Search

Abstract The preservation of the left colic artery (LCA) during rectal cancer resection remains a topic of controversy, and there is a notable absence of robust evidence regarding the outcomes associated with LCA preservation. And the advantages of robotic-assisted laparoscopy (RAL) surgery in rectal resection remain uncertain. The objective of this study was to assess the influence of LCA preservation surgery and RAL surgery on intraoperative and postoperative complications of rectal cancer resection. Patients who underwent laparoscopic (LSC) or RAL with or without LCA preservation resection for rectal cancer between April 2020 and May 2023 were retrospectively assessed. The patients were categorized into two groups: low ligation (LL) which with preservation of LCA and high ligation (HL) which without preservation of LCA. A one-to-one propensity score-matched analysis was performed to decrease confounding. The primary outcome was operative findings, operative morbidity, and postoperative genitourinary function. A total of 612 patients were eligible for this study, and propensity score matching yielded 139 patients in each group. The blood loss of the LL group was significantly less than that of the HL group (54.42 ± 12.99 mL vs. 65.71 ± 7.37 mL, p

Abstract Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism. Targeting NICD1 to mitochondria induces more EndMT compared with wild-type NICD1, and small molecule activation of PDH during pregnancy improves the phenotype in a mouse model of congenital heart defect. A NOTCH1 mutation observed in non-syndromic tetralogy of Fallot patients decreases NICD1 mitochondrial localization and subsequent PDH activity in heart tissues. Altogether, our findings demonstrate NICD1 enrichment in mitochondria of the developing mouse heart, which induces EndMT by activating PDH and subsequently improving mitochondrial metabolism.

Abstract Background Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism. Results HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders. Conclusion This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract

Abstract Tropical cyclones have a big impact on flood risk, and understanding how their activity interacts with population exposure under climate change is critical. Here we investigate spatiotemporal changes in flood risk using numerical models together with historical observations and future projections of tropical cyclone tracks. We find that tropical cyclone-related flood risk shifts from the Mekong Delta to the eastern lower Mekong Basin, driven by the interaction between tropical cyclones and population exposure. Historically, extreme precipitation from tropical cyclones increased flood risk in about 14% and decreased in 7% of the basin. Future tropical cyclones may increase flood risk in about 7% and reduce in nearly 18% of the basin. Moreover, population exposure growth has historically increased flood risk in 3% of the basin and is projected to result in a 1% increase. These findings highlight the complex interactions of tropical cyclone hazards and socioeconomic factors influencing flood risk.

Abstract Sepsis is a clinical syndrome caused by infection, leading to organ dysfunction due to a dysregulated host response. In recent years, its high mortality rate has made it a significant cause of death and disability worldwide. The pathophysiological process of sepsis is related to the body’s dysregulated response to infection, with microcirculatory changes serving as early warning signals that guide clinical treatment. The Peripheral Perfusion Index (PI), as an indicator of peripheral microcirculation, can effectively evaluate patient prognosis. This study aims to develop two new prediction models using PI and other common clinical indicators to assess the mortality risk of sepsis patients during hospitalization and within 28 days post-ICU admission. This retrospective study analyzed data from sepsis patients treated in the Intensive Care Unit of Peking Union Medical College Hospital between December 2019 and June 2023, ultimately including 645 patients. LASSO regression and logistic regression analyses were used to select predictive factors from 35 clinical indicators, and two clinical prediction models were constructed to predict in-hospital mortality and 28-day mortality. The models’ performance was then evaluated using ROC curve, calibration curve, and decision curve analyses. The two prediction models performed excellently in distinguishing patient mortality risk. The AUC for the in-hospital mortality prediction model was 0.82 in the training set and 0.73 in the validation set; for the 28-day mortality prediction model, the AUC was 0.79 in the training set and 0.73 in the validation set. The calibration curves closely aligned with the ideal line, indicating consistency between predicted and actual outcomes. Decision curve analysis also demonstrated high net benefits for the clinical utility of both models. The study shows that these two prediction models not only perform excellently statistically but also hold high practical value in clinical applications. The models can help physicians accurately assess the mortality risk of sepsis patients, providing a scientific basis for personalized treatment.

Abstract Due to the influence of construction quality, engineering geology and hydrological environment, defects such as dehollowing and insufficient compaction can occur in tunnels. Aiming at the problems of complex detection model, poor real-time performance and low accuracy of the current tunnel lining defect detection methods, the study proposes a lightweight defect detection algorithm of tunnel lining based on knowledge distillation. Firstly, a high-precision teacher model based on yolov5s was constructed by constructing a C3CSFM module that combines residual structure and attention mechanism, a MDFPN network structure with multi-scale feature fusion and a reweighted RWNMS re-screening mechanism. Secondly, in the distillation process, the feature and output dimension results are fused to improve the detection accuracy, and the mask feature relationship is learned in the space and channel dimension to improve the real-time detection. Tests on the tunnel lining radar defect image dataset showed that the number of parameters of the improved model was reduced from 16.03 MB to 3.20 MB, a reduction of 80%, and the average accuracy was improved from 83.4 to 86.5%, an increase of 3.1%. On the basis of maintaining the structure and detection performance of the model, the lightweight degree of the model is greatly improved, and the high-precision and real-time detection of tunnel lining defects is realized.

Abstract Due to the polycrystalline cubic boron nitride tool has the characteristics of high hardness, brittleness, etc., it is easy to break the tool or produce defects in the laser cutting process, which affects the cutting performance of the tool. Traditional defect detection methods can no longer meet the needs of modern manufacturing. Aiming at the problems of low accuracy and poor real-time detection of surface defects on laser-cutting polycrystalline cubic boron nitride tools, this study proposes the surface defect detection model of laser cutting polycrystalline cubic boron nitride tool based on asymptotic fusion strategy, which fills the gap in the field. In the backbone network, the C3SE module is constructed by modeling the correlation between feature channels to improve the model’s focus on key features in order to enhance the feature extraction and processing capability of the backbone network; In the neck network, adaptive spatial fusion operation and direct interaction of non-adjacent layers are utilized for multi-scale information fusion, and the asymptotic feature pyramid network for object detection (AFPN) is used instead of the FPN structure to improve the detection performance; In the head network, a soft suppression mechanism is introduced to reduce the overlapping frame score using a decay function, thus improving the detection accuracy. The experimental results based on the self-constructed laser-cutting polycrystalline cubic boron nitride tool surface defects dataset show that the average accuracy of the AFFS-YOLO model is improved by 5.6% compared with that of the YOLOv5 model, reaching 86.1%, and the detection effect is better than that of the original network and other classical target detection networks.

Abstract Neurons often grow highly branched and cell-type specific dendrite morphologies to receive and integrate information, which is the basis of precise neural circuit formation. Previous studies have identified numerous mechanisms that promote dendrite branching. In contrast, it is much less understood how this process is negatively regulated. Here we show that EAT-17/EVI5 acts together with the dynein adaptor protein BICD-1 and the motor protein dynein in C. elegans epidermal cells to restrict branching of PVD sensory dendrites. Loss-of-function mutants of these genes cause both ectopic branching and accumulation of the dendrite branching ligand SAX-7/L1CAM on epidermal plasma membranes. Mutants of genes regulating endo-lysosomal trafficking, including rab-5/RAB5 and dyn-1/DNM1, show similar defects. Biochemical characterization, genetic analysis, and imaging results support that EAT-17 and BICD-1 directly interact with each other and function in the endocytic degradation pathway to remove ectopically localized dendrite branching ligands to restrict abnormal branching.

Abstract The 2023/24 El Niño ranks as the second strongest event in the twenty-first century thus far. The event exhibited a two-step warming tendency and two warming centers, which could not be explained by the heat content buildup. Here, by conducting observational analysis and model experiments, we show that the record-breaking pantropical warming in 2023 mitigated this El Niño and confined the warming to the eastern basin, and that a series of westerly wind bursts induced another warming center in the central equatorial Pacific toward the end of 2023. Yet the effects of pantropical forcing and wind bursts coincidentally offset each other, leaving the heat content buildup appearing as the primary cause of the 2023/24 El Niño. Our results not only confirm the essential role of equatorial ocean heat recharge for El Niño development, but also demonstrate the necessity of accounting for multi-scale interactions from a global perspective to predict El Niño.

In this paper, the content of active ingredients and antioxidant capacity of different parts of Hoxylon and Red Willow Cistanche deserticola, from Hotan Cele County, Xinjiang, were evaluated. The results showed that the active substances, including total phenols, total flavonoids, total sugars, and verbascoside of Red Willow Cistanche deserticola, were the highest in the lower part of the plant, and decreased in the middle and upper parts. In terms of total phenols and total flavonoids, the contents of the lower part of Red Willow Cistanche deserticola (38.35 mg GAE/g DW, 35.61 mg RE/g DW) were 2.47 and 10.95 times compared to the lower part of Hoxylon Cistanche deserticola, respectively. The upper part of Hoxylon Cistanche deserticola showed the highest content of echinacoside with 92.93 mg/g DW. And the total triterpene content of the lower part-especially that of Hoxylon Cistanche deserticola was significantly higher than the upper and middle part (P

Introduction: The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. Object: High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. Method: Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. Results: In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. Conclusion: These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat.

At the altitude of low-Earth-orbiting satellites, most details of lithospheric magnetic anomalies observed near surface are attenuated, and only slowly decaying long-wavelength magnetic anomalies can be detected. Long-wavelength magnetic anomalies are generated by large-scale magnetized rocks in the Earth's crust and uppermost mantle at depths shallower than the Curie depth. Interpretation of such lithospheric magnetic anomalies has been used in geological mapping, crustal composition and structure studies, plate tectonic reconstruction, and geodynamics. To introduce the origin of long-wavelength magnetic anomalies at a global scale, we first reviewed satellite magnetic anomaly maps in early periods and calculated anomaly maps using four main lithospheric magnetic field models, including the CHAOS-7, CM6, MF7, and CSES models. Then, based on the result of the CHAOS-7 model at 500 km altitude, 29 long-wavelength magnetic anomalies with amplitudes greater than 4 nT were identified and their geological origins were reviewed. Among these, there were twenty magnetic anomalies over continents and nine over the ocean. The long-wavelength magnetic anomalies over continental areas were mostly located in Precambrian basements related to the Archean nuclei, Proterozoic terrane, and iron-rich formations, with a few located in the orogenic background. The long-wavelength magnetic anomalies in the ocean region were all located in oceanic plateau, generally related to the breakup of Gondwana during the Cretaceous Period, and have the characteristics of thickened crust. Hence, the long-wavelength magnetic anomalies reveal a significant magnetization difference in the deep crust during crustal growth, a key issue that requires further study. Compared to satellite magnetic surveys in some other nations, detecting lithospheric magnetic anomalies by satellite started relatively late in China. The China Seismo-Electromagnetic Satellite (CSES) was launched in February 2018. It was China's first satellite designed to monitor earthquakes with multiple geophysical payloads, including magnetometers capable of measuring weak signals from the lithosphere. The Macau Science Satellite-1 (MSS-1) was launched in 2023 and is specially used for monitoring the geomagnetic field in low latitudes. Furthermore, a subsequent CSES-02 satellite is planned to be launched in 2024. With the vigorous development of satellite magnetic surveys in China, it is expected that progressively more Chinese researchers will pay attention to long-wavelength magnetic anomalies and promote the study of their origin.

Low Earth orbit (LEO) satellites have emerged as a primary tool for global geomagnetic field detection and model refinement, owing to their wide coverage, high resolution, and absence of geographical limitations. This paper provides a comprehensive review of the history, key characteristics, measurement accuracy, and future trends in LEO satellite magnetic field measurements. The first part of the paper outlines the evolution of LEO satellites, highlighting their unique advantages. The focus then shifts to the calibration methodology for in-orbit LEO satellite magnetic measurements, with a specific emphasis on vector magnetic field intrinsic calibration and alignment algorithms. Calibration results are presented to demonstrate the effectiveness of these methodologies. In the third section, the paper introduces the theory behind global geomagnetic field modeling. An overview of current global geomagnetic field models is provided, encompassing their sources, spatial resolutions, and other relevant attributes. The paper concludes by presenting the global morphology and features of the main field, lithospheric field, magnetospheric, and ionospheric field. Despite the significant progress enabled by LEO satellite technology, global geomagnetic field modeling faces challenges such as limited spatio-temporal resolution. To address this, incorporating near-surface observation data and continuously optimizing modeling technology are deemed essential solutions.

Abstract Chronic pain dramatically affects life qualities of the sufferers. It has posed a heavy burden to both patients and the health care system. However, the current treatments for chronic pain are usually insufficient and cause many unwanted side effects. Chemokine C–X–C motif ligand 13 (CXCL13), formerly recognized as a B cell chemokine, binds with the cognate receptor CXCR5, a G-protein-coupled receptor (GPCR), to participate in immune cell recruitments and immune modulations. Recent studies further demonstrated that CXCL13–CXCR5 signaling is implicated in chronic pain via promoting neuroimmune interaction and neuroinflammation in the sensory system. In addition, some latest work also pointed out the involvement of CXCL13–CXCR5 in the pathogenesis of certain neurological diseases, including ischemic stroke and amyotrophic lateral sclerosis. Therefore, we aim to outline the recent findings in regard to the involvement of CXCL13–CXCR5 signaling in chronic pain as well as certain neurological diseases, with the focus on how this chemokine signaling contributes to the pathogenesis of these neurological diseases via regulating neuroimmune interaction and neuroinflammation. Strategies that can specifically target CXCL13–CXCR5 signaling in distinct locations may provide new therapeutic options for these neurological diseases.

Abstract The Equilibrium Optimiser (EO) has been demonstrated to be one of the metaheuristic algorithms that can effectively solve global optimisation problems. Balancing the paradox between exploration and exploitation operations while enhancing the ability to jump out of the local optimum are two key points to be addressed in EO research. To alleviate these limitations, an EO variant named adaptive elite‐guided Equilibrium Optimiser (AEEO) is introduced. Specifically, the adaptive elite‐guided search mechanism enhances the balance between exploration and exploitation. The modified mutualism phase reinforces the information interaction among particles and local optima avoidance. The cooperation of these two mechanisms boosts the overall performance of the basic EO. The AEEO is subjected to competitive experiments with state‐of‐the‐art algorithms and modified algorithms on 23 classical benchmark functions and IEE CEC 2017 function test suite. Experimental results demonstrate that AEEO outperforms several well‐performing EO variants, DE variants, PSO variants, SSA variants, and GWO variants in terms of convergence speed and accuracy. In addition, the AEEO algorithm is used for the edge server (ES) placement problem in mobile edge computing (MEC) environments. The experimental results show that the author’s approach outperforms the representative approaches compared in terms of access latency and deployment cost.

Abstract Background With the improvement of living standards, the quality of chicken has become a significant concern. Chinese Dagu Chicken (dual-purpose type) and Arbor Acres plus broiler (AA+ broiler) (meat-type) were selected as the research subjects in this study, the meat quality of the breast and leg muscles were measured. However, the molecular mechanism(s) underlying regulation of muscle development are not yet fully elucidated. Therefore, finding molecular markers or major genes that regulate muscle quality has become a crucial breakthrough in chicken breeding. Unraveling the molecular mechanism behind meat traits in chicken and other domestic fowl is facilitated by identifying the key genes associated with these developmental events. Here, a comparative transcriptomic analysis of chicken meat was conducted on breast muscles (BM) and leg muscles (LM) in AA+ broilers (AA) and Dagu chicken (DG) to explore the differences in their meat traits employing RNA-seq. Results Twelve cDNA libraries of BM and LM from AA and DG were constructed from four experimental groups, yielding 14,464 genes. Among them, Dagu chicken breast muscles (DGB) vs AA+ broilers breast muscles (AAB) showed 415 upregulated genes and 449 downregulated genes, Dagu chicken leg muscles (DGL) vs AA+ broilers leg muscles (AAL) exhibited 237 upregulated genes and 278 downregulated genes, DGL vs DGB demonstrated 391 upregulated genes and 594 downregulated genes, and AAL vs AAB displayed 122 upregulated genes and 154 downregulated genes. 13 genes, including nine upregulated genes (COX5A, COX7C, NDUFV1, UQCRFS1, UQCR11, BRT-1, FGF14, TMOD1, MYOZ2) and four downregulated genes (MYBPC3, MYO7B, MTMR7, and TNNC1), were found to be associated with the oxidative phosphorylation signaling pathway. Further analysis revealed that the differentially expressed genes (DEGs) from muscle were enriched in various pathways, such as metabolic pathways, oxidative phosphorylation, carbon metabolism, glycolysis, extracellular matrix-receptor interaction, biosynthesis of amino acids, focal adhesion, vascular smooth muscle contraction, and cardiac muscle contraction, all of which are involved in muscle development and metabolism. This study also measured the meat quality of the breast and leg muscles from the two breeds, which demonstrated superior overall meat quality in Chinese Dagu Chicken compared to the AA+ broiler. Conclusions Our findings show that the meat quality of dual-purpose breeds (Chinese Dagu chicken) is higher than meat-type (AA+ broiler), which may be related to the DEGs regulating muscle development and metabolism. Our findings also provide transcriptomic insights for a comparative analysis of molecular mechanisms underlying muscle development between the two breeds, and have practical implications for the improvement of chicken breeding practices.

Abstract Grassland is a widely distributed land use type that provides essential resources for livestock production and serves as a crucial ecosystem component. Over the past decades, grassland has significantly degraded and shrunk due to climate change and human activities, with ongoing changes in its area. This study utilized the Google Earth Engine (GEE) and the Res-UNet++ model to analyze the phenological and spectral characteristics of grasslands in Landsat images for long-term annual monitoring. Additionally, the LandTrendr algorithm was utilized to correct long-term time series data for grasslands, yielding a map of grassland distribution in Inner Mongolia from 1991 to 2020. The results indicate that the overall spatial accuracy from 1991 to 2020 exceeded 96%, with a Kappa coefficient over 0.92, demonstrating high monitoring accuracy. In particular, the 2019 grassland monitoring area showed high consistency with data from the Third National Land Survey (TNLS), with a coefficient of determination (R^2) reaching 0.97, reflecting the high accuracy and reliability.

Abstract This paper explores the mapping from specific digitalization practices to specific resilient performance against a great shock. Based on an adapted structure–conduct–performance framework, this paper hypothesizes by theoretically analyzing how the pre-shock establishment of digital retailing practices could trigger physical retailers’ bounce-back and bounce-forward performance against the COVID-19 crisis. Using a difference-in-differences strategy, the hypotheses are examined with a sample including 549 observations of 50 Chinese listed retailers from the first quarter of 2018 to the third quarter of 2020. The empirical results mainly indicate the following binary findings. First, regardless of the differences in triggering bounce-back performance, different digital retailing practices are found to be effective in triggering physical retailers’ bounce-forward performance against the COVID-19 crisis. This somewhat addresses the concern about the temporality of digitalization-enabled resilience by revealing the generality across digital retailing practices in the sense of triggering resilient performance. Second, it is shown that physical retailers’ bounce-back performance at a specific stage of the COVID-19 crisis could only be triggered by digital retailing practices that coincidentally apply to the shock-induced market structure changes at the stage. The results emphasize each digitalization practice’s individuality in triggering resilient performance. This justifies the non-negligibility of the direct mapping from specific digitalization practices to specific resilient performance in digitalization-enabled resilience evaluation.

Abstract Background Recent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD). Method Pan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters. Results ADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p

Abstract Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

Abstract This study investigates the microstructural characteristics and mechanical properties of a laser welded AZ80 magnesium alloy. The welding process led to the formation of coarse-grained fusion zone (FZ), where a secondary phase formed continuous network. Mg17Al12 precipitation and coarsening of grain boundaries occurred in the heat affected zone. The welded joint exhibited excellent mechanical properties with a yield strength of 202 MPa and a joint efficiency of 92%. The microstructure analysis via EPMA and EBSD in conjunction with synchrotron X-ray diffraction analysis reveals that precipitates and increased dislocation density in the fusion zone are primary strengthening mechanisms for the laser welded AZ80 Mg alloy.

Abstract In this study, XPS sputtering depth, SEM and electrochemical tests (CV, EIS, M-S, i-t, DPP) were used to study the structural composition and formation mechanism of surface passive film of Nb microalloyed rebar in SCPS with different pH. The results showed that after passivation for 10 d in SCPS with different pH, compared with CS rebar, the stability and compactness of surface passive film of 34Nb rebar gradually increased with the decreases of pH. Firstly, with the decreases of pH, the outer layer of surface passive film of 34Nb rebar was composed of Fe oxides and Fe hydroxides, and the inner layer was composed of Fe oxides and Nb oxides, thus increasing the mass ratio of Fe3+/Fe2+ and Nb2O5/(NbO2 + NbO). Secondly, with the decreases of pH, the addition of Nb promoted the formation of Fe oxides in 34Nb rebar, obtaining the excellent Rct, Ecorr and Ep. Finally, with the decreases of pH, the addition of Nb promoted the enrichment of Nb oxides in 34Nb rebar, inhibiting the degradation of Fe oxides, and the passive film exhibited the P-N type semiconductor, thus significantly decreasing the carrier density and enhancing the passivation rate of 34Nb rebar.

Abstract The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.

Abstract Eukaryotic Argonaute proteins (eAgos) utilize short nucleic acid guides to target complementary sequences for RNA silencing, while prokaryotic Agos (pAgos) provide immunity against invading plasmids or bacteriophages. The Sir2-domain associated short pAgo (SPARSA) immune system defends against invaders by depleting NAD+ and triggering cell death. However, the molecular mechanism underlying SPARSA activation remains unknown. Here, we present cryo-EM structures of inactive monomeric, active tetrameric and active NAD+-bound tetrameric SPARSA complexes, elucidating mechanisms underlying SPARSA assembly, guide RNA preference, target ssDNA-triggered SPARSA tetramerization, and tetrameric-dependent NADase activation. Short pAgos form heterodimers with Sir2-APAZ, favoring short guide RNA with a 5′-AU from ColE-like plasmids. RNA-guided recognition of the target ssDNA triggers SPARSA tetramerization via pAgo- and Sir2-mediated interactions. The resulting tetrameric Sir2 rearrangement aligns catalytic residue H186 for NAD+ hydrolysis. These insights advance our understanding of Sir2-domain associated pAgos immune systems and should facilitate the development of a short pAgo-associated biotechnological toolbox.

Abstract Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.

Abstract Magnetic skyrmions are potential candidates for high-density storage and logic devices because of their inherent topological stability and nanoscale size. Two-dimensional (2D) Janus transition metal chalcogenides (TMDs) are widely used to induce skyrmions due to the breaking of inversion symmetry. However, the experimental synthesis of Janus TMDs is rare, which indicates that the Janus configuration might not be the most stable MXY structure. Here, through machine-learning-assisted high-throughput first-principles calculations, we demonstrate that not all MXY compounds can be stabilized in Janus layered structure and a large proportion prefer to form other configurations with lower energy than the Janus configuration. Interestingly, these new configurations exhibit a strong Dzyaloshinskii–Moriya interaction (DMI), which can generate and stabilize skyrmions even under a strong magnetic field. This work provides not only an efficient method for obtaining ferromagnetic materials with strong DMI but also a theoretical guidance for the synthesis of TMDs via experiments.

Abstract Ferroptosis is a regulated cell death process dependent on iron, triggered by the accumulation of lipid peroxidation. The environmental context significantly impacts cellular sensitivities to ferroptosis. Serum, constituting the extracellular fluid composition in vivo, provides crucial environmental biomolecules. In this study, we investigated the influence of sera on ferroptosis induction, pinpointing the serum protein apolipoprotein H (APOH) as a pivotal inhibitor of ferroptosis. Moreover, we elucidated that APOH suppresses ferroptosis by activating the phosphoinositide 3-kinase (PI3K)-AKT-sterol regulatory element-binding proteins (SREBPs) pathway, thereby elevating stearoyl-CoA desaturase (SCD) levels and augmenting cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs). Furthermore, ApoHinfer, the peptide derivative of the active region of APOH, mimics its ferroptosis inhibitory activity. Our findings underscore the critical role of serum protein APOH in the inhibition of ferroptosis and indicates potential therapeutic applications in treating cancer and diseases associated with ferroptosis.

Abstract Well-functioning vascular access (VA) is essential for hemodialysis treatment in patients with end-stage renal disease (ESRD). However, continuous and accurate monitoring of blood flow to assess high-flux VA during hospitalization or at home is not feasible for either clinical instruments or wearable sensors. Here, we report the design and preclinical validation of a high-precision, long-term, epidermal blood flow sensor that self-adapts to unavoidable sensor-mounting deviations on the skin and is compatible with individual tissue differences. Specifically, the technology is based on thermal dissipation of the skin, and improves the signal-to-error ratio surpassing 4 times when measuring high-flux blood (100–600 mL/min). In preclinical validation, the sensor is compared with the Doppler ultrasound and demonstrate a blood flow resolution of 10–50 mL/min. Furthermore, it is highly-integrated and wearable, measuring 36 × 50 mm2. The sensor paves the way for accurate, convenient, high-flux blood monitoring, offering significant potential to extend the lives of patients with ESRD.

Abstract Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained‐release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady‐state trough concentrations (Ctrough) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20–50 kg. As a result, the PK characteristics of VPA were described using a one‐compartment model with first‐order absorption. The absorption rate constant (ka) was set at 2.64 and 0.46 h−1 for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target Ctrough, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.

Abstract In this study, we conducted a comprehensive investigation on the influence of waste perlite powder (WPP) on the various properties of mortar and paste, including slurry performance, mechanical strength, hydration products, and microstructure. Additionally, we also aimed to uncover the underlying mechanism behind these effects. It was found that WPP reduced the workability and facilitated the setting process of cement-WPP pastes. WPP decreased the mechanical strength of mortar, but it exhibited significant strength enhancement during the subsequent stages. The incorporation of WPP worsened the water absorption behavior; however, this negative effect was mitigated as the curing age of the mortar was prolonged. The drying shrinkage cement-WPP binary system was significantly improved, with the prolongation of curing age. Moreover, WPP reduced the early heat release of the binary system, which may be beneficial for reducing the temperature gradient in mass concrete. It was confirmed that WPP accelerated the transformation from AFt to AFm, promoted the formation of C-A-S-H and optimized the pore structure of the system. It was confirmed that WPP was involved in the hydration reaction, which accelerated the transformation from AFt to AFm and promoted the formation of C-A-S-H. Such results suggested that the reuse of WPP in concrete production was technically feasible owing to its high pozzolanic reactivity.

Abstract Leaf senescence represents the final stage of leaf development, involving transcription factors (TFs)-mediated genetic reprogramming events. The timing of crop leaf senescence has a major influence on the yield and quality of crop in agricultural production. As important regulator of plant growth, the significance of TFs in the regulation of leaf senescence have been highlighted in various plant species by recent advances in genetics. However, studies on underlying molecular mechanisms are still not adequately explained. In this study, for analyzing the regulation of TFs on senescence of tobacco leaves, we combined gene differential expression analysis with weighted gene co-expression network analysis (WGCNA) to analyze the time-series gene expression profiles in senescing tobacco leaf. Among 3517 TF genes expressed in tobacco leaves, we identified 21, 35, and 183 TFs that were associated with early, middle, and late stages of tobacco leaf senescence, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation results reveal that these senescence response TFs are correlated with several biological pathways such as plant hormone signal transduction, ubiquitin mediated proteolysis and MAPK signaling pathway, indicating the roles of TFs in regulating leaf senescence. Our results provide implications for future studies of the potential regulatory mechanisms of TFs involved in senescence of tobacco leaves.

Abstract Nanozymes have been attracting widespread interest for the past decade, especially in the field of cancer therapy, due to their intrinsic catalytic activities, strong stability, and ease of synthesis. However, enhancing their catalytic activity in the tumor microenvironment (TME) remains a major challenge. Herein, we manipulate catalytic activities of Ru nanozymes via modulating lattice spacing in Ru nanocrystals supported on nitrogen-doped carbon support, to achieve improvement in multiple enzyme-like activities that can form cascade catalytic reactions to boost cancer cell killing. In addition, the lattice expansion in Ru nanocrystals improve the responsiveness of the nanozymes to self-powered electric field, achieving maximized cancer therapeutic outcome. Under the electrical stimulation provided by a human self-propelled triboelectric device, the Ru-based nanozyme (Ru1000) with a lattice expansion of 5.99% realizes optimal catalytic performance and cancer therapeutic outcome of breast cancer in female tumor-bearing mice. Through theoretical calculations, we uncover that the lattice expansion and electrical stimulation promote the catalytic reaction, simultaneously, by reducing the electron density and shifting the d-band center of Ru active sites. This work provides opportunities for improving the development of nanozymes.

Abstract Alhagi-honey (AH) is a well-established traditional ethnic medicine with advantageous effects against diarrhea and headaches. We aimed to explore the preventive effect of AH on liver damage induced by heat stress (HS) and its underlying mechanism. HS models were established by thermostat, and mice were treated at 39 ℃ for 10 h, lasting for 7 days. Hematoxylin–eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining were used for histological observation, and transmission electron microscopy (TEM) was used for ultrastructure examination of hepatocytes. Gut microbiota (GM) composition and liver metabolites were respectively analyzed by 16S rRNA sequencing and non-targeted metabolome sequencing. AH pretreatment alleviated liver damage caused by heat stress in mice. The main manifestation was that AH alleviated serum aspartate transferase (AST) and aspartate transaminase (ALT). It was found that AH improved symptoms of hepatocyte damage. In addition, the relative abundance of f_Rikenellaceae, g_Incertae_Sedis and s_Staphylococcus_Orisratti, g_Lachnoclostridium, g_GCA-900066575, and s_Alistipes_inops were modified by AH and these bacterial genera showed association with 6 metabolites (2- (3,4-dihydroxyphenyl) acetamide, 3-hydroxy-3-methylpentanedioic acid, PC (17:0/17:1), Y-L-Glutamy-L-glutamic acid, L-Isoleucine, 5-Methyluridine, 8,8-dimethyl-2-phenyl-4H,8H-pyrano [2, 3-h] chromen-4-one). The Pearson analysis also showed a strong correlation between these microbes and 2 risk indicators (AST and ALT) of liver damage. AH alleviated HS-induced liver damage by regulating liver metabolism and maintaining normal GM. It demonstrated that AH held potential as a prophylactic drug for the prevention of HS-induced liver damage.

Abstract Device-to-device (D2D) communications allow short-range communication devices to multiplex cellular-licensed spectrum to directly establish local connections for ultra-high number of terminal connections and greater system throughput. However, spectrum sharing also brings serious interference to the network. Therefore, a reliable and efficient resource allocation strategy is important to mitigate the interference and improve the system spectral efficiency. In this paper, we investigated spectrum access and power allocation in D2D communications underlay cellular networks based on deep reinforcement learning with the aim of finding a feasible resource allocation strategy to maximize data rate and system fairness. We proposed a value decomposition network-based resource allocation scheme for D2D communication networks. Our proposed scheme avoids frequent information exchanges among D2D users by centralized training, while allowing D2D users to make distributed joint resource allocation decisions. Simulation results show that the proposed scheme has stable convergence and good scalability, and can effectively improve the system capacity.

Understanding the relationship between attribute performance (AP) and customer satisfaction (CS) is crucial for the hospitality industry. However, accurately modeling this relationship remains challenging. To address this issue, we propose an interpretable machine learning-based dynamic asymmetric analysis (IML-DAA) approach that leverages interpretable machine learning (IML) to improve traditional relationship analysis methods. The IML-DAA employs extreme gradient boosting (XGBoost) and SHapley Additive exPlanations (SHAP) to construct relationships and explain the significance of each attribute. Following this, an improved version of penalty-reward contrast analysis (PRCA) is used to classify attributes, whereas asymmetric impact-performance analysis (AIPA) is employed to determine the attribute improvement priority order. A total of 29,724 user ratings in New York City collected from TripAdvisor were investigated. The results suggest that IML-DAA can effectively capture non-linear relationships and that there is a dynamic asymmetric effect between AP and CS, as identified by the dynamic AIPA model. This study enhances our understanding of the relationship between AP and CS and contributes to the literature on the hotel service industry.

Abstract Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Despite of a steadily increasing in morbidity and mortality, there is still no effective therapy. Gut microbial dysbiosis and its derived-metabolites disorder have been shown to play an important role in the development of AP, however, little is known regarding the crosstalk between gut microbiota and metabolites. In this study, we assessed the alterations in gut microbiota and metabolites by constructing three AP mouse models by means of metagenomic and metabolomic sequencing, and further clarified their relationship by correlation analysis. The results revealed that each model exhibited unique flora and metabolite profiles. KEGG analysis showed that the differential flora and metabolite-enriched pathway functions were correlated with lipid metabolism and amino acid metabolism. Moreover, two core differential bacterial species on Burkholderiales bacterium YL45 and Bifidobacterium pseudolongum along with eleven differential metabolites appeared to exert certain effects during the course of AP. In conclusion, further exploration of the crosstalk between microbiota and derived metabolites may provide novel insights and strategies into the diagnosis and treatment of AP.

Abstract Background Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). Methods PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. Results TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. Conclusions In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

Abstract Background Although high-density lipoprotein cholesterol (HDL-C) exerts a significant influence on the development of metabolic dysfunction-associated fatty liver disease (MAFLD), the association of dynamic changes in HDL-C levels with the risk of MAFLD remains unclear. Thus, the aim of the current study was to explore the association between the changing trajectories of HDL-C and new-onset MAFLD. The findings of this study may provide a theoretical basis for future personalized intervention and prevention targeting MAFLD. Methods A total of 1507 participants who met the inclusion criteria were recruited from a community-based physical examination population in Nanjing, China from 2017 to 2021. Group-based trajectory models were constructed to determine the heterogeneous HDL-C trajectories. The incidence of MAFLD in each group in 2022 was followed up, and the Cox proportional hazards regression model was applied to investigate the associations between different HDL-C trajectories and the risk of new-onset MAFLD. Results The incidences of MAFLD in the low-stable, moderate-stable, moderate-high-stable, and high-stable groups of HDL-C trajectory were 26.5%, 13.8%, 7.2% and 2.6%, respectively. The incidence rate of MAFLD in the order of the above trajectory groups exhibited a decreasing trend (χ2 = 72.55, P trend

Abstract Alzheimer’s disease (AD), characterized by cognitive decline, is increasingly recognized as a disorder marked by synaptic loss and dysfunction. Despite this understanding, the underlying pathophysiological mechanisms contributing to synaptic impairment remain largely unknown. In this study, we elucidate a previously undiscovered signaling pathway wherein the S-nitrosylation of the Cdk5 activator p39, a post-translational modification involving the addition of nitric oxide to protein cysteine residues, plays a crucial role in synaptic dysfunction associated with AD. Our investigation reveals heightened p39 S-nitrosylation in the brain of an amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD. Additionally, soluble amyloid-β oligomers (Aβ), implicated in synaptic loss in AD, induce p39 S-nitrosylation in cultured neurons. Notably, we uncover that p39 protein level is regulated by S-nitrosylation, with nitric oxide S-nitrosylating p39 at Cys265 and subsequently promoting its degradation. Furthermore, our study demonstrates that S-nitrosylation of p39 at Cys265 significantly contributes to amyloid-β (Aβ) peptide-induced dendrite retraction and spine loss. Collectively, our findings highlight S-nitrosylation of p39 as a novel aberrant redox protein modification involved in the pathogenesis of AD, suggesting its potential as a therapeutic target for the disease.

Abstract Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.

Abstract Background Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations. Results We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins. Conclusions These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications. Graphical Abstract

Abstract Background The formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum. Methods In the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum. Results In maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia. Conclusion In conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

Abstract Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD’s etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations—peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P

Abstract Sepsis-induced cardiomyopathy (SIC) is described as a reversible myocardial depression that occurs in patients with septic shock. Increasing evidence shows that microRNA-194-5p (miR-194-5p) participates in the regulation of oxidative stress, mitochondrial dysfunction, and apoptosis and its expression is associated with the occurrence and progression of cardiovascular disease; however, the effects of miR-194-5p in SIC are still unclear. This study explores whether miR-194-5p could modulate SIC by affecting oxidative stress, mitochondrial function, and apoptosis. Experimental septic mice were induced by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6J mice. The biological role of miR-194-5p in SIC in vivo was investigated using cardiac echocardiography, ELISA, western blot, qRT-PCR, transmission electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, bioinformatics analysis, and dual-luciferase reporter gene assay. Our major finding is that miR-194-5p antagomir mitigates sepsis-induced cardiac dysfunction, inflammation, oxidative stress, apoptosis and mitochondrial dysfunction in the hearts of septic mice, while miR-194-5p agomir triggers the opposite effects. Furthermore, dual-specificity phosphatase 9 (DUSP9) is a direct target of miR-194-5p and the cardioprotective effects of miR-194-5p antagomir on cardiac dysfunction, inflammation, apoptosis, mitochondrial dysfunction and oxidative stress are abolished through inhibiting DUSP9. Therefore, miR-194-5p inhibition could mitigate SIC via DUSP9 in vivo and the novel miR-194-5p/DUSP9 axis might be the potential treatment targets for SIC patients.

Abstract The surge in advanced imaging techniques has generated vast biomedical image data with diverse dimensions in space, time and spectrum, posing big challenges to conventional compression techniques in image storage, transmission, and sharing. Here, we propose an intelligent image compression approach with the first-proved semantic redundancy of biomedical data in the implicit neural function domain. This Semantic redundancy based Implicit Neural Compression guided with Saliency map (SINCS) can notably improve the compression efficiency for arbitrary-dimensional image data in terms of compression ratio and fidelity. Moreover, with weight transfer and residual entropy coding strategies, it shows improved compression speed while maintaining high quality. SINCS yields high quality compression with over 2000-fold compression ratio on 2D, 2D-T, 3D, 4D biomedical images of diverse targets ranging from single virus to entire human organs, and ensures reliable downstream tasks, such as object segmentation and quantitative analyses, to be conducted at high efficiency.

Abstract Global prevalence of microplastics underscores the urgent need to investigate the ecology and biogeochemistry of the plastisphere. However, plastisphere mycobiome, particularly in terrestrial environments, remains largely unexplored. We conducted a comparative analysis of soil and plastisphere fungal communities using 125 experimental microcosms. Our results revealed distinct taxonomic structures between these two environments, with the genera Penicillium and pathogenic Alternaria being specifically enriched in the plastisphere. In comparison with soil communities, plastisphere communities exhibited weaker associations with environmental variables. Stochastic processes were found to be primary drivers of plastisphere fungal community assembly. Limited dispersal of fungal communities on soil microplastics was obtained, suggesting potential implications for taxa isolation or even diversity loss. The expanding plastisphere would pose critical planetary ecology challenges. Our findings highlight plastisphere act as unique niches for fungal communities that are less influenced by environmental variables, providing new insights into the ecology of the soil plastisphere.

Abstract Purpose To summarize the abdominal computed tomography (CT) imaging and clinicopathological data of patients with SPNs of the pancreas and analyze the accuracy of preoperative CT diagnosis and features. Materials and methods Between June 2006 and June 2023, CT images of 120 histopathologically proven SPNs in the pancreas were retrospectively reviewed. Fifteen features, including age, sex, and CT-determined features, were included in a multiple stepwise regression analysis. The correlations between features and SPNs, including odds ratios (ORs) and 95% confidence intervals (CIs), were evaluated. Results Among the 120 patients, the diagnostic accuracy of CT was 43.3%. The baseline CT results of patients with a correct diagnosis and misdiagnosis revealed significant differences in sex (P = 0.043), age (P = 0.004), boundary (P = 0.037) and encapsulation (P = 0.002) between the two groups. The preoperative imaging diagnostic accuracy was significantly greater in females than in males (47.9% vs. 25.0%, P = 0.043). The immunohistochemical indices did not significantly differ between the two groups. The results of univariate analysis revealed significant differences in sex (P = 0.048), age (P = 0.014), tumor length (P = 0.023), tumor boundaries (P = 0.039) and capsule type (P = 0.003). The results of multivariate analysis revealed that encapsulation was closely related to the diagnostic accuracy of CT (P = 0.04). Conclusions The accuracy of CT in the diagnosis of SPNs is low, but a length‒diameter ratio of the tumor approaching 1.0, encapsulation and clear boundaries are important CT-determined features. The capsule is an independent CT predictor in the diagnosis of SPNs.

Abstract Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Abstract Red swamp crayfish, Procambarus clarkii, is the most cultured freshwater crayfish species. It attracts significant research attention due to its considerable economic importance. However, the limited availability of genome information has impeded further genetic studies and breeding programs. By utilizing Illumina, PacBio, and Hi-C sequencing technologies, we present a more comprehensive and continuous chromosome-level assembly for P. clarkii than the published one. The final genome size is 4.03 Gb, consisting of 2,358 scaffolds with a N50 of 42.87 Mb. Notably, 3.68 Gb, corresponding to 91.42% of the genome, was anchored to 94 chromosomes. The assembly comprises 70.64% repetitive sequences, including 5.21% tandem repeats and 65.40% transposable elements. Additionally, a total of 4,456 non-coding RNAs and 28,852 protein-coding genes were predicted in the P. clarkii genome, with 96.26% of the genes were annotated. This high-quality genome assembly not only represents a significant improvement for the genome of P. clarkii and provides insights into the unique genome evolution, but also offers valuable information for developing freshwater aquaculture and accelerating genetic breeding.