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Abstract Objective To assess the image quality of synthetic double inversion recovery (SyDIR) imaging and enhance the value of T2-weighted imaging (T2WI) in evaluating T stage for rectal cancer patients. Methods A total of 112 pathologically confirmed rectal cancer patients were retrospectively selected after undergoing MRI, including synthetic MRI. The image quality of T2WI and SyDIR imaging was compared based on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), overall picture quality, presence of motion artifacts, lesion edge sharpness, and conspicuity. The concordance between MRI and pathological staging results, using T2WI alone and the combination of T2WI and SyDIR for junior and senior radiologists, was assessed using the Kappa test. The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic efficacy of extramural infiltration in rectal cancer patients. Results No significant differences in imaging quality were observed between conventional T2WI and SyDIR (p = 0.07–0.53). The combination of T2WI and SyDIR notably improved the staging concordance between MRI and pathology for both junior (kappa value from 0.547 to 0.780) and senior radiologists (kappa value from 0.738 to 0.834). In addition, the integration of T2WI and SyDIR increased the AUC for diagnosing extramural infiltration for both junior (from 0.842 to 0.918) and senior radiologists (from 0.917 to 0.938). Conclusion The combination of T2WI and SyDIR increased the consistency of T staging between MRI and pathology, as well as the diagnostic performance of extramural infiltration, which would benefit treatment selection. Critical relevance statement SyDIR sequence provides additional diagnostic value for T2WI in the T staging of rectal cancer, improving the agreement of T staging between MRI and pathology, as well as the diagnostic performance of extramural infiltration. Key Points Synthetic double inversion recovery (SyDIR) and T2WI have comparable image quality. SyDIR provides rectal cancer anatomical features for extramural infiltration detections. The combination of T2WI and SyDIR improves the accuracy of T staging in rectal cancer. Graphical Abstract

Abstract Background Melanin in the black-bone chicken’s body is considered the material basis for its medicinal effects and is an economically important trait. Therefore, improving the melanin content is a crucial focus in the breeding process of black-bone chickens. Luning chickens are black-bone chickens, with black beaks, skin, and meat. To investigate the genetic diversity and molecular mechanisms of melanin deposition in Luning chickens, we conducted whole-genome resequencing to analyze their breeding history and identify candidate genes influencing their black phenotype, along with transcriptome sequencing of dorsal skin tissues of male Luning chickens. Results Population structure analysis revealed that Luning chickens tend to cluster independently and are closely related to Tibetan chickens. Runs of homozygosity analysis suggested potential inbreeding in the Luning chicken and Tibetan chicken population. By combining genetic differentiation index (Fst) and nucleotide diversity (θπ) ratios, we pinpointed selected regions associated with melanin deposition. Gene annotation identified 540 genes with the highest Fst value in LOC101750371 and LOC121108313, located on the 68.24–68.58 Mb interval of chromosome Z. Combining genomic and transcriptomic data, we identified ATP5E, EDN3, and LOC101750371 as candidate genes influencing skin color traits in black-bone chickens. Conclusions This study characterized the evolutionary history of Luning chickens and preliminarily excavated candidate genes influencing the genetic mechanism of pigmentation in black-bone chickens, providing valuable insights for the study of animal melanin deposition.

Abstract Conversation is an essential component of virtual avatar activities in the metaverse. With the development of natural language processing, significant breakthroughs have been made in text and voice conversation generation. However, face-to-face conversations account for the vast majority of daily conversations, while most existing methods focused on single-person talking head generation. In this work, we take a step further and consider generating realistic face-to-face conversation videos. Conversation generation is more challenging than single-person talking head generation, because it requires not only the generation of photo-realistic individual talking heads, but also the listener’s response to the speaker. In this paper, we propose a novel unified framework based on the neural radiance field (NeRF) to address these challenges. Specifically, we model both the speaker and the listener with a NeRF framework under different conditions to control individual expressions. The speaker is driven by the audio signal, while the response of the listener depends on both visual and acoustic information. In this way, face-to-face conversation videos are generated between human avatars, with all the interlocutors modeled within the same network. Moreover, to facilitate future research on this task, we also collected a new human conversation dataset containing 34 video clips. Quantitative and qualitative experiments evaluate our method in different aspects, e.g., image quality, pose sequence trend, and natural rendering of the scene in the generated videos. Experimental results demonstrate that the avatars in the resulting videos are able to carry on a realistic conversation, and maintain individual styles.

The goal of this paper is to derive closed-form approximation formulas for the spread option value and Greeks by using double integration and investigating the exercise boundary. We have found that the straight-line approximation suggested in previous research does not perform well for curved exercise boundaries. We propose a novel approach: to integrate in a sector and find a closed-form formula expressed in terms of the bivariate normal CDF. We call it the sector formula. Numerical tests show the good accuracy of our sector formula. We demonstrate applications of the formula to the market data of calendar spread options for three major commodities, WTI, Natural Gas, and Corn, listed on the CME site as of May, April, and June 2024.

Abstract The deep connection among braids, knots and topological physics has provided valuable insights into studying topological states in various physical systems. However, identifying distinct braid groups and knot topology embedded in non-Hermitian systems is challenging and requires significant efforts. Here, we demonstrate that an unsupervised learning with the representation basis of s u(n) Lie algebra on n-fold extended non-Hermitian bands can fully classify braid group and knot topology therein, without requiring any prior mathematical knowledge or any pre-defined topological invariants. We demonstrate that the approach successfully identifies different topological elements, such as unlink, unknot, Hopf link, Solomon ring, trefoil, and so on, by employing generalized Gell-Mann matrices in non-Hermitian models with n=2 and n=3 energy bands. Moreover, since eigenstate information of non-Hermitian bands is incorporated in addition to eigenvalues, the approach distinguishes the different parity-time symmetry and breaking phases, recognizes the opposite chirality of braids and knots, and identifies out distinct topological phases that were overlooked before. Our study shows significant potential of machine learning in classification of knots, braid groups, and non-Hermitian topological phases.

Abstract Introduction The Ilizarov bone transport technique is widely recognised as an effective method for treating large segment bone defects in clinical practice. However, axial deviation is a common complication in the treatment of tibial large segment bone defects, which can have a serious impact on the clinical efficacy of bone transport. Our study aims to construct and validate a nomogram for predicting axial deviation of tibial bone transport. Method This study retrospectively collected data from 363 patients who underwent the tibial Ilizarov technique for bone transport. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for axial deviation, which were later used to construct a nomogram. The nomogram was evaluated using the decision curve analysis (DCA), the calibration curve, and the area under the receiver operating characteristic curve (AUC). Results Of the 363 patients who underwent Ilizarov tibial bone transport, 31.7% (115/363) experienced axial deviation. Multivariate logistic regression analysis showed that gender, height, defect site, and external fixation index were important risk factors for axial deviation. The AUC value of the nomogram model was 0.705. The calibration curve and the decision curve analysis showed a good consistency between the actual axial deviation and the predicted probability. Conclusion The model assigns a quantitative risk score to each variable, which can be used to predict the risk of axial deviation during tibial bone transport.

The regulation of glial cell activation is a critical step for the treatment or prevention of neuroinflammation‐based brain diseases. However, the development of therapeutic drugs that pass the blood–brain barrier (BBB) and inhibit the glia cell activation remains a significant challenge. Herein, an ultrasmall 2D vanadium carbide quantum dots (V2C QDs) that are capable of crossing the BBB are prepared, and the admirable anti‐neuroinflammatory effects are presented. The prepared 2D V2C QDs with an average size of 2.54 nm show good hydrophilicity, physiological stability, and effective BBB‐crossing ability. The biological effect of V2C QDs on inflammatory reactions demonstrates fascinating results in preventing the impairment of learning and memory in BALB/c mice stimulated by lipopolysaccharide. Investigation of molecular mechanism reveals that V2C QDs not only inhibit the toll‐like receptor 4/myeloid differentiation factor 88‐mediated nuclear factor kappa B and mitogen‐activated protein kinase pathways, but also prevent eukaryotic translation initiation factor 2α/activating transcription factor 4/C/EBP homologous protein‐signaling pathway and reduce oxidative stress via activating the NF‐E2‐related factor‐2/heme oxygenase‐1‐signaling pathway, leading to greatly inhibited activation of microglia and astrocytes and weakened production of inflammatory cytokines. In summary, V2C QDs exert potent anti‐inflammatory effects through multiple pathways, thus offer great potential for the treatment of neurodegenerative diseases.

Background: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. Methods: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. Results: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. Conclusion: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

Abstract Dynamic manipulation of an object's infrared radiation characteristics is a burgeoning technology with significant implications for energy and information fields. However, exploring efficient stimulus–spectral response mechanism and realizing simple device structures remains a formidable challenge. Here, a novel dynamic infrared emissivity regulation mechanism is proposed by controlling the localized surface plasmon resonance absorption of aluminum‐doped zinc oxide (AZO) nanocrystals through ultraviolet photocharging/oxidative discharging. A straightforward device architecture that integrates an AZO nanocrystal film with an infrared reflective layer and a substrate, functioning as a photo‐induced dynamic infrared emissivity modulator, which can be triggered by weak ultraviolet light in sunlight, is engineered. The modulator exhibits emissivity regulation amount of 0.72 and 0.61 in the 3–5 and 8–13 µm ranges, respectively. Furthermore, the modulator demonstrates efficient light triggering characteristic, broad spectral range, angular‐independent emissivity, and long cyclic lifespan. The modulator allows for self‐adaptive daytime radiative cooling and nighttime heating depending on the ultraviolet light in sunlight and O2 in air, thereby achieving smart thermal management for buildings with zero‐energy expenditure. Moreover, the potential applications of this modulator can extend to rewritable infrared displays and deceptive infrared camouflage.

BackgroundRestricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière’s disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD.MethodsSummary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias.ResultsThe primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429–1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427–1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555–1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993–1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987–1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985–1.011; p = 0.72).ConclusionThis MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.

Modulation of immune microenvironment is critical for inflammatory bowel disease (IBD) intervention. Epigallocatechin gallate (EGCG), as a natural low toxicity product, has shown promise in treating IBD. However, whether and how EGCG regulates the intestinal microenvironment is not fully understood. Here we report that EGCG lessens colitis by orchestrating Th1 polarization and self-amplification in a novel manner that required multilevel-regulated intestinal microecosystem. Mechanistically, EGCG activates GPR43 on IEC to inhibit Th1 polarization dependently of short chain fatty acid (SCFA)-producing gut microbiota. Inhibition of GPR43 activity weakens the protective effects of EGCG on colitis development. Moreover, we confirm that fecal SCFAs and/or intestinal GPR43 are limited in patients with colitis and are correlated with Th1 cell number. Taken together, our study reveals an intestinal microenvironment-dependent immunoregulatory effects of EGCG in treating IBD and provides insight into mechanisms of EGCG-based novel immunotherapeutic strategies for IBD.

Cardiotoxicity is a common side effect of cisplatin in cancer treatment, often complicating patient care. Tangeretin (TG), a natural compound found in citrus peel, shows promise in protecting against cisplatin-induced heart damage. Our study investigated TG’s protective effects both in cell culture and in animal models. TG effectively countered cisplatin-induced damage in heart cells, promoting mitochondrial health and glucose transporter expression. In animal studies, TG reduced markers of heart damage and improved cardiac function. Mechanistically, TG activated AMPK, reduced the inactivation of Acetyl-CoA Carboxylase (ACC) protein and inhibited p38 MAPK and prevented mitochondrial dysfunction and cell death. This research sheds light on TG’s potential in safeguarding the heart from cisplatin-induced harm.

To improve the reliability of the incremental dynamic analysis, the Monte Carlo simulation technique is introduced to fully consider the uncertainties in the characteristics of earthquakes. To match the computational efficiency of Monte Carlo simulation, structural seismic responses are calculated by neural networks. To consider the failure risks under 3 safety requirements imposed on the structural seismic performance by the Chinese standard, the equivalent failure probability is employed to compare the safety of 4 different design schemes composed of high-rise frame structures. The workflow of the proposed method is demonstrated by taking the 4 design schemes as examples; good agreement is found between the failure probabilities of the entire structures and their stories with their failure states. Furthermore, the safety of these schemes is compared, and some design advice is discussed.

High voltage electrical pulse fracturing technology based on electrohydraulic effect is a new type of rock mass fracturing technology. This technique is characterized by its safety, high efficiency, environmental friendliness and controllable energy usage. It holds a significant potential for its application in the stress control of surrounding rock in coal mines because the complex stress conditions present in underground rock mass. To further investigate the cracking effect of the technology on hard rock mass under different surrounding rock stress conditions, the numerical simulation of high voltage electric pulse rock mass cracking was carried out on the rock sample based on the RHT damage constitutive model by LS-DYNA. The processes of damage evolution and effective stress evolution inside the rock mass were collected. The cracking characteristics and crack propagation mechanism of the rock mass were analyzed. The numerical simulation overcomes the problem that it is difficult to effectively monitor the internal rock mass during the cracking process due to the fast discharge process and large electromagnetic interference in the indoor test. The self-developed high-voltage electrical pulse rock fracturing test platform was used to carry out the high voltage electrical pulse rock fracturing test under different surrounding rock stress conditions, and the reliability of the numerical simulation results was verified by the obtained rock surface fracture characteristics. The following conclusions are obtained: ① The numerical model of LS-DYNA high voltage electric pulse rock mass fracturing is established based on the RHT constitutive model. The equivalent parameters for the numerical simulation are derived according to the energy equivalent relationship between explosive blasting and high voltage electric pulse. The reliability of these parameters is confirmed by comparing the laboratory tests results with the numerical simulation results. ② By analyzing the crack propagation on the upper surface of specimens, it reveals that the crack will deflect in the direction of the maximum compressive initial stress. Initially, the total length of the crack first decreases gradually during this process. As the angle between all cracks and the maximum initial compressive stress becomes less than 45°, the total crack length begins to increase gradually. ③ Numerical simulations demonstrate that the dynamic stress resulting from high voltage electric pulse discharge is much greater than the initial stress in the surrounding rock during the early stages of fracturing. Dynamic stress plays a leading role in rock failure in this process. As the dynamic stress quickly diminishes during propagation, the initial surrounding rock stress is gradually close to the dynamic stress and finally dominates the initiation and propagation of cracks. The results indicate that surrounding rock stress plays a crucial role in determining the development and expansion characteristics of rock mass cracks. It notably influences the direction of crack expansion. When the high voltage electric pulse fracturing technology is used to crack the deep rock mass, the stress state of the rock mass should be considered. The scientific fracturing scheme should be formulated to achieve an efficient fracturing of the rock mass. The research results provide a reliable numerical simulation method for high voltage electric pulse rock fracturing and a reference for the formulation of deep rock mass fracturing scheme.

Abstract Background Recent Convolutional Neural Networks (CNNs) perform low-error reconstruction in fast Magnetic Resonance Imaging (MRI). Most of them convolve the image with kernels and successfully explore the local information. Nonetheless, the non-local image information, which is embedded among image patches relatively far from each other, may be lost due to the limitation of the receptive field of the convolution kernel. We aim to incorporate a graph to represent non-local information and improve the reconstructed images by using the Graph Convolutional Enhanced Self-Similarity (GCESS) network. Methods First, the image is reconstructed into the graph to extract the non-local self-similarity in the image. Second, GCESS uses spatial convolution and graph convolution to process the information in the image, so that local and non-local information can be effectively utilized. The network strengthens the non-local similarity between similar image patches while reconstructing images, making the reconstruction of structure more reliable. Results Experimental results on in vivo knee and brain data demonstrate that the proposed method achieves better artifact suppression and detail preservation than state-of-the-art methods, both visually and quantitatively. Under 1D Cartesian sampling with 4 × acceleration (AF = 4), the PSNR of knee data reached 34.19 dB, 1.05 dB higher than that of the compared methods; the SSIM achieved 0.8994, 2% higher than the compared methods. Similar results were obtained for the reconstructed images under other sampling templates as demonstrated in our experiment. Conclusions The proposed method successfully constructs a hybrid graph convolution and spatial convolution network to reconstruct images. This method, through its training process, amplifies the non-local self-similarities, significantly benefiting the structural integrity of the reconstructed images. Experiments demonstrate that the proposed method outperforms the state-of-the-art reconstruction method in suppressing artifacts, as well as in preserving image details.

The relationship between support and surrounding rock is of great significance to the control of surrounding rock in mining process. In view of the fact that most of the existing numerical simulation methods construct virtual elements and stress servo control to approximately replace the hydraulic support problem, this paper establishes a new numerical model of hydraulic support with the same working characteristics as the actual hydraulic support by integrating numerical simulation software Rhino, Griddle and FLAC3D, which can realize the simulation of different working conditions. Based on this model, the influence mechanism of the supporting strength of hydraulic support on surrounding rock stress regulation and coal stability in front of the top coal caving face in extra thick coal seam were researched. Firstly, under different support intensity, the abutment pressure of the bearing coal and the coal in front of it presents the “three-stage” evolution characteristics. The influence range of support intensity is 15%–30%. Secondly, 1.5 MPa is the upper limit of impact that the support strength can have on the front coal failure area. Thirdly, within a displacement range of 2.76 m from the coal wall, a support strength of 1.5 MPa provides optimal control of the horizontal displacement of the coal.

Abstract Background Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. Methods A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. Results Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. Conclusions These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Chemical mutagenesis-driven forward genetic screens are pivotal in unveiling gene functions, yet identifying causal mutations behind phenotypes remains laborious, hindering their high-throughput application. Here, we reveal a non-uniform mutation rate caused by Ethyl Methane Sulfonate (EMS) mutagenesis in the C. elegans genome, indicating that mutation frequency is influenced by proximate sequence context and chromatin status. Leveraging these factors, we developed a machine learning enhanced pipeline to create a comprehensive EMS mutagenesis probability map for the C. elegans genome. This map operates on the principle that causative mutations are enriched in genetic screens targeting specific phenotypes among random mutations. Applying this map to Whole Genome Sequencing (WGS) data of genetic suppressors that rescue a C. elegans ciliary kinesin mutant, we successfully pinpointed causal mutations without generating recombinant inbred lines. This method can be adapted in other species, offering a scalable approach for identifying causal genes and revitalizing the effectiveness of forward genetic screens.

Backgroundβ-thalassemia (β-TH) is a hereditary hemolytic anemia that results in deficient hemoglobin (Hb) synthesis. It is characterized by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload. Exploration new potential biomarkers and drug candidates is important to facilitate the prevention and treatment of β-TH.MethodsWe applied quasi-targeted metabolomics between wild type (Wt) and heterozygous β-TH mice (Th3/+), a model of non-transfusion-dependent β-TH intermedia, in plasma and peripheral blood (PB) cells. Futher data was deeply mined by Kyoto Encyclopedia of Genomes (KEGG) and machine algorithms methods.ResultsUsing KEGG enrichment analysis, we found that taurine and hypotaurine metabolism disorders in plasma and alanine, aspartate and glutamate metabolism disorders in PB cells. After systematically anatomize the metabolites by machine algorithms, we confirmed that alpha-muricholic acidUP and N-acetyl-DL-phenylalanineUP in plasma and Dl-3-hydroxynorvalineUP, O-acetyl-L-serineUP, H-abu-OHUP, S-(Methyl) glutathioneUP, sepiapterinDOWN, and imidazoleacetic acidDOWN in PB cells play key roles in predicting the occurrence of β-TH. Furthermore, Sepiapterin, Imidazoleacetic acid, Methyl alpha-D-glucopyranoside and alpha-ketoglutaric acid have a good binding capacity to hemoglobin E through molecular docking and are considered to be potential drug candidates for β-TH.ConclusionThose results may help in identify useful molecular targets in the diagnosis and treatment of β-TH and lays a strong foundation for further research.

The rapid development of urban agglomeration harms the ecological environment, which makes the research of its correlation mechanism become an urgent task of sustainability. This study introduces a two-dimensional Ecological Quality of Green Space Index (EQGS) comprising Landscape Pattern Index (LPI) and Remote Sensing Ecological Index (RSEI). Utilizing Coupling Coordination Degree (CCD) model, it examines the dynamics between Regional Urban Development Index (RUDI) and EQGS within five of China’s urban agglomerations between 2014 and 2022. Additionally, it identifies driving factors through Geographically Weighted Regression (GWR) model. The findings reveal a general decline in the CCD between RUDI and LPI, except in the Chengdu-Chongqing urban agglomeration (CCUA), while the CCD with RSEI has seen substantial improvements, with the exception of the Northeast urban agglomeration (NEUA). Regression analysis indicates significant variability in the leading indicators and spatial intensity influencing the coordination degrees across different urban agglomerations. Key factors like landscape dominance and Normalized Difference Vegetation Index positively affect coordination degrees. Developing green corridors to mitigate urban heat islands is crucial for enhancing NEUA’s efficiency, particularly in northern cities. Conversely, CCUA’s sustainable development hinges on improving urban humidity. These insights offer tailored planning suggestions for policymakers to implement scientific strategies in urban green space development.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

Sarcopenia, a geriatric syndrome characterized by progressive loss of muscle mass and strength, and osteoarthritis, a common degenerative joint disease, are both prevalent in elderly individuals. However, the relationship and molecular mechanisms underlying these two diseases have not been fully elucidated. In this study, we screened microarray data from the Gene Expression Omnibus to identify associations between sarcopenia and osteoarthritis. We employed multiple statistical methods and bioinformatics tools to analyze the shared DEGs (differentially expressed genes). Additionally, we identified 8 hub genes through functional enrichment analysis, protein–protein interaction analysis, transcription factor-gene interaction network analysis, and TF-miRNA coregulatory network analysis. We also discovered potential shared pathways between the two diseases, such as transcriptional misregulation in cancer, the FOXO signalling pathway, and endometrial cancer. Furthermore, based on common DEGs, we found that strophanthidin may be an optimal drug for treating sarcopenia and osteoarthritis, as indicated by the Drug Signatures database. Immune infiltration analysis was also performed on the sarcopenia and osteoarthritis datasets. Finally, receiver operating characteristic (ROC) curves were plotted to verify the reliability of our results. Our findings provide a theoretical foundation for future research on the potential common pathogenesis and molecular mechanisms of sarcopenia and osteoarthritis.

BackgroundPrevious studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate the causal association between gut microbiota/immune cells and the likelihood of developing IS, employing a two-sample Mendelian randomization (MR) analysis.MethodsOur comprehensive analysis utilized summary statistics from genome-wide association studies (GWAS) on gut microbiota, immune cells, and IS. The primary MR method employed was the inverse variance-weighted (IVW) approach. To address potential pleiotropy and identify outlier genetic variants, we incorporated the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity was assessed using Cochran’s Q-test. Additionally, leave-one-out analysis was conducted to pinpoint any individual genetic variant influencing the observed causal associations. Finally, a reverse MR analysis was performed to explore the potential of reverse causation.ResultsOur investigation revealed four gut microbial taxa and 16 immune cells with a significant causal relationship with IS (p < 0.05). Notably, two bacterial features and five immunophenotypes were strongly associated with a lower IS risk: genus.Barnesiella.id.944 (OR: 0.907, 95% CI: 0.836–0.983, p = 0.018), genus.LachnospiraceaeNK4A136group.id.11319 (OR: 0.918, 95% CI: 0.853–0.983, p = 0.988), Activated & resting Treg % CD4++ (OR: 0.977, 95% CI: 0.956–0.998, p = 0.028). Additionally, significant associations between IS risk and two bacterial features along with eleven immunophenotypes were observed: genus.Paraprevotella.id.962 (OR: 1.106, 95% CI: 1.043–1.172, p < 0.001), genus.Streptococcus.id.1853 (OR: 1.119, 95% CI: 1.034–1.210, p = 0.005), CD127 on granulocyte (OR: 1.039, 95% CI: 1.009–1.070, p = 0.011). Our analyses did not reveal heterogeneity based on the Cochrane’s Q-test (p > 0.05) nor indicate instances of horizontal pleiotropy according to MR-Egger and MR-PRESSO analyses (p > 0.05). Furthermore, the robustness of our MR results was confirmed through leave-one-out analysis.ConclusionOur study provides further evidence supporting the potential association between gut microbiota and immune cells in relation to IS, shedding light on the underlying mechanisms that may contribute to this condition. These findings lay a solid foundation for future investigations into targeted prevention strategies.

Abstract Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.

Abstract PRMT5, a type II arginine methyltransferase, is involved in transcriptional regulation, RNA processing and other biological processes and signal transduction. Secondary metabolites are vital pharmacological compounds in Ganoderma lucidum, and their content is an important indicator for evaluating the quality of G. lucidum. Here, we found that GlPRMT5 negatively regulates the biosynthesis of secondary metabolites. In further in-depth research, GlPP2C1 (a type 2C protein phosphatase) was identified out as an interacting protein of GlPRMT5 by immunoprecipitation-mass spectrometry (IP-MS). Further mass spectrometry detection revealed that GlPRMT5 symmetrically dimethylates the arginine 99 (R99) and arginine 493 (R493) residues of GlPP2C1 to weaken its activity. The symmetrical dimethylation modification of the R99 residue is the key to affecting GlPP2C1 activity. Symmetrical demethylation-modified GlPP2C1 does not affect the interaction with GlPRMT5. In addition, silencing GlPP2C1 clearly reduced GA content, indicating that GlPP2C1 positively regulates the biosynthesis of secondary metabolites in G. lucidum. In summary, this study reveals the molecular mechanism by which GlPRMT5 regulates secondary metabolites, and these studies provide further insights into the target proteins of GlPRMT5 and symmetric dimethylation sites. Furthermore, these studies provide a basis for the mutual regulation between different epigenetic modifications.

In this paper, we demonstrate a stable output single-longitudinal-mode (SLM) Erbium-doped fiber laser (EDFL) with eight selectable wavelengths. The EDFL achieves wavelength selection through a 1 × 8 arrayed waveguide grating (AWG) and generates SLM output using the passive triple subring resonator (PTSR) architecture. In the experimental measurements, we separately measured the wavelength, power, and optical signal-to-noise ratio (OSNR) for all eight channels. The experimental results show a wavelength spacing of approximately 0.8 nm, with OSNRs around 60 dB and powers around 2.5 dBm for each channel. The power and OSNR for all eight wavelengths show very little variation. Finally, we measured that the laser outputs are all SLM, and the measured linewidths are all less than 2.5 kHz.

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

Abstract Dielectric metasurfaces, composed of planar arrays of subwavelength dielectric structures that collectively mimic the operation of conventional bulk optical elements, have revolutionized the field of optics by their potential in constructing high-efficiency and multi-functional optoelectronic systems on chip. The performance of a dielectric metasurface is largely determined by its constituent material, which is highly desired to have a high refractive index, low optical loss and wide bandgap, and at the same time, be fabrication friendly. Here, we present a new material platform based on tantalum pentoxide (Ta2O5) for implementing high-performance dielectric metasurface optics over the ultraviolet and visible spectral region. This wide-bandgap dielectric, exhibiting a high refractive index exceeding 2.1 and negligible extinction coefficient across a broad spectrum, can be easily deposited over large areas with good quality using straightforward physical vapor deposition, and patterned into high-aspect-ratio subwavelength nanostructures through commonly-available fluorine-gas-based reactive ion etching. We implement a series of high-efficiency ultraviolet and visible metasurfaces with representative light-field modulation functionalities including polarization-independent high-numerical-aperture lensing, spin-selective hologram projection, and vivid structural color generation, and the devices exhibit operational efficiencies up to 80%. Our work overcomes limitations faced by scalability of commonly-employed metasurface dielectrics and their operation into the visible and ultraviolet spectral range, and provides a novel route towards realization of high-performance, robust and foundry-manufacturable metasurface optics.

Background and Aims: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored. Methods: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD. Results: Distinct sets of factors are associated with the progression to ESLD. The PNPLA3 rs738409:G and TM6SF2 rs58542926:T alleles, body mass index (BMI), age, and female sex were positively associated with progression from a healthy state to MASH. The PNPLA3 rs738409:G allele, age, male sex, and having type 2 diabetes mellitus were positively associated, while BMI was negatively associated with progression from MASH to MASLD-associated ESLD. The PNPLA3 rs738409:G and GCKR rs780094:T alleles, age, and male sex were positively associated, while BMI was negatively associated with progression from a healthy state to ALD-associated ESLD. The findings indicate that the PNPLA3 rs738409:G allele increases susceptibility to ESLD regardless of etiology, the TM6SF2 rs58542926:T allele increases susceptibility to MASH, and the GCKR rs780094:T allele increases susceptibility to ALD-associated ESLD. Conclusion: The PNPLA3, TM6SF2, and GCKR minor alleles influence the progression of MASLD-associated or ALD-associated ESLD. Genotyping for these variants in MASLD and ALD patients can enhance risk assessment, prompting early interventions to prevent ESLD.

In order to meet realistic requirements for flexible and reliable power supply in special scenarios such as remote areas and deep ocean exploration, a novel megawatt portable nuclear power system called SUPERHERO (SUPERcritical carbon dioxide cycle-HEat pipe ReactOr power system) is proposed in this paper. The system consists of a heat pipe-cooled reactor and a closed supercritical carbon dioxide (S–CO2) Brayton power cycle. Different cycle concepts were compared, and the simple recuperated cycle was adopted for compactness and simplicity of the system. The multi-objective optimization is performed to maximize cycle efficiency and minimize system volume, resulting in optimized parameters for a 1MWe system. By utilizing uranium nitride (UN) modular fuel elements and high heat transfer capacity potassium heat pipes, a compact reactor scheme with 3.13MWt is determined that can operate for 15 years without refueling. The neutronics and thermal analysis of the reactor are carried out, and the results show that the reactor has safety features such as a low peak factor, negative temperature feedback coefficient, sufficient reactivity compensation and control, and anti-failure of single heat pipe. The primary heat exchanger is also designed using the CFD method, and the heat exchange tubes combined with ribbed plates and self-supporting structures are used to enhance heat transfer and ensure structural stability. All these studies outline the general features of SUPERHERO, demonstrating that SUPERHERO has great development potential.

The construction of rural transportation infrastructure is of great significance to promote the organic integration of transportation construction with resource exploitation and industrial development in rural areas, and realize poverty alleviation and poverty reduction driven by convenient transportation. In order to understand the research status of rural transport infrastructure at home and abroad, this paper adopts CiteSpace, VOSviewer, Pajek, SPSS and other software and makes quantitative analysis and knowledge map drawing of the literature on rural transportation infrastructure collected in Web of Science database. The results show that the emphasis of this field is different in different periods, Chinese scholars' attention to this field increased significantly after the rural revitalization strategy was put forward. Based on the classification results of keyword clustering, the following conclusions are drawn: The planning mode of rural transportation infrastructure under rural revitalization is relatively backward and the lack of theoretical analysis of the root causes has achieved the purpose of rational allocation of transportation resources. Moreover, there are few studies on the mechanism and empirical analysis of transport infrastructure's effect on rural poverty reduction. From the analysis of research hotspots, the integration of urban and rural areas and rural road safety will be the main research direction in the future, and rural road accidents and other topics have research potential.

Abstract CAR-T cell therapy did not achieve the desired efficacy in some patients with diffuse large B-cell lymphoma (DLBCL). We conducted single-cell RNA and TCR sequencing as well as methylation chip profiling of peripheral blood samples in DLBCL patients. Patients who achieved complete remission (CR) showed an upward trend in T-cell levels, especially CD8-effector T cells. The responders exhibited T-cell clone expansion, more active T-cell transformation, and frequent cell communication. Highly expressed genes in the CR group were enriched in functions like leukocyte-mediated cytotoxicity and activation of immune response, while the non-CR group was enriched in pathways related to DNA damage and P53-mediated intrinsic apoptotic. More differentially methylated probes (DMPs) were identified in the baseline of the non-CR group (779 vs 350). GSEA analysis revealed that the genes annotated by DMPs were associated with cellular immune functions in T cells, including the generation of chemokines, leukocyte-mediated cytotoxicity, and cell-killing functions. The genes with low expression in the non-CR group exhibited a high methylation status. There is heterogeneity in the cellular, molecular, and epigenetic characteristics of host T cells in patients with different clinical outcomes. Intrinsic defects in T cells are important factors leading to poor efficacy of CAR-T therapy.

Abstract Background It remains controversial whether the long-term use of statins or newer nonstatin drugs has a positive effect on human longevity. Therefore, this study aimed to investigate the genetic associations between different lipid-lowering therapeutic gene targets and human longevity. Methods Two-sample Mendelian randomization analyses were conducted. The exposures comprised genetic variants that proxy nine drug target genes mimicking lipid-lowering effects (LDLR, HMGCR, PCKS9, NPC1L1, APOB, CETP, LPL, APOC3, and ANGPTL3). Two large-scale genome-wide association study (GWAS) summary datasets of human lifespan, including up to 500,193 European individuals, were used as outcomes. The inverse-variance weighting method was applied as the main approach. Sensitivity tests were conducted to evaluate the robustness, heterogeneity, and pleiotropy of the results. Causal effects were further validated using expression quantitative trait locus (eQTL) data. Results Genetically proxied LDLR variants, which mimic the effects of lowering low-density lipoprotein cholesterol (LDL-C), were associated with extended lifespan. This association was replicated in the validation set and was further confirmed in the eQTL summary data of blood and liver tissues. Mediation analysis revealed that the genetic mimicry of LDLR enhancement extended lifespan by reducing the risk of major coronary heart disease, accounting for 22.8% of the mediation effect. The genetically proxied CETP and APOC3 inhibitions also showed causal effects on increased life expectancy in both outcome datasets. The lipid-lowering variants of HMGCR, PCKS9, LPL, and APOB were associated with longer lifespans but did not causally increase extreme longevity. No statistical evidence was detected to support an association between NPC1L1 and lifespan. Conclusion This study suggests that LDLR is a promising genetic target for human longevity. Lipid-related gene targets, such as PCSK9, CETP, and APOC3, might potentially regulate human lifespan, thus offering promising prospects for developing newer nonstatin therapies.

Abstract Background Bifid nose is a rare congenital deformity and the etiology is unknown. The purpose of this study was to report genetic variation in family of patients with bifid nose. Methods Twenty-three consecutive patients who were diagnosed with mild bifid nose were operated with z-plasty from 2009 to 2021. Three underage patients (a pair of twins and a girl) from two family lines, who came to our hospital for surgical treatment, were enrolled. Whole exome sequencing and Sanger sequencing were conducted. Z-shaped flaps were created and the cartilago alaris major were re-stitched. Photographs and CT scan before and after surgery were obtained. Clinical outcomes, complications and patients’ satisfaction were evaluated and analyzed. The follow-up time ranges from 2 to 3 years (2.4 ± 1.2 years). Results Most patients were satisfied with the outcome (96.2%). The nasal deformities were corrected successfully with z-plasty technique in one-stage. FREM1 c.870_876del and c.2 T > C were detected with Whole exome sequencing, which have not been reported before. The results of Sanger sequencing were consistent with those of Whole exome sequencing. Conclusions The newly detected mutations of FREM1 have a certain heritability, and are helpful to make an accurate diagnosis and provide a better understanding of bifid nose mechanism. Z-plasty technique can be an effective technical approach for correcting mild bifid nose deformity.

Large-size and high-resolution AMOLED displays have become one of the most attractive display technologies. However, the dependence of the luminance of AMOLED on temperature severely limits wider applications. The accurate temperature distribution is important for implementing compensation into a panel to improve display uniformity. With the increase in size and resolution, the voltage drop (IR-drop) caused by the resistance of the power supply line cannot be ignored, which has influence on temperature distribution. Therefore, this paper proposes a temperature distribution analysis method based on IR-drop. Firstly, an accurate solution of IR-drop of AMOLED panels is achieved by exploiting the sparse representation in the field of artificial intelligence. Secondly, the IR-drop-based power model is established, and the output of the power model is used as the input of the AMOLED thermal simulation model. Finally, the temperature distribution of the AMOLED panel is obtained by finite-element analysis. The temperature measurements are performed on a 95-inch 8K AMOLED panel. The simulation results are compared with the actual measurements, and it is found that the temperature distribution based on IR-drop matches well with the actual measurements than that without considering IR-drop. The analysis method proposed in this paper presents high accuracy and high practicability.

Hypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, the effect of NC on the hypoxic injury of BMECs and its molecular mechanisms are still unknown. Here, an immunofluorescence assay, transmission electron microscopy (TEM), and flow cytometry, combined with untargeted metabolomics, were used to investigate the protective effect of NC on hypoxic stress injury in BMECs. It was found that NC can significantly reduce cell activity (p < 0.05) and inhibit cellular oxidative stress (p < 0.05) and cell apoptosis (p < 0.05). A significant decrease in mitophagy mediated by the PINK1-Parkin pathway was observed after NC pretreatment (p < 0.05). In addition, a metabolic pathway enrichment analysis demonstrated that the mechanisms of NC against hypoxic stress may be related to the downregulation of pathways involving aminoacyl tRNA biosynthesis; arginine and proline metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Thus, NC has a protective effect on hypoxic mitochondria, and it can regulate amino acid metabolism in response to hypoxic stress. The present study provides a reference for the application of nitidine chloride to regulate the mammary lactation function of milk buffalo.

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted pathogenesis disease and the exact mechanisms driving HFpEF have not been completely elucidated. Pressure overload hypertrophy (POH) related fibroblasts and M2 macrophages in HFpEF myocardium have been recently identified and are now of great interest. Sympathetic overdrive has also been implicated in HFpEF. This study is designed to dynamically observe the potential roles of aforementioned mechanisms in pathological remodeling and cardiac dysfunction in chronic PO rats. Surgical constriction of the abdominal aorta was used for induction of HFpEF. Echocardiography, electrocardiogram, hemodynamic measurement, hematoxylin and eosin staining, Masson staining, immunohistochemistry and immunofluorescence were performed to assess the changes in heart dysfunction, cardiac remodeling and driving mechanisms at different time points (2, 18, 24 weeks). The PO induced HFpEF model was well established, which was confirmed by the persistent increase in carotid artery systolic and diastolic blood pressure, and left ventricle hypertrophy at the corresponding postoperative stage. Meanwhile, PO hypertrophy gradually developed into HFpEF, associated with QT and QTc intervals prolongation, normal systolic (EF was maintained at >50%) but impaired diastolic function (increasing LVEDP and LV -dP/dtmin, abnormal E/A ratio), increased myocytes size, and observed relatively slight inflammatory infiltration but robust reactive fibrosis. IHC staining further confirmed that macrophages (CD68) but not neutrophils (MPO) or T cells (CD3) accounted for a predominant proportion of infiltrating cells. Mechanistically, we found that the infiltrating macrophages in the heart expressed high levels of CD206 which was simultaneously adjacent to POH fibroblasts appeared to overexpression of α-SMA in PO rats at late stages. Interestingly, we distinguished two different POHF sub-populations during PO induced HFpEF development, according to non overlapping signals of α-SMA and PDGFRα/β proteins. Additionally, PO led to a pronounced exaggeration in sympathetic fibers at all time points. These findings suggest that the establishing model here begins with cardiac sympathetic overdrive, subsequently along with immune cells especially M2 macrophage accumulation and fibroblast heterogeneity at later stages is associated with the development of cardiac maladaptive remodeling and diastolic dysfunction thus further progression to HFpEF.

Background and objectivesUrban scenic forests are a main component of forest parks, and a quantitative study of the landscape color of urban scenic forests can provide a scientific reference for the planning of forest parks and the design of scenic forest management measures. The purpose of the study is to find the quantitative correlation between autumn landscape color and ecological service functions and to obtain the important influencing factors.Materials and methodsThis study focuses on Purple Mountain National Forest Park in Nanjing as a case study area and uses forest resource survey data from Purple Mountain National Forest Park in 2020, autumn landscape color photograph data from Purple Mountain National Forest Park in 2020, and digital elevation model data as the main information sources. The correlation between two ecological functions of above-ground biomass (AGB), tree species diversity (TSD), and influencing factors (including color factors, stand factors, and terrain factors) were both analyzed by Pearson correlation analysis. Then, multiple linear regression (MLR) and random forest (RF) methods were used to perform the quantitative relationship between the functions.ResultsThe results show that, in the established quantitative models of AGB, with TSD as the dependent variable, the correlation coefficients of the MLR model are both above 0.784, while the correlation coefficients of the RF model are all above 0.872. Moreover, the brightness value of the main color (BRI), the number of yellow-green blocks (NYG), and the number of yellow blocks (NY) have important effects on the two ecological service functions.ConclusionIn conclusion, there are complex non-linear relationships between the ecological service functions of AGB, TSD, and influencing factors, and the landscape color can reflect the ecological function of the scenic forest to some extent. In addition, stand factors and color factors have important effects on the ecological function of AGB. Color factors and terrain factors have important effects on the ecological function of TSD. BRI, NYG, and NY have important effects on the two ecological functions. Finally, this quantitative method has universal applicability in the temperate zone, warm temperate zone, and subtropical zone of China.

Summary: Tumor tissues often contain high extracellular adenosine, promoting an immunosuppressed environment linked to mesenchymal transition and immune evasion. Here, we show that loss of the epithelial transcription factor, GRHL2, triggers NT5E/CD73 ecto-enzyme expression, augmenting the conversion of AMP to adenosine. GRHL2 binds an intronic NT5E sequence and is negatively correlated with NT5E/CD73 in breast cancer cell lines and patients. Remarkably, the increased adenosine levels triggered by GRHL2 depletion in MCF-7 breast cancer cells do not suppress but mildly increase CD8 T cell recruitment, a response mimicked by a stable adenosine analog but prevented by CD73 inhibition. Indeed, NT5E expression shows a positive rather than negative association with CD8 T cell infiltration in breast cancer patients. These findings reveal a GRHL2-regulated immune modulation mechanism in breast cancers and show that extracellular adenosine, besides its established role as a suppressor of T cell-mediated cytotoxicity, is associated with enhanced T cell recruitment.

BackgroundA mounting body of evidence suggests a strong connection between gut microbiota and the risk of frailty. However, the question of causality remains unanswered. In this study, we employed a Mendelian randomization (MR) approach to assess potential causal relationships between gut microbiota and the risk of frailty.Materials and methodsSummary statistics for the gut microbiome were obtained from a genome wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). Our primary analysis utilized the inverse variance weighted (IVW) method. To enhance the robustness of our results, we also applied weighted median methods, MR Egger regression, and MR pleiotropy residual sum and outlier test. Finally, we conducted reverse MR analysis to investigate the potential for reverse causality.ResultsIVW method identified 7 bacterial taxa nominally associated with the risk of FI. Class Bacteroidia (p = 0.033) and genus Eubacterium ruminantium group (p = 0.028) were protective against FI. In addition, class Betaproteobacteria (p = 0.042), genus Allisonella (p = 0.012), genus Bifidobacterium (p = 0.013), genus Clostridium innocuum group (p = 0.036) and genus Eubacterium coprostanoligenes group (p = 0.003) were associated with a higher risk of FI. No pleiotropy or heterogeneity were found.ConclusionThe MR analysis indicates a causal relationship between specific gut microbiota and FI, offering new insights into the mechanisms underlying FI mediated by gut microbiota.

Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galactose-induced N2a cells subacute aging model to investigate AFG's anti-aging activity and potential mechanisms. Results indicated that AFG treatment (8 μM) significantly reduces the overexpression of aging-related proteins (p53/p21/p16) induced by D-galactose, highlighting its anti-aging efficacy. AFG concurrently diminishes ROS accumulation, lowering extracellular lactate dehydrogenase and alleviating intracellular oxidative stress. Notably, AFG suppresses the PERK/CHOP/caspase 12 pathway, reducing intracellular Ca2+ concentration and mitigating endoplasmic reticulum (ER) stress. Additionally, AFG decreases Bax and caspase 3 expression, elevates Bcl-2 and mitochondrial membrane potential, mitigating apoptosis. NAC with 4-PBA validated the results. Overall, AFG protects N2a cells from aging by reducing ER stress and apoptosis, suggesting its potential as a key substance for treating aging and neurodegenerative diseases.

Background: Skin cutaneous melanoma (SKCM) is one of the most lethal skin malignancies worldwide. Sphingosine 1-phosphate (S1P) regulates tumor cells through S1P receptors (S1PRs). Unlike S1PR1/2/3/5, whose anti-apoptotic effects have been widely studied, the regulatory effect of S1PR4 on tumors has not been studied extensively. In this study, we aimed to investigate the correlation between S1PR4 expression and survival, clinical manifestations, tumor microenvironment, and immune infiltration in patients with SKCM. Results: Low S1PR4 expression was associated with poor prognosis in patients with SKCM. Patients in the high-expression group had significantly longer disease survival and progression-free survival than those in the low-expression group. Conclusion: High S1PR4 expression was highly associated with better prognosis and milder clinical manifestations; thus, S1PR4 may be used as a prognostic marker to help physicians monitor patients with SKCM.

Abstract Reconfigurable intelligent surface (RIS) is an emerging technology to improve the spectral efficiency of wireless communication systems. However, the high complexity of beam design and the non-negligible overhead associated with RIS limit the number of elements that can be deployed in practice. In this paper, we investigate the downlink communications of irregularly deployed intelligent reflecting surfaces that assist non-orthogonal multiple access (NOMA) systems. To address this challenge, we propose a novel four-step resource allocation algorithm. Specifically, we first obtain a sub-optimal solution for the sparse deployment of RIS elements using a Simulated Annealing Algorithm. We then solve the power allocation problem by employing an integer optimization algorithm that continuously iterates the immobile point. To simplify and optimize the reflection coefficient matrix, we propose a construction inequality algorithm. Finally, we optimize the channel assignment using a genetic algorithm. The simulation results demonstrate that the proposed irregular RIS-assisted NOMA system outperforms the traditional RIS-assisted orthogonal multiple access system, with a maximum throughput increase of approximately 30%.

Abstract Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of PTR-8/Patched is responsible for the proteostasis and lifespan defects of acs-20. Furthermore, the conserved NHR-23 nuclear receptor serves as a transcriptional repressor of ptr-8 and a key regulator of dietary restriction-induced longevity. Mechanistically, a specific region in the ptr-8 promoter plays a key role in mediating the transcription regulation and lifespan extension under dietary restriction. Altogether, these findings identify a highly conserved lipid metabolism enzyme as a key mediator of dietary restriction-induced lifespan and healthspan extension and reveal the downstream transcriptional regulation mechanisms.

Abstract Background Since diagnosis of mood disorder heavily depends on signs and symptoms, emerging researches have been studying biomarkers with the attempt to improve diagnostic accuracy, but none of the findings have been broadly accepted. The purpose of the present study was to construct a preliminary diagnostic model to distinguish major depressive disorder (MDD) and bipolar disorder (BD) using potential commonly tested blood biomarkers. Methods Information of 721 inpatients with an ICD-10 diagnosis of MDD or BD were collected from the electronic medical record system. Variables in the nomogram were selected by best subset selection method after a prior univariable screening, and then constructed using logistic regression with inclusion of the psychotropic medication use. The discrimination, calibration and internal validation of the nomogram were evaluated by the receiver operating characteristic curve (ROC), the calibration curve, cross validation and subset validation method. Results The nomogram consisted of five variables, including age, eosinophil count, plasma concentrations of prolactin, total cholesterol, and low-density lipoprotein cholesterol. The model could discriminate between MDD and BD with an area under the ROC curve (AUC) of 0.858, with a sensitivity of 0.716 and a specificity of 0.890. Conclusion The comprehensive nomogram constructed by the present study can be convenient to distinguish MDD and BD since the incorporating variables were common indicators in clinical practice. It could help avoid misdiagnoses and improve prognosis of the patients.

Abstract Introduction This study aimed to analyze the risk factors affecting the recurrence of cervical spondylotic radiculopathy after surgery, construct a nomogram predictive model, and validate the model’s predictive performance using a calibration plot. Methods In this study, 304 cervical spondylotic radiculopathy patients who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) of cervical intervertebral discs or low-temperature plasma RFA for cervical radiculopathy were enrolled at the Pain Department of Jiaxing College Affiliated Hospital from January 2019 to March 2022. The patients were randomly divided into training (n = 213) and testing (n = 91) groups in a 7:3 ratio. Lasso regression analysis was used to screen for independent predictors of recurrence 1 year after surgery. A nomogram predictive model was established based on the selected factors using multiple logistic regression analysis. Results One year after surgery, 250 of the 304 cervical spondylotic radiculopathy patients did not have recurrences, while 54 had recurrences. Lasso regression combined with multiple logistic regression analysis revealed that duration, numbness, and the Numeric Rating Scale (NRS) were significant predictors of recurrence 1 year after surgery (P 0.05). Decision curve analysis (DCA) indicated that the nomogram predictive model had a higher net benefit for predicting the risk of postoperative recurrence in cervical radiculopathy patients when the threshold probability was between 0 and 0.603. Conclusion This study successfully developed and validated a high-precision nomogram prediction model (predictive variables include duration, numbness, and NRS) for predicting the risk of postoperative recurrence in cervical radiculopathy patients. The model can help improve the early identification of high-risk patients and screening for postoperative recurrence.

Although the Linux kernel is widely used, its complexity makes errors common and potentially serious. Traditional formal verification methods often have high overhead and rely heavily on manual coding. They typically verify only specific functionalities of the kernel or target microkernels and do not support continuous verification of the entire kernel. To address these limitations, we introduce LMVM (Linux Kernel Modeling and Verification Method), a formal method based on type theory that ensures the correct design of the Linux architecture. In the model, the kernel is treated as a top-level type, subdivided into the following sublevels: subsystem, dentry, file, struct, function, and base. These types are defined in the structure and relationships. The verification process includes checking the design specifications for both type relationships and the presence of each type. Our contribution lies primarily in the following two points: 1. This is a lightweight verification. As long as the modeling is complete, architectural errors in the design phase can be identified promptly. 2. The designed “model refactor” module supports kernel updating, and the kernel can be continuously verified by extending the kernel model. To test its usefulness, we develop a set of security communication mechanisms in the kernel, which are verified using our method.

Bismuth-based compounds have been regarded as a kind of promising material due to their narrow bandgap, high carrier mobility, low toxicity, and strong oxidation ability, showing potential applications in the field of photoelectrochemical (PEC) activities. They can be applied in sustainable energy production, seawater desalination and treatment, optical detection and communication, and other fields. As a member of the broader family of bismuth-based materials, β-Bi2O3 exhibits significant advantages for applications in engineering, including high photoelectric response, stability in harsh environments, and excellent corrosion resistance. This paper presents the synthesis of β-Bi2O3 thin films utilizing the mist chemical vapor deposition (CVD) method at the optimal temperature of 400 °C. Based on the β-Bi2O3 thin film synthesized at optimal temperature, a PEC-type photodetector was constructed with the highest responsivity R of 2.84 mA/W and detectivity D of 6.01 × 1010 Jones, respectively. The photodetection performance was investigated from various points like illumination light wavelength, power density, and long-term stability. This study would broaden the horizontal and practical applications of β-Bi2O3.

This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment.

Abstract This study investigates the emotional management strategies employed by the Chinese maintream media Huanqiu Shibao (HQSB), through the use of nationalistic rhetoric during the Covid-19 pandemic. By conducting a discourse analysis of the coverage of Covid-19 on HQSB’s WeChat account, this research reveals two primary emotional management strategies: defensive nationalism and aggressive nationalism. Defensive nationalism utilizes fear and positive emotions to uphold and defend Chinese politics, while aggressive nationalism employs disgust to counter external criticisms and delegitimize the US democratic system and international leadership. By examining how HQSB emotionally differentiates the world, the study unveils that tactics Chinese mainstream media use to construct national identity, drawing a divisive line between a despised ‘them’ and an innocent ‘us’. The Covid-19 pandemic presents a unique opportunity to reflect on the emotionalisation of Chinese digital propaganda and the evolution of state-led nationalism during a public health crisis. The research concludes that the use of emotion in HQSB’s Covid-19 coverage aligns with China’s broader strategy of nation-building and global influence promotion. It underscores the need for greater awareness of the emotional mobilization used in political communication, particularly during times of crisis.