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Abstract Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

Abstract Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3′ UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

Abstract Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Abstract Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.

Background: China is confronted with the significant menace posed by hemorrhagic fever with renal syndrome (HFRS). Nevertheless, the long-term spatial-temporal variations, regional prevalence patterns, and fundamental determinants' mechanisms for HFRS remain inadequately elucidated. Methods: Newly diagnosed cases of HFRS from January 2004 to December 2019 were acquired from the China Public Health Science Data repository. We used Age-period-cohort and Bayesian Spacetime Hierarchy models to identify high-risk populations and regions in mainland China. Additionally, the Geographical Detector model was employed to quantify the determinant powers of significant driver factors to the disease. Results: A total of 199,799 cases of HFRS were reported in mainland China during 2004–2019. The incidence of HFRS declined from 1.93 per 100,000 in 2004 to 0.69 per 100,000 in 2019. The incidence demonstrated an inverted U-shaped trend with advancing age, peaking in the 50–54 age group, with higher incidences observed among individuals aged 20–74 years. Hyperendemic areas were mainly concentrated in the northeastern regions of China, while some western provinces exhibited a potential upward trend. Geographical detector model identified that the spatial variations of HFRS were significantly associated with the relative humidity (Q = 0.36), forest cover (Q = 0.26), rainfall (Q = 0.18), temperature (Q = 0.16), and the surface water resources (Q = 0.14). Conclusions: This study offered comprehensive examinations of epidemic patterns, identified high-risk areas quantitatively, and analyzed factors influencing HFRS transmission in China. The findings may contribute to the necessary implementations for the effective prevention and control of HFRS.

Abstract Background Multiple myeloma (MM) is a prevalent hematological tumor, and recent clinical data have highlighted the significance of atrial fibrillation (AF) as a crucial complication affecting the prognosis of MM. This review aims to consolidate findings from published clinical studies, focusing on the epidemiological characteristics of AF in MM patients and the associated risks arising from MM treatments such as autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory agents. Main body While existing data partially demonstrate a strong correlation between MM and AF, further clinical studies are necessary to comprehensively investigate their association. These studies should encompass various aspects, including the risk of AF resulting from MM treatment, the impact of AF-induced embolic events and heart failure on MM prognosis, as well as the influence of AF management methods like catheter ablation or left atrial appendage closure on MM prognosis. Conclusions The supplementation of future data will provide more precise guidance for managing MM patients. By incorporating information regarding AF risk associated with MM treatment and examining the effects of AF management strategies on MM prognosis, healthcare professionals can enhance their decision-making process when caring for individuals with MM.

[Objective] Digital transformation is an inevitable trend for urban rail transit enterprises during the shift from high-speed growth to high-quality development. It is necessary to study the top-level design, path selection, and implementation strategies for enterprise digital transformation. [Method] Taking the digital transformation practice of Nanjing Metro as example, the steps, working contents, main methods and tools used in the top-level design of digital planning are introduced. The overall framework and application schemes of Nanjing Metro digital transformation are expounded from five levels: digital base layer, digital application layer, digital service layer, security protection system, and IT governance and management system. The implementation strategy of Nanjing Metro digital transformation is made clear. [Result & Conclusion] Nanjing Metro digital transformation is ′customer-oriented′, focusing on digital application scenarios such as happy travel service for passengers, digital intelligent decision-making service for decision makers and managers, and digital collaboration service for employees. The overall architecture and application scheme of digital transformation is designed from the top level. By formulating a scientific and feasible implementation path, Nanjing Metro is advanced towards a ′digitalized, networking, intelligent, and smart′ high-quality development.

Estimating ecological environmental flow in tidal rivers is one of the major challenges for sustainable water resource management in estuaries and river basins. This paper presents an ecological environmental flow framework that was developed to accommodate highly dynamic medium tidal estuaries found along the Yellow Sea coast of China. The framework not only proposes a method of water quality-based ecological flow for tidal gate-controlled rivers but also proposes a method of water demand for scouring and silting to protect ports in coastal viscous sediment environments. The framework integrates the instream water requirements of water quality, sediment and basic ecological flow, and considers the temporal and spatial variation differences for the environmental flow requirements of tidal rivers. This study emphasizes the significance and necessity of continuous monitoring of ecological data in determining the environmental flow of tidal rivers. The output of this study could provide vital references for decision-making and management of the water resource allocation and ecological protection in tidal rivers. HIGHLIGHTS This study develops an ecological environmental flow framework for highly dynamic medium tidal estuaries.; This study suggests a method of water quality-based ecological flow for tidal gate-controlled rivers.; This study proposes a method of water demand for scouring and silting.;

Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.

Abstract Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody‐based lysosome‐targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer‐based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin‐streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono‐targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono‐/dual‐targets degradation, expanding the possibilities of targeted protein degradation.

ABSTRACT Objective: The objective of this study was to evaluate the impact of drainage tube placement on postoperative pain, recovery, and opioid consumption within a 72-hour period following unicompartmental knee arthroplasty (UKA). Methods: Patients with medial knee osteoarthritis who underwent UKA from January 2019 to August 2020 were enrolled in the study and divided into two groups based on whether they received a drain postoperatively. Results: The drainage group had significantly lower VAS scores on day 1, day 2, and day 3, in addition to significantly smaller changes in the circumference of the knee joint within 3 days postoperatively (P

Abstract Background Catheter-associated urinary tract infection (CAUTI) ranks second among nosocomial infections in elderly patients after lung infections. Improper treatment can lead to death. This study analysed the risk factors, pathogen distribution, clinical characteristics and outcomes of CAUTI in elderly inpatients with a large sample size to provide evidence for clinical prevention and control. Methods Based on the HIS and LIS, a case‒control study was conducted on all hospitalized patients with indwelling urinary catheters ≥ 60 years old from January 1, 2019, to December 31, 2022, and the patients were divided into the CAUTI group and the non-CAUTI group. Results CAUTI occurred in 182 of 7295 patients, and the infection rate was 3.4/per 1000 catheter days. Urine pH ≥ 6.5, moderate dependence or severe dependence in the classification of self-care ability, age ≥ 74 years, male sex, hospitalization ≥ 14 days, indwelling urinary catheter ≥ 10 days, diabetes and malnutrition were independent risk factors for CAUTI (P

The cut-ins (one kind of lane-changing behaviors) have result in severe safety issues, especially at the entrances and exits of urban expressways. Risk prediction and characteristics analysis of cut-ins are part of the essential research for advanced in-vehicle technologies which can reduce crash occurrences. This paper makes some efforts on these purposes. In this paper, twenty-four participants were recruited to conduct the experiments of multi-driver simulation for risky driving data collection. The surrogate measures, Time Exposure Time-to-Collision (TET) and Time Integrated Time-to-collision (TIT) were employed to quantify the risk of cut-ins, then k-means clustering was applied for risk classification of 3 levels. Multiple candidate variables of two kinds were extracted including 10 behavioral variables and 7 driver trait variables. Based on these variables, three prediction models including decision tree (DT), gradient boosting decision tree (GBDT) and long short-term memory (LSTM) are used for predicting the risks of cut-ins. Results from data validity verification show that the data collected from multi-driver simulation experiments is valid compared with real-world data. From results of risk prediction models, the LSTM, with an overall accuracy of 87%, outperforms the GBDT (80.67%) and DT (76.9%). Despite this, this paper also concludes the merits of the DT over the GBDT and LSTM in variable explanation and the results of DT suggest that controlling the proper lane-changing gap and short duration of cut-ins can help reduce risks of cut-ins.

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross-complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P>0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple-negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han-Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer.

BackgroundMultimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown.MethodsSummary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases.ResultsLDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (PConclusionsThis study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.

Carbon dots (CDs) are a fascinating new type of fluorescent carbon nanomaterial with excellent photoelectric properties. However, preparing long-wavelength and multicolor-emitting CDs has been challenging, limiting their large-scale applications. Fortunately, a new efficient method has been proposed to co-regulate CDs' multicolor spectra using an ultrasonic microreactor. Inspired by plant leaves, a bionic vein microchannel was designed with good fluidity and high energy transfer efficiency. The optimal microchannel structural parameters were determined after investigating the effects of fractal angle, depth-to-width ratio, and inlet angle on the flow uniformity of the microchannel using numerical simulations. The efficiency of ultrasonic energy transfer was improved by directly coupling the microreactor and the sandwich transducer to fabricate the ultrasonic microreactor. Simulation results showed that the ultrasonic microreactor's vibration resonated along the longitudinal direction, and the ultrasonic intensity of the microreactor was maximal and uniform. A high-efficiency and controllable ultrasonic microreactor system was built to synthesize the CDs in situ. The influence of the ultrasound field intensity on CDs' preparation in a microreactor was simultaneously investigated to verify the ultrasound enhancement, and the PLQY of the high-performance CDs was found to be 83.1%. The CDs' multicolor spectra from the blue to the red region can be precisely tuned by adjusting key reaction parameters such as reaction temperature, flow rate, and precursor concentration. This new method shows promising applications in lighting, display, and other fields, making CDs a versatile and exciting new material to explore.

Abstract Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases. Applied to PacBio RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. Additionally, our analysis uncovered novel insights about RNA editing occurrences in single molecules and double-stranded RNA structures. L-GIREMI provides a valuable means to study nucleotide variants in long-read RNA-seq.

Abstract Kinase inhibitors against Cyclin Dependent Kinase 4 and 6 (CDK4/6i) are promising cancer therapeutic drugs. However, their effects are limited by primary or acquired resistance in virtually all tumor types. Here, we demonstrate that Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) controls CDK4/6i response in lung cancer by forming a feedback loop with CDK6. LRPPRC binds to CDK6-mRNA, increasing the stability and expression of CDK6. CDK6 and its downstream E2F Transcription Factor 1 (E2F1), bind to the LRPPRC promoter and elevate LRPPRC transcription. The activation of the LRPPRC-CDK6 loop facilitates cell cycle G1/S transition, oxidative phosphorylation, and cancer stem cell generation. Gossypol acetate (GAA), a gynecological medicine that has been repurposed as a degrader of LRPPRC, enhances the CDK4/6i sensitivity in vitro and in vivo. Our study reveals a mechanism responsible for CDK4/6i resistance and provides an enlightening approach to investigating the combinations of CDK4/6 and LRPPRC inhibitors in cancer therapy.

Slag and fly ash (FA) are mostly used as precursors for the production of alkali-activated materials (AAMs). FA is the waste discharged by power plants, while slag and steel slag (SS) both belong to the iron and steel industry. The effects of SS and FA on the strength, microstructure, and volume stability of alkali-activated slag (AAS) materials with different water glass modulus (Ms) values were comparatively investigated. The results show that adding SS or FA decreases the compressive strength of AAS mortar, and the reduction effect of SS is more obvious at high Ms. SS or FA reduce the non-evaporable water content (Wn) of AAS paste. However, SS increases the long-term Wn of AAS paste at low Ms. The cumulative pore volume and porosity increase after adding SS or FA, especially after adding FA. The hydration products are mainly reticular C-(A)-S-H gels. Adding SS increases the Ca/Si ratio of C-(A)-S-H gel but decreases the Al/Si ratio. However, by mixing FA, the Ca/Si ratio is reduced and the Al/Si ratio is almost unchanged. The incorporation of SS or FA reduces the drying shrinkage of AAS mortar, especially when SS is added. Increasing Ms increases the compressive strength and improves the pore structure, and it significantly increases the drying shrinkage of all samples. This study provides theoretical guidance for the application of steel slag in the alkali-activated slag material.

The effects of steel slag (SS) and fly ash (FA) on hydration heat, fluidity, setting time and rheological properties of alkali-activated slag (AAS) pastes with different silicate modulus (Ms) values were comparatively investigated. The results show that the incorporation of SS shortens the induction period, increases the cumulative hydration heat, improves the initial fluidity and decreases the setting time at low Ms, but the opposite trend is found at high Ms. FA significantly retards the reaction, reduces the hydration heat, increases the fluidity and prolongs the setting time. The addition of SS or FA reduces the yield stress and plastic viscosity of AAS paste. SS improves the rheological properties of AAS paste more significantly than that of FA at high Ms. The yield stress and plastic viscosity of AAS paste with SS or FA rise with the increasing Ms and decline with the increasing water/binder (w/b) ratio.

Backgrounds: Visceral leishmaniasis (VL) is a vector-borne disease posing increasing public health concerns. Although efforts to eliminate VL are underway, its global risk distribution remains unclear, because of changes in transmission risk. Methods: Worldwide province-level data on VL incidence were obtained from multiple sources. We analyzed the global evolution features of VL and estimated its ecological niches with boosted regression tree models. A risk map was generated to analyze regions with high VL risk. Results: A total of 558 articles and 2,694 records from 310 provinces were included. The model indicated that precipitation in the warmest quarter and poor socio-demographic index were the most significant risk factors affecting VL distribution. The risk map indicated that Brazil, Iran, Ethiopia, and India were the regions with the highest probability of infection. We estimated that 5.3 billion people live in regions at risk of VL. Conclusions: VL is undergoing geographic expansion. Our study increases understanding of VL’s global-risk distribution and how risk factors influencing the disease transmission. Our findings may aid in promoting disease control in future surveillance activities.

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures. Compared to antibody-drug conjugates (ADC), aptamer‒drug conjugate (ApDC) is also an efficient, targeted drug for cancer therapy with a smaller size, higher chemical stability, lower immunogenicity, faster tissue penetration, and facile engineering. Despite all these advantages, several key factors have delayed the clinical translation of ApDC, such as in vivo off-target effects and potential safety issues. In this review, we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

This paper presented a real-time millimeter wave radar-based system for tracking vehicle trajectories in a wide area (continuously along a roadway with essentially no length limit in practice). The trajectory tracking results were first validated for single vehicle trajectory tracking using the Real-Time Kinematic positioning technology based on the Beidou satellite navigation systems. The validation showed that the vehicle positions were captured with a mean lateral offset of −0.284 m and a mean longitudinal offset of −0.352 m. The mean estimated speeds were found to have a difference of only −0.048 km/h from the ground truths. The trajectory tracking results were also validated through multi-object tracking using video data from an unmanned aerial vehicle (UAV). Compared with the UAV video footage, the millimeter wave-based system was found to correctly capture around 92% of the total number of vehicles. For the correctly captured vehicles, their positions were found to be within 0.99 m (about a quarter of the width of a regular traffic lane) of the ground truth. In this paper, we also would like to share openly the entire validated datasets which has been recently published online as the TJRD TS platform. Additionally, a demonstration in using the dataset to detect aggressive driving behaviors, such as speeding was presented. It is expected that the open dataset will help enable researchers and practitioners to further explore the behaviors of road users, track the dynamics of safety risks and congestion formation, and evaluate incident impacts in a more microscopic but comprehensive way.

Osteogenesis imperfecta (OI) is an inherited congenital disorder, characterized primarily by decreased bone mass and increased bone fragility. Bone morphogenetic protein-2 (BMP-2) is a potent cytokine capable of stimulating bone formation, however, its rapid degradation and unanticipated in vivo effects restrict its application. The sustained release characteristic of silk fibroin (SF) microspheres may potentially address the aforementioned challenges, nevertheless they have not previously been tested in OI treatment. In the current investigation, recombinant BMP-2 (rBMP-2) loaded SF (rBMP-2/SF) microspheres-based release carriers were prepared by physical adsorption. The SF microparticles were characterized by scanning electron microscopy (SEM) and were investigated for their cytotoxicity behavior as well as the release profile of rBMP-2. The rBMP-2/SF microspheres were administered via femoral intramedullary injection to two genotypes of OI-modeled mice daily for two weeks. The femoral microstructure and histological performance of OI mice were evaluated 2 weeks later. The findings suggested that rBMP-2/SF spheres with a rough surface and excellent cytocompatibility demonstrated an initial rapid release within the first three days (22.15 ± 2.88% of the loaded factor), followed by a transition to a slower and more consistent release rate, that persisted until the 15th day in an in vitro setting. The factor released from rBMP-2/SF particles exhibited favorable osteoinductive activity. Infusion of rBMP-2/SF microspheres, as opposed to blank SF spheres or rBMP-2 monotherapy, resulted in a noteworthy enhancement of femoral microstructure and promoted bone formation in OI-modeled mice. This research may offer a new therapeutic approach and insight into the management of OI. However, further investigation is required to determine the systematic safety and efficacy of rBMP-2/SF microspheres therapy for OI.

AIM: To investigate the progression of myopia and risk factors among university students in central China. METHODS: A total of 7359 first-year undergraduate students at Huazhong University of Science and Technology in central China were recruited to the study and invited to a centralized clinic for medical examination, including optometry, and re-examined after one year. Correlation analyses were performed to assess the associations between one-year myopia progression and various parameters. RESULTS: The spherical equivalent refraction for the overall population was -3.14±2.28 D at baseline. The rate of myopia progression over 0.50 D after one year was 41.9%, and the 1-year progression of myopia was -0.47±0.58 D. There was no difference of mean 1-year myopia progression between male and female or difference among age group. The myopia progression of original myopia was severer than progression of new-onset myopia. There was also difference of mean myopia progression among different degrees of myopia at baseline. The under corrected eyes had a higher percentage of myopia progression than well corrected eyes (χ2=7.90, P0.05). CONCLUSION: Myopes still progress in undergraduate students, especially in high myopes.

Broad-area semiconductor lasers, coupled with asymmetric transverse photonic crystals (TPCs), are designed by the effective index method and the transfer matrix method. Due to the propagation constant of the fundamental mode lying in the forbidden band of the TPCs, but those of the high-order modes lying in the allowed band of the TPCs, the fundamental mode is mainly concentrated in the active ridge waveguide, while all the high-order modes extend into the lossy TPCs on both sides of the active ridge waveguide. Therefore, the fundamental mode possesses larger optical confinement factor than those of the high-order modes, and reaches the lasing threshold more easily, which is demonstrated by the single-lobe horizontal far-field pattern of the TPC broad-area laser under an injection current of 0.3 A near the threshold. The proposed TPC broad-area laser provides a new strategy of designing broad-area semiconductor lasers with narrow divergence angles.

The lacrimal gland is responsible for maintaining the health of the ocular surface through the production of tears. However, our understanding of the immune system within the lacrimal gland is currently limited. Therefore, in this study, we utilized single-cell RNA sequencing and bioinformatic analysis to identify and analyze immune cells and molecules present in the lacrimal glands of normal mice. A total of 34,891 cells were obtained from the lacrimal glands of mice and classified into 18 distinct cell clusters using Seurat clustering. Within these cell populations, 26 different immune cell subpopulations were identified, including T cells, innate lymphocytes, macrophages, mast cells, dendritic cells, and B cells. Network analysis revealed complex cell-cell interactions between these immune cells, with particularly significant interactions observed among T cells, macrophages, plasma cells, and dendritic cells. Interestingly, T cells were found to be the main source of ligands for the Thy1 signaling pathway, while M2 macrophages were identified as the primary target of this pathway. Moreover, some of these immune cells were validated using immunohistological techniques. Collectively, these findings highlight the abundance and interactions of immune cells and provide valuable insights into the complexity of the lacrimal gland immune system and its relevance to associated diseases.

Summary: Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.

Cardiac fibroblasts (CFs) are of vital importance for post-myocardial infarction (MI) remodeling. This study explored the role of Placenta specific 8 (Plac8) in MI on the basis of single-cell RNA-Seq (scRNA-Seq) data (GSE136088) and micro-array data (GSE153485). Through bioinformatics analysis, Plac8 was finally identified as a key gene related to fibroblasts. In addition, primary CFs of the neonatal mice were isolated, cultured and treated with hypoxia for in vitro cell model construction. Hydroxyproline assay demonstrated enhanced collagen production in hypoxic CFs, and qRT-PCR revealed increased relative contents of type I and type III collagen (Col1a1 and Col3a1). Western blot showed increased protein expression level of α-smooth muscle actin (α-SMA), and transwell assay and wound-healing assay collectively suggested enhanced cell migration. Moreover, Plac8 was found to be upregulated in hypoxic CFs. Then, after transfection with siNC or siPlac8, it was revealed that down-regulating Plac8 protein expression in hypoxic CFs reduced the levels of collagen secretion, the number of activated CFs and the degree of cell migration, indicating the regulation of Plac8 on hypoxic CFs’ transformation into myofibroblasts, cell migration and collagen deposition. Excessive myocardial fibrosis can cause adverse cardiac remodeling, leading to malignant arrhythmia and even heart failure.

Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia.

Safety of drivers in freeway work zones has been a problem. Real-time crash prediction helps prevent crashes before they happen. This paper looks at real-time crash prediction in freeway work zones by using machine learning approaches. Both the Convolutional Neural Network and the Binary Logistic Regression model are introduced. For training and testing the models, crash data and traffic data from several freeways in D7 zone, Los Angeles, California, were used. Crash data were collected from California Highway Patrol Incident System, and traffic data were obtained from the Caltrans Performance Measurement System. Data processing and matching were conducted. Both the two models were trained and tested. Results show that the Convolutional Neural Network performed slightly better over the Binary Logistic Regression model in predicting crashes with a global accuracy of 79.50%. Despite this, the main merit of the Binary Logistic Regression model is that it is able estimate the impact of affecting variables on the probability of crashes and can help identify the factors related to risks in work zones. Machine learning approaches applied in this study perform well in crash prediction. In general, machine learning techniques and reliable real-time crash prediction applications can be promising in helping drivers and transportation engineers make timely responses to potential crashes on freeways.

BackgroundCardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence.Methods and findingsWe performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11–1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation.ConclusionOur data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.

As an essential component of chip laboratories and microfluidic systems, micromixers are widely used in fields such as chemical and biological analysis. In this work, a square cavity micromixer with multiple structural parameters (baffles, obstacles, and gaps) has been proposed to further improve the mixing performance of micromixers. This study examines the comprehensive effects of various structural parameters on mixing performance. The impact of baffle length, obstacle length-to-width ratio, gap width, and obstacle shape on the mixing index and pressure drop were numerically studied at different Reynolds numbers (Re). The results show that the mixing index increases with baffle length and obstacle length-to-width ratio and decreases with gap width at Re = 0.1, 1, 10, 20, 40, and 60. The mixing index can reach more than 0.98 in the range of Re ≥ 20 when the baffle length is 150 μm, the obstacle length-to-width ratio is 600/100, and the gap width is 200 μm. The pressure drop of the microchannel is proportional to baffle length and obstacle length-to-width ratio. Combining baffles and obstacles can further improve the mixing performance of square cavity micromixers. A longer baffle length, larger obstacle length-to-width ratio, narrower gap width, and a more symmetrical structure are conducive to improving the mixing index. However, the impact of pressure drop must also be considered comprehensively. The research results provide references and new ideas for passive micromixer structural design.

Abstract In recent years, Hybrid Cellular Automata Method (HCAM) has been successfully applied to solve structural topology optimization problems. However, there was no report on HCAM research of three-dimensional composite structure composed of multiple materials and multiple bodies. Therefore, in this paper, three-dimensional non-cube cells of irregular size (such as tetrahedral cells with adaptive changes inside length) and Finite Element Method (FEM) are introduced to extend HCAM, which is better and more flexibly to fit complex geometric shapes. Furthermore, a better structure configuration of multi-material and multi-body structure is obtained. The typical example study showed that the proposed topology optimization method could effectively remove the redundant materials of multi-material and multi-body structure, and the optimized structure configuration could still meet the requirements of the original condition after geometric reconstructed. Thus it provided a reference for the intelligent design of other products.

Vehicle trajectory data is in high demand for transportation research due to its rich detail. Lane information is an important aspect of trajectory data, which is typically obtained using sensors such as cameras or LiDAR, which are able to extract road lane features. However, some sensors for trajectory tracking (e.g., MMW radar sensors) are unable to provide lane information. Vehicle detection and trajectory tracking systems based on these sensing technologies can integrate with lane information through manual calibration during initial installation, but this process is labor-intensive and requires frequent recalibration as the sensors gradually become deviated by wind and vibration. This has posed a challenge for trajectory tracking, particularly for real-time applications. To address this challenge, this paper proposes a method for estimating lane-level road geometrics using microscopic trajectory data. The method involves segmenting the trajectory points using direction vectors and clustering them and fitting a series of cluster center points. The mean error (ME) of the distance between the estimated result and the ground truth reference is used to measure the accuracy of the lane-level road geometrics estimation in different conditions. Results show that when the average trajectory data includes at least approximately 30 points per meter in each segment, the ME is always less than 0.1 m. The method has also been tested on MMW wave radar data and found to be effective. This demonstrates the feasibility of our approach for dynamic calibration of road alignment in vehicle trajectory tracking systems.

Previous studies on pedestrian crossing have mostly focused on pedestrian crossing decisions; while as an important behavioral aspect, the pedestrian crossing process, i.e., their motions during the entire crossing process, has been narrowly studied. Understanding how pedestrian moves across the street during their entire crossing process helps identify risky movements and reasons for such movements, which can further help in the implementation of effective countermeasures. Therefore, this paper proposed a new and easily applied approach for investigating and understanding the pattern of the pedestrian crossing process at crosswalks based on vision-based trajectory tracking technology and UAV (unmanned aerial vehicle) data. This study uses UAV for collecting video data which is timesaving and has a sufficient coverage area, compared to other methods. For trajectory extraction, the vision-based Deep-SORT-Yolov5 architecture is applied. An improved DBSCAN (density-based spatial clustering of applications with noise) algorithm is introduced for clustering and identification of patterns of pedestrian crossing processes based on their trajectories. This approach is tested via a case study involving six marked crosswalks in Shanghai, China. By using the proposed method, different crossing patterns are extracted and compared. The results show reasonable outputs of trajectory patterns, which reasonably explain the potential instincts of the pedestrians and affecting factors on the behavior of the pedestrian crossing process. Suggestions are made based on the results. This paper contributes to a more comprehensive safety analysis of pedestrian crossings by considering the pedestrian crossing process. The model, along with the UAV-based trajectory observation method, provides an easily-applied and low-cost way of traffic data collection for the purpose of pedestrian safety evaluation.

With the booming of worldwide agriculture intensification, brucellosis, one of the most neglected zoonotic diseases, has become an increasing challenge for global public health. Although the transmission patterns of human brucellosis (HB) have been studied in many regions, the dynamic transfer processes of risk and its driving factors remain poorly understood, especially in the context of agricultural intensification. This study attempted to explore the risk transfer of HB between the exact epidemic areas and the neighboring or distant low-risk areas to explain the impact of livestock agriculture intensification and foodborne infections on the transmission of HB in Shaanxi Province as a case study. We adopted multiple approaches, including test-based methods, model-based methods, and a geographical detector to detect the spatial-temporal dynamic changes of high-risk epidemic areas of HB at the county scale. We also quantitatively estimated how the related factors drove the risk transfer of the disease. Results confirmed the risk transfer pattern of HB with an expansion from north to south in Shaanxi Province and identified two primary transfer routes. In particular, in the traditional epidemic areas of the Shaanbei plateau, the farm agglomeration effect can significantly increase the risk of HB. Meanwhile, retail outlets for milk and dairy products were partially responsible for the foodborne infections of HB in the emerging epidemic areas of Xi'an. This study not only contributed helpful insights to support HB control and prevention in the rapid transition of livestock agriculture but also provided possible directions for further research on foodborne HB infections in urbanized areas.

Due to the fact that the permeability coefficient of salinized frozen soil is difficult to measure through experimental test, this paper develops a model of the permeability coefficient of salinized frozen soil by using SFCC curves, which takes into account the effects of velocity slip on pore wall and seepage of unfrozen water film. This model is on the basis of capillary bundle model, and combines with phase diagram theory of water-salt binary system. For the silty clay from Qinghai-Tibet Plateau and silts from Onedia, the permeability coefficient fluctuation vs. temperature is calculated using the model. The estimated calculations of the permeability coefficient model were all found to be in good agreement with the experimental data by comparison. Additionally, the variation trend of permeability coefficient of NaCl, Na2SO4, and Na2CO3 type saline soils containing different salt contents is examined. The results indicate that before saline soils freeze, NaCl does not crystallize and thus has little impact on the permeability coefficient, whereas Na2SO4 and Na2CO3 both crystallize and block the pores, the permeability coefficient decreases with decreasing temperature. Once the saline soils have frozen, the freezing temperature has a larger impact on the permeability coefficient. During the early stage of freezing, the lower the freezing temperature is, the larger the permeability coefficient is. In the late stage of freezing, the permeability coefficients with various salt contents tended to be the same.

AIM:To figure out the sequence of vessel density(VD)changes in the retina and deformation induced by mechanical force in the optic nerve head(ONH)tissue during intraocular pressure(IOP)elevation.METHODS: This prospective study tested 34 eyes from 34 healthy volunteers. Group A had 23 subjects. Their testing protocol included a baseline phase, two elevated IOP phases(15 mmHg and 30 mmHg respectively for 2min), and a recovery phase. Group B had 11 subjects, and their protocol included an IOP elevation of 15 mmHg for 10min. In each phase the deformation in the ONH and macular region were scanned by optical coherence tomography(OCT), and Bruch's membrane opening(BMO)distance, the optic nerve head surface depth(ONHSD), the subfoveal choroidal thickness(SFCT)were measured, the VD was measured by OCTA.RESULTS: After the first IOP elevation in group A, the VD in the ONH decreased(superficial capillary plexuses, from 67.39±7.65% to 43.78±5.89%, P0.05).CONCLUSION:The ONH tissue is more sensitive to hemodynamics than to morphological change. Hemodynamics during IOP elevation differs in the ONH and the macular tissue.

9xx nm laser diodes (LDs) with aluminum component continuous gradient photonic band crystal (CCG-PBC) waveguide structure are designed and fabricated. The simulation results indicate that the CCG-PBC structure can significantly reduce the heterojunction barrier and carrier accumulation at the interface of the conventional PBC structure. We demonstrate that the LD with CCG-PBC structure can achieve a narrow vertical divergence angle of 16.2° at full width at half maximum, and the divergence angle changes with current not more than 0.5°. Meanwhile, the power conversion efficiency (PCE) of the narrow divergence angle LD can reach 66.7%, and the PCE at 20 W is still over 60%. After optimizing the coating reflectivity and cavity length of the CCG-PBC structure LD, the peak PCE and power are 71.5% and 17.2 W at 25 °C and 77.7% and 23.3 W at 0 °C, respectively, which are optimal results for any edge-emitting LD. Our device provides valuable guidance for researching high power and high efficiency narrow vertical divergence angle LDs.

Abstract To improve the heat transfer performance of microchannels, a novel microchannel embedded with connected grooves crossing two sidewalls and the bottom surface (type A) was designed. A comparative study of heat transfer was conducted regarding the performances of type A microchannels, microchannels embedded with grooves on their bottom (including types B and C), or on the sidewalls (type D) as well as smooth rectangular microchannels (type E) via a three-dimensional numerical simulation and experimental validation (at Reynolds numbers from 118 to 430). Numerical results suggested that the average Nusselt number of types A, B, C, and D microchannels were 106, 73.4, 50.1, and 12.6% higher than that of type E microchannel, respectively. The smallest synergy angle β and entropy generation number N s,a were determined for type A microchannels based on field synergy and nondimensional entropy analysis, which indicated that type A exhibited the best heat transfer performance. Numerical flow analysis indicated that connected grooves induced fluid to flow along two different temperature gradients, which contributed to enhanced heat transfer performance.

Antibiotic resistance in Staphylococcus aureus is associated with reduced neutrophil recruitment. Here, Payne et al. link formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin and show that these hybrid compounds improve clearance of S. aureus by neutrophils.

Purpose – Efficient traffic incident management is needed to alleviate the negative impact of traffic incidents. Accurate and reliable estimation of traffic incident duration is of great importance for traffic incident management. Previous studies have proposed models for traffic incident duration prediction; however, most of these studies focus on the total duration and could not update prediction results in real-time. From a traveler’s perspective, the relevant factor is the residual duration of the impact of the traffic incident. Besides, few (if any) studies have used dynamic traffic flow parameters in the prediction models. This paper aims to propose a framework to fill these gaps. Design/methodology/approach – This paper proposes a framework based on the multi-layer perception (MLP) and long short-term memory (LSTM) model. The proposed methodology integrates traffic incident-related factors and real-time traffic flow parameters to predict the residual traffic incident duration. To validate the effectiveness of the framework, traffic incident data and traffic flow data from Shanghai Zhonghuan Expressway are used for modeling training and testing. Findings – Results show that the model with 30-min time window and taking both traffic volume and speed as inputs performed best. The area under the curve values exceed 0.85 and the prediction accuracies exceed 0.75. These indicators demonstrated that the model is appropriate for this study context. The model provides new insights into traffic incident duration prediction. Research limitations/implications – The incident samples applied by this study might not be enough and the variables are not abundant. The number of injuries and casualties, more detailed description of the incident location and other variables are expected to be used to characterize the traffic incident comprehensively. The framework needs to be further validated through a sufficiently large number of variables and locations. Practical implications – The framework can help reduce the impacts of incidents on the safety of efficiency of road traffic once implemented in intelligent transport system and traffic management systems in future practical applications. Originality/value – This study uses two artificial neural network methods, MLP and LSTM, to establish a framework aiming at providing accurate and time-efficient information on traffic incident duration in the future for transportation operators and travelers. This study will contribute to the deployment of emergency management and urban traffic navigation planning.

BackgroundHepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss.Methods29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed.ResultsMultivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was “U-shaped”.ConclusionsCytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.

Background and aimChronic hepatitis B (CHB) can be divided into immune tolerance (IT), immune clearance (IC), hepatitis B e antigen (HBeAg)-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. The conventional biomarkers used to distinguish these phases have limitations. We examined the clinical significance of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as novel biomarkers.MethodsOne hundred eighty-nine patients without treatment currently were categorized by CHB phase (IT = 46, IC = 45, ENQ = 49, ENH = 49). The associations of HBV RNA and HBcrAg with HBV DNA and alanine transaminase (ALT) were analyzed. The decision tree model was used to distinguish the four phases in the natural course of CHB.ResultsThe concentrations of HBV RNA and HBcrAg were highest in the IT and IC phases (P < 0.01). Serum HBV RNA was similar to HBcrAg in treatment-naïve patients. HBV RNA and HBcrAg correlated with HBV DNA in the HBeAg+ and HBeAg− status (HBV RNA: e+ r = 0.51, e− r = 0.62; HBcrAg: e+ r = 0.51, e− r = 0.71), but their association with HBV DNA differed among phases. The accuracy, sensitivity, and specificity of HBcrAg with ALT in distinguishing the CHB phases were 95.65%, 95.83%, and 95.55%, respectively.ConclusionSerum HBV RNA and HBcrAg may be useful to monitor CHB progression.

Summary: PODXL, a protein that is dysregulated in multiple cancers, plays an important role in promoting cancer metastasis. In this study, we report that RNA editing promotes the inclusion of a PODXL alternative exon. The resulting edited PODXL long isoform is more prone to protease digestion and has the strongest effects on reducing cell migration and cisplatin chemoresistance among the three PODXL isoforms (short, unedited long, and edited long isoforms). Importantly, the editing level of the PODXL recoding site and the inclusion level of the PODXL alternative exon are strongly associated with overall patient survival in Kidney Renal Clear Cell Carcinoma (KIRC). Supported by significant enrichment of exonic RNA editing sites in alternatively spliced exons, we hypothesize that exonic RNA editing sites may enhance proteomic diversity through alternative splicing, in addition to amino acid changes, a previously under-appreciated aspect of RNA editing function.

Osteogenesis imperfecta (OI) is a congenital bone dysplasia mainly caused by either defective production or assembly of type I collagen. The skeletal phenotypes especially fractures are often seen in OI adolescents. Studies have found that an increased number of osteoclasts and excessive bone resorption existed in collagen-related OI, which has not been well understood. Emerging evidence has suggested that inflammation may be associated with OI. We speculated that the bone marrow (BM) niche had similar inflammatory changes and performed RNA-sequencing (RNA-seq) in BM cells derived from young male mice to analyze the related differentially expressed genes (DEGs) and pathways. Data showed that there were 117 shared DEGs (Q ≤ 0.05, |log2FC| ≥ 1) in BM cells isolated from two types of OI murine models that respectively simulate different OI types. Gene Ontology (GO) (Q ≤ 0.05) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) (Q ≤ 0.05) analysis and real-time PCR validation indicated the dysregulated biology process of cellular response to interferon (Ifn) together with upregulated IL-17 signaling, tumor necrosis factor (Tnf) signaling and osteoclast differentiation in OI BM niche. Either defective collagen production or abnormal collagen assembly shared similar alterations in gene profiles and pathways involving inflammation and osteoclast activation. Data presented here not only contributed to understanding of the mechanism of the enhanced bone absorption in the bones of OI, but also provided more evidence to develop potential anti-inflammation therapies.