Specifically, during stair ascent, scoliosis patients exhibit a seemingly more rigid movement pattern, whereas descent is characterized by an unstable pattern.

Based on a critical examination of type specimens, images of living plants, and the literature has shown Rhododendron oligocarpum to be conspecific with R. leishanicum. Although slight variations in corolla colour exist amongst different populations of R. oligocarpum, it does not serve as a key distinguishing trait. Therefore, we reduced R. oligocarpum to a synonym of R. leishanicum, and recommend placing it in Subsection Maculifera.

Abstract The role of circDHX8 in the interplay between autophagy and gastric cancer (GC) progression remains unclear. In this study, we investigated the mechanism underlying the role of hsa_circ_003899 (circDHX8) in the malignancy of GC. Differential expression of circRNAs between GC and normal tissues was determined using circle-seq and microarray datasets (GSE83521). These circRNAs were validated using qPCR and Sanger sequencing. The function of circDHX8 was investigated through interference with circDHX8 expression experiments using in vitro and in vivo functional assays. Western blotting, immunofluorescence, and transmission electron microscopy were used to establish whether circDHX8 promoted autophagy in GC cells. To elucidate the mechanism underlying the circDHX8-mediated regulation of autophagy, we performed bioinformatics analysis, RNA pull-down, mass spectrometry (MS), RNA immunoprecipitation (RIP), and other western Blot related experiments. Hsa_circ_0003899 (circDHX8) was identified as upregulated and shown to enhance the malignant progression in GC cells by promoting cellular autophagy. Mechanistically, circDHX8 increased ATG2B protein levels by preventing ubiquitin-mediated degradation, thereby facilitating cell proliferation and invasion in GC. Additionally, circDHX8 directly interacts with the E3 ubiquitin-protein ligase RNF5, inhibiting the RNF5-mediated degradation of ATG2B. Concurrently, ATG2B, an acetylated protein, is subjected to SIRT1-mediated deacetylation, enhancing its binding to RNF5. Consequently, we established a novel mechanism for the role of circDHX8 in the malignant progression of GC.

Gas therapy is currently popular in cancer treatment because of its controllability, effectiveness, and biosafety, as well as the fast development of carriers for gas delivery. Here, we introduce the various gas molecules with exact anticancer effects, including nitric oxide (NO), carbon monoxide (CO), oxygen (O2), hydrogen (H2), etc., and their anticancer mechanisms. Besides, recent advances in stimuli-responsive delivery systems for gas therapy are summarized. In terms of the various stimulation methods, the design of delivery systems for gases is introduced. In addition, the strategies of gas therapy combined with other therapeutic modalities, including chemotherapy, radiotherapy (RT), photodynamic therapy (PDT), photothermal therapy (PTT), etc., are described. Finally, the current challenges and prospects of delivery platforms for gases, and the future development and clinical translational value of gas therapy are also discussed.

Currently, a gap in understanding the mechanism of interlayer explosives exists. This study systematically investigated this mechanism using TP 270C/SUS 821L1 to fill this knowledge gap. By comparing the outcomes of direct and interlayer welding through methods such as optical microscope (OM), computed tomography (CT), electron probe micro-analysis (EPMA), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), nanoindentation, and tensile shear test, it was found that an interlayer can significantly lessen the energy at the target interface. This was further evident when comparing welds with varying interlayer thicknesses, showing that thinner interlayers lead to less energy transfer between the flying plate and the interlayers. Notably, at an interlayer thickness of 0.1 mm, the welding interface appeared irregular. The smoothed particle hydrodynamics (SPH) method was employed to simulate the welding, highlighting the interlayer's impact on factors like pressure, jet, temperature, and melting. This simulation also explained why the 0.1 mm interlayer had an irregular interface due to jetting affecting the welding between the flyer plate and interlayer. The study also analyzed the weldability window in interlayer explosive welding, noting how the interlayer influenced its upper and lower limits. The relation between interlayer thickness and the constant k in the lower limit was examined, along with the minimum velocity needed for the flyer plate to generate a jet VP. Their relationship satisfied exponential functions in the detonation velocity range of 1800–3000 m/s. This study thus established a link between traditional and interlayer explosive welding.

Abstract Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.

Abstract Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn .

Abstract Stabilization of topological spin textures in layered magnets has the potential to drive the development of advanced low-dimensional spintronics devices. However, achieving reliable and flexible manipulation of the topological spin textures beyond skyrmion in a two-dimensional magnet system remains challenging. Here, we demonstrate the introduction of magnetic iron atoms between the van der Waals gap of a layered magnet, Fe3GaTe2, to modify local anisotropic magnetic interactions. Consequently, we present direct observations of the order-disorder skyrmion lattices transition. In addition, non-trivial topological solitons, such as skyrmioniums and skyrmion bags, are realized at room temperature. Our work highlights the influence of random spin control of non-trivial topological spin textures.

Abstract The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body’s immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.

Confocal microscopy has evolved to be a widely adopted imaging technique in molecular biology and is frequently utilized to achieve accurate subcellular localization of proteins. Applying colocalization analysis on image z-stacks obtained from confocal fluorescence microscopes is a dependable method of revealing the relationship between different molecules. In addition, despite the established advantages and growing adoption of 3D visualization software in various microscopy research domains, there have been few systems that can support colocalization analysis within a user-specified region of interest (ROI). In this context, several broadly employed biological image visualization platforms are meticulously explored in this study to understand the current landscape. It has been observed that while these applications can generate three-dimensional (3D) reconstructions for z-stacks, and in some cases transfer them into an immersive virtual reality (VR) scene, there is still little support for performing quantitative colocalization analysis on such images based on a user-defined ROI and thresholding levels. To address these issues, an extension called ColocZStats (pronounced Coloc-Zee-Stats) has been developed for 3D Slicer, a widely used free and open-source software package for image analysis and scientific visualization. With a custom-designed user-friendly interface, ColocZStats allows investigators to conduct intensity thresholding and ROI selection on imported 3D image stacks. It can deliver several essential colocalization metrics for structures of interest and produce reports in the form of diagrams and spreadsheets.

BackgroundClinical observations indicate that blood lipids may be risk factors for lateral epicondylitis (LE) of the humerus, and lipid-lowering drugs are also used for the prevention and treatment of tendon diseases, but these lack high-quality clinical trial evidence and remain inconclusive. Mendelian randomization (MR) analyses can overcome biases in traditional observational studies and offer more accurate inference of causal relationships. Therefore, we employed this approach to investigate whether blood lipids are risk factors for LE and if lipid-lowering drugs can prevent it.MethodsGenetic variations associated with lipid traits, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), were obtained from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in LE were sourced from FinnGen, including 24,061 patients and 275,212 controls. Subsequently, MR analyses were conducted to assess the potential correlation between lipid traits and LE. Additionally, drug-target Mendelian randomization analyses were performed on 10 drug targets relevant to LE. For those drug targets that yielded significant results, further analysis was conducted using colocalization techniques.ResultsNo correlation was found between three blood lipid traits and LE. Lipoprotein lipase (LPL) enhancement is significantly associated with a decreased risk of LE (OR = 0.76, [95% CI, 0.65–0.90], p = 0.001). The expression of LPL in the blood is associated with LE and shares a single causal variant (12.07%), greatly exceeding the probability of different causal variations (1.93%), with a colocalization probability of 86.2%.ConclusionThe three lipid traits are not risk factors for lateral epicondylitis. LPL is a potential drug target for the prevention and treatment of LE.

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions in vitro, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6−/− and TNF-α−/− mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts in vitro. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6−/− mice, significantly enhanced osteoclast differentiation in vitro. In contrast, supernatants from TNF-α−/− mice did not significantly affect osteoblast or osteoclast differentiation in vitro. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of TNF-α and IL-6 genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.

Abstract Carrier dynamics detection in different dimensions (space, time, and energy) with high resolutions plays a pivotal role in the development of modern semiconductor devices, especially in low‐dimensional, high‐speed, and ultrasensitive devices. Here, a femtosecond electron‐based versatile microscopy is reported that combines scanning ultrafast electron microscopy (SUEM) imaging and time‐resolved cathodoluminescence (TRCL) detection, which allows for visualizing and decoupling different dynamic processes of carriers involved in surface and bulk in semiconductors with unprecedented spatiotemporal and energetic resolutions. The achieved spatial resolution is better than 10 nm, and the temporal resolutions for SUEM imaging and TRCL detection are ≈500 fs and ≈4.5 ps, respectively, representing state‐of‐the‐art performance. To demonstrate its unique capability, the surface and bulk carrier dynamics involved in n‐type gallium arsenide (GaAs) are directly tracked and distinguished. It is revealed, in real time and space, that hot carrier cooling, defect trapping, and interband‐/defect‐assisted radiative recombination in the energy domain result in ordinal super‐diffusion, localization, and sub‐diffusion of carriers at the surface, elucidating the crucial role of surface states on carrier dynamics. The study not only gives a comprehensive physical picture of carrier dynamics in GaAs, but also provides a powerful platform for exploring complex carrier dynamics in semiconductors for promoting their device performance.

Abstract Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin‐specific protease 22 (USP22) as a pro‐oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin‐specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial–mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration‐approved drug library screening and identified topotecan as a clinically applicable USP22‐targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3‐induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22‐targeting drug to limit melanoma metastasis.

IntroductionGut microbiota are associated with the health and performance of ruminant species, and they are affected by altitude, host genetics, and sex. However, there has been little research on comparing the fecal microbiota of indigenous small ruminants such as sheep and goats in Guizhou province, China. In the present study, we revealed the effect of altitude, genetics, and sex on fecal microbiota profiles and enterotypes in indigenous small ruminants of Guizhou province, China.MethodsFecal samples were collected from Hei and Qianbei Ma goats and Weining sheep in the Chinese province of Guizhou. 16S rRNA gene sequencing targeting the V3–V4 region was performed using the Illumina MiSeq platform. Sequences were processed using QIIME2, and the qualified sequences were processed using the plugin DADA2 to generate amplicon sequence variants (ASVs). The statistical analysis was performed using R studio.ResultsThe fecal microbial profile was found to vary by herd (influenced by genetics/altitude) and sex. All samples were categorized into two enterotypes. The first enterotype is dominated by UCG-005, and the second enterotype is dominated by the Christensenellaceae_R-7_group, which may be highly driven by the host's genetics (breed). The predicted functional profiles of the fecal microbiota were also assigned to two clusters that corresponded exactly to the enterotypes. Cluster 1 of the functional profiling was characterized by biosynthesis pathways, and cluster 2 was characterized by energy metabolism pathways.DiscussionOur findings may provide new insights into the fecal microbial community and enterotypes in small ruminants by herds, offering clues for understanding the mechanisms by which the fecal microbiota contribute to divergent host phenotypes in indigenous small ruminants in Guizhou.

Objectives: This meta-analysis aims to synthesize the available data on the effectiveness of hamstring stretching exercises in relieving pain intensity and improving function for patients with low back pain. Methods: Google Scholars, PubMed, Embase, Cochrane, MEDLINE, CNKI, Wanfang, and VIP were searched from inception to August 2023. We included randomized controlled trials that investigated the effectiveness of hamstring stretching exercises in patients with low back pain. The primary outcomes assessed were pain intensity, hamstring muscle flexibility, and function. Study selection, data extraction, and assessment of risk of bias were performed independently by two reviewers. Results: Our searches retrieved 344 trials, of which 14 met the inclusion criteria for this review ( n = 735 participants). The combined meta-analysis showed hamstring stretching resulted in lower pain scores (standardized mean difference = −0.72, 95% confidence interval: −1.35 to −0.09; I 2 = 89%, p = 0.03) in different categories of low back pain. Subgroup analysis showed that hamstring stretching led to a larger range of motion for cases of back pain with radiating pain (standardized mean difference = 2.39, 95% confidence interval: 1.76 to 3.02; I 2 = 0%, p

IntroductionInherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs.MethodsSingle-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell–cell communication analysis, and trajectory inference analysis.ResultsThe cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs.ConclusionWe identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

ObjectiveFructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inborn error due to mutations in the FBP1 gene. The genetic spectrum of FBP1D in China is unknown, also nonspecific manifestations confuse disease diagnosis. We systematically estimated the FBP1D prevalence in Chinese and explored genotype-phenotype association.MethodsWe collected 101 FBP1 variants from our cohort and public resources, and manually curated pathogenicity of these variants. Ninety-seven pathogenic or likely pathogenic variants were used in our cohort to estimate Chinese FBP1D prevalence by three methods: 1) carrier frequency, 2) permutation and combination, 3) Bayesian framework. Allele frequencies (AFs) of these variants in our cohort, China Metabolic Analytics Project (ChinaMAP) and gnomAD were compared to reveal the different hotspots in Chinese and other populations. Clinical and genetic information of 122 FBP1D patients from our cohort and published literature were collected to analyze the genotype-phenotypes association. Phenotypes of 68 hereditary fructose intolerance (HFI) patients from our previous study were used to compare the phenotypic differences between these two fructose metabolism diseases.ResultsThe estimated Chinese FBP1D prevalence was 1/1,310,034. In the Chinese population, c.490G>A and c.355G>A had significantly higher AFs than in the non-Finland European population, and c.841G>A had significantly lower AF value than in the South Asian population (all p values < 0.05). The genotype-phenotype association analyses showed that patients carrying homozygous c.841G>A were more likely to present increased urinary glycerol, carrying two CNVs (especially homozygous exon1 deletion) were often with hepatic steatosis, carrying compound heterozygous variants were usually with lethargy, and carrying homozygous variants were usually with ketosis and hepatic steatosis (all p values < 0.05). By comparing to phenotypes of HFI patients, FBP1D patients were more likely to present hypoglycemia, metabolic acidosis, and seizures (all p-value < 0.05).ConclusionThe prevalence of FBP1D in the Chinese population is extremely low. Genetic sequencing could effectively help to diagnose FBP1D.

Objective This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy.Design Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models.Results In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system.Conclusions The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

The hot-mix epoxy resin commonly used in the market has insufficient toughness, resulting in cracking of steel bridge deck pavement. To obtain the excellent toughness of hot mix epoxy resin, the collaborative toughen is put forward to overcome the shortcoming. In order to character epoxy resins and epoxy asphalts affected by toughening agent, standard test method of tensile properties for plastics is used. The synergistic toughening mechanism and lyotropy of 1# rubber additive and 2# rubber additive are approved by analyzing scanning electron microscope. Synchronous thermal analyzer is applied to study reactivity of epoxy resin. The viscosity, reactivity and rheological performance of epoxy asphalt, which affected by toughen agent, are investigated by Brinell rotary viscometer and Dynamic shear rheometer respectively. According to the results, the excellent epoxy resin is obtained, when the dosage of toughen agent is 15 %. The activation energy of epoxy resin before and after toughen are 48.6 KJ/mol and 42.4 KJ/mol, respectively. Besides the toughen agent can reduce the viscosity of epoxy asphalt. Finally, R1 and R2 can enhance the elastic of epoxy asphalt and reduce the glass transition temperature of epoxy asphalt. In summary, with R1 and R2 added, the toughen of epoxy resin improved obviously. The application of toughened epoxy resin to the pavement of orthotropic steel bridge deck will has a very broad prospect.

As an emerging technology relevant to materials science, 3D printing technology simplifies material production process, shortens the preparation cycle, and provides a broader space for disease treatment. This review introduces the latest development in 3D printing, the goal is showing summary of the preparation and the utilization of this technology. We first describe the familiar biological ink for 3d printing. Then, we focus on different applications, including drug delivery, tumor modeling, and organ printing. Later, we described the application of this technology in some disciplines, including neurosurgery, gastrointestinal surgery, and orthopedics. Finally, the recent challenges and prospects of 3D printing are presented.

Abstract Non-volatile phase-change memory devices utilize local heating to toggle between crystalline and amorphous states with distinct electrical properties. Expanding on this kind of switching to two topologically distinct phases requires controlled non-volatile switching between two crystalline phases with distinct symmetries. Here, we report the observation of reversible and non-volatile switching between two stable and closely related crystal structures, with remarkably distinct electronic structures, in the near-room-temperature van der Waals ferromagnet Fe5−δ GeTe2. We show that the switching is enabled by the ordering and disordering of Fe site vacancies that results in distinct crystalline symmetries of the two phases, which can be controlled by a thermal annealing and quenching method. The two phases are distinguished by the presence of topological nodal lines due to the preserved global inversion symmetry in the site-disordered phase, flat bands resulting from quantum destructive interference on a bipartite lattice, and broken inversion symmetry in the site-ordered phase.

Abstract Background With long-term research on the reproductive ability of Qianbei Ma goat, we found that the puberty of the male goats comes at the age of 3 months and reaches sexual maturity at 4 months,the male goats are identified as physically mature at 9 months and able to mate. Compared with other kinds of breeds of goats, Qianbei Ma goat is featured with more faster growth and earlier sexual maturity.Therefore, in order to explore the laws of growth of Qianbei Ma goat before sexual maturity(3-month-old)and after sexual maturity (9-month-old). The testicular tissue was collected to explore their changes in morphology through HE staining, the serum was collected to detect the hormone content, and the mRNA expression profile of the testis was analyzed by transcriptomics. In this way, the effect of testicular development on the reproduction of Qianbei ma goats was further analyzed. Results The results showed that the area and diameter of spermatogenic tubules were larger at 9 months than 3 months, and the number of spermatocytes, interstitial cells, spermatogonia and secondary spermatocytes in the lumen of the tubules showed a similar trend. The appearance of spermatozoa at age 3 months indicated that puberty had begun in Qianbei Ma goats. The Elasa test for testosterone, luteinizing hormone, follicle stimulating hormone and anti-Müllerian hormone showed that the levels of these hormones in the serum at age 9 months were all highly significantly different than those at age 3 months (P 1 and p value

Abstract Background The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. Results Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P

Abstract Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation of iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in the biological processes of tumors. Intriguingly, mesenchymal and dedifferentiated cancer cells, which are usually resistant to apoptosis and traditional therapies, are exquisitely vulnerable to ferroptosis, further underscoring its potential as a treatment approach for cancers, especially for refractory cancers. However, the impact of ferroptosis on cancer extends beyond its direct cytotoxic effect on tumor cells. Ferroptosis induction not only inhibits cancer but also promotes cancer development due to its potential negative impact on anticancer immunity. Thus, a comprehensive understanding of the role of ferroptosis in cancer is crucial for the successful translation of ferroptosis therapy from the laboratory to clinical applications. In this review, we provide an overview of the recent advancements in understanding ferroptosis in cancer, covering molecular mechanisms, biological functions, regulatory pathways, and interactions with the tumor microenvironment. We also summarize the potential applications of ferroptosis induction in immunotherapy, radiotherapy, and systemic therapy, as well as ferroptosis inhibition for cancer treatment in various conditions. We finally discuss ferroptosis markers, the current challenges and future directions of ferroptosis in the treatment of cancer.

Abstract The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p

Global climate change leads to frequent occurrence of low-temperature stress (LTS), which poses a serious threat to global food security. Here, environment-control phytotron experiments were conducted on cold-responsive cv. XM26 and cold-tolerant cv. YN19 during the anther differentiation period. Six LTS levels (4, 2, 0, -2, -4, -6 °C) and a control treatment (10 °C) were set to study the effects of different levels of LTS on wheat seed-setting characteristics and yield. LTS significantly decreased grain number per spike, 1 000-grain weight, and grain yield per plant (GYPP) of the two wheat cultivars. Each spike's grain number and weight distribution showed a quadratic curve, and the near-medium dominance of grain development was not affected by temperature. The grain number percentage and grain weight of wheat at different grain positions were G2 (2nd grain position) ≥ G1 (1st grain position) > G3 (3rd grain position) > G4 (4th grain position), in which G3 and G4 grain positions were more sensitive to LTS. In summary, LTS during the anther differentiation in wheat mainly led to a decrease in GYPP by significantly reducing the number and weight of inferior grains. Improving wheat cultivation measures and promoting the development of inferior grains are significant ways to prevent disasters and increase wheat quality and productivity in the future.

The safety of aviation platforms has always been a major concern in the design of aviation vehicles. Airborne high-speed maneuvering targets are currently the most significant threat to all types of aviation platforms due to their high flexibility and anti-jamming capability. This paper presents a new technology of airborne flexible net for high-speed maneuvering target capture. The analysis of flexible net dynamics in this paper includes two aspects: net-expansion dynamics and capture collision dynamics. To solve the technical difficulties of the airborne unfolding of the flexible net, two symmetric design schemes, namely, the traction method and the rotation method, are developed. The mechanical analyses of the two net-expansion methods are carried out. Meanwhile, this paper establishes a collision dynamics model based on the continuous contact force method, and carries out several collision capture tests using two flexible nets. The results show that a transient acceleration is applied in all directions of the target during the collision, capable of reaching the magnitude of 104. The maximum stress inside the target aerodynamic surface reaches the magnitude of GPa, and the strong impact produced in the capture process will cause damage to the aerodynamic parts. Finally, the flight experiments of damaged targets are carried out based on six-degree-of-freedom-model, and the effect of damaged targets on the safety of aircraft platforms after contact collisions is further analyzed. The results of this paper can provide a theoretical reference for the research and development of airborne flexible nets.

In this paper, we address a class of distributed robust cooperative fault-tolerant control problems for discrete-time multi-agent systems (MASs). The discrete-time MASs considered in this paper have both uncertainties and actuator faults, and a distributed intermediate variable estimator that does not require a fault estimation matching condition is designed for obtaining the estimation information of the actuator faults. In addition, to further obtain higher design freedom and better estimation performance, the intermediate variable estimator considers both centralised and distributed output estimation errors as feedback terms. A fault-tolerant control protocol is designed using the fault estimation information to ensure the reliable operation of discrete-time MASs. It is worth noting that in the method proposed in this paper, there is no need to know the boundary information about the faults and their changing rates, and the method is applicable to discrete-time MASs with directed communication topology. In order to ensure the solvability of the Linear Matrix Inequality (LMI) for better obtaining of the gain matrices of the designed fault estimators, further decoupling and dimensionality reduction of the LMI are carried out in this paper. Finally, a numerical simulation and a network of four one-link flexible joint manipulator systems simulation verify the truthfulness and effectiveness of the method proposed in this paper.

Abstract Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.

Abstract Background Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia. Methods We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants’ categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia. Results Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia. Conclusions This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia.

Background & Aims: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. Methods: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. Results: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. Conclusions: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

In this work, friction stir welding (FSW) and tungsten inert gas welding (TIG) were applied to prepare two kinds of dissimilar AZ31/AM60 Mg joints. The relationship between mechanical properties, deformation behavior, and microstructure characteristics of both joints was investigated. Microstructural characterization demonstrated that a significant grain orientation fluctuation occurred in the weld zone (WZ) of the FSW joint, but this was not obvious for the TIG joint. Compared with the base metals, the grain size of the FSW joint slightly decreased, but the grain of the TIG joint obviously coarsened. Locally strong texture appeared in the WZ of the FSW joint with a symmetrical distribution, while a random texture character occurred in the TIG joint. Furthermore, the WZ of the TIG joint possessed more and larger second phases than the FSW joint. Tensile tests indicated that both joints had equivalent yield strength (∼120 MPa) and ultimate tensile strength (∼255 MPa), but the elongation (9.0 %) of the FSW joint was lower than that of the TIG joint (12.1%). The similar strength originated from the higher Schmid factors (SFs) of basal slip and extension twinning in the WZ side of the FSW joint and the larger grain size and lower dislocation degree in the heat-affected zone of the TIG joint. The decreased elongation in the FSW joint was due to the apparent inhomogeneous deformation caused by significant SFs (basal slip) fluctuation, while the weaker SFs fluctuation and notable twinning behavior in the TIG joint contributed to the relatively higher elongation.

Particle surface thermal field (PSTF) is an inhomogeneous thermal field that concentrates the heat effect on the surface of particles, and it can be utilized to fabricate composite materials with large differences in physical properties. However, it is difficult to form PSTF with large temperature gradients to meet the preparation requirement of materials with extreme differences in physical properties. In our work, a PSTF is proposed and realized by an ultra-high pulse pressure (UHPP) to prepare W–Al composite, the PSTF has a heating effect on the powder interface with a low-temperature interior of the powders. The combination of ex-situ microstructural observation and in-situ molecular dynamic simulation microstructural snapshot is used to demonstrate the densification mechanism. The PSTF is characterized as the temperature higher than 1200 °C on the W–Al powders interface but lower than 200 °C interior of the powders. The densification mechanisms are explained as interfacial jet penetration, interfacial friction welding and interfacial melting. In addition, interfacial temperature distribution creating gradient pressure on the W–Al interface illustrated the generation of gradient Al grains on the W surface, thus creating a high mechanical micro-hardness of 249.8 Hv and compressive strength of 473.2 MPa for the W–Al composite.

Abstract Background Pyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one of the most commonly used models for immunotherapy development, though an inadequate immune response can occur. Moreover, the development of pyroptosis-related therapy and combinations with other therapeutic strategies is limited due to insufficient understanding of the role of pyroptosis in the context of different tumor immune microenvironments (TMEs). Methods Here, we present a computational model (pyroptosis-related gene score, PScore) to assess the pyroptosis status. We applied PScore to 1388 melanoma samples in our in-house cohort and eight other publicly available independent cohorts and then calculated its prognostic power of and potential as a predictive marker of immunotherapy efficacy. Furthermore, we performed association analysis for PScore and the characteristics of the TME by using bulk, single-cell, and spatial transcriptomics and assessed the association of PScore with mutation status, which contributes to targeted therapy. Results Pyroptosis-related genes (PRGs) showed distinct expression patterns and prognostic predictive ability in melanoma. Most PRGs were associated with better survival in metastatic melanoma. Our PScore model based on genes associated with prognosis exhibits robust performance in survival prediction in multiple metastatic melanoma cohorts. We also found PScore to be associated with BRAF mutation and correlate positively with multiple molecular signatures, such as KRAS signaling and the IFN gamma response pathway. Based on our data, melanoma with an immune-enriched TME had a higher PScore than melanoma with an immune-depleted or fibrotic TME. Additionally, monocytes had the highest PScore and malignant cells and fibroblasts the lowest PScore based on single-cell and spatial transcriptome analyses. Finally, a higher PScore was associated with better therapeutic efficacy of immune checkpoint blockade, suggesting the potential of pyroptosis to serve as a marker of immunotherapy response. Conclusions Collectively, our findings indicate that pyroptosis is a prognostic factor and is associated with the immune response in metastatic melanoma, as based on multiomics data. Our results provide a theoretical basis for drug combination and reveal potential immunotherapy response markers.

With the goal of promoting the development of myoelectric control technology, this paper focuses on exploring graph neural network (GNN) based robust electromyography (EMG) pattern recognition solutions. Given that high-density surface EMG (HD-sEMG) signal contains rich temporal and spatial information, the multi-view spatial-temporal graph convolutional network (MSTGCN)is adopted as the basic classifier, and a feature extraction convolutional neural network (CNN) module is designed and integrated into MSTGCN to generate a new model called CNN-MSTGCN. The EMG pattern recognition experiments are conducted on HD-sEMG data of 17 gestures from 11 subjects. The ablation experiments show that each functional module of the proposed CNN-MSTGCN network has played a more or less positive role in improving the performance of EMG pattern recognition. The user-independent recognition experiments and the transfer learning-based cross-user recognition experiments verify the advantages of the proposed CNN-MSTGCN network in improving recognition rate and reducing user training burden. In the user-independent recognition experiments, CNN-MSTGCN achieves the recognition rate of 68%, which is significantly better than those obtained by residual network-50 (ResNet50, 47.5%, p < 0.001) and long-short-term-memory (LSTM, 57.1%, p=0.045). In the transfer learning-based cross-user recognition experiments, TL-CMSTGCN achieves an impressive recognition rate of 92.3%, which is significantly superior to both TL-ResNet50 (84.6%, p = 0.003) and TL-LSTM (85.3%, p = 0.008). The research results of this paper indicate that GNN has certain advantages in overcoming the impact of individual differences, and can be used to provide possible solutions for achieving robust EMG pattern recognition technology.