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Relict subtropical coniferous forests in China face severe fragmentation, resulting in declining populations, and some are under significant threat from invasive alien species. Despite the crucial importance of understanding forest dynamics, knowledge gaps persist, particularly regarding the impact of invasive plants on vulnerable natives like Keteleeria evelyniana. In this study, we investigated the impact of invasive plants on the regeneration of forests dominated by K. evelyniana, a subtropical relict species in southwestern China. For this purpose, we characterized forest dynamics of 160 forest plots featuring K. evelyniana as the primary dominant species and determined whether the presence of invasive plants was correlated with regeneration of K. evelyniana. We identified four distinct forest types in which K. evelyniana was dominant. We found that radial growth of K. evelyniana trees is faster in younger age-classes today than it was for older trees at the same age. The population structure of K. evelyniana in each forest type exhibited a multimodal age-class distribution. However, three forest types lacked established saplings younger than 10 years old, a situation attributed to the dense coverage of the invasive alien Ageratina adenophora. This invasive species resulted in a reduction of understory species diversity. Additionally, our analysis uncovered a significant negative correlation in phylogenetic relatedness (net relatedness index) between native and invasive alien plant species in eastern Yunnan. This suggests closely related invasive species face heightened competition, hindering successful invasion. Taken together, our findings indicate that successful establishment and habitat restoration of K. evelyniana seedling/saplings require effective measures to control invasive plants.

Abstract Spinal cord injury (SCI) is a debilitating condition characterized by significant sensory, motor, and autonomic dysfunctions, leading to severe physical, psychological, and financial burdens. The current therapeutic approaches for SCI show limited effectiveness, highlighting the urgent need for innovative treatments. MicroRNAs (miRNAs) like miR-10b-5p are known to play pivotal roles in gene expression regulation and have been implicated in various neurodegenerative diseases, including SCI. Polypyrimidine tract binding protein 1 (PTBP1) has also been associated with neural injury responses and recovery. This study aims to explore the interaction between miR-10b-5p and PTBP1 in the context of SCI, hypothesizing that miR-10b-5p regulates PTBP1 to influence SCI pathogenesis and recovery using a rat model of SCI and lipopolysaccharide (LPS)-induced PC12 cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to measure miR-10b-5p levels, revealing its low expression in SCI rats. We then assessed neurological function, histopathological changes, and spinal cord water content. We found that administering the agomiR-10b-5p significantly improved neurological function and decreased the spinal cord water content and normal motor neuron loss in SCI rats. Additionally, we explored the functions of miR-10b-5p in LPS-treated PC12 cells. Our results showed that miR-10b-5p repressed LPS-stimulated apoptosis, inflammation, and oxidative stress in PC12 cells. PTBP1 was predicted as a potential target gene of miR-10b-5p using the TargetScan database. Pulldown and luciferase reporter assays further demonstrated that miR-10b-5p binds to the 3’ untranslated region (UTR) of PTBP1. RT-qPCR revealed that miR-10b-5p negatively modulated PTBP1 expression both in vivo and in vitro. Furthermore, rescue assays indicated that miR-10b-5p alleviated SCI in rats and LPS-triggered injury in PC12 cells by downregulating PTBP1. We also investigated the regulation of miR-10b-5p and PTBP1 on the transforming growth factor-beta 1 (TGF-β1)/small mother against decapentaplegic (Smad3) pathway. We found that miR-10b-5p targeted PTBP1 to repress TGF-β1 decay and facilitated TGF-β1/Smad3 pathway activation. In conclusion, our results demonstrate that miR-10b-5p alleviates SCI by repressing TGF-β1 decay and inducing TGF-β1/Smad3 pathway activation through PTBP1 downregulation. This study provides novel insights into potential targeted therapy plans for SCI.

Abstract This study presents an innovative scraper pump design. The design utilizes the synchronized movement of the upper and lower scrapers of the rotor to adjust the cavity volumes on either side, facilitating efficient fluid transfer. Unlike previous studies, scraper pumps face the challenge of dynamic contact between the scraper and the rotor due to their unique structure. A viscous wall strategy was employed to address hydrodynamic challenges at the point of contact, significantly improving performance prediction accuracy. The experimental data verified the accuracy of the simulation model, and the mass flow rate deviation between the simulation results and the experimental results was maintained within 10% when the viscosity at the contact point was set to 40 times the original medium viscosity. In addition, the study examined the effect of different operating speeds and load pressures on the pump performance. The results indicated that the outlet flow rate decreased by 22% when the pressure was increased from 2 MPa to 10 MPa and increased by 88.24% when the speed was increased from 900 r/min to 2200 r/min. These quantitative analyses provided valuable insights into optimizing scraper pump design and offered clear guidance for improving hydraulic performance and operational efficiency.

Abstract The destructiveness of earthquakes is often linked to their magnitude, but two similar-magnitude earthquakes in Yunnan, China in 2014 caused vastly different damage. The Ms 6.6 Jinggu earthquake triggered about 441 landslides, while the Ms 6.5 Ludian earthquake caused 10,559 landslides. In this paper, we focus on the correlations between distribution pattern of these landslides and seismic factors like seismogenic fault and epicenter. The results show that the landslides triggered by the Jinggu earthquake are mainly distributed along the blind northwest segment of the NW-striking Puwen fault, with more scattered and larger individual areas to the northwest of the epicenter, and more concentrated but smaller ones to the southeast. The distribution pattern of landslides triggered by the Ludian earthquake is predominantly controlled by the NW-striking Xiaohe-Baogunao fault. The landslides are concentrated within an area of 360 km2, with a greater number and larger size occurring in the southeastern section compared to the northwestern section. The distribution of coseismic landslides reveals key differences in rupture characteristics between the Jinggu and Ludian earthquakes. The Jinggu rupture mainly propagated deeper southeast, while the Ludian rupture in the southeast was shallower, reaching the surface. This was confirmed by aftershock data and field investigations. The larger rupture angle in the Ludian earthquake concentrated damage energy, causing more numerous and larger landslides. The contrasting rupture processes are a major factor behind the differing damage levels of these two similar-magnitude earthquakes.

Abstract Background Autophagy is a crucial mechanism for maintaining cellular homeostasis and responding to environmental stress, and it is closely linked to tumor drug resistance. Through multi-omics analysis, this study explores the expression patterns, functions, and potential role of the autophagy-related gene Angiotensinogen (AGT) in colorectal cancer (CRC), particularly in relation to chemotherapy resistance. Methods This study first compared AGT expression between CRC and normal tissues using the GTEx and TCGA databases. Differences in expression were assessed using Wilcoxon Rank Sum Tests, and the prognostic impact of AGT was evaluated through univariate Cox survival analysis and meta-analysis. Functional enrichment was performed using the limma and fgsea packages. Drug sensitivity analysis was conducted based on the CTRP database, while immune infiltration was assessed using the CIBERSORT and ESTIMATE methods. Spatial transcriptomic characteristics were explored through 10x Visium technology and deconvolution analysis to investigate the correlation between AGT expression levels and tumor cell content.scRNA-seq data from CRC tissues were sourced from Tumor Immune Single Cell Hub (TISCH).Functional annotation was performed with Single-sample gene set enrichment analysis (SSGSEA), and pseudotime analysis using Monocle 2 mapped their developmental trajectories. The potential of AGT inhibitors in the treatment of CRC was analyzed using drug-target Mendelian randomization.Finally, Phenome-Wide Association Study (PheWAS) was conducted to evaluate genetic associations and potential side effects of AGT inhibitors. Results AGT expression was significantly higher in CRC tissues compared to normal tissues and was associated with shorter recurrence-free survival (RFS). Autophagy signaling pathways were markedly enriched in the high AGT expression group. AGT expression was positively correlated with resistance to chemotherapeutic agents such as gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. Spatial transcriptomic analysis revealed that AGT was predominantly expressed in malignant tumor regions. Single-cell analysis identified 21 distinct cell subpopulations across 13 major types. AGT expression was significantly higher in tumor samples, especially in the fibroblast C6 subpopulation. Tumor-related pathways were enriched in C1, C5, C6, and C8 subpopulations. Pseudotime analysis revealed that these subpopulations, particularly C6, were in terminal developmental stages.Drug-target Mendelian randomization analysis indicated a negative causal relationship between AGT inhibitors and the risk of both heart failure(ORdrug = 0.950, 95% CI, 0.912–0.990; P = 0.014) and CRC(ORdrug = 0.874, 95% CI: 0.792–0.964; P = 0.007).PheWAS analysis showed no genetic associations between AGT inhibitors and other traits, indicating its specificity and low risk of side effects. Conclusion Elevated AGT expression in CRC is associated with resistance to chemotherapy, and its inhibition may offer a therapeutic avenue for the treatment of colorectal cancer.

Abstract A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).

Abstract Background With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population. Methods By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis. Result One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2). Conclusion We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD.

Abstract Spotted sea bass (Lateolabrax maculatus) is a species of significant economic importance in aquaculture. However, genetic degeneration, such as declining growth performance, has severely impeded industry development, necessitating urgent genetic improvement. Here, we conducted a genome‐wide association study (GWAS) and genomic prediction for growth traits using insertion and deletion (InDel) markers, and systematically compared the results with our previous studies using single nucleotide polymorphism (SNP) markers. A total of 97 significant InDels including a 6 bp insertion in an exon region were identified. It is worth noting that only 5 and 1 candidate genes for DY and TS populations were also detected in previous GWAS using SNPs, and numerous novel genes including c4b, fgf4, and dnajb9 were identified as vital candidate genes. Moreover, several novel growth‐related procedures, such as the growth and development of the bone and muscle, were also detected. These findings indicated that InDel‐based GWAS can provide valuable complement to SNP‐based studies. The comparison of genomic predictive performance for total length trait under different marker selection strategies and genomic selection models indicated that GWAS selection strategy exhibits more stable predictive performance compared to the evenly selection strategy. Additionally, support vector machine model demonstrated better predictive accuracy and efficiency than traditional best linear unbiased prediction and Bayes models. Furthermore, the superior predictive performance using InDel markers compared to SNP markers highlighted the potential of InDels to enhance genomic predictive accuracy and efficiency. Our results carry significant implications for dissecting genetic mechanisms and contributing genetic improvement of growth traits in spotted sea bass through genomic resources.

Abstract To promote the energy accommodation of both electrical and heating power while considering the source–load uncertainties, a peer‐to‐peer (P2P) energy trading model among prosumers in the integrated electric–thermal system is proposed here, considering the energy trading agent (ETA) with self‐build energy system. The solar heat‐pump hybrid thermal water system (SPTS) and the transferring loss of heating power is considered and modelled based on the principle of steady‐state thermal transfer. Since the variations of load and PV cannot be described by any single common distribution, the chance‐constraints programming based on the Gaussian mixture model (GMM) is proposed to handle the uncertainty of the net load. As the proposed power trading problem is a non‐convex problem with binary variables, an improved alternating direction method of multiplier (ADMM) based on the predictor‐corrector and two‐stage cycle iterations is proposed to enhance the convergence performance of standard ADMM. Finally, an example simulation verifies the effectiveness; this results show that the proposed model can decrease the total cost by 26.7% and enhance local energy balance by 61.8% compared to other cases.

Abstract Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (Padj

Abstract The quantification of centipede populations is one of the key measures in achieving intelligent management of edible centipedes and promoting the upgrade of the rural centipede industry chain. However, current centipede counting techniques still face several challenges, including low detection accuracy, large model size, and difficulty in deployment on mobile devices. These challenges have limited existing network models to the experimental stage, preventing their practical application. To tackle the identified challenges, this study introduces a lightweight centipede detection model (FCM-YOLO), which enhances detection performance while ensuring fast processing and broad applicability. Based on the YOLOv5s framework, this model incorporates the C3FS module, resulting in fewer parameters and increased detection speed. Additionally, it integrates an attention module (CBAM) to suppress irrelevant information and improve target focus, thus enhancing detection accuracy. Furthermore, to enhance the precision of bounding box positioning, this study proposes a new loss function, CMPDIOU, for bounding box loss. Experimental results show that FCM-YOLO, while reducing parameter size, achieves an improved detection accuracy of 97.4% (2.7% higher than YOLOv5s) and reduces floating-point operations (FLOPs) to 11.5G (4.3G lower than YOLOv5s). In summary, this paper provides novel insights into the detection and enumeration of centipedes, contributing to the advancement of intelligent agricultural practices.

Abstract Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2–4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (

Abstract Kindergarten activity rooms benefit children’s growth and development under good natural indoor lighting conditions. Therefore, it is of great significance to conduct research on the indoor daylighting effects of kindergarten activity rooms under different orientations. However, most of the existing studies are based on the analysis and simulation of fixed orientations and single elements, and lack of comprehensive evaluation and analysis. Based on the above problems, this study utilizes China’s light climate data and daylighting standards for kindergartens, and selects Linzhi, Kunming, Zhengzhou, Hangzhou, and Guiyang as the research locations, and comprehensively evaluates the indoor daylighting effects. The results of the study show that: (1) The daylighting effect of kindergarten activity rooms in China’s different light climate zones varies greatly, mainly affected by the daylighting orientation, and the high-quality daylighting orientations of the five cities mainly focuses on the range of 210°–255°; (2) The value of sDA of the five cities is basically more than 75%, the uniformity of daylighting effects has all achieved good or higher standards; (3) Guiyang is the least affected by glare, with the smallest impact time range, while the other four cities are more serious. This study explores the impact of sDA, illuminance, and DGP in kindergarten activity rooms on children. The results provide a valuable baseline and technical reference for the daylighting design of kindergarten activity rooms.

Abstract Automatic analysis of facial expressions has emerged as a prominent research area in the past decade. Facial expressions serve as crucial indicators for understanding human behavior, enabling the identification and assessment of positive and negative emotions. Moreover, facial expressions provide insights into various aspects of mental activities, social connections, and physiological information. Currently, most facial expression detection systems rely on cameras and wearable devices. However, these methods have drawbacks, including privacy concerns, issues with poor lighting and line of sight blockage, difficulties in training with longer video sequences, computational complexities, and disruptions to daily routines. To address these challenges, this study proposes a novel and privacy-preserving human behavior recognition system that utilizes Frequency Modulated Continuous Wave (FMCW) radar combined with Machine Learning (ML) techniques for classifying facial expressions. Specifically, the study focuses on five common facial expressions: Happy, Sad, Fear, Surprise, and Neutral. The recorded data is obtained in the form of a Micro-Doppler signal, and state-of-the-art ML models such as Super Learner, Linear Discriminant Analysis, Random Forest, K-Nearest Neighbor, Long Short-Term Memory, and Logistic Regression are employed to extract relevant features. These extracted features from the radar data are then fed into ML models for classification. The results show a highly promising classification accuracy of 91%. The future applications of the proposed work will lead to advancements in technology, healthcare, security, and communication, thereby improving overall human well-being and societal functioning.

Abstract The redox status is intricately linked to the development and progression of cancer, a process that can be modulated by long non-coding RNAs (lncRNAs). Previous studies have demonstrated that redox regulation can be considered a potential therapeutic approach for cancer. However, the redox-related lncRNA predictive signature specific to bladder cancer (BCa) has yet to be fully elucidated. The purpose of our study is to establish a redox-related lncRNA signature to improve the prognostic prediction for BCa patients. To achieve this, we downloaded transcriptome and clinical data from the Cancer Genome Atlas (TCGA) database. Prognostic redox-related lncRNAs were identified through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis, resulting in the establishment of two risk groups. A comprehensive analysis corresponding to clinical features between high-risk and low-risk groups was conducted. Eight redox-related lncRNAs (AC018653.3, AC090229.1, AL357033.4, AL662844.4, AP003352.1, LINC00649, LINC01138, and MAFG-DT) were selected to construct the risk model. The overall survival (OS) in the high-risk group was worse than that in the low-risk group (p

Abstract Background Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of varieties of tumors. Previous studies have shown that lncRNA GClnc1 is highly expressed in osteosarcoma (OS). However, the mechanism of lncRNA GClnc1 in osteosarcoma has not been fully elucidated. In this study, we investigated the biological roles of lncRNA GClnc1 in osteosarcoma and unveiled its underlying mechanisms. Methods The expression of lncRNA GClnc1 in OS cells was detected by real-time quantitative PCR (qRT-PCR). The functional roles of lncRNA GClnc1 were examined by CCK8, trans-well, scratch wound healing assay, colony formation, and apoptosis assays in osteosarcoma cells upon silencing or overexpressing GClnc1. Western blot analysis, qRT-PCR, and RNA co-immunoprecipitation (RIP) assays were used to detect the interaction between lncRNA GClnc1 and NONO. Results The expression of lncRNA GClnc1 was up-regulated in osteosarcoma cell lines. Knockdown of lncRNA GClnc1 suppressed the cell growth, migration, and invasion of OS cells, whereas the over-expression of GClnc1 improved the proliferation, migration, and invasion of OS cells. Mechanistically, we identified that lncRNA GClnc1 regulates the stability of NONO by blocking FBXW7-mediated ubiquitination degradation. Additionally, overexpression of NONO can reverse GClnc1 silencing exerted suppression of the cell proliferation, migration, and invasion, and vice versa. Conclusions Our study elucidated that lncRNA GClnc1 participates in the progression of OS by regulating the NONO signal pathway. Targeting GClnc1 provides a potential target for future clinical treatment of OS.

Abstract Background Pseudomyxoma peritonei (PMP) is a rare malignant peritoneal tumor that readily recurs and metastasizes. Studies have shown that cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and prognosis. Objective In this study, our aim was to isolate CSCs from various tissues of PMP patients and compare their proliferation, migration, and anti-inflammatory abilities. Methods We identified CSCs subsets with markers CD133+, CD166+, and CD133+/CD166+ at the gene level using single-cell mRNA sequencing (scRNA-seq). Appendiceal CSCs (AC), peritoneal CSCs (PC), and mucous CSCs (MC) were obtained using MACSQuant Tyto sorting technology and FlowSight imaging flow cytometry. The cells were cultured and markers were identified. Finally, the functional phenotypes of the three cell types were compared. Results CSCs content was highest in the appendiceal tumor tissue and lowest in the mucous tissue. The cell viability rate of the sorted CSCs was above 98%, and the positive rate of CD133+ and CD166+ was 70–80%, and CD133+/CD166+ was about 30%. Among the three types of CSCs, MC had the highest proliferation ability, and TNF-α has the greatest inhibitory effect on AC migration. Conclusion AC in patients was more inert and anti-inflammatory, whereas abdominal cavity MC and PC were more active. This study revealed the biological characteristics of CSCs in different tumor tissues of patients with PMP, providing a reference for future targeted CSCs therapy.

Abstract Background Compliance with screen time guidelines among children worldwide remains low, and there is insufficient evidence on the current prevalence in China. This study aimed to investigate the prevalence of compliance with screen time guidelines among children under 3 years old in Fujian Province, East China, identify risk factors and their independent effects, and develop a risk discrimination model for targeted interventions. Methods A cross-sectional survey was conducted among low-income families recruited from welfare programs at 96 sites in both urban and rural areas of Fujian Province, China. Face-to-face interviews gathered sociodemographic data, lifestyle information, attitudes towards screen exposure, and details on screen media device ownership. A multivariable logistic regression model was employed to identify independent risk factors for compliance with screen time guidelines, while the area under the receiver operating characteristic curve (AUC) was used to evaluate the model’s discrimination ability. Results A total of 4,707 children participated in the survey. The rates of compliance with screen time guidelines were 56.8% for children under 1 year old, 18.8% for those between 1 and 2 years old, and 81.9% for those between 2 and 3 years old. The multivariable regression analysis identified negative attitudes towards screen exposure, co-viewing and engagement, as well as single child, as significant positive independent factors for compliance with the guidelines. The risk discrimination model demonstrated good performance, with an AUC of 0.845 and 0.812 in the two younger age groups, but showed medium discrimination with an AUC of 0.691 for children between 2 and 3 years old. Conclusions Compliance with screen time guidelines among young children in Fujian Province, East China, is generally adequate, but notably low among children between 1 and 2 years old. Targeted interventions are needed to improve compliance, particularly for this age group.

Abstract Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Abstract An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca2+-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

Abstract The Chinese authorities issued the “Guiding Opinions on Further Deepening the Reform of the Household Registration System” in 2014. This policy maintained strict controls on urban hukou in megacities, while slightly less stringent controls were applied in large cities. However, the restrictions on obtaining urban hukou were significantly relaxed in medium-sized cities and completely lifted in small cities. This study examines the causal effects and underlying mechanisms of hukou reform on urban innovation in cities of different sizes, using DID method based on a quasi-natural experiment by the 2014 hukou reform in China. The findings suggest that the hukou reform can significantly promote urban innovation, with particularly strong positive effects observed in large cities in the eastern region, small- and medium-sized cities in the central and western regions, as well as cities with favourable conditions for innovation. The primary mechanisms in which hukou reform influences urban innovation involve enhancing both the quantity and quality of urban labor force, as well as creating a better environment for innovation in cities.

Abstract In this study, a controllable mass‒frequency tuning method is presented using the etching of rib structures on a single-crystal PZT membrane. The rib structures were optimized to reduce the membrane mass while maintaining the stiffness; therefore, the center frequency could be increased to improve the low-frequency bandwidth of microphones. Additionally, this methodology could reduce the modulus and improve the sensitivity for the same resonant frequency, which typically indicates the maximum acoustic overload point (AOP). The PZT film was chosen because of its greater density; the simulation results showed that PZT could provide a greater frequency tuning (24.9%) compared to that of the AlN film (5.8%), and its large dielectric constant enabled the optimal design to have small electrodes at the maximum stress location while mitigating the sacrificial capacitance effect on electrical gain. An analytical model of rib-structure microphones was established and greatly reduced the computing time. The experimental results of the impedance tests revealed that the center frequencies of the six microphones shifted from 74.6 kHz to 106.3 kHz with rib-structure inner radii ranging from 0 μm to 340 μm; this result was in good agreement with the those of the analytical analysis and finite element modeling. While the center frequency greatly varied, the measured sensitivities at 1 kHz only varied within a small range from 22.3 mV/Pa to 25.7 mV/Pa; thus, the membrane stiffness minimally changed. Moreover, a single-crystal PZT film with a (100) crystal orientation and 0.24-degree full width at half maximum (FWHM) was used to enable differential sensing and a low possibility of undesirable polarization. Paired with a two-stage differential charge amplifier, a differential sensing microphone was experimentally demonstrated to improve the sensitivity from 25.7 mV/Pa to 36.1 mV/Pa and reduce the noise from −68.2 dBV to −82.8 dBV.

Abstract Cadmium (Cd) is a detrimental heavy metal propagated from soil to the food chain via plants, posing a great risk to human health upon consumption. Despite the understanding of Cd tolerance mechanisms in plants, whether and how plants actively respond to Cd and in turn restrict its uptake and accumulation remain elusive. Here, we identify a cell wall-associated receptor-like kinase 4 (WAKL4) involved in specific tolerance to Cd stress. We show that Cd rapidly and exclusively induces WAKL4 accumulation by promoting WAKL4 transcription and blocking its vacuole-dependent proteolysis in roots. The accumulated WAKL4 next interacts with and phosphorylates the Cd transporter NRAMP1 at Tyr488, leading to the enhanced ubiquitination and vacuole-dependent degradation of NRAMP1, and consequently reducing Cd uptake. Our findings therefore uncover a mechanism conferred by the WAKL4-NRAMP1 module that enables plants to actively respond to Cd and limit its uptake, informing the future molecular breeding of low Cd accumulated crops or vegetables.

Abstract The reconstruction of damaged neural circuits is critical for neurological repair after brain injury. Classical brain-computer interfaces (BCIs) allow direct communication between the brain and external controllers to compensate for lost functions. Importantly, there is increasing potential for generalized BCIs to input information into the brains to restore damage, but their effectiveness is limited when a large injured cavity is caused. Notably, it might be overcome by transplantation of brain organoids into the damaged region. Here, we construct innovative BCIs mediated by implantable organoids, coined as organoid-brain-computer interfaces (OBCIs). We assess the prolonged safety and feasibility of the OBCIs, and explore neuroregulatory strategies. OBCI stimulation promotes progressive differentiation of grafts and enhances structural-functional connections within organoids and the host brain, promising to repair the damaged brain via regenerating and regulating, potentially directing neurons to preselected targets and recovering functional neural networks in the future.

Abstract Graphene oxide (GO) possesses specific properties that are revolutionizing materials science, with applications extending from flexible electronics to advanced nanotechnology. A key method for harnessing GO’s potential is its laser-induced reduction, yet the exact mechanisms — photothermal versus photochemical effects — remain unclear. Herein, we discover the dominant role of photochemical reactions in the laser reduction of GO under visible light, challenging the prevailing assumption that photothermal effects are dominant. Employing a combination of Raman thermometry, X-ray photoelectron and photoluminescence spectroscopies, and electrical atomic force microscopy, we quantify the temperature and map the reduction process across micro and nano scales. Our findings demonstrate that the photochemical cleavage of oxygen-containing groups below a reduction threshold temperature is a decisive factor in GO reduction, leading to distinct characteristics that cannot be replicated by heating alone. This work clarifies the fundamental mechanisms of GO transformation under visible laser irradiation, highlighting the dominant role of photochemical processes. Distinguishing these subtleties enables the development of laser-reduced GO platforms for graphene-based applications compatible with industrial scales. We illustrate this potential by encoding information on GO surfaces as optical storage, allowing us to write binary sequences in long-term memory encoding invisible even through an optical microscope.

Abstract The clinical treatments of maxillofacial bone defects pose significant challenges due to complex microenvironments, including severe inflammation, high levels of reactive oxygen species (ROS), and potential bacterial infection. Herein, we propose the de novo design of an efficient, versatile, and precise electron-donable heterojunction with synergetic Ru-Cu pair sites (Ru-Cu/EDHJ) for superior biocatalytic regeneration of inflammatory mandible defects and pH-controlled antibacterial therapies. Our studies demonstrate that the unique structure of Ru-Cu/EDHJ enhances the electron density of Ru atoms and optimizes the binding strength of oxygen species, thus improving enzyme-like catalytic performance. Strikingly, this biocompatible Ru-Cu/EDHJ can efficiently switch between ROS scavenging in neutral media and ROS generation in acidic media, thus simultaneously exhibiting superior repair functions and bioadaptive antibacterial properties in treating mandible defects in male mice. We believe synthesizing such biocatalytic heterojunctions with exceptional enzyme-like capabilities will offer a promising pathway for engineering ROS biocatalytic materials to treat trauma, tumors, or infection-caused maxillofacial bone defects.

Abstract Gas therapy has emerged as a promising approach for treating cancer, with gases like NO, H2S, and CO showing positive effects. Among these, NO is considered a key gas molecule with significant potential in stopping cancer progression. However, due to its high reactivity and short half-life, delivering NO directly to tumors is crucial for enhancing cancer treatment. NO-driven nanomedicines (NONs) have been developed to effectively deliver NO donors to tumors, showing great progress in recent years. This review provides an overview of the latest advancements in NO-based cancer nanotherapeutics. It discusses the types of NO donors used in current research, the mechanisms of action behind NO therapy for cancer, and the different delivery systems for NO donors in nanotherapeutics. It also explores the potential of combining NO donors with other treatments for enhanced cancer therapy. Finally, it examines the future prospects and challenges of using NONs in clinical settings for cancer treatment. Graphical Abstract

Abstract Background Advance care planning (ACP) is pivotal in mitigating end-of-life suffering and ensuring healthcare congruence with the values of older adults and dignity in death. Despite its paramount importance, the current readiness for ACP among community-dwelling older adults and the intricate influencing factors have yet to be explored. Objective To review the literature focusing on ACP readiness among community-dwelling older adults and the influencing factors. Methods A scoping review conducted using the Arksey and O’Malley (2005) framework. Electronic databases (PubMed, CINAHL, Cochrane, Web of Science, PsycINFO), as well as grey literature databases (OpenGrey and GreyLit.org) were searched to identify studies published in English between January 2012 and March 2023. Results 19 studies were selected, comprising 3 qualitative, 13 quantitative, 2 mixed-methods, and 1 review article. The study evaluated the readiness of older adults for ACP by examining their knowledge and attitudes. It categorizes influencing factors into intrinsic and extrinsic levels. This review revealed that the knowledge about ACP among older adults across all settings was limited. However, they had positive attitudes toward it. In addition, intrinsic factors including sociodemographic characteristics, psychological factors, and family relationships, along with extrinsic factors including health care professionals’ attitudes and experience, as well as policies and laws, influenced the ACP readiness among older adults. Conclusions This study established the groundwork for future ACP intervention trials, providing a theoretical framework to guide their design and implementation. operationalization.

Mars is the terrestrial planet in the solar system that is closest to the Earth. Studying the atmospheric parameters of Mars and studying the evolutionary history of the Martian environment on this basis is helpful for people to discover signs of extraterrestrial life and to study the trend of climate change on Earth. Mie–Rayleigh scattering lidar is an important technology for detecting parameters from the surface to the middle and upper atmosphere. Because of the different aerosol distributions, Mie scattering and Rayleigh scattering have their own optimal detection ranges. Given the long period and high cost of any deep space exploration program, it is important to conduct sufficient feasibility studies and parameter simulations before the payload is launched. In this study, a parameterized lidar mathematical model and Earth’s atmospheric mode are used to compare with the measured signals of ground-based Mie–Rayleigh scattering lidar, and the correctness of the lidar mathematical model is verified. Using the model, we select the landing area of Tianwen-1 and substitute it into the Martian atmospheric mode, and then the Mie–Rayleigh lidar backscattering signal and the key parameters of the lidar system are systematically analyzed under the conditions of a clean Martian atmosphere and a global sandstorm. In addition, the optimal detection altitude ranges of Mie scattering and Rayleigh scattering on Mars under different atmospheric conditions are obtained, which provides a reference for the practical design and development of the subsequent lidar system for the Martian atmospheric environment.

Objective Nicotinamide (NAM) is easily degraded in the rumen, but the rumen-protected NAM (RPN) supplementation might enable the use of NAM in ruminants. This study aimed to elucidate the effects of RPN supplementation on growth performance, rumen fermentation, antioxidant status and amino acid (AA) metabolism in growing lambs. Methods A total of 128 healthy and similar lambs (21.3±0.28 kg, 70±6.3 days of age) were allotted to 1 of 4 groups. The treatments were 0, 0.5, 1, and 2 g/d RPN supplementation. The RPN products (50% bioavailability) were fed at 0700 h every day for 12 weeks. All lambs were fed the same pelleted total mixed rations to allow ad libitum consumption and had free access to water. Results The RPN tended to increase the average daily gain and feed efficiency. The tendencies of RPN×day interaction were found for dry matter intake during the entire study (p = 0.078 and 0.073, respectively). The proportions of acetic acid, isobutyric acid and isovaleric acid were decreased, whereas the proportions of propionic acid and valeric acid were increased (p

Abstract When treating perimembranous ventricular septal defect, median sternotomy leads to unsightly scar, right subaxillary thoracotomy requires cardiopulmonary bypass, and transcatheter device closure constrained by vascular condition. Using small left intercostal incision, we employed transthoracic device closure to get around these issues. During this study, right subaxillary thoracotomy was used for surgical repair in 117 patients (Surgical group), whereas small left intercostal incision was used for transthoracic device closure in 131 patients (Device group). Retrospective data collection and analysis were conducted. The success rate was comparable (117/117 vs. 130/131, P = 1.000). The device group experienced notably reduced operating time, mechanical ventilation duration, ICU stay, and postoperative hospital stay (All P

Abstract Terahertz communications are envisioned as a promising technology for the sixth generation and beyond wireless systems, which can support wireless links with Terabits-per-second (Tbps) data rates. As the foundation of designing terahertz communications, channel modeling and characterization are crucial to scrutinize the potential of this spectrum. However, current channel modeling in the terahertz band heavily relies on time-consuming and costly measurements. Here, we propose a transfer learning enabled transformer based generative adversarial network to mitigate this problem in terahertz channel modeling. Specifically, as a fundamental building block, a generative adversarial network is exploited to generate channel parameters. To improve the accuracy, a transformer structure with a self-attention mechanism is incorporated in generative adversarial network. Still incurring errors compared with ground-truth measurement, a transfer learning is designed to solve the mismatch between the formulated network and measurement. The proposed method can achieve high accuracy in channel modeling, while requiring only rather limited amount of measurement, which is a promising complement of current channel modeling techniques.

Since the late Cenozoic, the reactivated Tianshan orogenic belt has accommodated crustal shortening exceeding 200 km, primarily due to the far-field effects of the India-Eurasia plate collision. However, the details of the strain partitioning in the Tianshan Mountain range remain elusive. We interpret a new compilation of GPS velocities covering the whole Tianshan range with a classic elastic block model. Compared to previous studies with a block modeling approach, the Tianshan orogenic belt is further subdivided into several blocks based on geological fault traces and a clustering analysis approach. In addition to obvious crustal shortening on the bounding thrust faults of the Tianshan, our inverted fault slip rates also reveal that faults within the Tianshan orogenic belt, such as the Nalati Fault and the southern margin of the Issyk-Kul Lake Fault, which plays a crucial role in accommodating the tectonic crustal shortening. In the 72°E−78°E region, the internal shortening rate within the mountain is approximately 5–7 mm/yr. Besides crustal shortening, strike-slip motion occurs on faults in the interior of the mountain range as well as in the foreland fold-and-thrust belts, especially in the southern margin of the Tianshan. These findings suggest that the crustal deformation in the Tianshan Mountain range is more complex than previously thought, and the oblique convergence between the Tarim Basin and the Tianshan probably results in both strike-slip and thrust motion.

This study provides a comprehensive investigation into the effects of different scanning strategies on the material properties of IN939 fabricated using the PBF-LB process. The scanning strategies examined included alternating bi-directional scanning with rotation angles of 0°, 45°, 67°, and 90° between adjacent layers (named as shown), as well as alternating chessboard scanning with rotation angles of 67° and 90° (named as Q67° and Q90°). The results revealed that the 45° and 67° samples had the highest relative density, while the 0° and Q67° samples showed the highest average porosity. Moreover, various types of cracks, including solidification, solid-state, and oxide-induced cracks, were observed. Among the bi-directional scan samples, the 0° sample displayed the most extensive cracking and the highest σmax residual stress values in both XZ and XY planes. Conversely, the 45° and 67° samples exhibited fewer cracks. Notably, the lowest σmax residual stress in the XZ planes among the bi-directional scan samples was observed in the 67° sample. Additionally, microstructural analyses indicated differences in grain size and morphology, among the samples. Texture analysis indicated that the 0° and 90° samples exhibited strong cube textures, whereas the texture intensity weakened for the 45° and 67° samples. Moreover, the alternating chessboard scanning strategy led to rougher surfaces (higher Sa and Sz values) compared to the alternating bi-directional scanning strategy, regardless of the rotation angles. Furthermore, the microhardness values among the samples showed minimal variance, ranging between 321 ± 14 HV and 356± 7 HV.

To investigate preservative effects of exogenous melatonin (MT) treatment on pitaya fruit, different concentrations (0.05, 0.10, and 0.50 mmol/L) of MT were used to treat harvested pitaya fruit, and the storage quality and scavenging capacity of reactive oxygen species (ROS) of MT treatment were measured. The results showed that preservative effects of MT depended on treatment concentration, and 0.10 mmol/L MT treatment significantly enhanced storage quality in relative to 0.05 mmol/L and 0.50 mmol/L concentrations. 0.10 mmol/L MT treatment effectively inhibited scale yellowing, reduced weight loss, delayed the decline in total soluble solids and titratable acid content, as well as minimized decay rate. Furthermore, 0.10 mmol/L MT treatment significantly enhanced the activities of catalase, peroxidase, and ascorbate peroxidase, along with the total antioxidant capacity, thereby enhancing the scavenging ability to DPPH· and superoxide anion radicals. The above results suggested that MT treatment enhanced antioxidant enzyme activity, facilitating the timely removal of ROS generated during fruit senescence and reducing oxidative damages caused by ROS.

Leaf senescence is the final stage of leaf development, where the nutrients and energy of senescent leaves are redistributed to developing tissues or organs for plant growth, reproduction, and defense. Outer leaves are photosynthetic organs that usually senesce at the late heading stage in Chinese cabbage, and premature leaf senescence often reduces leafy head yield and quality. In this study, 11 premature leaf senescence mutants were screened from an ethyl methanesulfonate-mutagenized population of the double haploid line ‘FT’ in Chinese cabbage. At the early heading stage, the mutants exhibited edge yellowing within its outer leaves, and at the mature stage, its leafy head weight decreased significantly. Genetic analysis revealed that the mutated trait of all 11 mutants corresponds to single gene recessive inheritance. Semi-diallel cross tests showed that 5 of the 11 were allelic mutants. MutMap and Kompetitive Allele Specific PCR genotyping revealed that BraA01g001400.3C was the candidate gene, which is orthologous of Arabidopsis SUPPRESSOR OF rps4-RLD 1, encoding an immune regulator, so we named it as BrSRFR1. All the BrSRFR1 in the five allelic mutants exhibited single nucleotide polymorphisms at different positions on their exons and led to premature translation termination, which confirmed that defect in BrSRFR1 led to premature leaf senescence. These results verify the role of BrSRFR1 on leaf senescence and provide a new insight into the mechanisms of leaf senescence in Chinese cabbage, which reveals a novel function of SRFR1 in plant development.

This study reveals the mechanisms by which efficiency parameters affect surface quality, mechanical properties, and configuration offset in incremental sheet forming (ISF), focusing on surface morphology and microstructural evolution. By constructing an efficiency-quality graph, a method is developed to determine efficiency parameters that balance quality and efficiency synergistically. The results show that increasing the step depth (Z) and decreasing the feed rate (v) intensify plowing and adhesion effects at the interface, degrading surface quality and enriching the presence of {001} Cube and {112} Copper textures, while the cross-sectional crystal orientation remains unaffected. Additionally, increasing Z enlarges grain size and reduces high-angle grain boundaries (HAGBs), amplifying micro-stress and defects, which deteriorates mechanical properties and increases configuration offset. Conversely, increasing v has minimal impact on mechanical properties but significantly increases configuration offset due to the rise in HAGBs, micro-stress, and defects. The efficiency-quality graph elucidates the complex synergistic relationship between forming efficiency and comprehensive quality of the formed parts, and the optimal efficiency parameters are identified by considering the priority order of different quality dimensions. Specifically, when prioritizing surface quality and hardness, the optimal parameters are Z = 0.1 mm and v = 5000 mm/min; when prioritizing configuration offset, the optimal parameters are Z = 0.1 mm and v = 1000 mm/min. Therefore, this study provides a comprehensive method for evaluating efficiency parameters in ISF, emphasizing the importance of balancing efficiency with quality.

Introduction: Synthetic lethality (SL) provides an opportunity to leverage different genetic interactions when designing synergistic combination therapies. To further explore SL-based combination therapies for cancer treatment, it is important to identify and mechanistically characterize more SL interactions. Artificial intelligence (AI) methods have recently been proposed for SL prediction, but the results of these models are often not interpretable such that deriving the underlying mechanism can be challenging. Objectives: This study aims to develop an interpretable AI framework for SL prediction and subsequently utilize it to design SL-based synergistic combination therapies. Methods: We propose a knowledge and data dual-driven AI framework for SL prediction (KDDSL). Specifically, we use gene knowledge related to the SL mechanism to guide the construction of the model and develop a method to identify the most relevant gene knowledge for the predicted results. Results: Experimental and literature-based validation confirmed a good balance between predictive and interpretable ability when using KDDSL. Moreover, we demonstrated that KDDSL could help to discover promising drug combinations and clarify associated biological processes, such as the combination of MDM2 and CDK9 inhibitors, which exhibited significant anti-cancer effects in vitro and in vivo. Conclusion: These data underscore the potential of KDDSL to guide SL-based combination therapy design. There is a need for biomedicine-focused AI strategies to combine rational biological knowledge with developed models.

ObjectiveAs traditional ship crack detection methods based on artificial visual inspection and ultrasonic methods in ship repair and inspection processes have the characteristics of low efficiency, high cost and high danger, a ship crack detection method based on deep learning is proposed. Methods First, a lightweight convolutional structure (GSConv) is used to replace the standard convolution and introduce an attention mechanism in the backbone of YOLOv5s to achieve the reduction of network parameters and computational complexity while enhancing the ability to extract crack features. Second, C3_Faster constructed by a fast convolutional structure is used instead of the original C3 module in the neck of the network to improve the processing speed of the model and enhance its rapidity. Finally, an improved bidirectional weighted feature fusion network (BiFFN) is used to enrich the semantic and positional information of cracks in the feature map and improve the model's crack identification accuracy and location precision. ResultsBy training on both original and augmented ship crack datasets, the proposed method achieves a detection accuracy of over 94.11% and a recall rate of over 93.50%, while reducing the computational complexity by 17.93% and parameter count by 15.81%. ConclusionThis study demonstrates that the proposed ship crack detection method based on GSConv and BiFFN achieves lightweight model architecture and high detection accuracy and recall rates, providing useful references for the development of UAV/ship autonomous inspection systems.

The relentless advancement of modern technology has given rise to increasingly intricate and sophisticated engineering systems, which in turn demand more reliable and intelligent fault diagnosis methods. This paper presents a comprehensive review of fault diagnosis in uncertain environments, focusing on innovative strategies for intelligent fault diagnosis. To this end, conventional fault diagnosis methods are first reviewed, including advances in mechanism-driven, data-driven, and hybrid-driven diagnostic models and their strengths, limitations, and applicability across various scenarios. Subsequently, we provide a thorough exploration of multi-source uncertainty in fault diagnosis, addressing its generation, quantification, and implications for diagnostic processes. Then, intelligent strategies for all stages of fault diagnosis starting from signal acquisition are highlighted, especially in the context of complex engineering systems. Finally, we conclude with insights and perspectives on future directions in the field, emphasizing the need for the continued evolution of intelligent diagnostic systems to meet the challenges posed by modern engineering complexities.

Abstract The giant freshwater prawn (Macrobrachium rosenbergii) has many advantages in aquaculture, such as fast growth rate, short breeding cycle and good nutrition, which makes it a freshwater shrimp with high economic value. Herein, high-quality chromosome-level genome of both female and male prawns were obtained by combining Illumina paired-end sequencing, PacBio single molecule sequencing technique and High-through chromosome conformation capture (Hi-C) technologies. In ZZ male prawn, a final contig assembly of 3118.58 Mb with a N50 length of 956,237 bp was obtained. In WW female prawn, a final contig assembly of 3333.31 Mb with a N50 length of 1,143,555 bp was obtained. The assembled genome sequences from prawns were anchored to 59 chromosomes. Moreover, the sex chromosomes including W chromosome and Z chromosome were generated in prawn with the length of 36.23 Mb and 27.33 Mb, respectively. The sequence similarity of Z chromosome and W chromosome reached to 74.90%. The high-quality genome resource will be useful for further molecular breeding and functional genomic research of giant freshwater prawns.

Abstract The somatic BRCA1 or BRCA2 Pathogenic Variant (PV)/Likely PV (LPV) from Next Generation Sequencing (NGS) is the most important biomarker for PARP inhibitor use and maintenance-targeted therapies. A discrepancy in the detection rates of BRCA1 and BRCA2 PV/LPV was identified among the NGS platforms. The objective of this study was to compare the somatic BRCA results from two distinct platforms using the same cohort and to identify the causes of these differences. Patients with epithelial ovarian cancer who concurrently underwent tumor NGS using two different platforms between January 2022 and June 2023 were included in this study. The two platforms used were in-house tumor NGS (Illumina NextSeq 550Dx, SureSelectXT library kit, and datasets from 1000 Genomes, ESP6500, ExAC, and ClinVar) and GreenPlan homologous recombination deficiency (HRD) test (Illumina NextSeq 550Dx, customized Twist Bioscience library kit, and datasets from COSMIC and OncoKB). The results of somatic mutations in BRCA1 and BRCA2 were compared between the two platforms. Of the 118 patients, 11.9% (n = 14) exhibited a discordant interpretation of BRCA1 or BRCA2 between the two platforms. Eleven patients (9.3%) exhibited negative results in the in-house platform but positive results (eight seven as PV of BRCA1, one as PV of BRCA2, one as LPV of BRCA1, and two as LPV of BRCA2) in the GreenPlan HRD test, while three patients (2.6%) had positive BRCA pathogenic variants (two as PV of BRCA1 [c.3340G > T, c.5152 + 3 A > C], one as LPV of BRCA2 [c.8174G > T], and one as LPV of BRCA1 [c.5017_5019delCAC]) in the in-house platform but a negative result in the GreenPlan HRD test. The discordance rate of somatic BRCA1 or BRCA2 mutations from different platforms was approximately 12%. In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed.

Abstract Purpose To develop and validate a preoperative prediction model based on multimodal ultrasound and biochemical indicator for identifying microvascular invasion (MVI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. Methods From May 2022 to November 2023, a total of 318 patients with pathologically confirmed single HCC ≤ 5 cm from three institutions were enrolled. All of them underwent preoperative biochemical, conventional ultrasound (US), and contrast-enhanced ultrasound (CEUS) (Sonazoid, 0.6 mL, bolus injection) examinations. Univariate and multivariate logistic regression analyses on clinical information, biochemical indicator, and US imaging features were performed in the training set to seek independent predictors for MVI-positive. The models were constructed and evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis in both validation and test sets. Subgroup analyses in patients with different liver background and tumor sizes were conducted to further investigate the model’s performance. Results Logistic regression analyses showed that obscure tumor boundary in B-mode US, intra-tumoral artery in pulsed-wave Doppler US, complete Kupffer-phase agent clearance in Sonazoid-CEUS, and biomedical indicator PIVKA-II were independently correlated with MVI-positive. The combined model comprising all predictors showed the highest AUC, which were 0.937 and 0.893 in the validation and test sets. Good calibration and prominent net benefit were achieved in both sets. No significant difference was found in subgroup analyses. Conclusions The combination of biochemical indicator, conventional US, and Sonazoid-CEUS features could help preoperative MVI prediction in patients with a single HCC ≤ 5 cm. Critical relevance statement Investigation of imaging features in conventional US, Sonazoid-CEUS, and biochemical indicators showed a significant relation with MVI-positivity in patients with a single HCC ≤ 5 cm, allowing the construction of a model for preoperative prediction of MVI status to help treatment decision making. Key Points MVI status is important for patients with a single HCC ≤ 5 cm. The model based on conventional US, Sonazoid-CEUS and PIVKA-II performs best for MVI prediction. The combined model has potential for preoperative prediction of MVI status. Graphical Abstract

Abstract Loss of ARID1A has been reported to drive the progression of lung adenocarcinoma, yet the underlying mechanism remains elusive. In this study, we performed secretome analysis to identify the key secreted proteins regulating lung adenocarcinoma progression. We showed that the VASN level was significantly elevated in the conditioned medium from ARID1A-depleted A549 and H1299 cells. Restoration of ARID1A in ARID1A-depleted lung adenocarcinoma cells prevented the upregulation and secretion of VASN. Clinical analysis demonstrated a negative correlation between ARID1A and VASN expression in ARID1A-mutated lung adenocarcinomas. The patients with ARID1A-mutated lung adenocarcinoma had significantly higher concentrations of serum VASN than healthy controls. Moreover, serum VASN concentrations were associated with TNM stage, lymph node metastasis, and overall survival of the patients with ARID1A-mutated lung adenocarcinoma. Functional studies indicated that VASN overexpression potentiated the proliferation, invasion, and tumorigenesis of lung adenocarcinoma cells. Antibody neutralization of VASN suppressed the aggressiveness of ARID1A-depleted lung adenocarcinoma cells both in vitro and in vivo. Addition of recombinant VASN protein promoted the proliferation and invasion of lung adenocarcinoma cells. Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease.

Abstract Background The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Abstract Recently, the application of finger vein recognition has become popular. Studies have shown finger vein presentation attacks increasingly threaten these recognition devices. As a result, research on finger vein presentation attack detection (fvPAD) methods has received much attention. However, the current fvPAD methods have two limitations. (1) Most terminal devices cannot train fvPAD models independently due to a lack of data. (2) Several research institutes can train fvPAD models; however, these models perform poorly when applied to terminal devices due to inadequate generalisation. Consequently, it is difficult for threatened terminal devices to obtain an effective fvPAD model. To address this problem, the method of federated finger vein presentation attack detection for various clients is proposed, which is the first study that introduces federated learning (FL) to fvPAD. In the proposed method, the differences in data volume and computing power between clients are considered. Traditional FL clients are expanded into two categories: institutional and terminal clients. For institutional clients, an improved triplet training mode with FL is designed to enhance model generalisation. For terminal clients, their inability is solved to obtain effective fvPAD models. Finally, extensive experiments are conducted on three datasets, which demonstrate the superiority of our method.

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Objective To investigate the morphological and proteomic differences in exosomes (EXOs) during the storage of leukocyte-free apheresis platelets (LFA-Plt), evaluate the quality of platelets in storage and predict the function of EXOs at different storage periods. Methods EXOs were isolated by ultracentrifugation, then the morphological observation was performed by electron microscope. Particle size analysis and WB protein index detection were performed. 4D Label-free quantitative proteomics technology was used to perform quantitative and bioinformatics analysis on identified proteins. Protein differential analysis on the LFA- Plt EXO between group day 3 and day 5 was performed, and GO function and KEGG pathway enrichment analysis on differential proteins was conducted. Results Cup shaped, CD9/TSG101 enriched and Calnexin (-) EXO was successfully obtained. The particle size (nm) of LFA-Plt EXO for day 3 and day 5 were (82.2±19.6) and (83.4±19.4) respectively, and the protein concentration(μ g/uL) were (0.55±0.13) and (0.51±0.08) respectively, with no statistically significant difference between two groups (P>0.05). 1 504 proteins were identified in all samples. GO functional enrichment analysis showed that the LFA-Plt EXO proteins were mainly concentrated in the cell membrane, extracellular domain and proteasome core complex, and were related to the binding ability of proteins, ATP, calcium ions and GTP, and mainly participated in processes such as redox, protein hydrolysis and signal transduction. KEGG functional annotation showed that the EXO proteins mainly participated in material transportation and catabolism, genetic information processing, and were closely related to human tumors and viral bacterial infections, affecting the metabolism of human immune system. Compared with day 3, day 5 EXO showed significant up-regulation in 16 proteins. The GO enrichment analysis showed that 16 upregulated proteins were mainly associated with adenosine homocysteine activity and 6-phosphofructose kinase activity, and were mainly involved in the metabolism of organic nitrogen compound. KEGG enrichment pathway analysis showed that the most important function of upregulated proteins was participating in signaling pathway for oocyte maturation mediated by progesterone. Conclusion Under the preparation and storage conditions of LFA-Plt in our center, platelet quality can be relatively stable. The functions of EXO proteins varies with different storage periods, which may affect the effectiveness of platelet transfusion.

Abstract Dietary specialization between insect stages can reduce intraspecific food competition. The involvement of gut bacteria and the mechanisms underlying this phenomenon received limited attention. Plagiodera versicolora is a pest harming Salicaceae trees. Here, we confirmed dietary specialization in P. versicolora, wherein adults prefer new leaves, while larvae predominantly consume mature leaves when both types are available. We demonstrated the larval preference for mature leaves confers ecological advantages by promoting growth, development and immunity and this advantage is contingent upon the presence of gut bacteria. Gut microbiota in larvae revealed a significant enrichment of Pantoea when feeding new leaves, with P. anthophila exhibiting the most pronounced inhibitory effect on larval development. Further exploration identified specific metabolites, such as Tyrosyl-valine, with higher content in new leaves, which serve as substrates for the entomopathogenic gut bacterium to facilitate its proliferation. This study provides a fresh perspective on the ecological role of gut bacteria.