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Abstract Objective The study aimed to examine the role of the C-reactive protein to albumin ratio (CAR) as an inflammatory biomarker in relation to subclinical myocardial injury (SC-MI), addressing the limited knowledge of their association. Methods The study included 5,949 individuals without cardiovascular disease (CVD) from the National Health and Nutrition Examination Survey. SC-MI was identified through a Cardiac Infarction Injury Score (CIIS) of ≥ 10 units based on a 12-lead electrocardiogram. The study used multivariate logistic regression models, adjusted for potential confounders, to evaluate the relationship between CAR and SC-MI. Subgroup analyses were conducted to substantiate the results, and the non-linear correlation was assessed via restricted cubic spline (RCS) regression. Results The RCS curve showed a significant positive correlation between CAR and SC-MI (P for nonlinear = 0.2496). When adjusted for all confounders, individuals in the highest tertile of CAR exhibited a higher likelihood of SC-MI compared to those in the lowest tertile, with an odds ratio (OR) of 1.21 (95% CI: 1.06–1.39, P for trend = 0.029). A 10-unit increment in CAR was linked to a 3.6% heightened risk of SC-MI [OR = 1.036 (95% CI: 1.006, 1.066)], with this association being more prominent among male adults, non-smokers, married individuals, those without diabetes mellitus, and those with no history of cancer. Conclusion The findings of this study suggest a positive correlation between CAR and SC-MI among the US adult population, indicating the potential of CAR in enhancing SC-MI prevention strategies in the general population.

Abstract Many datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While biospecimen and experimental information is often captured, detailed metadata standards related to data matrices and analysis workflows are currently lacking. To address this, we develop the matrix and analysis metadata standards (MAMS) to serve as a resource for data centers, repositories, and tool developers. We define metadata fields for matrices and parameters commonly utilized in analytical workflows and developed the rmams package to extract MAMS from single-cell objects. Overall, MAMS promotes the harmonization, integration, and reproducibility of single-cell data across platforms.

Abstract Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication, radar, navigation, etc. However, the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process, which places the fundamental limit on its sensing speed and energy efficiency. Here, we propose the super-resolution diffractive neural networks (S-DNN) to process electromagnetic (EM) waves directly for the DOA estimation at the speed of light. The multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction limit. The spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of view. The S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in principle. The results achieve the angular resolution over an order of magnitude, experimentally demonstrated with four times, higher than diffraction-limited resolution. We also apply S-DNN’s edge computing capability, assisted by reconfigurable intelligent surfaces, for extremely low-latency integrated sensing and communication with low power consumption. Our work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

Abstract The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB–IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

This study introduces a holistic framework for optimising road-rail intermodal hub locations based on real regional freight data and railway station information. The primary objective is to enhance railway transportation capacity, thereby facilitating the development of a low-carbon transport system. Research begins by scrutinising the freight landscape in the region, focusing on transport volume, freight intensity, goods types and average delivery distances. Subsequently, data mining techniques, including DBSCAN clustering and frequent itemset mining, are employed to uncover freight demand hotspots across both spatial and temporal dimensions. Based on these findings, a mathematical model for hub location selection is constructed, along with criteria for goods categories suitable for rail transportation. Ultimately, using the Beijing-Tianjin-Hebei region as a case study, 12 road-rail intermodal hubs are identified, along with the main cargo types best suited for rail transport within their respective service areas. This transition is expected to result in an annual reduction of 470,000 tons of regional carbon emissions. The proposed method framework provides valuable guidance and practical insights for the optimisation of freight structures in various regions. Furthermore, it aligns with contemporary environmental and sustainability objectives, contributing to the broader goal of establishing low-carbon transport systems.

Abstract Objectives To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. Methods Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). Results The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p 0.05). Conclusions rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. Critical relevance statement The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. Key Points Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI. Graphical Abstract

Abstract Research and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Abstract Background Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. Methods In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. Results Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. Conclusion This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.

Abstract Background The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. Methods In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. Results The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39–70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893–0.977) for experienced readers, and 0.910 (95% CI: 0.831–0.959) for inexperienced readers, and 0.932 (95% CI: 0.892–0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0–80.9%) and 94.1% (range: 88.6–97.7%) for experienced readers, and 63.9% (range: 59.6–68.1%) and 86.4% (range: 84.1–88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79–0.92). Conclusions VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

On-Load Tap-Changer (OLTC) is the only core equipment in the ultra-high voltage (UHV) converter transformer that moves frequently, and flexible connection structure (FCS) is the moveable actuating part of the vacuum interrupter drive mechanism of OLTC. Minimizing the transient stress during the movement of FCS is essential for prolonging its fatigue life, thus is pursued by optimizing the shape of the flexible sheet in this paper. Peak transient stress of FCS is defined as the optimization objective, and eight geometrical parameters controlling the shape of flexible sheet are defined as the optimization variables. A progressive three-stage shape optimization strategy is proposed by combing four techniques: Multi-body Dynamic (MBD), Finite Element Analysis (FEA), Correlation Coefficient Analysis (CCA) and Adaptive Single-objective Optimization (ASO). MBD analysis of the vacuum interrupter drive mechanism and FEA of the FCS are utilized for calculating the transient stress distribution. Spearman CCA is performed to quantitively determine the correlation and sensitivity between the optimization variables and the optimization objective. Shape optimization of FCS using ASO is carried out, and results show that the stress concentration is basically eliminated and the peak transient stress decrease by 34.35% after shape optimization. Further analysis of the FCS with multi-layered flexible sheet is conducted, again demonstrating the effectiveness of the shape optimization on minimizing transient stress.

BackgroundAlzheimer disease and related dementias (ADRD) rank as the sixth leading cause of death in the United States, underlining the importance of accurate ADRD risk prediction. While recent advancements in ADRD risk prediction have primarily relied on imaging analysis, not all patients undergo medical imaging before an ADRD diagnosis. Merging machine learning with claims data can reveal additional risk factors and uncover interconnections among diverse medical codes. ObjectiveThe study aims to use graph neural networks (GNNs) with claim data for ADRD risk prediction. Addressing the lack of human-interpretable reasons behind these predictions, we introduce an innovative, self-explainable method to evaluate relationship importance and its influence on ADRD risk prediction. MethodsWe used a variationally regularized encoder-decoder GNN (variational GNN [VGNN]) integrated with our proposed relation importance method for estimating ADRD likelihood. This self-explainable method can provide a feature-important explanation in the context of ADRD risk prediction, leveraging relational information within a graph. Three scenarios with 1-year, 2-year, and 3-year prediction windows were created to assess the model’s efficiency, respectively. Random forest (RF) and light gradient boost machine (LGBM) were used as baselines. By using this method, we further clarify the key relationships for ADRD risk prediction. ResultsIn scenario 1, the VGNN model showed area under the receiver operating characteristic (AUROC) scores of 0.7272 and 0.7480 for the small subset and the matched cohort data set. It outperforms RF and LGBM by 10.6% and 9.1%, respectively, on average. In scenario 2, it achieved AUROC scores of 0.7125 and 0.7281, surpassing the other models by 10.5% and 8.9%, respectively. Similarly, in scenario 3, AUROC scores of 0.7001 and 0.7187 were obtained, exceeding 10.1% and 8.5% than the baseline models, respectively. These results clearly demonstrate the significant superiority of the graph-based approach over the tree-based models (RF and LGBM) in predicting ADRD. Furthermore, the integration of the VGNN model and our relation importance interpretation could provide valuable insight into paired factors that may contribute to or delay ADRD progression. ConclusionsUsing our innovative self-explainable method with claims data enhances ADRD risk prediction and provides insights into the impact of interconnected medical code relationships. This methodology not only enables ADRD risk modeling but also shows potential for other image analysis predictions using claims data.

As a crucial maritime search and rescue method, infrared object detection is critical in influencing the success rate. Research on infrared maritime images is limited, and the problems of smaller object sizes, more substantial noise, and less detailed information still need to be solved. To tackle these problems, we proposed an infrared maritime object detection network with feature enhancement and adjacent fusion. A spatial feature enhancement module and a semantic feature enhancement module are designed to enhance the location information of dim small targets and the deep semantic information, respectively. We designed a feature adjacent fusion network to fully use multiscale feature information. We built a maritime infrared dataset and compared the proposed method with existing advanced traditional and learning methods. The proposed method achieves better detection results.

Porcine epidemic diarrhea (PED) is a highly contagious intestinal infection primarily affecting pigs. It is caused by the porcine epidemic diarrhea virus (PEDV). PEDV targets the villus tissue cells in the small intestine and mesenteric lymph nodes, resulting in shortened intestinal villi and, in extreme cases, causing necrosis of the intestinal lining. Moreover, PEDV infection can disrupt the balance of the intestinal microflora, leading to an overgrowth of harmful bacteria like Escherichia coli. Exosomes, tiny membrane vesicles ranging from 30 to 150 nm in size, contain a complex mixture of RNA and proteins. MicroRNA (miRNA) regulates various cell signaling, development, and disease progression processes. This study extracted exosomes from both groups and performed high-throughput miRNA sequencing and bioinformatics techniques to investigate differences in miRNA expression within exosomes isolated from PEDV-infected porcine small intestine tissue compared to healthy controls. Notably, two miRNA types displayed upregulation in infected exosomes, while 12 exhibited downregulation. These findings unveil abnormal miRNA regulation patterns in PEDV-infected intestinal exosomes, shedding light on the intricate interplay between PEDV and its host. This will enable further exploration of the relationship between these miRNA changes and signaling pathways, enlightening PEDV pathogenesis and potential therapeutic targets.

Hf-based carbides are highly desirable candidate materials for oxidizing environments above 2000 ​°C. However, the static oxidation behavior at their potential service temperatures remains unclear. To fill this gap, the static oxidation behavior of (Hf, Ti)C and the effect of Ti substitutions were investigated in air at 2500 ​°C under an oxygen partial pressure of 4.2 ​kPa. After oxidation for 2000 ​s, the thickness of the oxide layer on the surface of (Hf, Ti)C bulk ceramic is reduced by 62.29 ​% compared with that on the HfC monocarbide surface. The dramatic improvement in oxidation resistance is attributed to the unique oxide layer structure consisting of various crystalline oxycarbides, HfO2, and carbon. The Ti-rich oxycarbide ((Ti, Hf)CxOy) dispersed within HfO2 formed the major structure of the oxide layer. A coherent boundary with lattice distortion existed at the HfO2/(Ti, Hf)CxOy interface along the (111) crystal plane direction, which served as an effective oxygen diffusion barrier. The Hf-rich oxycarbide ((Hf, Ti)CxOy) together with (Ti, Hf)CxOy, HfO2, and precipitated carbon constituted a dense transition layer, ensuring favorable bonding between the oxide layer and the matrix. The Ti content affects the oxidation resistance of (Hf, Ti)C by determining the oxide layer's phase distribution and integrity.

The Dynamic Gait Event Identifier (DGEI) introduces a pioneering approach for real-time gait event detection that seamlessly aligns with the needs of embedded system design and optimization. DGEI creates a new standard for gait analysis by combining software and hardware co-design with real-time data analysis, using a combination of first-order difference functions and sliding window techniques. The method is specifically designed to accurately separate and analyze key gait events such as heel strike (HS), toe-off (TO), walking start (WS), and walking pause (WP) from a continuous stream of inertial measurement unit (IMU) signals. The core innovation of DGEI is the application of its dynamic feature extraction strategies, including first-order differential integration with positive/negative windows, weighted sleep time analysis, and adaptive thresholding, which together improve its accuracy in gait segmentation. The experimental results show that the accuracy rate of HS event detection is 97.82%, and the accuracy rate of TO event detection is 99.03%, which is suitable for embedded systems. Validation on a comprehensive dataset of 1550 gait instances shows that DGEI achieves near-perfect alignment with human annotations, with a difference of less than one frame in pulse onset times in 99.2% of the cases.

Wild ungulates play crucial roles in maintaining the structure and function of local ecosystems. The alpine musk deer (Moschus chrysogaste), white-lipped deer (Przewalskium albirostris), and red serow (Capricornis rubidus) are widely distributed throughout the Nyenchen Tanglha Mountains of Tibet. However, research on the mechanisms underlying their coexistence in the same habitat remains lacking. This study aimed to investigate the mechanisms underlying the coexistence of these species based on their dietary preferences through DNA barcoding using the fecal samples of these animals collected from the study area. These species consume a wide variety of food types. Alpine musk deer, white-lipped deer, and red serow consume plants belonging to 74 families and 114 genera, 62 families and 122 genera, and 63 families and 113 genera, respectively. Furthermore, significant differences were observed in the nutritional ecological niche among these species, primarily manifested in the differentiation of food types and selection of food at the genus level. Owing to differences in social behavior, body size, and habitat selection, these three species further expand their differentiation in resource selection, thereby making more efficient use of environmental resources. Our findings indicate these factors are the primary reasons for the stable coexistence of these species.

Introduction: Chylothorax is caused by lymphatic chyle fluid leaking back through the thoracic duct and accumulating in the pleural cavity. It is related to a thoracic duct injury or occlusion. It is rare to have bilateral chylothorax after cervical lymph node dissection for thyroid cancer diagnosis. Case report: A 28-year-old woman was admitted to our hospital with bilateral hypoechoic thyroid nodules and cervical lymph node abnormalities. She underwent thyroidectomy and lymphadenectomy but developed chylothorax 3 days after surgery. She was treated with bilateral thoracic drainage, electrolyte supplementation, and somatostatin, and was discharged 17 days post-treatment. Conclusion: Bilateral chylothorax is a rare complication of thyroid cancer surgery. Early diagnosis and treatment, especially the detection of dyspnea, are key. Also, unobstructed bilateral thoracic drainage, improved surgical skills, and reduced thoracic duct injuries can help reduce complications.

The crust of the Moon records the complete history of collisions by different-sized projectiles from various sources since its early solidification. Planetary bodies in the inner Solar System experienced similar sources of impactors, and the Moon is an ideal witness plate for the impact history. Impact flux on the Moon connects planetary endogenic evolution with orbital dynamics of celestial bodies, and the resulting crater chronology enables remote age estimation for geological units on extraterrestrial bodies. Therefore, defining the lunar impact history has long been a core pursuit in planetary sciences. Ubiquitous impact structures on the Moon and their widespread impact melt deposits are the major agents used to untangle lunar crater chronology. Anchored by 10 successful sample return missions from the Moon, cumulative crater densities were derived for 15 geological units based on their interpreted exposure ages (~3.92 Ga to 25 Ma) and superposed crater densities. Afterword, crater production rates in the entire history of the Moon were constructed on the basis of hypothesized change patterns of impact flux. Following this commonly adapted strategy, it has been a consensus that impact flux in the first billion years of the lunar history was orders of magnitude larger than that afterward, and the latter was not only more or less stable but also punctuated by discrete spikes. However, different versions of lunar crater chronology exist because of insufficient constraints by available anchor points and widespread disagreements on both sample ages and crater densities of existing anchor points. Endeavors from various disciplines (e.g., sample analyses, remote observation, and modeling crater formation and accumulation) are making promising progresses, and future sample return missions with both optimized sampling strategy and analyzing techniques are appealed to fundamentally improve the understanding of lunar impact flux.

Plants lack behavioral responses to avoid dramatic environmental changes associated with the annual seasons. For survival, they have evolved complex sensory systems to sense fluctuations in light and optimize their architecture in response to changes in these cues. Phytochrome A (phyA) was initially identified as a photoreceptor that senses far-red light signals. It was then identified as playing a central role in promoting hypocotyl growth, fiber development, and flowering time in a variety of plants including Arabidopsis, rice, soybean and cotton. Under dark conditions, phyA is present in the cytoplasm in the physiologically inactive (Pr) form. Far-red light signals induce the transformation of Pr into the physiologically active (Pfr) form, after which Pfr-phyA is recognized by FAR-RED ELONGATED HYPOCOTYL 1 (FHY1) and FHY1-LIKE (FHL) and translocated to the nucleus, initiating a series of signaling cascades. The current review comprehensively summarizes recent advances in understanding the function of phyA in plants, including phyA-mediated shade avoidance and flowering time. Remaining issues and possible directions for future research on phyA are also discussed.

Abstract Background The prevalence of thyroid cancer (ThyC), a frequent malignant tumor of the endocrine system, has been rapidly increasing over time. The mitophagy pathway is reported to play a critical role in ThyC onset and progression in many studies. This research aims to create a mitophagy-related survival prediction model for ThyC patients. Methods Genes connected to mitophagy were found in the GeneCards database. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided information on the expression patterns of ThyC-related genes. To identify differentially expressed genes (DEGs), R software was employed. The prognostic significance of each DEG was assessed using the prognostic K-M curve. The prognostic model was built using LASSO, ROC, univariate, and multivariate Cox regression analyses. Finally, a nomogram model was developed to predict the survival outcome of ThyC patients in the clinical setting. Results Through differential analysis, functional enrichment analysis, and protein–protein interaction (PPI) network analysis, we screened 10 key genes related to mitophagy in ThyC. The risk model was eventually developed using LASSO and Cox regression analyses based on the six DEGs related to mitophagy. An altered expression level of a mitophagy-related prognostic gene, GGCT, was found to be the most significant one, according to the KM survival curve analysis. An immunohistochemical (IHC) investigation revealed that ThyC tissues expressed higher levels of GGCT than normal thyroid tissues. The ROC curve verified the satisfactory performance of the model in survival prediction. Multivariate Cox regression analysis showed that the pathological grade, residual tumor volume, and initial tumor lesion type were significantly linked to the prognosis. Finally, we created a nomogram to predict the overall survival rate of ThyC patients at 3-, 5-, and 7- year time points. Conclusion The nomogram risk prediction model was developed to precisely predict the survival rate of ThyC patients. The model was validated based on the most significant DEG GGCT gene expression in ThyC. This model may serve as a guide for the creation of precise treatment plans for ThyC patients.

Abstract Background Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression. Methods Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression. Results CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages. Conclusions Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.

Abstract Breast cancer (BC) is one of the most common malignancies. However, the existing pathological grading system cannot accurately and effectively predict the survival rate and immune checkpoint treatment response of BC patients. In this study, based on The Cancer Genome Atlas (TCGA) database, a total of 7 immune-related genes (IRGs) were screened out to construct a prognostic model. Subsequently, the clinical prognosis, pathological characteristics, cancer-immunity cycle, tumour immune dysfunction and exclusion (TIDE) score, and immune checkpoint inhibitor (ICI) response were compared between the high- and low-risk groups. In addition, we determined the potential regulatory effect of NPR3 on BC cell proliferation, migration, and apoptosis. The model consisting of 7 IRGs was an independent prognostic factor. Patients with lower risk scores exhibited longer survival times. Moreover, the expression of NPR3 was increased but the expression of PD-1, PD-L1, and CTLA-4 was decreased in the high-risk group compared to the low-risk group. In addition, compared with si-NC, si-NPR3 suppressed proliferation and migration but promoted apoptosis in both MDA-MB-231 and MCF-7 cells. This study presents a model for predicting survival outcomes and provides a strategy to guide effective personalized immunotherapy in BC patients.

Peranakan, also called Baba Nyonya, are often defined by anthropologists as the offspring of Chinese fathers (from the 15th Century Ming marine trade expeditions) and local Malay mothers. The Eclectic style of Peranakan culture is a precious example of cross-cultural integration between countries, which reached its peak in the 19th and 20th centuries. The culture of Peranakan permeates all aspects of life, such as language, religion, food style, social rituals, architecture and material culture, and in many of these aspects, there is the use of decorative motifs. The hybrid identity of the Peranakan has long been recognized as an essential factor influencing the development of Peranakan decoration. However, under the influence of the booming trade in Eurasia, fashion also gradually became an important factor influencing the development of native Chinese decorative motifs in the 19th and 20th centuries. As the research is drawn from the past, this study employs the logic and methodology of comparative historical research. By comparing the different responses of European, local Southeast Asian, Chinese, and Peranakan decorative patterns to the Chinoiserie fashion event, it is determined that fashion has influenced the development of native Chinese decorative patterns. The interpretation is based on Simmel’s philosophy of fashion.

Background: Immune status is widely acknowledged as a valuable marker for predicting cancer prognosis and therapy response. However, there has been a limited understanding of the stromal landscape in cancer. Methods: By employing ESTIMATE, stromal- and immune-scores were inferred for 6193 tumor samples spanning 12 cancer types sourced from The Cancer Genome Atlas (TCGA). Subsequently, the samples were categorized into seven groups based on their stromal and immune scores. A comparison of prognosis, lymphocyte and stromal cell infiltration, and the response to programmed death ligand 1 (PD-L1) therapy was conducted among these subtypes. Results: It was unveiled by the analysis that, in the majority of cancer types, stromal score exhibited a more potent predictive capability for outcomes compared to the immune score. Furthermore, it was observed that in four cancer types, intermediate immune infiltration coupled with low stromal infiltration correlated with the most favorable overall survival, whereas an unfavorable outcome was predicted in colorectal cancer (CRC) and stomach adenocarcinoma (STAD) when high immune infiltration coexisted with intermediate or high stromal infiltration. Conclusion: In summary, while high immune scores frequently correlate with a positive prognosis, such correlation is not universal. A potential strategy to address the current limitations of the immune score in specific circumstances could involve a focus on stromal scores or a subtle integration of stromal and immune status.

BackgroundPatients with advanced chronic kidney disease (CKD), end-stage kidney disease (ESKD), and kidney transplants (KT) are at an elevated risk for COVID-19 infection, hospitalization, and mortality. A comprehensive comparison of morbidity and mortality between these populations with kidney disease and individuals without any kidney disease is lacking.MethodsWe analysed the 2020 Nationwide Inpatient Sample (NIS) database for non-elective adult COVID-19 hospitalizations, categorizing patients into advanced CKD, ESKD, KT, and kidney disease-free cohorts. Our analysis included a description of the distribution of comorbidities across the entire spectrum of CKD, ESKD, and KT. Additionally, we investigated in-hospital mortality, morbidity, and resource utilization, adjusting for potential confounders through multivariable regression models.ResultsThe study included 1,018,915 adults hospitalized for COVID-19 in 2020. The incidence of advanced CKD, ESKD, and KT in this cohort was 5.8%, 3.8%, and 0.4%, respectively. Patients with advanced CKD, ESKD, and KT exhibited higher multimorbidity burdens, with 90.3%, 91.0%, and 75.2% of patients in each group having a Charlson comorbidity index (CCI) equal to or greater than 3. The all-cause in-hospital mortality ranged from 9.3% in kidney disease-free patients to 20.6% in advanced CKD, 19.4% in ESKD, and 12.4% in KT patients. After adjusting for potential confounders at both the patient and hospital levels, CKD stages 3–5; ESKD; and KT were found to be associated with increased odds of mortality, with adjusted odds ratios (aOR) of 1.34, 1.80, 2.66, 1.97, and 1.69, respectively.ConclusionPatients hospitalized for COVID-19 with advanced CKD, ESKD, or KT demonstrated a higher burden of comorbidities and increased mortality rates compared to those without kidney disease. After adjusting for confounders, CKD stages 3–5; ESKD; and KT were identified as independent risk factors for in-hospital mortality, illustrating a dose-response relationship between the odds of mortality and adverse outcomes as CKD progressed from stages 3 to 5. Our study highlights the necessity for enhanced management of comorbidities, targeted interventions, and vigorous vaccination efforts to mitigate the risk of adverse outcomes in the vulnerable populations of patients with CKD, ESKD, and KT.

With the rapid development of meteorology, there requires a great need to better forecast dew point temperatures contributing to mild building surface and rational chemical control, while researches on time series forecasting barely catch the attention of meteorology. This paper would employ the seasonal-trend decomposition-based simplified dendritic neuron model (STLDNM*) to predict the dew point temperature. We utilize the seasonal-trend decomposition based on LOESS (STL) to extract three subseries from the original sequence, among which the residual part is considered as an input of an improved dendritic neuron model (DNM*). Then the back-propagation algorithm (BP) is used for training DNM* and the output is added to another two series disposed. Four datasets, which record dew points of four cities, along with eight algorithms are put into the experiments for comparison. Consequently, the combination of STL and simplified DNM achieves the best speed and accuracy.

Heterogeneous shock impedances of planetary materials cause abrupt changes of ejection angles, forming non-radial ejecta. Interpretations for provenances of surface deposits and ages derived from crater counts are affected by such untrackable ejecta.

This study experimentally explored the effects of equivalence ratio settings on ethanol fuel combustion oscillations with a laboratory-scale combustor. A contrary flame equivalence ratio adjusting trend was selected to investigate the dynamic characteristics of an ethanol atomization burner. Research findings denote that optimizing the equivalence ratio settings can prevent the occurrence of combustion instability in ethanol burners. In the combustion chamber, the sound pressure amplitude increased from 138 Pa to 171 Pa and eventually dropped to 38 Pa, as the equivalence ratio increased from 0.45 to 0.90. However, the sound pressure amplitude increased from 35 Pa to 199 Pa and eventually dropped to 162 Pa, as the equivalence ratio decreased from 0.90 to 0.45. The oscillation frequency of the ethanol atomization burner presents a migration characteristic; this is mainly due to thermal effects associated with changes in the equivalence ratio that increase/decrease the speed of sound in burnt gases, leading to increased/decreased oscillation frequencies. The trend of the change in flame heat release rate is basically like that of sound pressure, but the time-series signal of the flame heat release rate is different from that of sound pressure. It can be concluded that the reversible change in equivalence ratio will bring significant changes to the amplitude of combustion oscillations. At the same time, the macroscopic morphology of the flame will also undergo significant changes. The flame front length decreased from 25 cm to 18 cm, and the flame frontal angle increased from 23 to 42 degrees when the equivalence ratio increased. A strange phenomenon has been observed, which is that there is also sound pressure fluctuation inside the atomized air pipeline, and it presents a special square waveform. This study explored the equivalence ratio adjusting trends on ethanol combustion instability, which will provide the theoretical basis for the design of ethanol atomization burners.

Exposure to extreme temperatures can trigger a cascade of adverse cardiovascular and respiratory events. However, in Cyprus, a hotspot of climate change in the Eastern Mediterranean region, little is known about the temperature-related cardiorespiratory morbidity risks. We analyzed daily counts of hospital admissions for cardiovascular and respiratory diseases from four general hospitals in three districts in Cyprus from 2000 through 2019. For each district, we fitted time-series quasi-Poisson regression with distributed lag non-linear models to analyze the associations between daily mean temperature (lag 0–21 d) and hospital admissions for cardiorespiratory, cardiovascular, and respiratory diseases. A random-effects meta-analytical model was then applied to pool the district-specific estimates and obtain the national average associations. We analyzed 20 years of cause-specific hospitalization data with a total of 179 988 cardiovascular and respiratory events. The relationships between cardiorespiratory morbidity and temperature were overall U-shaped. During extreme temperature days, 15.85% (95% empirical CI [eCI]: 8.24, 22.40%) excess cardiovascular hospitalizations and 9.59% (95% eCI: −0.66, 18.69%) excess respiratory hospitalizations were attributable to extreme cold days (below the 2.5th percentile). Extreme hot days (above the 97.5th percentile) accounted for 0.17% (95% eCI: 0.03, 0.29%) excess cardiovascular hospitalizations and 0.23% (95% eCI: 0.07, 0.35%) excess respiratory hospitalizations. We found evidence of increased cardiovascular morbidity risk associated with extreme temperatures in Cyprus. Our study highlights the necessity to implement public health interventions and adaptive measures to mitigate the related temperature effects in an understudied region.

This study theoretically explored the effects of parameter settings on thermoacoustic oscillations with a low-order model. Three factors were explored—combustor length, inlet gas temperature and thermal power. The research findings indicate that optimizing the parameter settings can yield better thermoacoustic oscillation suppression results. The sound pressure amplitude decreased from 3.2 × 105 Pa to 2.1 × 105 Pa as the combustor length increased from 1.2 m to 6.0 m. The triggering time increased from 0.32 s to 0.91 s when the combustion chamber length increased. The climb rate declined from 23.38 × 105 Pa/s to 3.75 × 105 Pa/s when the combustor length was elongated. The sound pressure amplitude decreased from 3.44 × 105 Pa to 2.4 × 105 Pa as the gas temperature rose from 0 to 100 °C. The triggering time and climb rate variation tendency were similar when the gas temperature increased—both declined as the gas temperature rose. The sound pressure amplitude experienced a slight fluctuation when the thermal power rose. However, the triggering time decreased from 0.26 s to 0.043 s when the thermal power improved. The climb rate increased from 18.72 × 105 Pa/s to 27.65 × 105 Pa/s when the thermal power rose. The oscillation frequency presented was completely different in three cases that had different wavelengths and oscillation intensities. The triggering time and climb rate fluctuated extensively in varying conditions, and the above two factors were interrelated and contradictory to each other when thermoacoustic oscillation was excited. This study explored parameters’ effects on triggering time and climb rate, thereby providing references for constructing a model-based control system for thermoacoustic oscillation feedback control.

BackgroundOsteoporosis represents a significant health concern as a widespread metabolic bone condition. In this study, we aim to utilize path analysis to examine the intricate relationships among demographic information, Health Belief Model (HBM) constructs and osteoporosis preventive behavior among Shanghai residents over 40 years of age.MethodsA multi-center population study was conducted in 20 volunteer communities in Shanghai, China. Out of the 2,000 participants who volunteered, 1,903 completed the field survey.Results56.0% of participants were females. Their mean age was 63.64 ± 10.30 years. The self-efficacy score among females (42.27 ± 15.82) was also significantly higher than that among males (40.68 ± 15.20). in the pathway analysis. In the path analysis preventive behaviors were significantly predicted by education (β = 0.082, p < 0.001), knowledge (β = 0.132, p < 0.001) and self-efficacy (β = 0.392, p < 0.001).ConclusionsThis study highlights the importance of gender, education, knowledge and self-efficacy in promoting OP preventive behaviors using the Health Belief Model. The findings emphasize the need for tailored interventions to address the specific needs of different demographic groups.

Background Air pollution has been recognized as an untraditional risk factor for myocardial infarction (MI). However, the MI risk attributable to long‐term exposure to fine particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) is unclear, especially in younger populations, and few studies have represented the general population or had power to examine comorbidities. Methods and Results We applied the difference‐in‐differences approach to estimate the relationship between annual PM2.5 exposure and hospitalizations for MI among US residents and further identified potential susceptible subpopulations. All hospital admissions for MI in 10 US states over the period 2002 to 2016 were obtained from the Healthcare Cost and Utilization Project State Inpatient Database. In total, 1 914 684 MI hospital admissions from 8106 zip codes were included in this study. We observed a 1.35% (95% CI, 1.11–1.59) increase in MI hospitalization rate for 1‐μg/m3 increase in annual PM2.5 exposure. The estimate was robust to adjustment for surface pressure, relative humidity, and copollutants. In the population exposed to ≤12 μg/m3, there was a larger increment of 2.17% (95% CI, 1.79–2.56) in hospitalization rate associated with 1‐μg/m3 increase in PM2.5. Young people (0–34 years of age) and elderly people (≥75 years of age) were the 2 most susceptible age groups. Residents living in more densely populated or poorer areas and individuals with comorbidities were observed to be at a greater risk. Conclusions This study indicates long‐term residential exposure to PM2.5 could increase risk of MI among the general US population, people with comorbidities, and poorer individuals. The association persists below current standards.

Space weathering of graphite yields unnoticeable reflectance changes over 40 Earth years on the surface of Mercury, according to the time-series remote-sensing images acquired during the MESSENGER mission.

Abstract SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

Abstract Prior international studies have shown mixed results regarding the association of hepatitis B and hepatitis C with adverse pregnancy outcomes. We performed an updated evaluation of the prevalence of associated adverse pregnancy outcomes and evaluated trends over time of diagnosis of chronic hepatitis B (HBV) and chronic hepatitis C (HCV) in pregnant women in a national database. All pregnant women with HBV and HCV were identified from the National Inpatient Sample database 2012 to 2018. Multivariate logistic regression analyses were performed to compare pregnancy‐related complications, including rates of preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction, antepartum/intrapartum hemorrhage, preterm labor, and Cesarean section. We evaluated all‐cause in‐hospital mortality, length of stay, and total cost of hospitalizations. A total of 28.7 million pregnancy‐related hospitalizations that met our eligibility criteria were identified, including 51,200 with HBV and 131,695 with HCV. In comparison with the uninfected controls, the HBV group was significantly more likely to develop gestational diabetes (12.94% vs. 6.94%, p

In this study, the temporal regularity of pigments and key enzyme intermediates of Pistacia chinensis Bunge in the color-changing period was investigated to provide a theoretical basis for exploring the mechanism of leaf discoloration. The pigment content and activities of key enzymes of P. chinensis during leaf discoloration were investigated. The correlation between leaf discoloration and environmental factors (temperature, relative humidity, light) was also analyzed. During the color change, the chlorophyll content decreased, while no significant change in the carotenoid content was observed. The anthocyanin content significantly increased in the middle of the period of color change. The ratios of carotenoids/chlorophyll and anthocyanins/chlorophyll showed an upward trend during the period of color change. The lightness parameter (L) and hue parameter (B) of P. chinensis Bunge leaves showed a fluctuating tendency, reaching the highest value at the beginning of color conversion. The hue parameter (A) showed an upward trend at the color conversion stage. The 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) values showed an upward-downward-upward trend. The contents of ALA and PBG at the end of the color transformation were 2.01 times and 2.88 times higher than those at the beginning. The activity of phenylalaninammo-nialyase increased during the color change period. Chalcone isomerase and chalcone synthase first increased, then declined, reaching their highest level in the middle of color conversion, 261.0 u/g and 157.3 u/g, respectively. Although the activities of both enzymes declined at the end of the color conversion, they were higher than at the beginning of the color change. Anthocyanin content was negatively correlated with temperature, relative humidity, day length, and chalcone isomerase, whereas it was positively correlated with phenylalaninammo-nialyase. The results revealed the reasons for the discoloration of P. chinensis leaves in autumn and thus should be considered when exploring the mechanism of color-changing plants and performing color-changing plant applications.

Lichenicolous fungi are parasites of lichens. Many of these fungi are referred to as “black fungi”. A diversity of these black fungi include species that are pathogenic to humans and plants. A majority of black fungi reside in the phylum Ascomycota within the sub-classes Chaetothyriomycetidae and Dothideomycetidae. To explore the diversity of lichenicolous “black fungi” associated with lichens in China, we conducted several field surveys in the Inner Mongolia Autonomous Region and Yunnan Province between 2019 and 2020. We recovered 1,587 fungal isolates from the lichens collected during these surveys. During the preliminary identification of these isolates using the complete internal transcribed spacer (ITS), partial large subunit of nuclear ribosomal RNA gene (LSU), and small subunit of nuclear ribosomal RNA gene (SSU), we identified 15 fungal isolates from the genus Cladophialophora. However, these isolates had low sequence similarities with all known species from the genus. Therefore, we amplified additional gene regions, such as, translation elongation factor (TEF) and partial β-tubulin gene (TUB), and constructed a multi-gene phylogeny using maximum likelihood, maximum parsimony, and Bayesian inference. In our datasets, we included type sequences where available for all Cladophialophora species. Phylogenetic analyses revealed that none of the 15 isolates belonged to any of the previously described species in the genus. Therefore, using both morphological and molecular data, we classified these 15 isolates as nine new species within the genus Cladophialophora: C. flavoparmeliae, C. guttulate, C. heterodermiae, C. holosericea, C. lichenis, C. moniliformis, C. mongoliae, C. olivacea, and C. yunnanensis. The outcome from this study shows that lichens are an important refugia for black lichenicolous fungi, such as those from Chaetothyriales.

Background: Osteosarcoma (OS) is the most common primary malignant tumor originating in bone. Immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) participates in tumor immune tolerance and promotes tumor progression, while the study of IDO1 in OS is limited.Methods: Immunohistochemistry analysis was performed to test the expression of IDO1 and Ki67. The relationship between IDO1 or Ki67 positive count and clinical stage of the patient was analyzed. Laboratory test indexes including serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), white blood cell (WBC) count and C-reactive protein (CRP) at diagnosis of OS patients were collected. The relationship between positive count of IDO1 and Ki67 or laboratory test indexes was analyzed by Pearson’s correlation analysis. IDO1 stably overexpressed cell lines of these cells (MG63 OE, 143B OE and hFOB1.19 OE) were constructed and validated by Western blot and Elisa. Exosomes were isolated from conditioned culture media of these cells and were identified by Zetaview nanoparticle tracking analyzer. Next-generation sequencing was conducted to identify miRNAs enriched in exosomes. Differentially expressed miRNAs (DE miRNAs) were verified in clinical samples and cell lines by qPCR. Biological processes and cell components analysis of DE miRNAs was conducted by GO enrichment analysis using the protein interaction network database.Results: Immunosuppressive enzyme IDO1 was highly expressed in tumor tissues. 66.7% (6/9) of the tissues showed moderately or strongly positive immunostaining signal of IDO1, and 33.3% (3/9) were weakly positive. The expression of IDO1 was positively related to Ki67 and associated with prognostic-related clinical features of OS patients. Overexpression of IDO1 significantly affected the exosome-derived miRNA subsets from MG63, 143B and hFOB1.19 cells. A total of 1244 DE miRNAs were identified, and hsa-miR-23a-3p was further screened as key DE miRNA involved in the progression of OS. GO analysis of target genes of the DE miRNA results showed that target enrichment in the functions of immune regulation and tumor progression.Discussion: Our results indicate that IDO1 has the potential to promote the progression of OS that is related to miRNAs mediated tumor immunity. Targeting IDO1-mediated hsa-miR-23a-3p may be a potential therapeutic strategy for OS treatment.

Hybrid pairing of the corresponding silkworm species is a pivotal link in sericulture, ensuring egg quality and directly influencing silk quantity and quality. Considering the potential of image recognition and the impact of varying pupal postures, this study used machine learning and deep learning for global modeling to identify pupae species and sex separately or simultaneously. The performance of traditional feature-based approaches, deep learning feature-based approaches, and their fusion approaches were compared. First, 3600 images of the back, abdomen, and side postures of 5 species of male and female pupae were captured. Next, six traditional descriptors, including the histogram of oriented gradients (HOG), and six deep learning descriptors, including ConvNeXt-S, were utilized to extract significant species and sex features. Finally, classification models were constructed using the multilayer perceptron (MLP), support vector machine, and random forest. The results indicate that the {HOG + ConvNeXt-S + MLP} model excelled, achieving 99.09% accuracy for separate species and sex recognition and 98.40% for simultaneous recognition, with precision–recall and receiver operating characteristic curves ranging from 0.984 to 1.0 and 0.996 to 1.0, respectively. In conclusion, it can capture subtle distinctions between pupal species and sexes and shows promise for extensive application in sericulture.

Urbanization has a strong signal on the hydrologic cycle, leading to reduced infiltration and faster and larger runoff. However, the detailed analysis of the contribution of urbanization to different quantiles of discharge is still lacking; particularly, less is known in watersheds that have been experiencing such large and rapid urbanization as those in China. Here, we focus on the Wenyu watershed, a rapidly urbanizing basin located in the Beijing metropolitan area. Using a statistical attribution framework, we examine the hydrological response to the increasing urbanization across a wide range of discharge quantiles, from low to high flows; moreover, we perform analyses at the seasonal scale to capture differences in the physical processes at play during the year. Results indicate that the selected GAMLSS (generalized additive models for location, scale, and shape) models can capture well the variability in streamflow in this highly urbanized basin, with the average Spearman correlation coefficients between observations and the median of the fitted models of 0.84, 0.79, and 0.81 in spring, summer, and winter, respectively. Overall, urbanization played a different role in the different seasons and discharge quantiles. More specifically, we find its strongest impact to be in winter and spring, and for low and median quantiles. The role of precipitation is the strongest in summer, and it increases as we move toward the upper tail of the discharge distribution, especially above the 55th percentile, for which precipitation is selected as the only important predictor. Recycled water, on the other hand, tends to play a more dominant role in winter and spring. HIGHLIGHTS Urbanization has a strong signal on the hydrologic cycle; however, less is known in watersheds that have been experiencing such large and rapid urbanization. In this research, we focus on a fast urbanizing basin, and the hydrological responses to the increasing urbanization have been examined.; The quantification of the impacts of drivers for different discharge quantiles and seasons has been examined.; Urbanization plays a decreasing role towards the upper tail of the distribution.;

The natural gas compressibility factor is a vital parameter in petroleum engineering calculation. Currently, the calculation models for calculating natural gas compressibility factors in engineering are not accurate and efficient enough. To solve this problem, multivariate nonlinear regression is used to fit the 6988 data of the Standing–Katz chart, a novel empirical formula of natural gas compressibility factors is obtained, which is suitable for the pseudo-reduced pressure range of 0.2 to 30. The mean absolute error, mean relative error and root mean square error between the fitted values and the Standing–Katz chart values are 0.01140, 0.01282 and 0.01663 respectively, hence the fitted values accord well with the chart values. The proposed correlation is verified by 270 measured data of natural gas compressibility factors under low and medium pressure conditions and 219 measured data under high pressure conditions and compared with the other five representative calculation models. The verification result shows that the mean absolute error, mean relative error and root mean square error between the calculated values and the measured values are 0.01962, 0.01626 and 0.02511 respectively, and the proposed correlation is superior to the other five methods because of its higher calculation accuracy. The new correlation is practical and accurate for predicting the natural gas compressibility factor under an extensive range of pressure conditions.

Gastroesophageal adenocarcinomas (GEAs) harbor recurrent amplification of KRAS, leading to marked overexpression of WT KRAS protein. We previously demonstrated that SHP2 phosphatase, which acts to promote KRAS and downstream MAPK pathway activation, is a target in these tumors when combined with MEK inhibition. We hypothesized that SHP2 inhibitors may serve as a foundation for developing novel combination inhibitor strategies for therapy of KRAS-amplified GEA, including with targets outside the MAPK pathway. Here, we explore potential targets to effectively augment the efficacy of SHP2 inhibition, starting with genome-wide CRISPR screens in KRAS-amplified GEA cell lines with and without SHP2 inhibition. We identify candidate targets within the MAPK pathway and among upstream RTKs that may enhance SHP2 efficacy in KRAS-amplified GEA. Additional in vitro and in vivo experiments demonstrated the potent cytotoxicity of pan-ERBB kinase inhibitions in vitro and in vivo. Furthermore, beyond targets within the MAPK pathway, we demonstrate that inhibition of CDK4/6 combines potently with SHP2 inhibition in KRAS-amplified GEA, with greater efficacy of this combination in KRAS-amplified, compared with KRAS-mutant, tumors. These results suggest therapeutic combinations for clinical study in KRAS-amplified GEAs.

Rosacea is a common chronic inflammatory skin disease with a fluctuating course of excessive inflammation and apparent neovascularization. Microbial dysbiosis with a high density of Bacillus oleronius and increased activity of kallikrein 5, which cleaves cathelicidin antimicrobial peptide, are key pathogenic triggers in rosacea. However, how these events are linked to the disease remains unknown. Here, we show that type I IFNs produced by plasmacytoid DCs represent the pivotal link between dysbiosis, the aberrant immune response, and neovascularization. Compared with other commensal bacteria, B. oleronius is highly susceptible and preferentially killed by cathelicidin antimicrobial peptides, leading to enhanced generation of complexes with bacterial DNA. These bacterial DNA complexes but not DNA complexes derived from host cells are required for cathelicidin-induced activation of plasmacytoid DCs and type I IFN production. Moreover, kallikrein 5 cleaves cathelicidin into peptides with heightened DNA binding and type I IFN–inducing capacities. In turn, excessive type I IFN expression drives neoangiogenesis via IL-22 induction and upregulation of the IL-22 receptor on endothelial cells. These findings unravel a potentially novel pathomechanism that directly links hallmarks of rosacea to the killing of dysbiotic commensal bacteria with induction of a pathogenic type I IFN–driven and IL-22–mediated angiogenesis.

ABSTRACT Umifenovir, a broad-spectrum nonnucleoside antiviral drug, has a promising efficacy against coxsackievirus B4 (CVB4) infection, but its mechanism remains unclear. CVB4 is a common human single-stranded RNA virus that belongs to the Picornaviridae family and the Enterovirus genus. Enterovirus can cause severe diseases, such as meningitis, myocarditis, pancreatitis, insulin-dependent diabetes, and several other diseases, in both adults and children. We have previously demonstrated the critical role of interleukin 10 (IL-10) in promoting CVB4 infection and the downregulation of IL-10 by umifenovir. To further explore the underlying mechanisms of umifenovir, we characterized the epigenetic regulation of IL-10 in IL-10 knockout RAW264.7 cells and a BALB/c mouse splenocyte model. Mechanistically, we found that umifenovir inhibited CVB4-activated IL-10 by enhancing the methylation level of the repressive histones H3K9me3 and H3K27me3 while reducing the acetylation level of the activating histone H3K9ac in the promoter region of the IL-10 gene. Furthermore, using a chromosome conformation capture approach, we discovered that CVB4 infection activated the IL-10 gene by forming an intrachromosomal interaction between the IL-10 gene promoter and an intronic enhancer of the downstream MK2 (mitogen-activated protein kinase [MAPK]-activated protein kinase 2 [MAPKAPK2]) gene, a critical component of the p38-MAPK signaling pathway, which is required for IL-10 gene expression. However, umifenovir treatment abolished this spatial conformation and chromatin interaction, thus reducing the continuous expression of IL-10 and subsequent CVB4 replication. In conclusion, this study reveals a novel epigenetic mechanism by which umifenovir controls CVB4 infections, thus laying a theoretical foundation for therapeutic use of umifenovir. IMPORTANCE Viral infections are major threats to human health because of their strong association with a variety of inflammation-related diseases, especially cancer. Many antiviral drugs are performing poorly in treating viral infections. This is probably due to the immunosuppressive effect of highly expressed IL-10, which is caused by viral infection. Umifenovir is a broad-spectrum antiviral drug. Our recent studies showed that umifenovir has a significant inhibitory effect on CVB4 infection and can reduce IL-10 expression caused by CVB4. However, another antiviral drug, rupintrivir, showed good antiviral activity but had no effect on the expression of IL-10. This suggests that the regulation of IL-10 expression is a key part of the antiviral mechanism of umifenovir. Therefore, due to the dual function of the inhibition of CVB4 replication and the regulation of immune antiviral pathway, the mechanism of umifenovir is of great value to study.

To improve the corrosion resistance of Cf/SiC composites in a water vapor oxygen coupled environment, the bi-layer Yb2Si2O7/SiC and tri-layer Yb2Si2O7/(SiCw-Mullite, SM)/SiC environment barrier coatings were designed and prepared on the surface of Cf/SiC composites by chemical vapor deposition and sol-gel method united with air spraying. Results show that the mass loss of bi-layer Yb2Si2O7/SiC coating coated samples was 17.24 ​× ​10−3 ​g ​cm−2 after 200 ​h oxidation at 1673 ​K, and the average compression strength retention rate was only 79.44% due to the formation of wide penetrating cracks. Comparatively, SiC whiskers in SM middle coating can not only increase the crack propagation resistance of mullite middle coating, but also alleviate the difference of coefficient of thermal expansion between Yb2Si2O7 outer coating and mullite middle coating. Therefore, the mass loss of tri-layer Yb2Si2O7/SM/SiC coating coated samples was only 2.93 ​× ​10−3 ​g ​cm−2 after 200 ​h oxidation at 1673 ​K, and the average compression strength retention rate was up to 98.79%.

Abstract Background Gastric mucosal lesions (GML) are common in gastric diseases and seriously affect the quality of life. There are inevitable side effects in drug therapy. Acupuncture is an important part of traditional Chinese medicine. Electro-acupuncture (EA) has unique curative effect in treatment of GML. However, there are still few reports on the central mechanism of electro-acupuncture in treatment of GML. In this study, NMR metabonomics was used to explore the central metabolic change mechanism of electro-acupuncture in treatment of GML. Methods SD rats were randomly divided into Control, GML and EA groups. According to different intervention time, each group was further divided into 3 subgroups. This study mainly established GML model rats by 75% ethanol. Dynamic expressions of metabolites in cerebral cortex and medulla were observed by 1D 1H Nuclear Magnetic Resonance (NMR) metabolomics, combined with gastric mucosal histopathological examination to evaluate the time-effect relationship of electro-acupuncture at Zusanli (ST36) and Liangmen (ST21) points for 1 day, 4 days and 7 days treatment of GML. Results The results showed that the repair effect of electro-acupuncture on gastric mucosal injury was the most obvious in 4 days and stable in 7 days, and 4 days electro-acupuncture can effectively inhibit GML gastric mucosal inflammation and the expression of inflammatory cells. Meanwhile, the NMR spectrum results of medulla and cerebral cortex showed that, 21 potential metabolites were identified to participate in the mechanism of pathogenesis of GML and the regulation of electro-acupuncture, including 15 in medulla and 10 in cerebral cortex. Metabolic pathway analysis showed that the differential metabolites involved 19 metabolic pathways, which could be divided into energy, neurotransmitters, cells and cell membrane and antioxidation according to their functions. The correlation analysis of stomach, medulla and cerebral cortex shows that the stimulation signal of GML may reach the cerebral cortex from the stomach through medulla, and electro-acupuncture can treat GML by regulating the central nervous system (CNS). Conclusions 4 days electro-acupuncture treatment can significantly improve gastric mucosal injury, and the curative effect tends to be stable in 7 days treatment. Meanwhile, the pathogenesis of GML and the efficacy of electro-acupuncture involve metabolic pathways such as energy, neurotransmitters, cells and antioxidation, and electro-acupuncture can treat GML by regulating CNS.

Quality control (QC) is a crucial step in single-cell RNA-seq data analysis. Here, the authors present the SCTK-QC pipeline which generates and visualizes a comprehensive set of QC metrics to streamline the process of detecting and removing poor quality cells and other artifacts.