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Abstract. Background:. Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. Methods:. Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). Results:. The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. Conclusions:. DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030. more...

ABSTRACT Objective There are many advantages to stabilize the posterior pelvic ring injuries with a transiliac‐transsacral (TITS) screw percutaneously. To identify the correct entry point and insert a guidewire accurately for a TITS screw, we propose a method of specifying the optimal entry point, and introduce a technique of enabling freehand placement of a guidewire with fluoroscopic guidance. Methods In this retrospective study, 116 patients who underwent pelvic CT scans and pelvic lateral radiographs at our institution from January 2020 to April 2022 were enrolled. The optimal entry point for a TITS screw was formulated in the strict mid‐sagittal CT plane, and then transferred to the pelvic lateral radiograph relying on the sacral cortexes which were easily visible even in the poor fluoroscopy. The relative position of this point to other anatomical markers was checked to confirm its feasibility as an entry point. With the method to locate the entry point, 18 patients suffered the posterior pelvic ring injuries were treated with TITS screws through hammering a reverse Kirschner wire (K‐wire) to insert a guidewire assisted by a canula, followed by the validation of the screw placement accuracy. Results The transferred point in radiograph was consistently beneath the sacral alar slope, and located posteroinferior to the iliac cortical density (ICD) and anterosuperior to the sacral nerve root tunnel in all 116 patients. In clinical practice, 18 TITS screws were successfully placed in 18 patients without cortex violation. The average operative time for each screw was 20.11 ± 6.29 min, with an average of 14.11 ± 6.81 fluoroscopic shots per screw. At the 3‐month follow‐up, fracture healing was confirmed in all patients. The average Majeed score was 89.61 ± 6.90 at the final follow‐up. Conclusions It's feasible to identify an entry point for a TITS screw based on the sacral cortexes, and hammering a reverse K‐wire assisted by a percutaneous kyphoplasty (PKP) canula is a safe and practical technique for guidewire insertion. more...

Abstract Enhancers serve as pivotal regulators of gene expression throughout various biological processes by interacting with transcription factors (TFs). While transcription factor binding sites (TFBSs) are widely acknowledged as key determinants of TF binding and enhancer activity, the significant role of their surrounding context sequences remains to be quantitatively characterized. Here we propose the concept of transcription factor binding unit (TFBU) to modularly model enhancers by quantifying the impact of context sequences surrounding TFBSs using deep learning models. Based on this concept, we develop DeepTFBU, a comprehensive toolkit for enhancer design. We demonstrate that designing TFBS context sequences can significantly modulate enhancer activities and produce cell type-specific responses. DeepTFBU is also highly efficient in the de novo design of enhancers containing multiple TFBSs. Furthermore, DeepTFBU enables flexible decoupling and optimization of generalized enhancers. We prove that TFBU is a crucial concept, and DeepTFBU is highly effective for rational enhancer design. more...

Abstract Cells are regulated at multiple levels, from regulations of individual genes to interactions across multiple genes. Some recent neural network models can connect molecular changes to cellular phenotypes, but their design lacks modeling of regulatory mechanisms, limiting the decoding of regulations behind key cellular events, such as cell state transitions. Here, we present regX, a deep neural network incorporating both gene-level regulation and gene-gene interaction mechanisms, which enables prioritizing potential driver regulators of cell state transitions and providing mechanistic interpretations. Applied to single-cell multi-omics data on type 2 diabetes and hair follicle development, regX reliably prioritizes key transcription factors and candidate cis-regulatory elements that drive cell state transitions. Some regulators reveal potential new therapeutic targets, drug repurposing possibilities, and putative causal single nucleotide polymorphisms. This method to analyze single-cell multi-omics data demonstrates how the interpretable design of neural networks can better decode biological systems. more...

Abstract Small extracellular vesicles (sEVs), carrying PD-L1, have been implicated in immune evasion and tumor progression. However, understanding how PD-L1 sEVs are secreted still needs to be improved. We found that the secretion dynamics of PD-L1 sEVs is similar to that of other sEVs. Intracellular calcium and the associated downstream PKC signaling plays pivotal roles in releasing PD-L1 sEVs in non-small cell lung cancer cells (NSCLC). Particularly, we observed that knocking down PKCα has profound impacts on PD-L1 sEVs secretion, especially in the resting state and in the activated state, when induced by an intracellular calcium rise. Furthermore, our study revealed that PKCα regulates PD-L1 expression and PD-L1 sEVs secretion by influencing STAT1 phosphorylation and nuclear translocation in a p53-dependent manner. Notably, p53 can regulate STAT1 phosphorylation and nuclear localization, but it does not affect PKCα expression. This suggests that PKCα plays a significant role in regulating PD-L1 expression. Our findings suggest that targeting PKCα to modulate PD-L1 dynamics in NSCLC may be a promising therapeutic strategy to enhance the efficacy of immunotherapeutic interventions. more...

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein. These EGFR-low cells are intrinsically more tolerant to EGFR inhibitors, more invasive, and exhibit an epithelial-to-mesenchymal-like phenotype compared to their EGFR-high counterparts. The EGFR-low cells secrete Transforming growth factor beta (TGFβ) family cytokines, leading to increased recruitment of cancer-associated fibroblasts and immune suppression, thus contributing to the drug-tolerant tumor microenvironment. Notably, pharmacological induction of EGFR using epigenetic inhibitors sensitizes the resistant cells to EGFR inhibition. These findings suggest that intrinsic drug resistance can be prevented or reversed using combination therapies. more...

To explore the effect of eugenol addition on the gel properties of myofibrillar protein emulsions, this study used porcine myofibrillar protein as the research object and simulated the processing of emulsified sausages. The effects of eugenol concentration (0, 5, 10, 20, 50, and 100 mg/g protein) on the protein secondary structure, gel strength, water retention, water distribution, rheology, and microstructure were determined to investigate the effect of eugenol on protein gel formation. The results showed that the addition of low-concentration eugenol (20 mg/g) significantly improved the gel strength and water retention rate of the protein (P more...

Super-resolution image reconstruction (SRR) is an important task in remote sensing image (RSI) processing, which can serve the application fields, such as natural resources exploration and agricultural monitoring. Recently deep learning based methods achieved great success in RSI-SRR, making RSI-SRR more efficient and accurate. However, homogeneous low-resolution (LR) and high-resolution RSI pairs from the same sensor are often difficult to obtain, and the use of simulated image pairs makes it difficult to apply these methods in real scenarios. Some RSI-SRR methods attempt to reconstruct image resolution from heterogeneous RSIs. But these methods, on the one hand, are difficult to deal with large-scale RSI-SRR; and on the other hand, they do not take into account the domain differences of heterogeneous RSIs. To address the above challenges, this article proposes a scale-decoupling super-resolution network with domain transfer for heterogeneous RSIs (SDDT-SR). The SDDT-SR breaks down the large-scale SSR (x8) into two cascaded smaller-scale steps (x2, x4), progressively restoring spatial details of the images. Specifically, in SDDT-SR, an SR module with domain transfer (DTSR) is designed to transfer the LR image from a specific domain to another one, and an SR module with unpaired learning (ULSR) is designed to further up-sample the output of DTSR to the target resolution. Experiments on SGSRD and satellite-UAV heterogeneous image change detection dataset (HTCD) dataset show that SDDT-SR outperforms existing methods in both metrics and visualization, with the fréchet inception distance (FID) of 181.8679 on SGSRD and of 163.3831 on HTCD. more...

Abstract Background Indigenous pig breeds in China have accumulated significant genetic diversity due to regional selection pressures. Investigating the selection signatures of these populations helps to understand their adaptive evolution and contributes to genetic improvement programs. Results We collected whole-genome sequencing data from 133 individuals, including South China and North China indigenous pigs and Asian wild boars. After data filtering, we retained 31,521,978 high-quality SNPs. Population structure analysis using PCA revealed distinct genetic clustering among these populations. Selection signature detection identified 5,227 loci under selection in South China indigenous pigs and 5,800 in North China indigenous pigs compared to Asian wild boars. Candidate genes were enriched in immune response pathways, reproductive traits, and pigmentation pathways. South China indigenous pigs exhibited selection signals for fat deposition and immune responses, while North China indigenous pigs showed stronger signals related to growth, blood physiology, and reproductive performance. Additionally, key genes such as MC1R and KIT were associated with coat color variation, and IGF1R and IGF2R were linked to growth regulation. Conclusion Our results demonstrate that indigenous pigs in China have undergone selection for distinct traits aligned with their regional environments and farming systems. South China indigenous pigs have been selected for traits related to fat deposition and immunity, while North China indigenous pigs have been selected for growth and reproductive traits. The findings offer crucial insights into the genetic architecture of indigenous pig breeds, providing a valuable foundation for future genetic breeding programs. more...

Abstract Background Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems. Results Here, we reported a Chinese SCA48 family exhibited typical features and defined a novel missense mutation STUB1 c.755A>C (CHIP p. Y252S) through whole-exome sequencing. The variant was interpreted as a variant of uncertain significance, so we conducted a series of experiments using minigene plasmids to evaluate the pathogenicity of the variant. We found that the variant STUB1 c.755A>C caused a significant reduction of CHIP level and the loss function of ubiquitin ligase activity as the pathogenic STUB1 mutations reported before. Besides, we also found that the CHIP p. Y252S could cause tau aggregation, which is considered to contribute to the progression of neurodegenerative disorders. Conclusions We diagnose the SCA48 pedigree in China and highlight the role of decreased ubiquitination and increased tau aggregation in the pathogenesis of the novel STUB1 c.755C>A mutation. more...

Molecular spectroscopy, with a legacy spanning over a century, has profoundly enriched our understanding of the microscopic world, driving major advancements across science and engineering. Over time, this field has steadily advanced, incorporating innovations such as lasers and digital computers to reach new levels of precision and sensitivity. Over the past decade, the integration of high-speed embedded electronic systems and advanced light sources has ushered molecular spectroscopy into a new era, characterized by extensive parallelism and enhanced sensitivity. This review delves into two pioneering technologies that embody recent advancements in molecular spectroscopy: Chirped-Pulse Fourier Transform Microwave (CP-FTMW) spectroscopy and optical frequency comb (OFC) spectroscopy. We provide an overview of the fundamental principles behind these methods, examine their most impactful applications across diverse fields, and discuss their potential to drive future developments in molecular spectroscopy. By highlighting these technologies, we aim to underscore the transformative impact of integrating high-speed digital electronics and advanced light sources with molecular spectroscopy, enabling extensive parallelism and paving the way for groundbreaking discoveries and innovations in this rapidly evolving field. more...

Abstract Integrated electricity‐heat system (IEHS) has been paid more and more attention in recent years for its advantage in improving energy efficiency, reducing carbon emissions and increasing renewable energy penetration. To ensure the safety, reliability and economic operation of IEHS, several centralised state estimation (SE) methods for IEHS have been proposed. However, power systems and heat systems often belong to different management entities, and there are industrial barriers such as information privacy, operational differences, and target differences between them, which leads to less applicability of centralised SE methods. In addition, the robustness of existing distributed SE methods for IEHS is not satisfactory. To this end, a distributed robust state estimation (DRSE) model for IEHS based on the alternating direction method of multipliers (ADMM) is proposed. Firstly, by introducing auxiliary state variables and measurements, a robust linear SE model based on weighted least absolute values (WLAV) is proposed. Then, second‐order cone constraints composed of auxiliary state variables are added to the SE model, leading a SOCP‐based robust SE model. Finally, the ADMM algorithm is used to solve the proposed SOCP‐based robust SE model. Simulations demonstrate that the proposed method has higher estimation accuracy in both general and strongly correlated adverse data tests and also can ensure data privacy, good robustness and high estimation accuracy. This indicates that the method proposed has good robustness and solves the problem of weak robustness of existing distributed static state estimation methods. more...

Abstract Under the background of achieving the dual‐carbon goal, the park is a natural experimental field for practicing the dual‐carbon goal. A low‐carbon optimal scheduling strategy for a multi‐agent park‐integrated energy system (P‐IES) based on the Stackelberg–Nash game is proposed. Firstly, a low‐carbon P‐IES scheduling model is established, considering the two‐stage operation of power‐to‐gas (P2G) technology and reward–punishment stepwise carbon trading mechanism. Then, a two‐layer game optimisation model is proposed with a park‐integrated energy system operator (P‐IESO) as the leader and multiple low‐carbon P‐IESs as followers. Among them, the parks are connected with each other through the power trading channels. Then, the Nash equilibrium solution is obtained by the iterative search method, and the uniqueness of the equilibrium solution of the game is proven, so as to determine the optimal pricing strategy of the operator. Finally, a typical industrial park is taken as an example for simulation verification. The example analysis verifies that the model can effectively reduce the system's carbon emissions and improve the park's economic benefits and low‐carbon levels, thereby achieving the coordinated development of low‐carbon and economic performance in the park. more...

Abstract To address the array aperture loss caused by mainstream direction of arrival (DOA) estimation algorithms for coherent signals using matrix interpolation techniques, a non‐circular (NC) coherent signal direction‐finding method that fully utilises covariance matrix information is proposed. The received data is firstly extended by leveraging its NC properties. Then, eigenvalue decomposition is performed on the covariance matrix to extract the signal subspace, which is mapped to a uniform linear array signal subspace via a mapping matrix. The first row of the covariance matrix corresponding to the signal subspace is employed to construct a Toeplitz matrix, and nuclear norm minimisation method is applied to recover the missing information. Finally, to avoid extra NC phase searching, the reduced‐dimension method is applied to obtain the estimation results. Performance analysis and simulation results show that the proposed algorithm achieves improvements in computational complexity, source estimation capability, and estimation accuracy. more...

Abstract The image protection of non‐fungible tokens based on zero‐watermark methods has received widespread attention. However, on the one hand, existing zero‐watermark methods are often limited to complex texture changes in the host image, and the features for constructing the zero‐watermark are vulnerable to geometric attacks. On the other hand, a single watermark image cannot adapt to the diverse usage scenarios of non‐fungible tokens. This paper proposes a robust personalized zero‐watermark scheme to address the challenges above. Firstly, the image regions suitable for constructing zero‐watermarks are highlighted by the non‐uniform weighted reconstruction, and the U‐Net is introduced for feature extraction against the geometric attacks. At the same time, the watermark images generated by generative models that are suitable for the usage scenario have achieved zero‐watermark addition and protection for non‐fungible token image content. The proposed method has been experimentally verified to have a certain degree of robustness in geometric and non‐geometric attacks. more...

Abstract Background Half of patients with heart failure are estimated to have sleep‐disordered breathing (SDB). However, many are undiagnosed as they do not report typical symptoms. This study aims to evaluate the implantable cardiac defibrillator (ICD) sleep‐disordered breathing algorithm in a cohort of multi‐racial Asian patients for detection of SDB against polysomnography (PSG). Methods In this prospective pilot study, participants who fulfill the American College of Cardiology (ACC) indication for ICD were recruited. The ICD algorithm uses transthoracic impedance sensing to calculate respiratory disturbance index (RDI). Results Twenty‐four patients were enrolled between August 2020 and December 2021. All patients underwent PSG exams and were followed up for up to 12 months. Eighteen participants completed the PSG study as of August 23, 2022. Severe SDB (defined as PSG‐AHI ≥30 episodes/h) was diagnosed in 66.7% of the patients. No significant direct linear correlation was found between the PSG‐AHI measurements and the RDI measurements (adjusted r2 = .224, r = .473, p = .027). Applying a binary threshold cut‐off RDI value of 32 episodes/h for the detection of severe SDB yielded a sensitivity of 91.7% and specificity of 16.7%. Conclusions Transthoracic impedance sensing with an advanced inbuilt algorithm may be helpful as a screening test in detecting severe SDB in patients with heart failure and cardiomyopathy, potentially by applying a binary threshold cut‐off value. This is the first study known to validate the algorithm in an exclusively multi‐ethnic Asian population with heart failure. more...

The variability of soil organic carbon (SOC) extends across three dimensions. However, quantitative analyses of the factors influencing spatiotemporal variations of SOC in various soil depth is scarce. This study leverages legacy data from two soil surveys conducted in the Dongting Lake Basin during the 1980s and the 2010s, employing Random Forest models to generate three-dimensional SOC maps. Through correlation analysis and permutation importance, we identified the primary factors driving temporal and spatial changes of SOC. The results showed that in the 2010s, SOC storage up to a depth of 1 m in the Dongting Lake Basin was approximately 2.95 Pg, increasing at an average rate of 0.0047 Pg C per year since the 1980s. Regions with higher average SOC contents were predominantly found in the western, southern, and eastern parts of the basin, despite significant losses over the 30-year period. In contrast, the central and northern areas, which initially had lower SOC contents in the 1980s, exhibited increases by the 2010s. Soil depth was the most influential predictor of SOC patterns in both the 1980s and 2010s. Meanwhile, relief and organism factors were primarily responsible for spatial variations in SOC, with the influence of organism factors diminishing by the 2010s. The temporal variations of SOC were chiefly attributed to changes in soil conservation practices, extreme precipitation events, and grain production. Consequently, it is imperative to prioritize ecological restoration and conservation tillage practices to mitigate the impacts of extreme weather conditions and safeguard food security. more...

Abstract Previous studies have explored the associations between parental and offspring’s depression and parent-child communication. However, few studies have investigated their symptomatic associations and potential sex differences. Therefore, this study aims to examine their associations and sex differences in parents and offspring. Based on the China Family Panel Studies (CFPS)-2020 study, depressive symptoms and parent-child communication were measured by the 8-item Center for Epidemiologic Studies Depression Scale (CESD-8) and independent questions, respectively. Network analysis was used to investigate the associations and to compare the sex differences of parents and offspring. A total of 1710 adolescents were included after cleaning process (N = 28,530). There were significantly stronger associations in boys’ “anhedonia” and “arguments with parents”, and in girls’ “happiness” and parents’ “joyfulness”. Furthermore, there were same-sex depression associations between children and parents (e.g., boys’ “despair”–fathers’ “joyfulness”; girls’ “anhedonia”–mothers’ “loneliness”). These results would help us to better understand the in depression and communication nuanced associations and to develop effective strategies for improving parental and offspring’s mental health. more...

This study investigates the impact of warm-rolling and subsequent annealing on the microstructure and tensile properties of a dual-phase Al0.45CoCrFeNiTi0.25 high-entropy alloy (HEA) containing both face-centered cubic and body-centered cubic phases. The HEA underwent warm-rolling at temperatures of 450, 600, and 750 °C with a 50% reduction in thickness, followed by annealing at various temperatures. Higher warm-rolling temperatures facilitated the precipitation of B2 particles, significantly influencing the alloy's phase distribution. Throughout the experiments, no new phases emerged, and annealing maintained the alloy's original phase composition.Warm-rolling at 450 °C, followed by annealing at 1200 °C, led to substantial microstructural changes, including the formation of distinctive annealed twins. These microstructural changes enhanced ductility significantly, increasing elongation to 13.4% (a 538% improvement over the as-cast state) while maintaining a fracture strength of 983 MPa. Overall, this comprehensive analysis demonstrates that optimizing the warm-rolling and annealing parameters can significantly enhance the properties of dual-phase HEA. more...

This study investigated the microstructure and mechanical properties of GdxCoCrFeNiV0.4 alloys. Various techniques such as XRD, SEM, EBSD, and TEM were utilized, alongside hardness and compression tests at room temperature. The findings revealed that the high-entropy alloy without Gd element exhibited a single face-centered cubic (FCC) phase. Upon the introduction of Gd element, the phase composition shifted to FCC + hexagonal structure (HS) phases, and further addition of Gd resulted in the presence of FCC + HS + body-centered cubic (BCC) phases. Additionally, the inclusion of Gd element led to the precipitation of Gd-rich particles within the alloy. The Vickers hardness test results revealed a significant increase in alloy hardness as the Gd content rose, from 177.5 HV for Gd0 to 848.4 HV for Gd0.4. This suggests that the presence of the HS phase and BCC phase notably influences alloy hardness. Furthermore, compressive test outcomes demonstrated that the alloy's yield strength rose from 173.74 MPa for Gd0 to 1356.17 MPa for Gd0.3 with increasing Gd content. However, the excessive addition of Gd elements results in significant precipitation of V and Cr elements, leading to grain coarsening, adversely affecting its mechanical properties. The high strength of Gd-containing high-entropy alloys can be attributed to various strengthening mechanisms, such as solid solution strengthening, the presence of the HS phase, the precipitation of a small number of Gd-rich particles, and the grain refinement caused by the addition of Gd. more...

Nanolayered Zr/Nb metals are considered promising for advanced nuclear reactors due to their superior resistance to irradiation. In this study, Zr/Nb multilayers were irradiated with 50 keV He+ ions to a fluence of 1 × 1017 ions/cm2 at temperatures of room temperature, 350 °C, and 500 °C to investigate irradiation-induced structural changes. X-ray diffraction (XRD) analysis indicated low-angle shifts of 0.08–0.54° and high-angle shifts of 0.08–0.42° in the irradiated Zr and Nb layers, suggesting tensile and compressive strains, respectively. At 500 °C, the selected-area electron diffraction (SAED) observed a 9.2% lattice expansion in Zr and a 0.13% contraction in Nb. Geometric phase analysis (GPA) revealed varying strain distributions, transitioning from incoherent to coherent interfaces with increasing irradiation damage. Transmission electron microscopy (TEM) identified the presence of He bubbles in the Zr layer as one of the reasons for strain differences. Nanoindentation tests showed an increase at a depth of 150 nm hardness of 0.831 GPa at 500 °C compared to 350 °C. These results are attributed to differences in crystal structure, vacancy dynamics, interfacial effects, and lattice strain influences. Stability of Zr/Nb interfaces after He irradiation was studied. This study provides insights into the radiation behavior of Zr/Nb nanoscale metallic materials, enhancing our understanding of their potential as structural materials in nuclear energy systems. more...

Abstract Purpose DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). Methods Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. Results High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. Conclusion In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications. more...

Abstract LncRNAs are highly implicated in oxidative stress (OS) during the growth of mammalian follicles. TAK1 binding protein 2 gene (TAB2) has been suggested to involve in the normal apoptosis and proliferation of granulosa cells (GCs), the main supporting cells in ovarian follicles. In this study, we found that TAB2 increased the expressions of SOD1, P50, and P65 to suppress the OS, thereby inhibiting the apoptosis and promoting the proliferation in GCs. Notably, DNMTs appeared to mediate the expression of TAB2 without the changes of DNA methylation at TAB2’s promoter. We identified an antisense lncRNA of TAB2, discovered that DNA methylation regulated the transcription of TAB2-AS in GCs, and found TAB2-AS medicated the follicular growth of ovaries in vivo. Mechanistically, the hypomethylation of the CpG site (−1759/−1760) activated the transcription of TAB2-AS, and the 1–155 nt and 156-241 nt of TAB2-AS were respectively complementary to 4368–4534 nt and 4215–4300 nt of TAB2’s mRNA to increase the expression of TAB2. Moreover, TAB2-AS inhibited the OS and apoptosis of GCs, while promoted the proliferation of GCs to expedite the follicular growth, which was in line with that of TAB2. Collectively, these findings revealed the antisense lncRNA mechanism mediated by DNA methylation, and TAB2-AS might be the target to control OS during follicular growth in mammals. more...

Abstract For light-element materials, X-ray phase contrast imaging provides better contrast compared to absorption imaging. While the Fourier transform method has a shorter imaging time, it typically results in lower image quality; in contrast, the phase-shifting method offers higher image quality but is more time-consuming and involves a higher radiation dose. To rapidly reconstruct low-dose X-ray phase contrast images, this study developed a model based on Generative Adversarial Networks (GAN), incorporating custom layers and self-attention mechanisms to recover high-quality phase contrast images. We generated a simulated dataset using Kaggle’s X-ray data to train the GAN, and in simulated experiments, we achieved significant improvements in Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM). To further validate our method, we applied it to fringe images acquired from three phase contrast systems: a single-grating phase contrast system, a Talbot-Lau system, and a cascaded grating system. The current results demonstrate that our method successfully restored high-quality phase contrast images from fringe images collected in experimental settings, though it should be noted that these results were achieved using relatively simple sample configurations. more...

Soil salinity is a big environmental issue affecting crop production. Although seed nanopriming has been widely used to improve seed germination and seedling growth under salinity, our knowledge about the underlying mechanisms is still insufficient. Herein, we newly synthesized selenium-doped carbon dots nanoparticles coated with poly acrylic acid (poly acrylic acid coated selenium doped carbon dots, PAA@Se-CDs) and used it to prime seeds of rapeseeds. The TEM (transmission electron microscope) size and zeta potential of PAA@Se-CDs are 3.8 ± 0.2 nm and −30 mV, respectively. After 8 h priming, the PAA@Se-CDs nanoparticles were detected in the seed compartments (seed coat, cotyledon, and radicle), while no such signals were detected in the NNP (no nanoparticle control) group (SeO2 was used as the NNP). Nanopriming with PAA@Se-CDs nanoparticles increased rapeseeds germination (20%) and seedling fresh weight (161%) under saline conditions compared to NNP control. PAA@Se-CDs nanopriming significantly enhanced endo-β-mannanase activities (255% increase, 21.55 µmol h−1 g−1 vs. 6.06 µmol h−1 g−1, at DAS 1 (DAS, days after sowing)), total soluble sugar (33.63 mg g−1 FW (fresh weight) vs. 20.23 mg g−1 FW) and protein contents (1.96 µg g−1 FW vs. 1.0 µg g−1 FW) to support the growth of germinating seedlings of rapeseeds under salt stress, in comparison with NNP control. The respiration rate and ATP content were increased by 76% and 607%, respectively. The oxidative damage of salinity due to the over-accumulation of reactive oxygen species (ROS) was alleviated by PAA@Se-CDs nanopriming by increasing the antioxidant enzyme activities (SOD (superoxide dismutase), POD (peroxidase), and CAT (catalase)). Another mechanism behind PAA@Se-CDs nanopriming improving rapeseeds salt tolerance at seedling stage was reducing sodium (Na+) accumulation and improving potassium (K+) retention, hence increasing the K+/Na+ ratio under saline conditions. Overall, our results not only showed that seed nanopriming with PAA@Se-CDs could be a good approach to improve salt tolerance, but also add more knowledge to the mechanism behind nanopriming-improved plant salt tolerance at germination and early seedling growth stage. more...

Abstract Despite the well‐documented mutation spectra of β‐thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long‐read sequencing (T‐LRS) is demonstrated to capture 20 genes/loci in 1,020 β‐thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci. The highly homologous regions of α‐/β‐globin gene clusters are then phased and 3 novel haplotypes in HBG1/HBG2 region are reported in this population of β‐thalassemia patients. Furthermore, one of the haplotypes is associated with ameliorated symptoms of β‐thalassemia. Similarly, 5 major haplotypes are identified in HBA1/HBA2 homologous region while one of them is found highly linked with deletional α‐thalassemia mutations. Finally, rare mutations in erythroid transcription factors in DNMT1 and KLF1 associated with increased expression of fetal hemoglobin and reduced transfusion dependencies are identified. This study presents the largest T‐LRS study for β‐thalassemia patients to date, facilitating precise clinical diagnosis and haplotype phasing of globin gene clusters. more...

Biodiversity is fundamental to human well-being and economic development. The Yangtze River, the largest river in China, faces biodiversity loss due to habitat degradation, climate change, and other anthropogenic threats. However, the long-term changes in the region's biodiversity remain poorly understood. Here, we constructed an optimized living planet index (LPIO) by combining Partial Least Squares Structural Equation Modeling and Random Forest Modeling. Using data from a monitoring network of 536 sites, we observed an increasing trend in terrestrial bird diversity and functional complexity across the entire watershed from 2011 to 2020. Our findings indicate that a large-scale ecological restoration program has contributed to increases in terrestrial and aquatic bird diversity in the Yangtze River Basin. In contrast, bird diversity in the downstream area has decreased by 2.83%, largely due to a rapid decline in wetland birds. The degradation of wetland habitats and insufficient conservation measures have negatively impacted bird diversity in the downstream region. This suggests that although there have been significant improvements in terrestrial bird diversity, more effective wetland restoration is necessary for biodiversity conservation. We recommend optimizing the national large-scale biodiversity monitoring network and increasing the number of upstream monitoring sites. more...

The tall and short traits of chickens are significant indicators for evaluating their growth and development. Tall chickens have longer growth cycles, allowing them to accumulate sufficient nutrients and resulting in superior meat quality. This study aims to investigate the tall and short traits of Baicheng Fatty chickens and to identify relevant candidate genes. A total of 25 Baicheng Fatty chickens were selected for this research, where whole genome resequencing was performed on all samples to uncover genetic variations influencing tall and short traits. Additionally, transcriptome sequencing was conducted on 15 of these chickens to identify important genes affecting these traits through combined analysis. Using methods such as population genetic structure analysis, principal component analysis (PCA), linkage disequilibrium analysis (LD), runs of homozygosity (ROH) analysis, as well as genetic differentiation index (FST) and nucleotide diversity (θπ), a total of 1,019 candidate genes were identified through whole genome resequencing analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these candidates. From the transcriptome data, 253 differentially expressed genes (DEGs) were identified, including 229 upregulated and 24 downregulated genes. GO and KEGG enrichment analyses were conducted on these differential genes, and a protein–protein interaction network for the DEGs was constructed. Through the combined analysis of whole genome resequencing and transcriptome data, six intersecting genes were identified: KLF15, NRXN1, LOC107050638, MHCY11, HAO1, and BORCS6. KEGG enrichment analysis revealed significant involvement in the Glyoxylate and Dicarboxylate Metabolism pathway, Peroxisome pathway, Carbon Metabolism, and Cell Adhesion Molecules (CAMs) pathway. These genes may influence the growth and developmental patterns of skeletal structures, though their regulatory mechanisms require further investigation. This study provides new insights for further research into the genetic mechanisms underlying chicken skeletal development and growth, as well as potential molecular markers for poultry breeding. more...

Abstract Generating computer‐generated holograms (CGHs) for 3D scenes by learning‐based methods can reconstruct arbitrary 3D scenes with higher quality and faster speed. However, the homogenization and difficulty of obtaining 3D high‐resolution datasets seriously limit the generalization ability of the model. A novel approach is proposed to train 3D encoding models based on convolutional neural networks (CNNs) using 2D image datasets. This technique produces virtual depth (VD) images with a statistically uniform distribution. This approach employs a CNN trained with the angular spectrum method (ASM) for calculating diffraction fields layer by layer. A fully convolutional neural network architecture for phase‐only encoding, which is trained on the DIV2K‐VD dataset. Experimental results validate its effectiveness by generating a 4K phase‐only hologram within only 0.061 s, yielding high‐quality holograms that have an average PSNR of 34.7 dB along with an SSIM of 0.836, offering high quality, economic and time efficiencies compared to traditional methods. more...

BackgroundEmergency departments (EDs) are high-pressure environments where clinicians diagnose patients under significant constraints, including limited medical histories, severe time pressures, and frequent interruptions. Current ED care practices often inadequately support meaningful patient participation. Most interventions prioritize clinical workflow and health care provider communication, inadvertently overlooking patients’ needs. Additionally, patient-facing technologies in EDs are typically developed without meaningful patient input, leading to solutions that may not effectively address patients’ specific challenges. To enhance both patient-centered care practices and the diagnosis process in EDs, patient involvement in technology design is essential to ensure their needs during emergency care are understood and addressed. ObjectiveThis study aimed to invite ED patients to participatory design sessions, identify their needs during ED visits, and present potential design guidelines for technological interventions to address these needs. MethodsWe conducted 8 design sessions with 36 ED patients and caregivers to validate their needs and identify considerations for designing patient-centered interventions to improve diagnostic safety. We used 10 technological intervention ideas as probes for a needs evaluation of the study participants. Participants discussed the use cases of each intervention idea to assess their needs during the ED care process. We facilitated co-design activities with the participants to improve the technological intervention designs. We audio- and video-recorded the design sessions. We then analyzed session transcripts, field notes, and design sketches. ResultsOn the basis of ED patients’ feedback and evaluation of our intervention designs, we found the 3 most preferred intervention ideas that addressed the common challenges ED patients experience. We also identified 4 themes of ED patients’ needs: a feeling of inclusion in the ED care process, access to sources of medical information to enhance patient comprehension, addressing patient anxiety related to information overload and privacy concerns, and ensuring continuity in care and information. We interpreted these as insights for designing technological interventions for ED patients. Therefore, on the basis of the findings, we present five considerations for designing better patient-centered interventions in the ED care process: technology-based interventions should (1) address patients’ dynamic needs to promote continuity in care; (2) consider the amount and timing of information that patients receive; (3) empower patients to be more active for better patient safety and care quality; (4) optimize human resources, depending on patients’ needs; and (5) be designed with the consideration of patients’ perspectives on implementation. ConclusionsThis study provides unique insights for designing technological interventions to support ED diagnostic processes. By inviting ED patients into the design process, we present unique insights into the diagnostic process and design considerations for designing novel technological interventions to enhance patient safety. International Registered Report Identifier (IRRID)RR2-10.2196/55357 more...

BackgroundFor patients who received transforaminal lumbar interbody fusion (TLIF) treatment for lumbar disc herniation, most of them can achieve good results, but there were still some patients who were not satisfied with the surgical results. The purpose of this study is to explore the factors that contribute to patient dissatisfaction after TLIF.MethodsFrom March 2018–December 2021, patients with lumbar disc herniation who received TLIF treatment were included in this study. Clinical data from preoperative and postoperative 2-year follow-up were analyzed. Associations between clinical variables and function of postoperative were examined in univariate and multivariate analysis.ResultOf all the 625 patients, including 296 (47.4%) male patients and 329 (52.6%) female patients. According to patient satisfaction index (PSI), patients were divided into two groups, 529 patients in satisfied group showing 1 or 2 stage in PSI and 96 patients in dissatisfied group showing 3 or 4 stage in PSI. Univariate analysis showed that body mass index (BMI), preoperative pain time, postoperative visual analog scale (VAS)-back, intraoperative bleeding volume, postoperative rehabilitation training, feel depression and symptom recurrence were related with patient's level of satisfaction 2 years after discectomy. When incorporated into a multivariate logistic regression analysis, it was found that BMI, preoperative pain duration, postoperative rehabilitation training, feel depression and symptom recurrence were individually correlated with patient dissatisfaction 2 years after discectomy.ConclusionThis study indicates that the factors that leading to postoperative dissatisfaction of patients include obesity, preoperative pain duration lasting no less than 6 months, feel depression and symptom recurrence. While postoperative rehabilitation training for three months is a protective factor. more...

IntroductionBrucellosis, an infectious zoonotic disease caused by members of the genus Brucella, results in chronic multi-organ injury. Improving the specificity and sensitivity of serological methods for diagnosing brucellosis necessitates the development of novel diagnostic antigens. The twin-arginine translocation (Tat) pathway is responsible for transporting folded proteins across the cytoplasmic membrane and has been implicated in the virulence of Brucella. Three Tat substrate proteins—L,D-transpeptidase ErfK (A0577), linear amide C-N hydrolase YxeI (A1479), and thioesterase domain-containing protein EntF (B0249)—contribute significantly to Brucella virulence. However, the roles of these Tat substrate proteins in diagnosing brucellosis remain unclear.MethodsIn this study, ErfK, YxeI, and EntF were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera from bovines and sheep diagnosed with brucellosis were analyzed using indirect ELISA with these proteins.ResultsFor bovine serum, the combined protein group (ErfK + YxeI + EntF) and YxeI demonstrated the highest diagnostic accuracy of 94.23% and 93.58%, respectively. Meanwhile, the combined protein group showed the strongest ability to detect Brucella in sheep serum, achieving an accuracy of 88.10%. Both the combined protein group and YxeI displayed no cross-reactivity with rabbit serum immunized against Yersinia enterocolitica O9, Escherichia coli O157:H7, Mycobacterium tuberculosis, Vibrio cholerae, Legionella, and Salmonella, indicating relatively good specificity.ConclusionThe findings of this study suggest that Tat substrate proteins serve as promising candidate antigens with significant potential value for the clinical diagnosis of brucellosis. more...

Background: With an increasing number of non-small cell lung cancer (NSCLC) patients being offered surgical treatment, postoperative rehabilitation is also being increasingly emphasized. Traditional Chinese medicine (TCM) holds promise for enhancing postoperative recovery, with treatment methods still in refinement. This study aims to evaluate the efficacy of Chinese herbal decoction and Liuzijue exercises in NSCLC patients during the rapid postoperative recovery period. Methods: A randomized, parallel-group clinical trial assigned 50 patients to receive Chinese herbal medicine and Liuzijue exercise plus symptomatic treatment, and 49 to symptomatic treatment alone. Treatment continued until postoperative complications resolved, chest tubes were removed, and no abnormal examination findings were reported. The primary outcome was Quality of Life Questionnare-Core 30 (QLQ-C30) score. Secondary outcomes included MOS item short form 36-Item Short Form Health Survey (SF-36) score, rate of complications, six-minute walk test (6MWT) distance, Leicester Cough Questionnaire (LCQ) score, numerical rating scale (NRS) score, and functional activity score (FAS). Results: Significant improvements in role (MD: 12.15, 95%CI: 2.99-21.32, P more...

BackgroundThis study aims to investigate the connection between serum lipids, per- and polyfluoroalkyl substances (PFAS), and age-related macular degeneration (AMD) risk and assess whether serum lipids mediate the association between PFAS and AMD.Methods1605 participants were enrolled from NHANES 2005-2008. Four serum PFAS levels with high detective rates, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) were examined. Restricted cubic spline analysis (RCS) and weighted quantile sum (WQS) analysis were employed to detect nonlinear and mixed exposure effects.ResultsPFOS level was associated with any AMD (OR, 1.54; 95% CI, 1.12 to 2.11; P = 0.011), early AMD (OR, 1.43; 95% CI, 1.06 to 1.95; P = 0.024), and late AMD (OR, 3.35; 95% CI, 1.55 to 7.23; P = 0.004) risk. PFHxS (OR, 1.72; 95% CI, 1.01 to 2.93; P = 0.045) and PFOA (OR, 2.10; 95% CI, 1.21 to 3.63; P = 0.011) levels were associated with late AMD risk. The RCS showed a nonlinear connection between PFOS exposure and AMD risk (P nonlinear = 0.006). WQS analysis indicated a positive relationship between mixed PFAS exposure and AMD risk (OR, 1.34; 95% CI, 1.03 to 1.75; P = 0.030). Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were associated with AMD risk (ORTC, 1.005; 95% CI, 1.001 to 1.009; P = 0.026. ORHDL, 1.028; 95% CI, 1.014 to 1.042; PConclusionsPFOS exposure was connected with AMD risk and serum TC and HDL mediated this relationship. more...

IntroductionEnterocytozoon bieneusi is one of the most frequent microsporidia species causing digestive disorder mainly diarrhea in humans and animals. Eld’s deer (Rucervus eldii) is the class I national key protected wildlife and only distributed on Hainan Island in China. No report on the prevalence and molecular characterization of E. bieneusi in wild Eld’s deer worldwide.Methods217 fecal samples were collected from Eld’s deer in two isolated habitats of a nature reserve in Hainan, and examined by nested Polymerase Chain Reaction (PCR) targeting the internal transcribed spacer (ITS) region.Results and discussionThe overall prevalence of E. bieneusi in Eld’s deer was 17.5% (38/217), with 13.5% (12/89) and 20.3% (26/128) in habitats 1 and 2, respectively. Seven ITS genotypes were identified, including five known genotypes: D (n = 19), Peru11 (n = 10), EbpC (n = 5), Peru8 (n = 1) and Type IV (n = 1), and two novel genotypes: HNED-I and HNED-II (one each). Genotypes Peru8 and Peru11 were firstly identified in cervids. Phylogenetic analysis showed that all the detected genotypes belonged to zoonotic Group 1. The results implied that the further research on threaten of E. bieneusi to endangered Eld’s deer and potential risks for public health is necessary. more...

BackgroundTo evaluate the efficacy and safety of clopidogrel-rivaroxaban combination compared to aspirin-rivaroxaban combination in patients with symptomatic peripheral artery disease (PAD).MethodsConsecutive patients with symptomatic PAD patients were analyzed from January, 2018 to June, 2022 at Nanjing Drum Tower Hospital. Patients were divided into two groups based on the antithrombotic therapy. The primary efficacy outcome was a composite of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and the primary safety outcome was major bleeding. Patients were followed until the first occurrence of any outcomes or the study end date (30 June 2024).ResultsA total of 695 patients were enrolled into this study. The clopidogrel-rivaroxaban combination significantly reduced the risk of composite outcome (HR: 0.59, 95%CI: 0.41–0.83) without increasing the risk of major bleeding (HR: 0.68, 95%CI: 0.27–1.69). When analyzed separately, clopidogrel-rivaroxaban combination was associated with a reduced risk of MALE (HR: 0.61, 95%CI: 0.41–0.91), although no significant differences were observed in terms of MACE (HR: 0.64, 95%CI: 0.34–1.20) or all bleeding events (HR: 1.00, 95%CI: 0.52–1.93). In the subgroup analysis, there were no significant interactions between the treatment groups and the subgroups of age, diabetes, lesion sites, Rutherford classifications and renal function for composite outcome, MACE and MALE.ConclusionThe clopidogrel-rivaroxaban combination in PAD patients may offer enhanced cardiovascular protection without increasing the risk of bleeding complications. These findings suggested that clopidogrel could be a superior alternative to aspirin in dual antithrombotic therapy for PAD management. more...

Abstract Muscular atrophy is among the systematic decline in organ functions in aging, while defective thermogenic fat functionality precedes these anomalies. The potential crosstalk between adipose tissue and muscle during aging is poorly understood. In this study, it is showed that UCP1 knockout (KO) mice characterized deteriorated brown adipose tissue (BAT) function in aging, yet their glucose homeostasis is sustained and energy expenditure is increased, possibly compensated by improved inguinal adipose tissue (iWAT) and muscle functionality compared to age‐matched WT mice. To understand the potential crosstalk, RNA‐seq and metabolomic analysis were performed on adipose tissue and muscle in aging mice and revealed that creatine levels are increased both in iWAT and muscle of UCP1 KO mice. Interestingly, molecular analysis and metabolite tracing revealed that creatine biosynthesis is increased in iWAT while creatine uptake is increased in muscle in UCP1 KO mice, suggesting creatine transportation from iWAT to muscle. Importantly, creatine analog β‐GPA abolished the differences in muscle functions between aging WT and UCP1 KO mice, while UCP1 inhibitor α‐CD improved muscle glycolytic function and glucose metabolism in aging mice. Overall, these results suggested that iWAT and skeletal muscle compensate for declined BAT function during aging via creatine metabolism to sustain metabolic homeostasis. more...

MuscleX is an integrated, open-source computer software suite for data reduction of X-ray fiber diffraction patterns from striated muscle and other fibrous systems. It is written in Python and runs on Linux, Microsoft Windows or macOS. Most modules can be run either from a graphical user interface or in a `headless mode' from the command line, suitable for incorporation into beamline control systems. Here, we provide an overview of the general structure of the MuscleX software package and describe the specific features of the individual modules as well as examples of applications. more...

Abstract Background There is a scarcity of evidence regarding the potential relationship between the size and location of necrotic lesions, which must be understood to provide optimal joint-preserving treatment. The purpose of this study was to characterize the distribution patterns of necrotic lesions of varying sizes in early-stage osteonecrosis of femoral head (ONFH) with the use of three-dimensional mapping. Methods We retrospectively evaluated clinical CT images of the hips that were performed in the Third Hospital of Hebei Medical University from January 2018 to December 2022 and collected all CT images diagnosed with stage I and II ONFH. Three-dimensional structures that included both necrotic lesions and normal areas of the femoral heads were reconstructed and divided into eight regions to record their size and location. CT images for all lesions were superimposed onto a standard template, and three-dimensional mapping was created to determine the presence of concentrated areas of lesions. Results In a cohort of 143 patients with stage I and II ONFH, a total of 150 hips were reviewed. For lesions with less than 15% of the femoral head volume, necrotic lesions predominantly involve regions I, III, and V, with region I showing concentration. For lesions with volumes ranging from 15 to 30%, necrotic lesions exhibited a wider distribution across regions I, II, III, IV, V, and VII, with significant concentrations in regions I, III, and V. For lesions exceeding 30% of the femoral head volume, the necrotic lesions were extensively distributed across nearly the entire femoral head, with a notable expansion of the concentrated necrotic areas. Conclusions The distribution of necrotic lesions varies with lesion size, with smaller lesions primarily concentrated in the anterior and medial regions of the femoral head, particularly in the anterosuperior region, while larger lesions expand to the lateral and inferior regions. These findings enhance existing classification systems and provide crucial insights for guiding hip-preserving surgical planning and approaches. more...

Abstract Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients. more...

Abstract Age at first farrowing (AFF) is a reproductive trait with low heritability and high importance in the pig industry. To enhance the statistical power of genome‐wide association study (GWAS) and further explore the genetic nature of AFF, we first conducted GWAS meta‐analysis using three Yorkshire populations, and then integrated the Pig Genotype‐Tissue Expression (PigGTEx) resources to interpret their potential regulatory mechanism. Additionally, we compared the AFF in pig with the age at first birth (AFB) of human using GWAS summary statistics. We detected 18 independent variants in GWAS meta‐analysis and 8 genes in gene‐based association analysis significantly associated with AFF. By integrating the PigGTEx resource, we conducted transcriptome‐wide association study (TWAS) and colocalization analysis on 34 pig tissues. In TWAS, we detected 18 significant gene‐tissue pairs, such as DCAF6 in uterus and CREG1 in blood. In colocalization, we found 111 potential candidate tissue‐gene pairs, such as GJD4 and LYPLAL1. We found that the homologous gene, CHST10, might be the potential candidate gene between humans in AFB and pigs in AFF. In conclusion, integrating GWAS meta‐analysis and PigGTEx resources is a meaningful way to decipher the genetic architecture of complex traits. We found that DCAF6, CREG1, GJD4, and LYPLAL1 are candidate genes with high reliability for AFF in swine. The comparative analysis showed that CHST10 might play a potentially critical role in AFB/AFF across human and pigs. more...

Abstract Background Studies have reported that polyphyllin I (PPI) had effective anti-tumor activity against hepatocellular carcinoma (HCC). However, the precise molecular mechanism of this action and the direct target remain unclear. The aim of this study was to discover the molecular targets and the exact mechanism of PPI in the treatment of HCC. Methods Various HCC cells and Zebrafish xenotransplantation models were used to examine the efficacy of PPI against HCC. A proteome microarray, surface plasmon resonance (SPR) analysis, small molecule transfection, and molecular docking were conducted to confirm the direct binding targets of PPI. Transcriptome and Western blotting were then used to determine the exact responding mechanism. Finally, the anticancer effect and its precise mechanism, as well as the safety of PPI, were verified using a mouse tumor xenograft study. Results The results demonstrated that PPI had significant anticancer activity against HCC in both in vitro studies of two cells and the zebrafish model. Notably, PPI selectively enhanced the action of the Zinc finger and BTB domain-containing 16 (ZBTB16) protein by directly binding to it. Furthermore, specific knockdown of ZBTB16 markedly attenuated PPI-dependent inhibition of HCC cell proliferation and migration caused by overexpression of the gene. The transcriptome and Western blotting also confirmed that the interaction between ZBTB16 and PPI also activated the PPARγ/RXRα pathway. Finally, the mouse experiments confirmed the efficacy and safety of PPI to treat HCC. Conclusions Our results indicate that ZBTB16 is a promising drug target for HCC and that PPI as a potent ZBTB16 agonist has potential as a therapeutic agent against HCC by regulating the ZBTB16/PPARγ/RXRα signaling axis. more...

Abstract N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) has a predictive value of cardiovascular disease (CVD). Pro-inflammatory diet has been proven to be related to CVD. Our study investigated whether the association between NT-proBNP and mortality differed among general U.S. adults with different dietary inflammatory index (DII) scores. This study utilized the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2004. Non-pregnant U.S. adults aged ≥ 20 years and without CVD were included. Cox regression model and restricted cubic splines were used to investigate the associations between NT-proBNP, DII, and mortality. A total of 9788 adults were included, and 2386 all-cause deaths with 668 CVD deaths occurred over 17.08 years of follow-up. NT-proBNP was positively associated with DII scores (P more...

Abstract Purpose This study aimed to preliminarily investigate the association and possible mechanisms between Helicobacter. pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM) through data collection, statistical analysis, and bioinformatics analysis. Methods A retrospective cohort study, including a total of 4406 participants who attended annual health checkups at Xian GEM Flower Changqing Hospital, was conducted to explore the correlation between the incidence of T2DM and H. pylori infection. To uncover the potential mechanisms underlying the interaction between the two diseases, differentially expressed genes (DEGs) common to T2DM and H. pylori infection were identified using the GEO database and Venn diagrams. These DEGs were then analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analysis. Results In total, 2053 participants were classified into the H. pylori-positive group and 2353 into the H. pylori-negative group. H. pylori infection was associated with a higher risk of T2DM occurrence (adjusted HR 1.59; 95% CI 1.17–2.15, P = 0.003). The average disease-free survival time was 34.81 months (95% CI 34.60-35.03 months) in the H. pylori positive group and 35.42 months (95% CI 35.28–35.56 months) in the H. pylori negative group. Multivariate analysis and subgroup analyses also showed that H. pylori infection increased the risk of developing T2DM. A total of 21 DEGs between T2DM and H. pylori infection were identified and enriched in 7 signaling pathways, indicating specific protein interactions. Conclusions The prevalence of T2DM was associated with H. pylori infection. T2DM and H. pylori infection may interact with each other through metabolic and immune pathways. more...

Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment. more...

Study region: The Yellow River Basin Study focus: Multi-element compensation schemes are crucial for promoting regional coordination and fostering sustainable socioeconomic development. This paper proposes a framework of supply-demand-flow-compensation continuum using modelling and ecological economics methods. The supply and demand analyses of water, food, and ecology elements were conducted. A flow relationship network was established based on the actual flows. A compensation direction and funds calculation method were proposed based on market price and revised ecological system value. New hydrological insights for the region: The results revealed that (1) the supply and demand of water, food, and ecology clearly varied spatially. The water yield was ''high in the south and low in the north'', and the food yield was distributed in several irrigated agricultural areas and the middle and lower plain areas. The habitat quality was high in upstream areas and low in downstream ones. High demand areas were concentrated in several urban agglomerations. (2) The compensation amount for habitat quality was the greatest, at 114.57 billion CNY; generally, the middle and lower reaches of the region compensated the upstream provinces of Qinghai and Gansu. (3) The compensation amount for water was 14.38 billion CNY. Owing to its limited natural yield of water resources and widely distributed population, Inner Mongolia paid the largest amount, whereas Gannan Prefecture in Gansu Province and Aba Prefecture in Sichuan Province received the largest amount. (4) The compensation for food was 3.42 billion CNY. Shanxi Province paid the largest compensation of 1.67 billion CNY, which went mainly to Henan Province. The findings indicate the importance of multi-element compensation and the rationality of compensation standard calculation. The results provide support for exploring multiple key elements compensation strategies in other basins worldwide. more...

Abstract Mitochondria are crucial sites for protein quality control within cells. When mitochondrial stress is triggered by protein misfolding, it can accelerate abnormal protein aggregation, potentially inducing various diseases. This study developed a cascade‐responsive sensor, named AggHX, to monitor the microenvironment of protein aggregation induced by zinc (II) ions and the accompanying mitochondrial dysfunction. The AggHX consists of two key components: (1) A Zn2+ recognition group for triggering a fluorescent enhance response, and (2) a near‐infrared BODIPY scaffold that detects viscosity changes in cell aggregation via HaloTag. This sensor's mechanism of action is elucidated through photochemical and biochemical characterizations. To further investigate the relationship between protein aggregation and mitochondrial homeostasis, we employ fluorescence lifetime imaging microscopy to assess viscosity changes in protein aggregates under intracellular Zn2+ stress. This research provides insights into the dynamic behavior and spatial distribution of protein aggregates and mitochondria, contributing to a deeper understanding of their physiological roles in cellular processes and potential implications in disease pathology. more...