Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.

Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.

Mitochondrial base editor induces substantial nuclear off-target mutations.

DddA-derived cytosine base editors (DdCBEs)-which are fusions of split DddA halves and transcription activator-like effector (TALE) array proteins from bacteria-enable targeted C•G-to-T•A conversions in mitochondrial DNA1. However, their genome-wide specificity is poorly understood. Here we show that the mitochondrial base editor induces extensive off-target editing in the nuclear genome. Genome-wide, unbiased analysis of its editome reveals hundreds of off-target sites that are TALE array sequence (TAS)-dependent or TAS-independent. TAS-dependent off-target sites in the nuclear DNA are often specified by only one of the two TALE repeats, challenging the principle that DdCBEs are guided by paired TALE proteins positioned in close proximity. TAS-independent off-target sites on nuclear DNA are frequently shared among DdCBEs with distinct TALE arrays. Notably, they co-localize strongly with binding sites for the transcription factor CTCF and are enriched in topologically associating domain boundaries. We engineered DdCBE to alleviate such off-target effects. Collectively, our results have implications for the use of DdCBEs in basic research and therapeutic applications, and suggest the need to thoroughly define and evaluate the off-target effects of base-editing tools.

Chemical reprogramming of human somatic cells to pluripotent stem cells.

Cellular reprogramming can manipulate the identity of cells to generate the desired cell types1-3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4-7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8-10. However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced plasticity13,14; it is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans.

Multimodal data fusion based on IGERNNC algorithm for detecting pathogenic brain regions and genes in Alzheimer's disease.

At present, the study on the pathogenesis of Alzheimer's disease (AD) by multimodal data fusion analysis has been attracted wide attention. It often has the problems of small sample size and high dimension with the multimodal medical data. In view of the characteristics of multimodal medical data, the existing genetic evolution random neural network cluster (GERNNC) model combine genetic evolution algorithm and neural network for the classification of AD patients and the extraction of pathogenic factors. However, the model does not take into account the non-linear relationship between brain regions and genes and the problem that the genetic evolution algorithm can fall into local optimal solutions, which leads to the overall performance of the model is not satisfactory. In order to solve the above two problems, this paper made some improvements on the construction of fusion features and genetic evolution algorithm in GERNNC model, and proposed an improved genetic evolution random neural network cluster (IGERNNC) model. The IGERNNC model uses mutual information correlation analysis method to combine resting-state functional magnetic resonance imaging data with single nucleotide polymorphism data for the construction of fusion features. Based on the traditional genetic evolution algorithm, elite retention strategy and large variation genetic algorithm are added to avoid the model falling into the local optimal solution. Through multiple independent experimental comparisons, the IGERNNC model can more effectively identify AD patients and extract relevant pathogenic factors, which is expected to become an effective tool in the field of AD research.

Plant cell-surface GIPC sphingolipids sense salt to trigger Ca2+ influx.

Salinity is detrimental to plant growth, crop production and food security worldwide. Excess salt triggers increases in cytosolic Ca2+ concentration, which activate Ca2+-binding proteins and upregulate the Na+/H+ antiporter in order to remove Na+. Salt-induced increases in Ca2+ have long been thought to be involved in the detection of salt stress, but the molecular components of the sensing machinery remain unknown. Here, using Ca2+-imaging-based forward genetic screens, we isolated the Arabidopsis thaliana mutant monocation-induced [Ca2+]i increases 1 (moca1), and identified MOCA1 as a glucuronosyltransferase for glycosyl inositol phosphorylceramide (GIPC) sphingolipids in the plasma membrane. MOCA1 is required for salt-induced depolarization of the cell-surface potential, Ca2+ spikes and waves, Na+/H+ antiporter activation, and regulation of growth. Na+ binds to GIPCs to gate Ca2+ influx channels. This salt-sensing mechanism might imply that plasma-membrane lipids are involved in adaption to various environmental salt levels, and could be used to improve salt resistance in crops.

Adult neurogenesis acts as a neural regularizer.

New neurons are continuously generated in the subgranular zone of the dentate gyrus throughout adulthood. These new neurons gradually integrate into hippocampal circuits, forming new naive synapses. Viewed from this perspective, these new neurons may represent a significant source of "wiring" noise in hippocampal networks. In machine learning, such noise injection is commonly used as a regularization technique. Regularization techniques help prevent overfitting training data and allow models to generalize learning to new, unseen data. Using a computational modeling approach, here we ask whether a neurogenesis-like process similarly acts as a regularizer, facilitating generalization in a category learning task. In a convolutional neural network (CNN) trained on the CIFAR-10 object recognition dataset, we modeled neurogenesis as a replacement/turnover mechanism, where weights for a randomly chosen small subset of hidden layer neurons were reinitialized to new values as the model learned to categorize 10 different classes of objects. We found that neurogenesis enhanced generalization on unseen test data compared to networks with no neurogenesis. Moreover, neurogenic networks either outperformed or performed similarly to networks with conventional noise injection (i.e., dropout, weight decay, and neural noise). These results suggest that neurogenesis can enhance generalization in hippocampal learning through noise injection, expanding on the roles that neurogenesis may have in cognition.

Protective Effect of Vitamin K2 (MK-7) on Acute Lung Injury Induced by Lipopolysaccharide in Mice.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

Reaction-Modulated Surface-Enhanced Raman Scattering Strategy for Stereoselective Differentiation and Identification of Amino Acids.

Surface-enhanced Raman scattering (SERS) sensing of racemates is a remarkably fascinating yet very sophisticated objective because of similar physicochemical features of enantiomers. Inspired by the enantiomeric selectivity of nucleophilic addition reaction (NAR) toward amino acids, we herein propose highly effective, robust SERS discrimination of d- and l-valine by synergizing asymmetric gold nanorods-embedded ZIF-8 nanoparticles (AGNZ) with NAR to engender stereoselective molecular fingerprint. Experimental and chemometric analyses disclose that enantioselectivity lies in dual aspects: (i) abundant interfacial cavities and 3D hot-spots in AGNZ offer necessary confined asymmetrical surroundings to trigger enantiospecific molecular adsorption and interaction affinity, and (ii) the specified NAR drags the racemates adjacent to the interfacial area of AGNZ for maximum analytes-substrate interaction. This strategy is universal and can be utilized for the recognition of different amino acid enantiomers. Importantly, multiple quantifications of the racemic ratio can be realized with superior prognostic performances. This synergizing strategy therefore provides a significant paradigm shift from traditional methods to realize highly effective SERS discrimination of racemates.

Role of Pmk1, Mpk1, or Hog1 in the mitogen-activated protein kinase pathway of Aspergillus cristatus.

Aspergillus cristatus is a probiotic fungus known for its safety and abundant secondary metabolites, making it a promising candidate for various applications. However, limited progress has been made in researching A. cristatus due to challenges in genetic manipulation. The mitogen-activated protein kinase (MAPK) signaling pathway is involved in numerous physiological processes, but its specific role in A. cristatus remains unclear. In this study, we successfully developed an efficient polyethylene glycol (PEG)-mediated protoplast transformation method for A. cristatus, enabling us to investigate the function of Pmk1, Mpk1, and Hog1 in the MAPK signaling pathway. Our findings revealed that Pmk1, Mpk1, and Hog1 are crucial for sexual reproduction, melanin synthesis, and response to external stress in A. cristatus. Notably, the deletion of Pmk1, Mpk1, or Hog1 resulted in the loss of sexual reproduction capability in A. cristatus. Overall, this research on MAPK will contribute to the continued understanding of the reproductive strategy and melanin synthesis mechanism of A. cristatus.

Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors.

Cytosine base editors (CBEs) have the potential to correct human pathogenic point mutations. However, their genome-wide specificity remains poorly understood. Here we report Detect-seq for the evaluation of CBE specificity. It enables sensitive detection of CBE-induced off-target sites at the genome-wide level. Detect-seq leverages chemical labeling and biotin pulldown to trace the editing intermediate deoxyuridine, thereby revealing the editome of CBE. In addition to Cas9-independent and typical Cas9-dependent off-target sites, we discovered edits outside the protospacer sequence (that is, out-of-protospacer) and on the target strand (which pairs with the single-guide RNA). Such unexpected off-target edits are prevalent and can exhibit a high editing ratio, while their occurrences exhibit cell-type dependency and cannot be predicted based on the sgRNA sequence. Moreover, we found out-of-protospacer and target-strand edits nearby the on-target sites tested, challenging the general knowledge that CBEs do not induce proximal off-target mutations. Collectively, our approaches allow unbiased analysis of the CBE editome and provide a widely applicable tool for specificity evaluation of various emerging genome editing tools.

Association of obesity with cardiovascular disease in the absence of traditional risk factors.

BACKGROUND: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors. METHODS: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations. RESULTS: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67). CONCLUSION: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old.

H2 18O vapour labelling reveals evidence of radial Péclet effects, but in not all leaves.

Contradictory evidence exists regarding the relevance of Péclet-like gradients in leaf water isotopes, making it difficult to accurately predict variation in isotope composition. Here, we use H2 18O vapour labelling to directly test whether leaf water isotopes diffuse back into the xylem to be carried forward to more distal leaf portions. Backward diffusion has been assumed, due to observations of increasing enrichment towards the tip and outer edges of some leaves. Further complicating the selection of leaf water isotope models is the observation that some, but not all, leaves demonstrate a radial Péclet effect in bulk leaf water and that the hydraulic design of leaves may influence the development of isotope gradients in leaves. Carry-forward of H2 18O vapour label was detected in the two monocot species assessed (oat and corn), but not in the two dicot species (foxglove and sunflower). Further, bulk leaf water measurements at differing transpiration rates indicated that a bulk leaf water Péclet effect was relevant for foxglove only. We conclude that both leaf hydraulic design and relative velocities of water within transport pathways influence leaf water isotope composition, reconciling seemingly contradictory previous results regarding the relevance of Péclet effects to leaf water isotopes.

Gradient-descent noise whitening techniques for short-reach IM-DD optical interconnects with severe bandwidth limitation.

Bandwidth limitation in optoelectrical components and the chromatic dispersion-induced power fading phenomenon cause severe inter-symbol interference (ISI) in high-speed intensity modulation and direct detection (IM-DD) optical interconnects. While the equalizer implemented in the receiver's digital signal processing procedure can mitigate ISI, it also inevitably enhances the noise located in the decayed frequency region, known as equalization-enhanced colored noise (EECN). Additionally, the nonlinear impairments of the modulator and photodetector also deteriorate the performance of the IM-DD system, especially for high-order modulation formats. In this work, we propose a gradient-descent noise whitening (GD-NW) algorithm to address EECN and extend it by introducing nonlinear kernels to simultaneously mitigate EECN and nonlinear impairments. The proposed algorithms are compared with conventional counterparts in terms of the achievable baud rate and the receiver optical power sensitivity. As a proof-of-concept experiment, we validate the principles of the proposed algorithms by successfully transmitting 360-GBd on-off-keying (OOK) and 180-GBd 4-level pulse-amplitude-modulation (PAM-4) signals in the back-to-back case under a 62-GHz brick-wall bandwidth limitation. 280-GBd OOK and 150-GBd PAM-4 transmissions are also demonstrated over 1-km standard single-mode fiber with a bit error rate below 7% hard-decision forward error correction aided by the proposed approach.

Weight-adaptive joint mixed-precision quantization and pruning for neural network-based equalization in short-reach direct detection links.

Neural network (NN)-based equalizers have been widely applied for dealing with nonlinear impairments in intensity-modulated direct detection (IM/DD) systems due to their excellent performance. However, the computational complexity (CC) is a major concern that limits the real-time application of NN-based receivers. In this Letter, we propose, to our knowledge, a novel weight-adaptive joint mixed-precision quantization and pruning approach to reduce the CC of NN-based equalizers, where only integer arithmetic is taken into account instead of floating-point operations. The NN connections are either directly cutoff or represented by a proper number of quantization bits by weight partitioning, leading to a hybrid compressed sparse network that computes much faster and consumes less hardware resources. The proposed approach is verified in a 50-Gb/s 25-km pulse amplitude modulation (PAM)-4 IM/DD link using a directly modulated laser (DML) in the C-band. Compared with the traditional fully connected NN-based equalizer operated with standard floating-point arithmetic, about 80% memory can be saved at a minimum network size without degrading the system performance. Quantization is also shown to be more suitable to over-parameterized NN-based equalizers compared with NNs selected at a minimum size.

112-GBaud mode-division-multiplexing IM-DD transmission beyond net 6.4†Tb/s over weakly coupled FMF for optical interconnections.

Weakly coupled mode-division-multiplexing (MDM) systems based on intensity modulation and direct detection (IM-DD) are a good candidate for further improving the capacity of short-reach optical interconnections. However, restrained by the modal crosstalk of the transmission link and the reception of degenerate mode groups (DMGs) utilizing bandwidth-limited multimode photodetectors (PDs), high-speed MDM IM-DD has encountered a capacity bottleneck. In this Letter, we investigate a high-speed weakly coupled MDM IM-DD transmission system utilizing a degenerate mode diversity receiver scheme adopting high-bandwidth single-mode PDs over a multiple-ring-core (MRC) few-mode fiber (FMF) and a low-crosstalk mode multiplexer/demultiplexer (MUX/DMUX). An MDM IM-DD transmission with four DMGs and eight wavelengths is experimentally demonstrated with 112-GBaud four-level pulse-amplitude modulation (PAM4) and probabilistically shaped PAM8 per lane over 200-m weakly coupled MRC-FMF. To the best of our knowledge, this is the first experimental demonstration of the MDM IM-DD transmission system with up to 112-GBaud baud rate and beyond 6.4-Tb/s net rate. Meanwhile, the experimental results show that the proposed MDM IM-DD transmission link has a superior performance only adopting a low-complexity feedforward equalizer, making it a promising candidate for high-speed optical interconnections.

Mode-division-multiplexing self-homodyne coherent transmission over a weakly coupled few-mode fiber for optical interconnections.

Self-homodyne coherent transmission has recently received extensive investigation as a coherent lite candidate for high-speed short-reach optical networks. In this Letter, we propose a weakly coupled mode-division-multiplexing (MDM) self-homodyne coherent scheme using a multiple-ring-core few-mode fiber, in which one of the modes transmits a self-homodyne local oscillator (LO) and the rest are utilized for carrying signals. Multiple rings of index perturbations in the fiber core are applied to achieve low modal crosstalk, allowing the signals and the remote LO to be transmitted independently. We experimentally demonstrate a 7.2-Tb/s (5.64-Tb/s net rate) self-homodyne coherent transmission with an 800-Gb/s data rate for each of the nine information-bearing modes formatted in 80-GBaud probabilistic constellation-shaped 64-quadrature-amplitude modulation. To the best of our knowledge, this is the first experimental demonstration of an MDM self-homodyne coherent transmission with up to 10 spatial modes. The proposed scheme may pave the way for future high-capacity data center interconnections.

Downregulation of HMGCS2 mediated AECIIs lipid metabolic alteration promotes pulmonary fibrosis by activating fibroblasts.

BACKGROUND: Abnormal lipid metabolism has recently been reported as a crucial signature of idiopathic pulmonary fibrosis (IPF). However, the origin and biological function of the lipid and possible mechanisms of increased lipid content in the pathogenesis of IPF remains undetermined. METHODS: Oil-red staining and immunofluorescence analysis were used to detect lipid accumulation in mouse lung fibrosis frozen sections, Bleomycin-treated human type II alveolar epithelial cells (AECIIs) and lung fibroblast. Untargeted Lipid omics analysis was applied to investigate differential lipid species and identified LysoPC was utilized to treat human lung fibroblasts and mice. Microarray and single-cell RNA expression data sets identified lipid metabolism-related differentially expressed genes. Gain of function experiment was used to study the function of 3-hydroxy-3-methylglutaryl-Coa Synthase 2 (HMGCS2) in regulating AECIIs lipid metabolism. Mice with AECII-HMGCS2 high were established by intratracheally delivering HBAAV2/6-SFTPC- HMGCS2 adeno-associated virus. Western blot, Co-immunoprecipitation, immunofluorescence, site-directed mutation and flow cytometry were utilized to investigate the mechanisms of HMGCS2-mediated lipid metabolism in AECIIs. RESULTS: Injured AECIIs were the primary source of accumulated lipids in response to Bleomycin stimulation. LysoPCs released by injured AECIIs could activate lung fibroblasts, thus promoting the progression of pulmonary fibrosis. Mechanistically, HMGCS2 was decreased explicitly in AECIIs and ectopic expression of HMGCS2 in AECIIs using the AAV system significantly alleviated experimental mouse lung fibrosis progression via modulating lipid degradation in AECIIs through promoting CPT1A and CPT2 expression by interacting with PPARα. CONCLUSIONS: These data unveiled a novel etiological mechanism of HMGCS2-mediated AECII lipid metabolism in the genesis and development of pulmonary fibrosis and provided a novel target for clinical intervention.

Copper metabolism and its role in diabetic complications: A review.

Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.

Measuring and optimizing the spatial accessibility of primary health care in remote and rural areas: a case study of Liannan Yao Autonomous County in China.

The need for equitable access to primary healthcare services in the current global context has attracted widespread attention, prompting nations to continuously enhance their grassroots medical service levels. In response, China launched the "Healthy China" initiative, which prioritizes the enhancement of national health as a core goal of the healthcare system and uses this opportunity to deepen reforms aimed at strengthening primary care. However, in remote and rural areas, the optimization of medical resource allocation and the achievement of balanced service development remain critical challenges owing to limited resources. This study selected Liannan Yao Autonomous County, which is situated in the northwestern corner of Guangdong Province, as a case study due to its remote mountainous location, underdeveloped economy, and minority region characteristics. Through field research and interviews, this study thoroughly explored the needs of both supply and demand, factoring in elements such as the service capability of healthcare facilities and residents' travel thresholds to enhance the two-step floating catchment area model, thus making it more applicable to remote villages. By integrating electric bikes and cars, which are the primary means of transportation in rural areas, this study conducted a thorough analysis and comparison of the accessibility of medical services in Liannan Yao Autonomous County (Liannan County) . The results reveal significant disparities in healthcare accessibility, an uneven distribution of medical resources, and varying impacts of transportation conditions and facility service capabilities on accessibility. Notably, the study revealed that improving transportation conditions alone has limited effects in rural areas; the key lies in balancing medical service capabilities and the rationality of overall layouts. From the perspectives of equity and efficiency, this study employs the equitable coverage model and the efficiency-driven model to construct two scenarios, comparing accessibility changes in Liannan County under both conditions and proposing strategies to improve the spatial layout of local healthcare facilities. This research not only deepens the understanding of healthcare service accessibility in rural areas but also provides a scientific basis for optimizing resource allocation and enhancing primary medical services, offering valuable guidance and reference for Liannan County and other similar rural regions.

Predictive Value of Combined Detection of Serum PSA, PCA3, and Apparent Diffusion Coefficient of Magnetic Resonance Imaging in Bone Metastasis of Prostate Cancer.

Objective: The objective of this study was to examine the utility of combining the detection of serum prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), and apparent diffusion coefficient (ADC) of magnetic resonance imaging for predicting bone metastases in prostate cancer. Methods: We looked back at 67 men with prostate cancer who were admitted to our hospital between December 2015 and December 2022. Based on the results of bone metastasis in ECT, men with prostate cancer were split into two groups: those with metastasis (26 cases) and those without (41 cases). The Gleason score, the levels of serum PSA and PCA3, and the difference between ADCmean and the difference between ADCmax and ADCmin (ADCdiff) were compared between the two groups. Results: Patients with bone metastases of prostate cancer exhibited significantly higher levels of PSA, PCA3, ADCmean, and ADCdiffer compared to the control group (P < .05). ADCmean and ADCdiffer were statistically significant (P < .05) greater in the metastatic group compared to the control group. Prostate cancer bone metastasis risk variables were shown to be elevated PSA, PCA3, ADCmean, and big ADCdiffer by logistic regression analysis (P < .05). ROC analysis showed that the AUC curves of PSA, PCA3, ADCmean, ADCmean, and their combination had certain predictive value. Conclusion: Patients with bone metastases of prostate cancer will have drastically different PSA and PCA3 serum values. Risk factors for prostate cancer bone metastases include elevated PSA and PCA3 levels as well as elevated ADCmean and big ADCdiffer. The combination of PSA, PCA3, and MRI ADC values demonstrated a strong predictive value for bone metastasis in prostate cancer patients.