Search

ABSTRACT Objective Aseptic loosening (AL) is a common mechanical complication following reconstruction of the distal femoral cemented prosthesis (DFCP), often resulting in severe bone loss, which complicates prosthesis revision. 3D‐printed personalized implants represent an emerging solution for the reconstruction of complex bone defects. This study aimed to investigate the early therapeutic effects of using a 3D‐printed, customized, uncemented stem prosthesis for revising aseptic AL in DFCP. Methods From June 2021 to December 2022, a retrospective review was conducted on six consecutive patients who underwent revision surgery due to AL of the DFCP with a 3D‐printed customized uncemented stem prosthesis. The study included four male and two female patients, with an average age of 58 ± 11 (range: 46–75) years. All six patients had previously undergone limb salvage surgery using a cemented megaprosthesis after tumor resection. Preoperative imaging evaluation was performed for all patients, and the personalized design of the prostheses was achieved through 3D printing based on CT imaging data. Regular clinical and radiographic follow‐up was conducted postoperatively, with the main outcome measures being oncological outcomes, prosthesis survival, osseointegration, complications, and lower limb function. Results All patients successfully underwent surgery and were followed up for a mean duration of 30.33 ± 6.15 (range: 24–38) months. All patients were alive at the last follow‐up, with no tumor recurrence or distant metastasis. No complications such as infection, loosening, or fracture of the prosthesis occurred. Osseointegration was satisfactory, with a mean MSTS score of 26 (range: 20–28) points. Conclusion 3D‐printed, customized, uncemented stem prosthesis exhibit immediate initial stability and reliable biocompatibility. Early clinical outcomes are satisfactory, making them an effective method for revision AL of DFCP.

Abstract Background The COVID-19 pandemic exposed significant limitations in health systems worldwide and emphasized the need for updated National Health Policies, Strategies, and Plans (NHPSPs). This study aimed to evaluate the NHPSPs of Organization for Economic Cooperation and Development (OECD) and BRICS (Brazil, Russia, India, China, and South Africa) countries before and after the COVID-19 pandemic. Specifically, it explored each country’s commitment to strengthening health systems to address health threats and analyzed the specific changes made. Methods NHPSP documents from the WHO document repository and official governmental websites were systematically searched. Data were extracted using a standardized template. A coding framework was inductively developed to sort qualitative texts into categories, with frequencies calculated and weighting evaluated, followed by organizing underlying content into subthemes. Results Out of 154 documents initially identified, 36 met the screening criteria, covering 14 OECD and 3 BRICS countries. The most predominant theme was prevention (88.9% pre-pandemic, 99.4% post-pandemic), which was addressed as a primary theme in 26 included NHPSPs. After the COVID-19 pandemic, 6 out of 14 analyzed themes saw higher occurrences, among which infection prevention and control (22.2–50.0%) and resilience to health crisis (22.2–44.4%) increased most significantly. Themes mainstreamed in post-pandemic NHPSPs included prevention (94.4%), health research and technology (61.1%), and One Health (66.7%). Primary healthcare emerged as the most concerned subtheme under prevention. Notably, OECD countries displayed more increased occurrences of themes (13 out of 14) or increased emphasis on themes with similar occurrences before and after COVID-19, while BRICS countries only differed in infection control. Additionally, OECD and BRICS countries varied in their subthemes and specific actions under similar primary themes. Conclusions COVID-19 exposed vulnerabilities in many countries' health systems, highlighting the need to build resilient health infrastructures through the optimization of NHPSPs. However, only about half of the OECD and BRICS countries have implemented new NHPSPs since the pandemic. Our findings highlight the critical need for global health system reforms and offer actionable recommendations for other countries in formulating their NHPSPs.

Abstract Background Alfalfa (Medicago sativa L.) is one of the most widely cultivated perennial leguminous forages globally, known for its high yield and quality. Leaf size plays a crucial role in influencing its photosynthetic capacity, forage yield, and quality. Therefore, understanding the genetic factors regulating leaf size is of great importance for breeding new alfalfa varieties with improved yield and quality. In this study, we performed a genome-wide association study on four leaf size-related traits in 176 alfalfa germplasm resources to identify candidate genes associated with leaf size. Results Phenotypic analysis revealed varying degrees of variation among the four traits, with coefficients of variation ranging from 3.43 to 36.84%. The broad sense heritability of these traits was found to be between 38.30% and 53.23%. Correlation analysis showed a significant positive correlation among the four traits (P

ABSTRACT Objective Ilizarov technology is highly effective in addressing complex orthopedic challenges. This study aims to describe our experience with distraction osteogenesis in managing bone tumors in the lower extremity, focusing on composite bone defects and associated complications. Methods A retrospective clinical study was conducted to analyze patients with primary bone tumors who underwent distraction osteogenesis using the Ilizarov method from 2010 to 2020. Some young children received epiphyseal distraction and bone transport as part of their sarcoma surgical treatment. Additionally, external fixation, bone transport, or limb lengthening were employed to address complex postoperative complications associated with bone tumors. The clinical outcomes assessed included the patient's general information, the location of bone defects, the length of bone repair, the status of bone healing, and limb function. Results Eleven patients were followed up for an average of 66 months (range, 24–132 months). The average length of repaired bone defects was 13 cm (range, 2.5–32 cm). The cohort comprised three females and eight males, with ages at presentation ranging from 6 to 42 years (mean, 18 years). The sites of involvement included the distal femur (n = 4), femoral diaphysis (n = 3), proximal tibia (n = 2), and the distal tibia (n = 2). Nine patients were diagnosed with osteosarcoma, while one presented with Ewing's sarcoma and another with a giant cell tumor of bone. Three young children were successfully treated with epiphyseal stretching; however, one patient experienced treatment failure. Additionally, seven patients underwent external fixation to address complex postoperative complications, including infection, bone defects, and limb shortening. At the last follow‐up, with the exception of one failure, the average Musculoskeletal Tumor Society (MSTS) limb function scores for the remaining 10 patients were 25 (range, 21–30). Three months post‐fixator removal, the Asociación Latinoamericana de Oncología (ASAMI) bone score was rated as excellent in 63.6% (7/11) of patients, whereas the ASAMI function score was excellent in 36.4% (4/11) and good in 54.5% (6/11) of cases. Conclusion The Ilizarov method demonstrates some clinical value in the resection and reconstruction of bone tumors, as well as in the management of postoperative complications associated with such tumors.

Capsule networks (CapsNet) are a pioneering architecture that can encode image features into vectors rather than scalars, addressing the limitations of traditional Convolutional Neural Networks (CNNs). This process is achieved by the dynamic routing algorithm and can maintain the image’s spatial hierarchies. CapsNet has demonstrated the state-of-the-art performance in simple datasets such as MNIST, but its performance degrades in more complex datasets. To solve this problem, AlexCapsNet architecture is proposed in this paper, in which the classic classification model AlexNet is used as the feature extraction layer. This allows CapsNet to capture deeper and more semantic features. The comprehensive evaluation with four datasets shows AlexCapsNet has improved performance when compared with the baseline and other CapsNet variants. Besides, our experiments on seven datasets show the reconstruction module in the CapsNet degrades the performance in the datasets with background noise. AlexCapsNet removes the reconstruction module and therefore can adapt to these complicated datasets. Our code is available at https://github.com/BaoBao0926/AlexCapsNet.

Hyperspectral anomaly detection (HAD) aims to classify each pixel in a hyperspectral image as either background or anomaly without requiring labeled data. Traditional reconstruction based methods model the background using a predefined static background dictionary and low-rank representation coefficients. However, when anomalies are present, the use of a static dictionary can lead to inaccurate background representation, which is easily disturbed by anomalous points. Moreover, existing methods typically focus on the low-rank and smooth characteristics of the background during reconstruction, overlooking deeper features of the background representation. This motivates us to reconsider how the background should be represented. To address these issues, we propose an innovative HAD method that integrates background dictionary learning into the anomaly decomposition process. By using projection operators to optimize the background dictionary, we overcome the limitations of traditional methods that rely on static dictionaries. In addition, we revisit the representation of the background and emphasize the importance of applying nonnegative full-rank constraint to the representation coefficients under the new background dictionary. These improvements result in a more accurate background representation, thereby enhancing anomaly detection performance. Experimental results on several hyperspectral datasets demonstrate that the proposed algorithm excels in anomaly detection tasks, offering new insights and approaches for HAD.

To achieve the United Nations Sustainable Development Goals (SDGs) by 2030, it is essential to understand the interlinkages between the goals. Previous research has investigated these interactions by focusing on their correlations. However, few studies have systematically prioritized them from a structural perspective through the complementarity measurements and empirically validated their policy effectiveness, such as which goals and indicators impact other SDGs most, especially in China. This study introduces a new concept known as the ‘SDG space’ by employing the “Product Space” approach in network science and economics. It measures the complementarities between SDGs and indicators through their network structures in investigating effective policy design. Using the most recent available but unpublished data for 31 Chinese provinces, the SDG space was constructed at the 17 SDG and 118 indicator levels by analyzing the probability of comparative advantage between each SDG or indicator pair co-occurring in the same place. Historical data confirm that in the ‘SDG Space’ network, a goal connected to other well-developed goals would enjoy better future growth and vice versa. The structure reveals that SDG 4 (Quality Education), 15 (Life on Land), and 1 (No Poverty) are critical goals with transformative synergies to other SDGs. Furthermore, we identified strong complementarities between land-based ecosystems and clean water and climate actions using the finer-grained indicator-level space. These findings help pave the way for China toward a sustainable future by providing science-based policy recommendations for decision-makers. They can be generally applied to other countries and regions to assist in navigating toward sustainable development.

Abstract Electron ptychography, recognized as an ideal technique for low-dose imaging, consistently achieves deep sub-angstrom resolution at electron doses of several thousand electrons per square angstrom (e−/Å2) or higher. Despite its proven efficacy, the application of electron ptychography at even lower doses—necessary for materials highly sensitive to electron beams—raises questions regarding its feasibility and the attainable resolution under such stringent conditions. Herein, we demonstrate the implementation of near-atomic-resolution ( ~ 2 Å) electron ptychography reconstruction at electron doses as low as ~100 e−/Å2, for metal-organic frameworks (MOFs), which are known for their extreme sensitivity. The reconstructed images clearly resolve organic linkers, metal clusters, and even atomic columns within these clusters, while unravelling various local structural features in MOFs, including missing linkers, extra clusters, and surface termination modes. By combining the findings from simulations and experiments, we have identified that employing a small convergence semi-angle during data acquisition is crucial for effective iterative ptychographic reconstruction under such low-dose conditions. This important insight advances our understanding of the rapidly evolving electron ptychography technique and provides a novel approach to high-resolution imaging of various sensitive materials.

Abstract Background Root rot is a major disease affecting alfalfa (Medicago sativa L.), causing significant yield losses and economic damage. The primary pathogens include Fusarium spp., Rhizoctonia spp., Pythium spp., and Phytophthora spp., with Fusarium being particularly severe. Breeding disease-resistant varieties is crucial for mitigating these losses. Results Under conditions of inoculation with Fusarium oxysporum, we conducted a statistical analysis of six phenotypic traits in alfalfa. Significant phenotypic variation was observed among different alfalfa varieties. Correlation analysis revealed significant relationships among traits such as relative yield, relative plant height (PH), and relative root number (NR), indicating potential synergistic roles of these traits in disease resistance. Through GWAS analysis, we identified 41 significant single nucleotide polymorphisms (SNP) associated with root rot resistance across eight chromosomes. The transcriptome analysis identified multiple differentially expressed genes (DEGs) associated with root rot stress, including transcription factors such as WRKY, NAC, AP2, GRAS, HLH, B3, MYB, and ARF. By integrating GWAS and transcriptome data, we identified four key DEGs significantly associated with root rot resistance, offering valuable insights for developing disease-resistant alfalfa varieties and enhancing overall crop resilience. Conclusion Our study identified significant phenotypic variation and key correlations among traits under root rot stress in alfalfa. We pinpointed 41 significant SNPs associated with root rot resistance across eight chromosomes and identified several key DEGs, including WRKY, NAC, and MYB transcription factors. The integration of GWAS and RNA-Seq data identified four key DEGs associated with root rot resistance, providing valuable insights for breeding disease-resistant alfalfa varieties and enhancing crop resilience.

Abstract Utilizing innovative methods to advance the research and development (R&D) of health products and enhance their accessibility has become crucial to achieving universal health coverage, addressing public health emergencies, and promoting population health and wellbeing. However, structural contradictions do exist in the supply and demand of health products in the Association of Southeast Asian Nations (ASEAN). With the joint support of the Ministry of Science and Technology of China, the Ministry of Education, and the China-ASEAN Center, Peking University established the China-ASEAN Science and Technology Cooperation Center for Public Health in April 2023. The Center held the Second Annual Forum on China-ASEAN Cooperation in Public Health on June 26–28, 2024, and the participants reached consensus on launching the China-ASEAN Beijing Declaration on Cooperation in Innovation of Health Products and Technologies, which calls on China and ASEAN countries to carry out the following actions: (1) Establish a more effective, open, and inclusive cooperation mechanism for health product innovation towards a China-ASEAN innovation ecosystem; (2) Enhance R&D capabilities by targeting new technologies, methods and appropriate and affordable health products for key populations and addressing diseases prevalent in China and ASEAN; (3) Establish a China-ASEAN Collaboration Center for Health Product Innovation, coordinate regional development plans, and enhance equitable access to pharmaceutical products at the regional level; (4) Accelerate regulatory harmonization in the region by optimizing and improving regulatory modalities of China and ASEAN Countries; and (5) Strengthen cross-sectoral cooperation to build resilient health system and achieve sustainable development of innovation cooperation. The Declaration will play an active role in regional public health governance and development cooperation, in order to promote the R&D and accessibility of health products in the region and to help achieve faster and more equitable access to health products for a broader population.

Abstract Data collection is an effective way to build a better Graph Neural Network (GNN) model, but it also makes it easy for attackers to implant backdoors into the model through data poisoning. In this work, we propose a backdoor detection method of graph for data collection scenarios (CGBD). Different from most existing backdoor detection methods of Neural Network (NN) models, especially the Deep Neural Network (DNN) models, the difference in predictions of backdoor samples in clean and backdoor models is exploited for backdoor detection in CGBD. Specifically, in the backdoor model, the backdoor samples with modified labels are predicted as the target class. However, in the clean model, they are predicted as the ground-truth labels since the clean model remains unaffected by the backdoor. Due to the detection methodology of CGBD is not based on the potential forms of triggers, it can detect backdoor samples with any type of trigger. Additionally, since data is associated with its providers, CGBD can detect not only backdoor data but also malicious data providers. Extensive experiments on multiple benchmark datasets demonstrate that data with varying poisoning rates exhibit significant anomalies compared to clean data. This validates the effectiveness of our proposed method.

Abstract Background Inflammatory diseases impair the reparative properties of endothelial progenitor cells (EPC); however, the involvement of diabetes in EPC dysfunction associated with myocardial infarction (MI) remains unknown. Methods A model was established combining high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice with myocardial infarction. The therapeutic effects of transplanted wild-type EPC, Nlrp3 knockout EPC, and Nlrp3 overexpression EPC were evaluated. Chip and Luciferase assay revealed CEBPB regulated the transcriptional expression of Nlrp3 as a transcription factor in EPC stimulated by high glucose (HG) or advanced glycation end products (AGEs). CO-IP results suggested that USP14 selectively suppressed NLRP3 degradation. KEGG enrichment revealed PI3K/ Akt/mTOR signaling showed striking significance in the entire pathway. Results In our study, wild-type, Nlrp3 knockout and Nlrp3 overexpressed EPC, intracardiac injections effectively improved cardiac function, increased angiogenesis, and reduced infarct size in mice with myocardial infarction. However, in the HFD/STZ-induced diabetic mice model combined with myocardial infarction, Nlrp3 knockout EPC significantly restored angiogenic capacity. Mechanically, CEBPB regulated the transcriptional level of Nlrp3 as a transcription factor in EPC. Meanwhile, we found that USP14 selectively suppressed NLRP3 protein degradation through the USP motif on the NACHT domain in mediating inflammasome activation. Cardiac functional outcomes in recipient mice after intramyocardial injection of shNlrp3 EPC overexpressing CEBPB or USP14 validated the modulation of EPC function by regulating Nlrp3 transcription or post-translational modification. Furthermore, KEGG enrichment and validation at the protein levels revealed PI3K/ Akt/mTOR cascade might be a downstream signal for NLRP3 inflammasome. Conclusion Our study provides a new understanding of how diabetes affected progenitor cell-mediated cardiac repair and identifies NLRP3 as a new therapeutic target for improving myocardial infarction repair in inflammatory diseases. Graphical abstract

Inflammatory mediators tumor necrosis factor (TNF) and interleukin 1 beta (IL1β), primarily derived from hepatic macrophages in the liver, play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Meanwhile, intravenously injected exosomes are mainly distributed in the liver and predominantly taken up by hepatic macrophage. Herein, we aimed to evaluate the feasibility of targeted inhibition of TNF and IL1β expression in hepatic macrophages via exosomes as a potential therapeutic strategy for NASH. In this study, we demonstrated that antisense oligodeoxynucleotide targeting TNF (ASO-TNF) or 2-deoxy-d-glucose (2DG) effectively suppressed the expression of TNF and/or IL1β in macrophages. Exosomes loaded with ASO-TNF or 2DG were able to suppress the expression of TNF and/or IL1β in macrophages in vitro or in vivo. Furthermore, infusion of Exo/ASO-TNF or Exo/2DG significantly attenuated experimental steatohepatitis in choline deficient amino acid-defined (CDAA) or methionine and choline deficient (MCD) diet-fed mice. RNA-seq results showed that treatment with Exo/ASO-TNF or Exo/2DG significantly inhibited pro-inflammatory signaling pathways. Mechanistically, we observed that administration of Exo/ASO-TNF or Exo/2DG could attenuate NASH progression by up-regulating the expression of superoxide dismutase 1 (Sod1). Combined, our findings demonstrated that infusion of exosomes loaded with ASO-TNF or 2DG alleviated experimental steatohepatitis in murine models. Thus, infusion of exosomes loaded with anti-inflammatory agents holds promise as a potential therapeutic strategy for NASH treatment.

ObjectivesTo assess the diagnostic accuracy of multimodal ultrasound in differentiating anaplastic thyroid carcinoma (ATC) from papillary thyroid carcinoma (PTC) and to evaluate its capability in detecting thyroid carcinoma (TC) aggressiveness.MethodsSixty nude mice were randomly assigned to ATC and PTC groups and injected subcutaneously with KHM-5M and TPC-1 cell lines, respectively. Tumors were analyzed using B-mode ultrasound (B-US), Color Doppler flow imaging (CDFI), elastography, and contrast-enhanced ultrasound (CEUS). A logistic model integrating multimodal ultrasound data was constructed, and Ki-67 and CD31 expressions in tumor tissues were analyzed immunohistochemically. Correlations between ultrasound features and aggressiveness markers were investigated.ResultsThe ATC group exhibited significantly higher strain-elastography scores (p=0.009) and Adler grades in CDFI (p=0.045). CEUS revealed a higher frequency of heterogeneous enhancement (95.2% vs. 48.1%, p

IntroductionFood security is the lifeblood of national security and an important cornerstone for world 15 peace, stability, and development. In this context, the study of the impact of land transfer (TF) on food security (FS) provides a new perspective for land resource optimization.MethodsBased on the empirical data of 30 provinces and regions in China from 2010 to 2022, this paper used the two-way fixed effect model to explore the causal relationship and the intermediary relationship between the two. Moreover, quantile regression is used to further explore the heterogeneity. In addition, the spatial Durbin model is used to analyze the spillover effect.ResultsFirst, land transfer has a significant promoting effect on food security. Secondly, land transfer has obvious heterogeneity to food security. Third, environmental regulation and green technology innovation play an intermediary role in land transfer to food security. Fourth, land transfer has a spatial spillover effect on food security.DiscussionThis paper not only enriches the theoretical research on the impact of land transfer on food security, but also provides empirical evidence. It provides an important reference for deepening China’s land transfer policy system, optimizing land transfer resources and ensuring the safety of grain industry.

Summary: Selectively harnessing photo-induced carriers to control surface photo-redox reactions can enable currently limited specificity in photocatalytic applications. By using a new approach to switching between dominant electron and hole charge transfer on the surfaces of metal oxide nanocrystals, depending on the optimal carrier for specific application functionality in photocatalytic pollutant degradation, H2 production, CO2 reduction, and gas sensing. The approach is based on the surface redox properties of custom-designed p-n hetero-structured hybrid nanoparticles (NPs) containing copper oxide, and wide-gap metal oxide semiconductors (MOSs). The customized CuxO/ZnO (CXZ) heterostructures ensure effective charge separation and surface reactions driven by UV-vis excited highly reactive holes and show high performance in the photo-oxidative degradation of organic dyes and NO2 gas sensing. By switching the dominant surface carrier type from holes to electrons, the hybrids exhibit excellent performance in photocatalytic H2 evolution and CO2 reduction. This work offers a generic approach to engineering multipurpose photocatalytic materials.

Background Development assistance for health (DAH) plays a vital role in supporting health programmes in low- and middle-income countries. While DAH has historically focused on infectious diseases and maternal and child health, there is a lack of comprehensive analysis of DAH trends, strategic shifts and their impact on health systems and outcomes. This study aims to provide a comprehensive review of DAH from 1990 to 2022, examining its evolution and funding allocation shifts.Methods We conducted a mixed-methods review, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search was performed across PubMed, Embase, Web of Science and the Cochrane databases, yielding 102 eligible studies. Quantitative data were obtained from the Institute for Health Metrics and Evaluation database, covering DAH data from 1990 to 2022. Qualitative data were analysed through thematic synthesis based on the WHO’s six health system building blocks.Results The DAH has predominantly focused on HIV/AIDS and maternal and child health. Despite the increasing global burden of non-communicable diseases (NCDs), the proportion of DAH allocated to NCDs remained low, increasing only from 1% in 1990 to 2% in 2022. Similarly, the overall funding for health system strengthening decreased from 19% in 1990 to 7% in 2022. Major contributors to DAH included the USA, the UK and the Bill & Melinda Gates Foundation. While associations between DAH and improvements in certain health outcomes were observed, establishing causality is challenging due to multiple influencing factors. The COVID-19 pandemic underscored the importance of robust health systems. However, DAH allocation did not show any substantial shift towards health system strengthening during this period. Economic evaluations calculated the median incremental cost-effectiveness ratio of DAH interventions,Conclusions This study reviews DAH trends from 1990 to 2022, showing a predominant focus on HIV/AIDS and maternal and child health, with insufficient attention to NCDs and health system strengthening. Despite the increasing burden of NCDs and the impact of COVID-19, DAH priorities have not significantly shifted, highlighting the need for ongoing evaluation and strategic adjustments. To enhance DAH effectiveness, it is crucial to adopt a more balanced approach and also align interventions with needs from recipient countries and implement evidence-based strategies with continuous monitoring and evaluation.

Objectives The purpose of this study was to evaluate the predictive value of the cough peak flow (CPF) for successful extubation in postcraniotomy critically ill patients.Design This was a single-centre prospective diagnostic study.Setting The study was conducted in three intensive care units (ICUs) of a teaching hospital.Participants Postcraniotomy patients who were 18 years or older, stayed in ICU for more than 24 hours and underwent mechanical ventilation for more than 24 hours were eligible for the study. Patients were excluded if one of the following was present: no extubation attempt during the ICU stay; underwent tracheostomy without extubation attempt; pregnant or lactating women; enrolled in other clinical trials; declined to participate in the study. A total of 4879 patients were screened and 1037 were eligible for the study, among whom 785 were included in the study.Outcome measures CPF, including involuntary (CPF-invol) and voluntary CPF (CPF-vol), were measured before extubation. The area under the receiver operating characteristic curve (AUC) was calculated to explore the diagnostic accuracy of CPF in predicting successful extubation.Results There were 641 successful extubation cases (81.7%). The AUC of CPF-invol for predicting successful extubation was 0.810 (95% CI 0.766 to 0.854), with a cut-off value of 63.2 L/min, a sensitivity of 87.4% and a specificity of 66.7%. For conscious patients, the AUC of CPF-invol for the prediction of successful extubation was 0.849 (95% CI 0.794 to 0.904), with a cut-off value of 63.2 L/min and the AUC of CPF-vol was 0.756 (95% CI 0.696 to 0.817), with a cut-off value of 68.2 L/min.Conclusions The CPF was much higher in patients with successful extubation than that in patients with failed extubation. CPF might be valuable for the prediction of extubation outcomes in postcraniotomy critically ill patients. Multicentre studies could be carried out to further validate the results of this study.Trial registration number NCT04000997.

IntroductionIn order to achieve the sustainable development goal set by the United Nations,it is necessary to promote the green transformation and sustainable development of agriculture. In the context of the global economic digital revolution, examining the impact of digital financial inclusion (DFl) on agricultural green total factor productivity (AGTFP) provided a new perspective for DFl to promote agricultural transformation and upgrading.MethodsBased on balanced panel data for 30 provinces in China from 2011 to 2022, the study used the slack-based measure (SBM) and global malmquist-luenberger (GML) index to measure AGTFP. Then the entropy method was used to measure the basic condition of digital logistics. Finally, causal relationship and potential mechanism of DFI on AGTFP were verified by means of bidirectional fixed effect and two-stage least square method.ResultsOur findings are as follows: firstly, DFl significantly increases AGTFP. This conclusion is still valid after a series of robustness tests and endogeneity control. Secondly, land transfer and digital logistics play positive mediating roles in the relationship between DFl and AGTFP. Thirdly, DFl has a higher impact on AGTFP in main grain-producing areas and the production-marketing balanced areas.DiscussionThis research provides not only theoretical and empirical support for optimizing China’s digital inclusive financial service system and promoting the green development of agriculture but also an important reference for the agricultural development of developing countries.

BackgroundThe 2021 Global Burden of Disease (GBD) study shows a continuous increase in the burden of chronic kidney disease due to diabetes mellitus type 2 (CKD-T2DM) from 1990 to 2021. This study examines the influence of dietary risk factors across various populations and socioeconomic groups.MethodsUtilizing the 2021 GBD data, we analyzed age-standardized CKD-T2DM metrics—including mortality, disability-adjusted life years (DALY), and age-standardized rates (ASR)—stratified by age, gender, and region. The study employs estimated annual percentage changes (EAPC) to monitor temporal trends and project future trends from 2022 to 2035 using bayesian age-period-cohort (BAPC) analysis.ResultsThe results indicate that, in 2021, 20.55% of CKD-T2DM mortality and 23.21% of CKD-T2DM DALY were attributed to poor diets, especially those low in fruits and high in red and high processed meat. Throughout this period, both mortality and DALY rates associated with dietary risks increased significantly, with the most rapid increase in diet high in sugar-sweetened beverages, highlighting the considerable impact of dietary factors on the global CKD-T2DM landscape. Geographic disparities in T2DM trends are evident, with the most significant increases in age-standardized mortality rates (ASMR) and age-standardized DALY rates (ASDR) observed in regions such as high-income North America and Central Latin America. Socio-demographic index (SDI) is negatively correlated with the CKD-T2DM burden attributable to dietary risk factors.ConclusionPublic health interventions that target dietary changes can significantly reduce the global burden of CKD-T2DM.

Background: Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide with an extremely poor prognosis. Previous studies have suggested that tripartite motif containing 47 (TRIM47) is involved in the progression of numerous cancers. However, the molecular mechanism and function of TRIM47 in GBC remain unclear. Methods: The clinical significance of TRIM47 was evaluated using immunohistochemistry. Functional assays were performed in vitro and in vivo to determine the role of TRIM47 in GBC. Mass spectrometric analysis, western blotting, and immunoprecipitation assays were performed to investigate the molecular mechanisms involved. Results: In this study, TRIM47 was upregulated in GBC tissues and associated with shorter overall survival rates and TRIM47 was involved in GBC cell proliferation, migration, and apoptosis. Mechanistically, TRIM47 interacts with PARP1 and mediates the K63-linked polyubiquitination of PARP1, thereby stabilizing its expression. Furthermore, TRIM47 activated the AKT signaling pathway via PARP1. Conclusion: The present study revealed that TRIM47 contributes to the progression of GBC and is therefore an important biomarker for predicting the prognosis of GBC and for therapeutic intervention.

Industrial fault diagnosis faces unique challenges with high-dimensional data, long time-series, and complex couplings, which are characterized by significant information entropy and intricate information dependencies inherent in datasets. Traditional image processing methods are effective for local feature extraction but often miss global temporal patterns, crucial for accurate diagnosis. While deep learning models like Vision Transformer (ViT) capture broader temporal features, they struggle with varying fault causes and time dependencies inherent in industrial data, where adding encoder layers may even hinder performance. This paper proposes a novel global and local feature fusion sequence-aware ViT (GLF-ViT), modifying feature embedding to retain sampling point correlations and preserve more local information. By fusing global features from the classification token with local features from the encoder, the algorithm significantly enhances complex fault diagnosis. Experimental analyses on data segment length, network depth, feature fusion and attention head receptive field validate the approach, demonstrating that a shallower encoder network is better suited for high-dimensional time-series fault diagnosis in complex industrial processes compared to deeper networks. The proposed method outperforms state-of-the-art algorithms on the Tennessee Eastman (TE) dataset and demonstrates excellent performance when further validated on a power transmission fault dataset.

Pregnancy failure in the first trimester of cows significantly impacts the efficiency of the dairy industry. As a type I interferon exclusively to ruminants, IFN-τ plays a key role in maternal recognition and immune tolerance of fetuses. Macrophages are the most common immune cells within the ruminant endometrium. Nevertheless, deeply analyzing the mechanisms of IFN-τ regulating macrophage polarization still needs further study. In this study, a notable decline of bta-miR-30b-5p expression via the increase of SOCS1 was observed in uterine tissues of pregnant cows. We then confirmed that the 3′UTR of SOCS1 was to be directly targeted by bta-miR-30b-5p. After that, we demonstrated that this obviously promoted the bovine macrophages (BoMac) polarized to M2 through enhancing SOCS1 expression with the treatment of IFN-τ. Furthermore, we found that SOCS1 restrained the expression of the key proteins p65 and p-P65 in the NF-κB pathway. Causing, the wide range of cross-species activities of IFN-τ, therefore we established a pregnant mouse model for the future confirmation of the above mechanism. The results verified that IFN-τ significantly improved this mechanism and maintained normal pregnancy status in mice, but miR-30b-5p significantly reduced the M2 polarization by inhibiting SOCS1, which activated the NF-κB signaling pathway, and then leading to the failure of embryo implantation. All these results indicated that IFN-τ can regulate immune tolerance during pregnancy by promoting M2 macrophage polarization through inhibiting bta-miR-30b-5p targeting SOCS1 to deactivate the NF-κB signaling pathway.

Background: Acute and critical neurological diseases are often accompanied with elevated intracranial pressure (ICP), leading to insufficient cerebral perfusion, which may cause severe secondary lesion. Existing ICP monitoring techniques often fail to effectively meet the demand for real-time noninvasive ICP monitoring and warning. This study aimed to explore the use of electrical impedance tomography (EIT) to provide real-time early warning of elevated ICP by observing cerebral perfusion. Methods: An intracranial hypertension model was prepared by injecting autologous un-anticoagulated blood into the brain parenchyma of twelve Landrace swine. Invasive ICP monitoring was used as a control method, and a high-precision EIT system was used to acquire and analyze the changing patterns of cerebral perfusion EIT image parameters with respect to ICP. Four EIT parameters related to cerebral perfusion were extracted from the images, and their potential application in detecting ICP elevation was analyzed. Results: When ICP increased, all EIT perfusion parameters decreased significantly (P < 0.05). When the subjects were in a state of intracranial hypertension (ICP > 22 mmHg), the correlation between EIT perfusion parameters and ICP was more significant (P < 0.01), with correlation coefficients ranging from −0.72 to −0.83. We tested the objects when they were in baseline ICP and in ICP of 15–40 mmHg. Under both circumstances, ROC curve analysis showed that the comprehensive model of perfusion parameters based on the random forest algorithm had a sensitivity and specificity of more than 90% and an area under the curve (AUC) of more than 0.9 for detecting ICP increments of both 5 and 10 mmHg. Conclusion: This study demonstrates the feasibility of using perfusion EIT to detect ICP increases in real time, which may provide a new method for real-time non-invasive monitoring of patients with increased ICP. [ABSTRACT FROM AUTHOR]

Background: Neutrophil-to-lymphocyte ratio (NLR) is a promising prognostic marker for patients undergoing hepatectomy for colorectal liver metastases (CRLM). However, its prognostic value in patients receiving neoadjuvant therapy (NAT) has not been sufficiently addressed. Methods: From 2013 to 2023, a cohort of 692 patients with CRLM receiving hepatectomy were enrolled in five centers. Clinicopathological characteristics were obtained from a prospectively maintained multi-center database. The effect of NLR (> 2 versus ≤ 2) on overall survival (OS) and recurrence-free survival was estimated by Kaplan–Meier analysis. Univariable and multivariable Cox regression analysis was applied to investigate the influence of individual clinicopathological parameters on OS. Results: In the entire cohort, the median NLR level was 2.11 (0.30–16.33). There were 307 (44.4%) patients receiving NAT followed by hepatectomy, while 385 (55.6%) patients undergoing upfront surgery. Notably, patients in the NAT group showed significantly lower NLR level than those in the upfront surgery group (1.83 versus 2.32, P < 0.001). In the upfront surgery group, high NLR was significantly associated with worse OS, independent of other factors (HR = 1.49, 95% CI 1.08–2.05, P = 0.02). In the NAT group, there was no significant difference in OS between the high NLR and low NLR group. Conclusion: The prognostic value of NLR in surgically resected CRLM is potentially influenced by NAT in the modern era. [ABSTRACT FROM AUTHOR]

Human group box protein 1 (HMGB1) is a nuclear protein critical in various cellular processes. It is released in response to stress, infection, or tissue damage and acts as a danger signal, triggering immunological responses. Elevated HMGB1 levels are linked to various diseases, including atherosclerosis. This review investigated the role of HMGB1 in atherosclerosis and assessed the effectiveness of current and emerging treatment approaches that target HMGB1. Data was obtained from various indexed scientific databases. The inclusion and exclusion criteria were based on the relevance to atherosclerosis and HMGB1, the types of intervention (herbal, synthetic, and experimental compounds), the mechanism of action, and the outcome measured (inflammatory markers, cellular responses, and atherosclerotic plaque evolution). The findings present a promising future for atherosclerosis treatment, with herbal extracts, and experimental and synthetic compounds showing significant potential in preclinical studies. Herbal compounds like glycyrrhizin, ginsenosides, and mogrosides demonstrate anti-inflammatory and antioxidant properties. Synthetic drugs like metformin, statins, and sodium-glucose transporter inhibitors (SGLT2) show significant promise by modulating HMGB1 activity and related pathways. Additionally, monoclonal antibodies and specific inhibitors targeting toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and receptors of advanced glycated endpoints (RAGE) show potential for reducing vascular inflammation. Atherosclerosis is a multifaceted condition that requires a comprehensive approach, including cholesterol-lowering therapy. However, to fully harness the potential of HMGB1-targeted treatments, further research and clinical trials are necessary. These trials will be crucial in developing HMGB1-targeted therapies as effective adjuvants to cholesterol-targeting compounds in managing cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Esophageal ulcers can arise not only from malignant lesions but also from benign diseases, such as tuberculosis. These ulcers may mimic the radiological features of esophageal malignancy or tuberculosis on PET/CT, leading to diagnostic challenges. Case presentation A 59-year-old woman was admitted to our hospital with a month-long history of progressive painful swallowing, fatigue, and loss of appetite. Whole-body 18 F-FDG PET/CT revealed a lesion in the mid-esophagus and swollen mediastinal lymph nodes with high FDG uptake, showing a maximum standardized uptake value (SUVmax) of 17.10 for the lymph nodes and 8.08 for the esophageal lesion. Esophageal cancer was initially suspected based on PET/CT findings. However, pathological examination of the esophageal lesion obtained via esophagoscopy showed only inflammation and granulation tissue, with no malignancy. A biopsy of the lymph nodes obtained through endoscopic ultrasonography revealed caseous necrosis but no atypical cells, and microbiological tests were positive for Mycobacterium tuberculosis. A final diagnosis of esophageal tuberculosis was made. Conclusions Esophageal lesions can result from both malignant and benign conditions, including tuberculosis, and may mimic the radiological features of esophageal malignancy on PET/CT or other imaging studies. When esophageal lesions resemble malignancy, pseudotumoral esophagus and esophageal tuberculosis should be considered as differential diagnoses. Endoscopy, particularly endoscopic ultrasonography, is strongly recommended to accurately distinguish between benign and malignant esophageal lesions, helping to avoid unnecessary invasive treatments and reduce potential physical and psychological harm to patients.

Background: Approximately 71% of antibiotics in England are prescribed in general practice settings. Whilst there are various impactful training resources available to support clinicians in antimicrobial stewardship (AMS) activities, implementation, reach, and uptake affect how successful they are nationally. This case study explores the feasibility, acceptability, and usefulness of embedding the TARGET (Treat Antibiotics Responsibly, Guidance, Education and Tools) AMS training into a local incentive scheme. Method: Black Country Integrated Care Board (ICB) invited a representative from all associated general practises to a TARGET AMS training event; attendance was linked to a local incentive scheme. Data were collected via a pre- and post-workshop survey capturing TARGET toolkit knowledge, AMS attitudes and behaviours, training feedback, and intention to implement AMS behaviours. Descriptive analyses were conducted. Results: 157 and 101 attendees completed the pre- and post-session surveys, respectively. In total, 89% agreed that attending the session was a good use of their time. The proportions of attendees stating an intention to use the TARGET toolkit and implement a range of AMS strategies following the session were high (TARGET Toolkit: >82%, AMS strategies: >90%). Most attendees planned to implement these actions within 3 months (47%) or within 3–6 months (30%). Conclusion: Results suggest that embedding the training into a local incentive scheme is a viable implementation approach in extending training reach. Although the impact on prescribing rates is not yet available, the high engagement and intention to implement AMS strategies observed should inspire confidence in this approach to training implementation.

Memristive in-memory computing has demonstrated potential for solving matrix equations in scientific computing. However, the inherent inaccuracies of analog mechanisms create challenges in achieving high-precision solutions while maintaining low-energy consumption. This study introduces a memristive matrix equation solver that considerably accelerates solutions by performing mathematical iterations directly within an analog domain. Our approach facilitates rapid approximate solutions with a scalable circuit topology and expedites the high-precision refinement process by substantially reducing the digital-to- analog conversion overhead. We experimentally validated this methodology using a heterogeneous computing system. We performed simulations of multiple scientific problems on these circuits, including solving the diffusion equation and modeling equilibration in silicon P-N junctions. Notably, our memristive solver, combined with digital refinement, achieved software-equivalent precision (with an error of 10-12). Compared to conventional digital processing units, this approach offered a 128-fold improvement in solution speed and a 160-fold reduction in energy consumption. This work establishes a foundation for future scientific computing using imprecise analog devices. [ABSTRACT FROM AUTHOR]

Abstract Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of rare variants on cerebellar traits. This study conducts a large-scale exome association analysis using data from approximately 35,000 UK Biobank participants, examining seven cerebellar traits, including total cerebellar volume and white matter microstructure. We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure. Gene enrichment analysis reveals associations with non-coding RNA processing, cognitive function, neurodegenerative diseases, and mental disorders, suggesting shared biological mechanisms between cerebellar phenotypes and neuropsychiatric diseases.

Abstract Background The integrity of brain function is at stake due to cerebral ischemia‐reperfusion injury (CIRI), which encompasses mitochondrial dysfunction, autophagy, and neuroinflammation. The role of E2F1 in mediating these processes in microglia during CIRI remains unclear. Methods A CIRI mouse model was utilized for single‐cell RNA transcriptome sequencing of brain tissues. The research comprised diverse gene expression, gene ontology (GO), and the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Experimental techniques included oxygen‐glucose deprivation (OGD/R) cell models, RT‐qPCR, Western Blot, ChIP assays, and microglia‐neuron co‐cultures. Results A significant aspect highlighted in the study was the involvement of CDK5 in the induction of mitochondrial abnormalities associated with CIRI. Upregulation of E2F1 and CDK5 in post‐CIRI microglia was observed. E2F1 facilitated CDK5 transcription, leading to DRP1 phosphorylation, exacerbating neurotoxic effects. Silencing E2F1 improved neurobehavioral outcomes in CIRI mice. Conclusions Activation of E2F1‐mediated CDK5 drives mitochondrial division while inhibiting mitophagy in microglia, triggering inflammation, neuronal apoptosis, and exacerbating CIRI damage. Targeting this pathway could offer novel therapeutic strategies for mitigating CIRI‐induced brain injury. Key points Identification of the E2F1/CDK5/DRP1 Axis in CIRI This study reveals that the E2F1 transcription factor upregulates CDK5 expression, which in turn phosphorylates DRP1, promoting excessive mitochondrial fission and inhibiting mitophagy in microglia. This mechanism plays a critical role in cerebral ischemia‐reperfusion injury (CIRI). Mitochondrial Dysfunction and Neuroinflammation The activation of DRP1 leads to mitochondrial fragmentation and excessive ROS accumulation, triggering microglial activation and inflammatory responses, exacerbating neuronal apoptosis and brain injury in CIRI. Therapeutic Potential of E2F1 Silencing Knockdown of E2F1 in microglia effectively reduces mitochondrial damage, restores mitophagy, suppresses inflammation, and improves neurological outcomes in a CIRI mouse model, highlighting a promising therapeutic target for ischemic stroke intervention.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), which is highly expressed in the central nervous system, is known to be involved in the regulation of mitochondrial biosynthesis, metabolic regulation, neuroinflammation, autophagy, and oxidative stress. This knowledge indicates a potential role of PGC-1α in a wide range of functions associated with neurological diseases. There is emerging evidence indicating a protective role of PGC-1α in the pathogenesis of several neurological diseases. As such, a deeper and broader understanding of PGC-1α and its role in neurological diseases is urgently needed. The present review provides a relatively complete overview of the current knowledge on PGC-1α, including its functions in different types of neurons, basic structural characteristics, and its interacting transcription factors. Furthermore, we present the role of PGC-1α in the pathogenesis of various neurological diseases, such as intracerebral hemorrhage, ischemic stroke, Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, and other PolyQ diseases. Importantly, we discuss some compounds or drug-targeting strategies that have been studied to ameliorate the pathology of these neurological diseases and introduce the possible mechanistic pathways. Based on the available studies, we propose that targeting PGC-1α could serve as a promising novel therapeutic strategy for one or more neurological diseases.

In this study, we obtain specific picture of the phase transitions for the 6-dimensional Gauss-Bonnet Anti-de Sitter (AdS) black hole with triple phases, using the generalized free energy we constructed and Kramers escape rate in stochastic motion. There are six possible phase transition processes between the three different stable states (small, medium, and large black hole states). During these phase transitions, there are two key temperatures. One is the temperature at which the medium black hole state emerges, and the other is the temperature at which the small black hole state annihilates. Meanwhile, two dynamic equilibrium processes are formed. One is a dynamic equilibrium of the transition from the medium black hole state to the large black hole state and the transition from the small black hole state to the medium black hole state. The other is a dynamic equilibrium of the transition from the small black hole state to the medium black hole state and the transition from the medium black hole state to the small black hole state.

BP-3 is the most widely used ultraviolet absorber, but its toxic effects and mechanisms far from being elucidated. This study evaluated the male developmental reproductive toxicities and mechanism of low-doses of BP-3. The results indicated that BP-3 (2.28 and 228 μg/L) led to a decrease in sperm quantity, quality and testosterone level, impaired blood-testis barrier (BTB) integrity and cytoskeleton, accompanied by aggravated oxidative stress in testes of mice on postnatal day 56 (PND 56). Notably, chemokine CCL27, a driver of oxidative stress, was significantly upregulated induced by BP-3. Similar disrupted effects were detected in testes of mice on PND14, which could be antagonized by ICI 182780 (estrogen receptor antagonist). Mechanistically, BP-3 directly interacted with ER, which boosted CCL27 expression, reactive oxygen species (ROS) accumulation, and BTB and cytoskeleton impairment. In vitro, si-CCL27 and/or ROS scavenger treatment significantly antagonized BP-3-induced oxidative stress and the decrease of BTB and cytoskeleton related genes in TM4 cells. These findings demonstrate that prolonged exposure to low-doses of BP-3 resulted in detrimental effects on testicular development through activation of the ER/CCL27/ROS axis. This study provides a novel perspective understanding the male reproductive toxicity risk caused by BPs exposure at low-doses.

Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway.