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The Northern Extended Millimeter Array (NOEMA) formIng Cluster survEy (NICE) is a NOEMA large programme targeting 69 massive galaxy group candidates at z > 2 over six deep fields with a total area of 46 deg2. Here we report the spectroscopic confirmation of eight massive galaxy groups at redshifts 1.65 ≤ z ≤ 3.61 in the Cosmic Evolution Survey (COSMOS) field. Homogeneously selected as significant overdensities of red IRAC sources that have red Herschel colours, four groups in this sample are confirmed by CO and [CI] line detections of multiple sources with NOEMA 3 mm observations, three are confirmed with Atacama Large Millimeter Array (ALMA) observations, and one is confirmed by Ha emission from Subaru/FMOS spectroscopy. Using rich ancillary data in the far-infrared and sub-millimetre, we constructed the integrated farinfrared spectral energy distributions for the eight groups, obtaining a total infrared star formation rate (SFR) of 260-1300 M⊙ yr-1. We adopted six methods for estimating the dark matter masses of the eight groups, including stellar mass to halo mass relations, overdensity with galaxy bias, and NFW profile fitting to radial stellar mass densities. We find that the radial stellar mass densities of the eight groups are consistent with a NFW profile, supporting the idea that they are collapsed structures hosted by a single dark matter halo. The best halo mass estimates are log(Mh/M⊙) = 12.8-13.7 with a general uncertainty of 0.3 dex. Based on the halo mass estimates, we derived baryonic accretion rates (BARs) of (1-8) × 103 M⊙/yr for this sample. Together with massive groups in the literature, we find a quasi-linear correlation between the integrated SFR/BAR ratio and the theoretical halo mass limit for cold streams, Mstream/Mh, with SFR/BAR = 10-0.46±0.22 (Mstream/Mh)0.71±0.16 with a scatter of 0.40 dex. Furthermore, we compared the halo masses and the stellar masses with simulations, and find that the halo masses of all structures are consistent with those of progenitors of Mh(z = 0) > 1014 M⊙ galaxy clusters, and that the most massive central galaxies have stellar masses consistent with those of the brightest cluster galaxy progenitors in the TNG300 simulation. Above all, the results strongly suggest that these massive structures are in the process of forming massive galaxy clusters via baryonic and dark matter accretion.

Process-induced porosity significantly affects the fatigue resistance of additive-manufactured components under cyclic loads. In this study, the influence of process-induced porosity defect characteristics on the fatigue properties of wire arc additive manufacturing (WAAM) Al–Si–Mg parts was quantitatively analyzed using the Kitagawa-Takahashi diagram and machine learning methods. Two specimens with different porosity and distributions were fabricated using two welding wires with different surface states. The cross-section porosity of the two groups was 0.42% and 2.06%, respectively. According to the test results, the static strength of the two groups was equivalent, but the elongation of the porosity group specimen was reduced by 58.7%, and the fatigue strength (139.8 MPa) was lower than that of the control group (160.2 MPa). Combining high-cycle fatigue post-mortem inspection and scanning electron microscopy analysis, the geometric features of the critical defects were obtained. The fatigue performance was assessed by combining extreme value statistics and the Kitagawa-Takahashi diagram according to critical defects, which showed good consistency but was still not conservative as some failure data were within the safe-life range. Therefore, four parameters of applied stress and the projected area, location, and morphology of the critical defects were trained using an extreme gradient boosting model (XGBoost) and random forest (RF). The XGBoost model is 95.7 % more accurate than the RF model in predicting fatigue life. The importance of four parameters in limiting fatigue life is ranked in the above order.

Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.

Abstract Background Hepatitis E virus (HEV) infection is an important etiology of liver failure. This study aimed to explore the associations of blood fibrosis profiles with HEV-related liver failure (HEV-LF) onset and evaluate their prediction performance in hospitalized patients with acute hepatitis E. Methods Participants were obtained from two tertiary medical centers in Jiangsu, China, between January 2018 and November 2024. Cox proportional hazards regression, restricted cubic splines, and threshold effect analysis were used to examine associations between fibrosis markers and HEV-LF risk. The predictive value of these markers was evaluated for importance ranking, discrimination, calibration, and net benefit. Results Among 504 included participants, 59 developed HEV-LF during hospitalization. After adjusting for covariates, elevated baseline laminin (HR = 1.432, 95% CI: 1.080–1.900), fibrosis-4 score (HR = 1.865, 95% CI: 1.375–2.530), and aspartate aminotransferase to platelet ratio index (APRI) (HR = 1.603, 95% CI: 1.315–1.954) were associated with a higher HEV-LF risk in a dose-dependent manner. Hyaluronic acid (≤ 740 ng/mL: HR = 1.797, 95% CI: 1.177–2.744) and type IV collagen (≤ 137 ng/mL: HR = 3.075, 95% CI: 1.709–5.533) showed nonlinear associations. APRI was ranked the highest in importance, and its combination with the other two top important markers provided good discrimination (7-day HEV-LF: AUROC = 84.98%, 95% CI: 78.55–91.41; 14-day HEV-LF: AUROC = 80.11%, 95% CI: 73.49–86.73), calibration, and clinical utility for predicting HEV-LF onset. Conclusions Several blood fibrosis markers are closely associated with HEV-LF risk and have promising predictive value. These findings may inform clinical risk stratification in patients with AHE. Trial registration Not applicable.

In the era of farming civilization, traditional villages serve as carriers for value retention. In the context of urban – rural integration, exploring the means for protecting the traditional Miao villages in Leigong Mountain, Qiandongnan, holds great significance. This region contains abundant cultural landscape resources. Revitalizing the environment for the survival of their cultural landscapes is also a crucial aspect. In the present study, 20 Miao traditional villages in Leigong Mountain, Qiandongnan, were selected as subjects. ArcGIS10.8 was used as the technical platform to construct five types of cultural landscape genome mapping systems, namely cultural landscape factor information mapping, spatial sequence mapping, public space pattern mapping, arrangement pattern mapping, and spatial pattern mapping. This was achieved by analyzing individual traditional villages, multiple traditional villages, and a specific study area. Based on this analysis, this study summarizes the four basic features of cultural landscape architecture, namely culture, environment, and layout of the traditional Miao villages in Leigongshan. This study clarifies the spatial distribution pattern of the cultural landscape genome of traditional gMiao villages in Leigong Mountain by constructing an atlas and identifying the relationship between the mutual influences of various elements during the development and evolution of the villages. Based on the findings, this study provides a reference basis for protecting the cultural landscape of traditional villages and promote further research at the regional level.

Abstract Spatially resolved transcriptomics (SRT) data provide critical insights into gene expression patterns within tissue contexts, necessitating effective methods for identifying spatial domains. We introduce stDyer, an end-to-end deep learning framework for spatial domain clustering in SRT data. stDyer combines Gaussian Mixture Variational AutoEncoder with graph attention networks to learn embeddings and perform clustering. Its dynamic graphs adaptively link units based on Gaussian Mixture assignments, improving clustering and producing smoother domain boundaries. stDyer’s mini-batch strategy and multi-GPU support facilitate scalability to large datasets. Benchmarking against state-of-the-art tools, stDyer demonstrates superior performance in spatial domain clustering, multi-slice analysis, and large-scale dataset handling.

Abstract The aim of this study was to investigate lymphocyte subsets, especially natural killer (NK) cells, in patients with systemic sclerosis (SSc) and evaluate the diagnostic value of NK cells in secondary pulmonary arterial hypertension (PAH). A total of 115 SSc patients and 100 age- and sex-matched health controls (HCs) were enrolled in this study. Flow cytometry was employed to quantify NK cells, while the association between NK cells and disease activity as well as PAH was investigated to further elucidate its diagnostic potential. The absolute count of NK (CD3-CD56+) cells significantly decreased in SSc patients. There was a negative correlation between the mRSS score and the injury index. The levels of cytokine exhibited significant elevation among SSc patients. Conversely, SSc-PAH patients demonstrated significantly elevated levels of CRP, UA, and BNP. Additionally, there was a significant reduction in the absolute level of NK cells. ROC curve analysis revealed that the optimal cut-off point for NK cells was 185 cells/µL, while for BNP it was 70.50 pg/mL and for UA it was 323.00 µmol/L. Our study revealed a significant inverse correlation between peripheral blood NK cell levels and the incidence of complicated PAH in patients with SSc.

Abstract Background Acute intermittent porphyria (AIP) is an inherited metabolic disorder that can affect the central, peripheral, and autonomic nervous systems. Therefore, its clinical presentation is diverse and may include abdominal pain, as well as neurological and psychiatric symptoms. Abdominal pain, though a common initial symptom, is often overlooked or misdiagnosed due to its lack of specificity. But early diagnosis and treatment are crucial, as untreated symptoms can progressively worsen. Case presentation This report describes a 26-year-old male who was admitted due to seizures and PRES changes on brain magnetic resonance imaging (MRI) for over 30 days, along with a 20-day history of sudden proximal weakness in both upper limbs. Additionally, he experienced recurrent vomiting and excessive sweating. Five months before admission, he was diagnosed with a urinary tract infection due to severe abdominal pain and tea-colored urine, and the symptoms resolved after treatment. Multiple examinations before and after admission consistently revealed hypertension, tachycardia, and hyponatremia. Electromyography (EMG) suggested axonal damage to the motor nerves of both upper limbs. During hospitalization, the patient's upper limb weakness progressively worsened, and around 12 days after admission, he began experiencing recurrent episodes of abdominal pain and limb pain. Then he was diagnosed with AIP based on the detection of positive PBG in urin and the identification of a c.445C > T (R149X) mutation in the hydroxymethylbilane synthase (HMBS) gene. Conclusions This case unveils that AIP is a disease that can be easily overlooked in its early stages. When a patient presents with central, peripheral, or autonomic nervous system symptoms and common causes are ruled out, AIP should be considered as a potential diagnosis. Additionally, unexplained symptoms such as abdominal pain, changes in urine color, hyponatremia should also raise suspicion. Timely screening through biochemical testing, including measurement of ALA, PBG and porphyrins in a random urine sample, is recommended. Timely administration of intravenous hemin and avoidance of precipitating factors can lead to a better prognosis.

Abstract Background Metastasis and chemoresistance are often major challenges in advanced-stage colorectal cancer. Bufalin has a therapeutic effect on both metastasis and drug resistance, but how bufalin affects chemoresistance-mediated metastasis remains unclear. Methods The role of BU in the inhibition of EMT and angiogenesis induced by chemoresistant cells using wound healing assays, invasion assays, HUVEC tube formation and adhesion assays. Western blot and immunofluorescence were used to explore the potential molecular changes. BU can precisely regulate c-Myc expression by targeting SRC-3 in chemoresistant cells was confirmed by Western blot. In vivo experiments were conducted to validate that both BU and cinobufacini can ameliorate drug resistance-promoted EMT and angiogenic effects. Results Bufalin inhibited resistance-induced epithelial-mesenchymal transition (EMT) and angiogenesis. Targeting of the SRC-3 protein by bufalin reduced the expression level of c-Myc and inhibited the prometastatic effect mediated by chemoresistance, and overexpression of SRC-3 or c-Myc reversed the inhibitory effect of bufalin on chemotherapeutic resistance, promoting metastasis. Moreover, the clinical drug cinobufacini and its main active monomer bufalin reduced liver metastasis of colorectal cancer caused by chemoresistance in vivo. Conclusion Bufalin can target the SRC-3/c-Myc signaling pathway to affect the prometastatic effect of chemoresistant cells, suggesting that bufalin may be used as a new adjuvant antimetastatic therapy for colorectal cancer.

Abstract The links between Thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) has received widespread attention, but the causal relationships and mediating factors have not been systematically studied. We used two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between TDFDs and OP. Moreover, we performed mediation MR analyses to explore the role of thyroid-related hormones and OP risk factors in the association between TDFDs and OP. Two sample MR analyses showed that hyperthyroidism increased OP (OR = 1.080, 95% CI 1.026 to 1.137; P = 0.0032) risk. Hypothyroidism increases OP (OR = 1.183, 95% CI 1.125 to 1.244; P

Abstract Background Cytoreductive radical prostatectomy (cRP) has emerged as a promising therapeutic approach for low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but the best candidates for cRP are still unknown. This study aims to explore the potential value of 18F-PSMA-1007 PET/CT-derived quantitative volumetric tumor parameters in cRP treatment selection among patients with low-volume mHSPC. Methods A total of 122 patients with primary low-volume mHSPC who underwent 18F-PSMA-1007 PET/CT followed by systemic therapy alone or plus cRP were included. The whole-body PSMA-derived tumor volume (PSMA-TV) was defined as the total volume of whole-body PSMA-avid tumor lesions, and prostate PSMA-TV was defined as the volume of prostate PSMA-avid tumor lesions. Spearman’s correlation was used to analyze the relationships between whole-body PSMA-TV and clinicopathological characteristics. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore the independent predictors for PFS. Results Among 122 patients, 37 (30.32%) underwent systemic therapy plus cRP. The median and optimal cutoff values of the whole-body PSMA-TV were 71.68 cm3 (41.28–157.41 cm3) and 78.57 cm3, respectively. Whole-body PSMA-TV was positively correlated with prostate-specific antigen (PSA), and patients with nonregional lymph node (NRLN) metastases had a greater whole-body PSMA-TV (P = 0.001). Cox regression analyses revealed that cRP, lower whole-body PSMA-TV and the absence of NRLN metastases were associated with better PFS (all P

Abstract Dielectric capacitors with high energy storage performance are highly desired for advanced power electronic devices and systems. Even though strenuous efforts have been dedicated to closing the gap of energy storage density between the dielectric capacitors and the electrochemical capacitors/batteries, a single-minded pursuit of high energy density without a near-zero energy loss for ultrahigh energy efficiency as the grantee is in vain. Herein, for the purpose of decoupling the inherent conflicts between high polarization and low electric hysteresis (loss), and achieving high energy storage density and efficiency simultaneously in multilayer ceramic capacitors (MLCCs), we propose an interlaminar strain engineering strategy to modulate the domain structure and manipulate the polarization behavior of the dielectric mediums. With a heterogeneous layered structure consisting of different antiferroelectric ceramics [(Pb0.9Ba0.04La0.04)(Zr0.65Sn0.3Ti0.05)O3/(Pb0.95Ba0.02La0.02)(Zr0.6Sn0.4)O3/(Pb0.92Ca0.06La0.02)(Zr0.6Sn0.4)0.995O3], our MLCC exhibits a giant recoverable energy density of 22.0 J cm−3 with an ultrahigh energy efficiency of 96.1%. Combined with the favorable temperature and frequency stabilities and the high antifatigue property, this work provides a strain engineering paradigm for designing MLCCs for high-power energy storage and conversion systems.

Abstract In contemporary times, cancer poses the most significant threat to human life and safety. Scientists have relentlessly pursued the intricacies of carcinogenesis and explored ways to prevent and treat cancer. Carcinogenesis is a complex, multi-faceted, and multi-stage process, with numerous underlying causes, including inflammation and fibrosis. Cancer-associated fibroblasts (CAFs), however, occupy a pivotal and substantial role within the tumor microenvironment, facilitating carcinogenesis through diverse mechanisms such as creating inflammation, fostering a fibrotic tumor microenvironment, and immunosuppression. In this paper, we introduce the concept of carcinogenesis, explain its causes, describe the characteristics of CAFs and their sources, and highlight the roles and mechanisms of CAFs in promoting carcinogenesis. Ultimately, our aim is to contribute to the development of novel therapeutic strategies for cancer treatment.

Abstract Gastric cancer (GC), one of the most common and heterogeneous malignancies, is the second leading cause of cancer death worldwide and is closely related to dietary habits. Fatty acid is one of the main nutrients of human beings, which is closely related to diabetes, hypertension and other diseases. However, the correlation between fatty acid metabolism and the development and progression of GC remains largely unknown. Here, we profiled the genetic alterations of fatty acid anabolism-related genes (FARGs) in gastric cancer samples from the TCGA cohort and GEO database to evaluate the possible relationships and their internal regulatory mechanism. Through consistent clustering and functional enrichment analysis, three distinct fatty acid anabolism clusters and three gene subtypes were identified to participate in different biological pathways, and correlated with the characteristics of immune cell infiltration and clinical prognosis. Importantly, a distinctive FA-score was constructed through the principal component analysis to quantify the characteristics of fatty acid anabolism in each GC patient. Further analysis showed patients grouped in the high FA-score group were characterized with greater tumor mutational burden (TMB) and higher microsatellite stability (MSI-H), which may be more aeschynomenous to immunotherapy and had a favorable prognosis. Altogether, our bioinformatics analysis based on FARGs uncovered the potential roles of fatty acid metabolism in GC, and may provide newly prognostic information and novel approaches for promoting individualized immunotherapy in patients with GC.

Abstract Background Head and neck squamous cell carcinoma(HNSCC) is the sixth most common malignancy worldwide, with more than 890,000 new cases and 450,000 deaths annually. Its major risk factors include smoking, alcohol abuse, aging, and poor oral hygiene. Due to the lack of early and effective detection and screening methods, many patients are diagnosed at advanced stages with a five-year survival rate of less than 50%. In this study, we deeply explored the expression of Aging-related genes(ARGs) in HNSCC and analyzed their prognostic significance using single-cell sequencing and spatial transcriptomics analysis. This research aims to provide new theoretical support and directions for personalized treatment. Annually, more than 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed globally, leading to 450,000 deaths, making it the sixth most common malignancy worldwide. The primary risk factors for HNSCC include smoking, alcohol abuse, aging, and poor oral hygiene. Many patients are diagnosed at advanced stages due to the absence of early and effective detection and screening methods, resulting in a five-year survival rate of less than 50%. In this research, single cell sequencing and spatial transcriptome analysis were used to investigate the expression of Aging-related genes (ARGs) in HNSCC and to analyse their prognostic significance. This research aims to provide new theoretical support and directions for personalized treatment. Methods In this study, we investigated the association between HNSCC and AGRs by utilizing the GSE139324 series in the GEO database alongside the TCGA database, combined with single-cell sequencing and spatial transcriptomics analysis. The data were analyzed using Seurat and tSNE tools to reveal intercellular communication networks. For the spatial transcriptome data, SCTransform and RunPCA were applied to examine the metabolic activities of the cells. Gene expression differences were determined through spacerxr and RCTD tools, while the limma package was employed to identify differentially expressed genes and to predict recurrence rates using Cox regression analysis and column line plots. These findings underscore the potential importance of molecular classification, prognostic assessment, and personalized treatment of HNSCC. Results This study utilized HNSCC single-cell sequencing data to highlight the significance of ARGs in the onset and prognosis of HNSCC. It revealed that the proportion of monocytes and macrophages increased, while the proportion of B cells decreased. Notably, high expression of the APOE gene in monocytes was closely associated with patient prognosis. Additionally, a Cox regression model was developed based on GSTP1 and age to provide personalized prediction tools for clinical use in predicting patient survival. Conclusions We utilized single-cell sequencing and spatial transcriptomics to explore the cellular characteristics of HNSCC and its interaction with the tumor microenvironment. Our findings reveal that HNSCC tissues show increased mononuclear cells and demonstrate enhanced activity in ARGs, thereby advancing our understanding of HNSCC development mechanisms.

Abstract Background Previous observational studies examining the relationship between cadmium exposure and various cancers have yielded conflicting results. This study aims to comprehensively clarify the relationship between blood cadmium concentration (BCC) and nine specific cancers. Methods A retrospective analysis of National Health and Nutrition Examination Survey (NHANES) 1999–2018 identified 36,991 participants. Multivariable logistic regression was used to assess the association between BCC and the risk of nine specific cancers. Additionally, Mendelian randomization (MR) analyses were conducted to investigate potential causal relationships. Results Multivariable logistic regression analysis of the NHANES data indicated a positive association between BCC and the risk of bladder and lung cancers (P

ABSTRACT The primary objective of this paper is to propose a method for predicting the safe mud weight window within the Bozi gas field situated in the Tarim Basin and establish a 3D wellbore stability model. The approach combines Mogi–Coulomb criterion using intermediate stress for wellbore shear failure. It considers rock shear breakdown in fracture pressure calculations and predicts reservoir shear slip with Jaeger criterion and drilling fluid invasion on the weak surface in calculating wellbore tensile failure. The study finds that instability in the well wall of this block is not solely due to the intermediate stress criterion or shear fracture of intact rock. Instead, during drilling with high‐density fluid, the weak surface (fracture) undergoes shear‐slip damage before intact rock. The collapse is a result of the interplay between bit replacement, dynamic drilling loads, and drilling fluid intrusion, causing tensile rupture on the weak surface and repeated fluid leakage. Analysis of wellbore instability in 16 wells within ultra‐deep complex formations shows that the collapse pressure prediction accuracy is 87.5%, and the loss pressure prediction accuracy is 93.7%. Compared to traditional methods, this approach is more accurate and practical, providing essential guidance for resolving wellbore instability issues in drilling operations. In conclusion, this paper introduces a novel and more precise method for predicting the safe mud weight window in the Bozi gas field.

In order to solve the problem of difficult deployment of existing deep learning-based defect detection models in terminal equipment with limited computational capacity, a lightweight steel surface defect testing model LSKA-YOLOv8 was proposed based on the YOLOv8n target detection framework. The model uses KernelWarehouse Conv (KWConv) with lower computational volumes, which significantly reduces the required computational resources. By updating the traditional Feature Pyramid Network (FPN) structure to Bi-directional Feature Pyramid Network (BiFPN), enhance the capture of contextual information and reduce the number of parameters of the model. In addition, the Spatial Pyramid Pooling Fast (SPPF) module was replaced with a more accurate Receptive Field Block (RFB) module, expanding the model’s sensory field and improving characteristic representation. At the same time, the Large Separable Kernel Attention (LSKAttention) module was introduced in the detection head, effectively enhancing the understanding and capture of the target characteristics, thus significantly improving the overall detection performance. Experiments on the NEU-DET dataset showed that the average accuracy of LSKA-YOLO increased by 4.4% on the map@0.5 indicator compared to the benchmark model, while the number of parameters and calculations of the model decreased by 26.7% and 50%, respectively. Provides valuable references and practical applications for deployment of defect detection models on computing-resource-limited terminal devices.

Abstract Machine-learned potentials (MLPs) have exhibited remarkable accuracy, yet the lack of general-purpose MLPs for a broad spectrum of elements and their alloys limits their applicability. Here, we present a promising approach for constructing a unified general-purpose MLP for numerous elements, demonstrated through a model (UNEP-v1) for 16 elemental metals and their alloys. To achieve a complete representation of the chemical space, we show, via principal component analysis and diverse test datasets, that employing one-component and two-component systems suffices. Our unified UNEP-v1 model exhibits superior performance across various physical properties compared to a widely used embedded-atom method potential, while maintaining remarkable efficiency. We demonstrate our approach’s effectiveness through reproducing experimentally observed chemical order and stable phases, and large-scale simulations of plasticity and primary radiation damage in MoTaVW alloys.

Abstract Background Dendrobium catenatum is a perennial herb of the genus Dendrobium orchidaceae. It has been known as “Golden Grass, Soft Gold” since ancient times with effects of strengthening the body, benefiting the stomach, generating body fluid, nourishing Yin and clearing internal heat. The flowers of D. catenatum have anti-oxidation, immune regulation and other biological activities. The composition analysis of flowers showed that flavonoid glycosides were significantly accumulated in floral tissue. However, in the flowers of D. catenatum, there was only one case of the UDP-glycosyltransferase (UGT) responsible for the glycosylation of flavonoids has been reported. Result In this study, a new UGT (named UGT708S6) was cloned from D. catenatum flowers rich in O-glycosides and C-glycosides, and its function and biochemical properties were characterized. Through homology comparison and molecular docking, we identified the key amino acid residues affecting the catalytic function of UGT708S6. The glycosyltransferase UGT708S6 was characterized and demonstrated C-glycosyltransferase (CGT) activity in vitro assay using phloretin and 2-hydroxynaringenin as sugar acceptors. The catalytic promiscuity assay revealed that UGT708S6 has a clear sugar donor preference, and displayed O-glycosyltransferase (OGT) activity towards luteolin, naringenin and liquiritigenin. Furthermore, the catalytic characteristics of UGT708S6 were explored, shedding light on the structural basis of substrate promiscuity and the catalytic mechanism involved in the formation of flavonoid C-glycosides. R271 was a key amino acid residue site that sustained the catalytic reaction. The smaller binding pocket resulted in the production of new O-glycosides and the reduction of C-glycosides. This highlighted the importance of the binding pocket in determining whether C-glycosides or O-glycosides were produced. Conclusions The findings suggest that UGT708S6 holds promise as a new glycosyltransferase for synthesizing flavonoid glycosides and offer valuable insights for further understanding the catalytic mechanisms of flavonoid glycosyltransferases.

Abstract Background To ensure workforce stability in China’s healthcare system and maintain high-quality care, it is essential to comprehensively understand the interplay of factors contributing to turnover intention of healthcare workers. This study aims to examine the associations between potential factors and turnover intention in healthcare workers and explore the mediating effect of job satisfaction and work engagement in the association between them. Methods In this cross-sectional study, a random sample of 1060 healthcare workers working in 98 public medical institutions were recruited to rate their turnover intention in 2018 in Shenzhen, China. Information on socio-demographic characteristics, job-related factors, turnover intention, job satisfaction, work engagement, work stress and doctor-patient relationship of participants were collected. Pearson’s chi-squared tests and binary logistic regression analyses were performed to explore the association between these factor and turnover intention. Mediation analysis was used to explore the roles of potential mediators and moderators. Results The results showed that age (OR: 0.35, 95%CI: 0.16 to 0.72), tenure (OR: 0.98, 95%CI: 0.96 to 0.99), administrative positions (OR: 0.33, 95%CI: 0.16 to 0.63), and night shift frequency (OR: 1.84, 95%CI: 1.26 to 2.67) were significantly associated with turnover intention. We identified the mediating effect of job satisfaction and work engagement in the relationship between administrative positions and turnover intention, while the suppressing effect in the relationship between professional titles and turnover intention. Additionally, we found that monthly income plays a moderating role in the relationship between work engagement and turnover intention, and in the association between professional titles and turnover intention. Conclusions Greater job satisfaction and engagement, along with reasonable remuneration, were found to be associated with lower turnover intention among healthcare workers. Employers should proactively monitor the dynamic interactions among these factors and then develop more tailored interventions in order to alleviate the ongoing loss of healthcare workers.

Abstract Objective The relationship between blood glucose levels and osteoarthritis (OA) is unclear. This study aimed to investigate the genetic causal relationship between blood glucose-related traits and OA. Methods We first performed univariate Mendelian randomization (UVMR) analyses using published genome-wide association study (GWAS) datasets with fasting glucose (FG), 2 h-glucose post-challenge glucose (2hGlu), and glycosylated hemoglobin (HbA1c) as exposures, and hip osteoarthritis (HOA) and knee osteoarthritis (KOA) as outcomes; then, we performed inverse analyses of them. We used Inverse-variance weighted (IVW) analysis as the primary analysis, and sensitivity analyses were performed. Moreover, we performed multivariate Mendelian randomization (MVMR) to estimate the independent effect of exposure on outcome after adjusting for body mass index (BMI). Summarized data for blood glucose-related traits were obtained from the MAGIC Consortium study of the glucose trait genome and for OA from the UK Biobank and arcOGEN. Summarized data for BMI were obtained from the GIANT Consortium meta-analysis of individuals of European ancestry. A two-sided p value

Abstract Inflammation underlies many conditions causing excess morbidity and mortality among people with HIV (PWH). A handful of single-trait epigenome-wide association studies (EWAS) have suggested that inflammation is associated with DNA methylation (DNAm) among PWH. Multi-trait EWAS may further improve statistical power and reveal pathways in common between different inflammatory markers. We conducted single-trait EWAS of three inflammatory markers (soluble CD14, D-dimers and interleukin-6) in the Veterans Aging Cohort Study (n = 920). The study population was all male PWH with an average age of 51 years, and 82.3% self-reported as Black. We then applied two multi-trait EWAS methods—CPASSOC and OmniTest—to combine single-trait EWAS results. CPASSOC and OmniTest identified 189 and 157 inflammation-associated DNAm sites, respectively, of which 112 overlapped. Among the identified sites, 56% were not significant in any single-trait EWAS. Top sites were mapped to inflammation-related genes including IFITM1, PARP9 and STAT1. These genes were significantly enriched in pathways such as “type I interferon signaling” and “immune response to virus.” We demonstrate that multi-trait EWAS can improve the discovery of inflammation-associated DNAm sites, genes and pathways. These DNAm sites might hold the key to addressing persistent inflammation in PWH.

Abstract Objective This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation.

Abstract Background The purpose of this study is to explore the feasibility and accuracy of a robot-assisted technique in four-corner fusion compared with traditional freehand operation. Methods Twenty cadaver specimens were randomly assigned to the robot-assisted group and freehand groups. Three screws were placed percutaneously to fix the capitate-lunate joint, lunate-triquetrum joint, and triquetrum-hamate-capitate joint in each specimen by robot-assisted or freehand technique. The offset between the actual and planned screw positions was determined by merging the images of intraoperative and postoperative CT scans in the robot-assisted group. The centrality of the screw, time-consuming, drilling attempts, and radiation exposure were compared between the two groups. Results The mean offset between the actual and planned screw position was 1.09 (SD: 0.56) mm. The offset at the start point of the screw was significantly lower than that at the endpoint. There was no significant difference in the centrality of the screws, surgical time between the two groups. The number of drilling attempts and the radiation dose received by surgeons were significantly lower in the robot-assisted group. Conclusions Although there was no significant difference in screw centrality between the two groups, the slight offset between the actual and planned screw positions confirmed the feasibility of the robot-assisted technique in four-corner fusion. The robot-assisted technique has advantages in reducing the difficulty of surgery and protecting the surgeon from exposure to large doses of radiation.

Abstract Background Calcaneal fractures are the most common type of tarsal fractures. The sustentaculum tali (ST) offers anatomical stability in calcaneal fractures, and recently, ST screws have been widely used in their treatment. This study aimed to investigate the clinical efficacy and value of ST screw fixation via a modified sinus tarsi approach (MSTA) for treating displaced intraarticular calcaneal fractures (DIACFs). Methods This study enrolled 64 patients (64 feet): 32 patients in the calcaneal locking plate combined with the ST screw group (CLP-STS Group) and 32 patients in the simple calcaneal locking plate internal fixation group (CLP Group). The minimum follow-up duration was 18 months. Ankle function was evaluated using VAS, AOFAS, and Short Form-36 scores. Imaging evaluation included the Böhler angle, Gissane angle, length, height, and width of the calcaneus, and the Böhler angle in both groups 1 year after surgery. Results Functional evaluation revealed that postoperative AOFAS and VAS scores in the CLP-STS Group were significantly better than those in the CLP Group. After surgery, the Böhler angle, Gissane angle, and length, height, and width of the calcaneus were significantly corrected compared to the preoperative values; however, the difference in these indicators between the two groups was not significant. Nevertheless, at the 1-year postoperative follow-up, the calcaneal Böhler angle loss in the CLP-STS Group was significantly better than that in the CLP Group. Conclusion Compared to simple calcaneal locking plate internal fixation, combining the plate with the additionally free ST screw can resolve the limited intraoperative exposure of MSTA, reduce postoperative foot pain in patients, and improve clinical efficacy.

Abstract Background Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors. Method CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors. Results Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P

Abstract Background The widespread acceptance of early surgery as a treatment for acute intertrochanteric fracture (ITF) has been accompanied by ongoing controversy due to conflicting conclusions presented in previous studies. This study aims to compare the occurrence of perioperative complications and mortality, as well as functional outcomes in older patients with ITF who underwent either early or delayed surgery. Methods A retrospective multicenter cohort study involving 7414 patients with ITF between Jan. 2017 and Dec. 2021 was conducted. After predefined participants selection inclusion and exclusion criteria, 2323 surgically treated ITF patients were included and analyzed utilizing propensity score matching (PSM) method. Their demographics, injury-related data, surgery-related data, and perioperative adverse outcomes during hospitalization were collected and compared between the early or delayed surgery groups by PSM with a 1:4 ratio. All participants received a minimum of two-year follow-up and perioperative outcomes, functional outcomes, and survival analyses were conducted and compared. Results After adjustment for potential confounders, there were no significant difference in surgery duration, intraoperative blood loss, transfusion rate, mortality rates, functional outcomes, and perioperative complications rates including severe complications, cardiac complications, pulmonary complications, and neurological complications regardless of whether the patient was treated with early or delayed surgery (all P > 0.05). Although length of hospital stay (mean, 11.5 versus 14.4 days, P

Abstract High‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

Abstract Methylation quantitative trait loci (meQTLs) quantify the effects of genetic variants on DNA methylation levels. However, most published studies utilize bulk methylation datasets composed of different cell types and limit our understanding of cell-type-specific methylation regulation. We propose a hierarchical Bayesian interaction (HBI) model to infer cell-type-specific meQTLs, which integrates a large-scale bulk methylation data and a small-scale cell-type-specific methylation data. Through simulations, we show that HBI enhances the estimation of cell-type-specific meQTLs. In real data analyses, we demonstrate that HBI can further improve the functional annotation of genetic variants and identify biologically relevant cell types for complex traits.

Abstract Background This study aimed to analyze the epidemic characteristics and influencing factors of school influenza outbreaks in Jiangsu Province, China from 2020 to 2023,following the COVID-19 pandemic, to inform prevention and control strategies. Methods Data on influenza-like illness(ILI) outbreaks from the Chinese Influenza Surveillance Information System and national-level influenza surveillance sentinel hospitals were analyzed. The temporal distribution, school type, virus strains, and outbreak scales were examined using descriptive statistics. Results From 2020 to 2023, 1142 influenza outbreaks occurred in schools, with primary schools(ages 6 to 12) accounting for 71.80%. Most large outbreaks were caused by A(H1N1) and A(H3N2), responsible for 8.99% of total outbreaks. Outbreaks were predominantly reported in the pre-peak periods of B(Victoria) and A(H1N1) circulation, accounting for 86.31% and 92.32% of their respective total outbreaks. No concurrent influenza and COVID-19 outbreaks were observed during the study period. Conclusion Primary and secondary schools are high-risk settings for influenza outbreaks. A(H3N2) shows higher adaptability and is more likely to co-circulate with other subtypes/lineages, especially A(H1N1), leading to larger outbreaks. B(Victoria)-caused outbreaks are more frequent but smaller in scale. School influenza outbreaks are more likely to occur during the early stages of seasonal peaks, particularly for B(Victoria) and A(H1N1). This suggests that influenza outbreaks in schools may play a crucial role in seeding and accelerating the spread of the virus within the broader community.

Abstract Gliomas are the most common primary malignant tumours of the central nervous system (CNS), which are highly aggressive, with increasing morbidity and mortality rates year after year, posing a serious threat to the quality and expected survival time of patients. The treatment of gliomas is a major challenge in the field of neuro-oncology, especially high-grade gliomas such as glioblastomas (GBMs). Despite considerable progress in recent years in the study of the molecular and cellular mechanisms of GBMs, their prognosis remains bleak. Tumour-associated macrophages (TAMs) account for up to 50% of GBMs, and they are a highly heterogeneous cell population whose role cannot be ignored. Here, we focus on reviewing the contribution of classically activated M1-phenotype TAMs and alternatively activated M2-phenotype TAMs to GBMs, and exploring the research progress in reprogramming M1 TAMs into M2 TAMs.

Abstract Currently, despite the vast amounts of time and money invested in cancer treatment, cancer remains one of the primary threats to human life. The primary factor contributing to the low treatment efficacy is cancer heterogeneity. The unclear molecular mechanisms underlying tumorigenesis, coupled with the complexity of human physiology, and the inability of animal models to accurately replicate the human tumor microenvironment, pose significant hurdles in the development of novel cancer therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture with microfluidic systems, simulating the essential components and physiological traits of the in vivo tumor microenvironment. It offers a dynamic setting within the chip system to study tumor progression, potentially heralding a breakthrough in cancer research. In this review, we will summarize the current advancements in this platform, encompassing various types of TMOCs and their applications in different types of cancer. From our perspective, the TMOC platform necessitates enhanced integration with tissue engineering techniques and microphysiological environments before it can evolve into a more refined preclinical model for cancer research.

To further elucidate the mechanism of acoustic emission (AE) response when a fractured rock is compressed, a new method for calculating the AE characteristics from the perspective of relative particle motion based on the moment tensor theory in seismology was proposed in discrete element simulation. The crack expansion process and mechanical-deformation characteristics were simulated by the particle flow code (PFC). Based on the new AE response simulation method, the spatial evolution of AE events, magnitude distribution and the orientation of the moment tensor were calculated. The results showed that the stress of the pre-cracked rock under uniaxial compressive conditions drops dramatically after the peak, the cracks expanded rapidly into a macroscopic crack, the acoustic emission events surge, and the brittle damage characteristics after the peak are obvious. The number of tensile and shear cracks obtained from PFC showed a similar growth trend temporally, while the number of tensile cracks was more than that of shear cracks. The acoustic emission magnitudes obtained based on seismology principally concentrated in the range of [−6.9, −5.9], and the slope of the G-R statistical relationship (b value) was 1.81. The spatial orientation of the AE moment tensor coincided with the tensile-shear cracks: the moment tensor is mainly transverse in the wing crack region, with more tensile cracks than shear cracks; while in the main crack region, the moment tensor was heterogeneous, and the percentage of tensile and shear cracks is close to each other. The tensile and shear properties of microcracks were determined based on the T-k diagram and R-value theory of moment tensor. The trends of the percentage of tensile and shear cracks were basically consistent with those obtained by PFC, while the comparison revealed that using [−20, 20] as the interval of tensile-shear crack was more reasonable than that suggested by Feignier et al. The findings provide beneficial reference for accurate analysis of the characteristics of rock cracking seismic sources and the identification of tensile shear properties.

Summary: There is scant research on the association between humidex exposure and urinary system diseases. Hospitalization records from Lanzhou city were collected for the period 2015 to 2019, alongside daily meteorological and air pollution data for the study duration. Daily humidex was calculated using temperature and relative humidity indices. The study employed a combined approach of generalized additive models and distributed lag non-linear models (DLNMs) to estimate the exposure-lag-response relationship between humidex and hospital admissions for urinary system diseases, as well as for subgroups of diseases (urolithiasis and tubule-interstitial diseases). A total of 55,365 patients with urinary system diseases were included. The single lag effect of overall urinary system diseases was most significant on lag13 with the relative risk (RR) = 1.066 (95% confidence interval [CI]: 1.011, 1.124), while the cumulative lag effect over lag0–14 was most significant with RR = 1.387 (95% CI: 1.240, 1.550). The goal of this study was to establish an early warning system and allocate medical resources effectively to reduce hospital admissions for urinary system diseases.

Introduction and Objectives: We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC). Materials and Methods: From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups. Results: Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055). Conclusions: Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

Purpose: Radiotherapy-induced oral mucositis is the most common side effect in nasopharyngeal carcinoma (NPC) patients. We aimed to evaluate the efficacy and safety of Rabdosia rubescens drop pills in NPC patients with radiation-induced oral mucositis (RTOM). Methods: The study involved 40 NPC patients who were given Rabdosia rubescens drop pills thrice daily from the start of radiation therapy. The study monitored the incidence and severity of oral mucositis and oral pain. The main outcomes measured were the occurrence rate of oral mucositis, grade 3 oral mucositis, oral pain assessment, and changes in immunological function, body weight, BMI, NRS2002, and albumin levels. Results: In the study, 38 patients completed the treatment. The incidence rates of Grade 0 to 3 oral mucositis were 5.26%, 21.05%, 47.37%, and 26.32% respectively. Pain levels were mild (42.11%), moderate (13.16%), and severe (13.16%). The onset of Grade 1, 2, and 3 oral mucositis occurred at 18, 24, and 30 days respectively. Grade 3 oral mucositis was associated with body weight, BMI, NRS2002 score, and albumin levels. Post-treatment, there was a decrease in CD4 + /CD8 + , CD3 + , and CD4 + immune cells, but an increase in CD8 + cells. Mild to moderate gastrointestinal adverse events were observed in 13.2% of patients. Conclusion: Rabdosia rubescens drop pills administration can reduce the incidence and severity of radiotherapy induced oral mucositis. Our finding suggested a positive impact of Rabdosia rubescens drops pills upon administration to NPC patients.