Biology subjects

Wang, M.

Publications and source records attributed to Wang, M..

At least 307 records · Page 17Linked to original sources

bioRxiv2024

The Landscape of Sex- and APOE Genotype-Specific Transcriptional Changes in Alzheimer's Disease at the Single Cell Level

Alzheimers disease (AD) is the most common form of dementia, with approximately two-thirds of AD patients are females. Basic and clinical research studies show evidence supporting sex-specific differences contributing to the complexity of AD. There is also strong evidence supporting sex-specific interaction between the primary genetic risk factor of AD, APOE4 and AD-associated neurodegenerative processes. Recent studies by us and others have identified sex and/or APOE4 specific differentially expressed genes in AD based on the bulk tissue RNA-sequencing data of postmortem human brain samples in AD. However, there lacks a comprehensive investigation of the interplay between sex and APOE genotypes at the single cell level. In the current study, we systematically explore sex and APOE genotype differences in single cell transcriptomics in AD. Our work provides a comprehensive overview of sex and APOE genotype-specific transcriptomic changes across 54 high-resolution cell types in AD and highlights individual genes and brain cell types that show significant differences between sexes and APOE genotypes. This study lays the groundwork for exploring the complex molecular mechanisms of AD and will inform the development of effective sex- and APOE-stratified interventions for AD.

genomics↗

bioRxiv2024

Hyperballistic intercellular signaling through growth assisted positive feedback

Intercellular signaling in bacteria is often mediated by small molecules secreted by cells. These small molecules disperse via diffusion which limits the speed and spatial extent of information transfer in spatially extended systems. Theory shows that a secondary signal and feedback circuits can speed up the flow of information and allow it to travel further. Here, we construct and test several synthetic circuits in Escherichia coli to determine to what extent a secondary signal and feedback can improve signal propagation in bacterial systems. We find that positive feedback-regulated secondary signals propagate further and faster than diffusion-limited signals. Additionally, the speed at which the signal propagates can accelerate in time, provided the density of the cells within the system increases. These findings provide the foundation for creating fast, long-range signal propagation circuits in spatially extended bacterial systems.

synthetic biology↗

bioRxiv2024

Divergent effects of 3-nitrooxypropanol on enteric methane emissions in Holstein and Brown Swiss cows, and its lack of synergy with Acacia mearnsii tannin extract

The objectives of this study were to investigate the combined effects of 3-nitrooxypropanol (3-NOP) and Acacia mearnsii tannin extract (TAN), and their interactions with dairy cattle breed [Brown Swiss (BS) vs. Holstein Friesian (HF)], on lactational performance, and enteric methane (CH4) emissions. Sixteen multiparous mid-lactation cows, including 8 BS and 8 HF cows were used in a split-plot design, with breed as the main plot. Cows within each subplot were arranged in a replicated 4 x 4 Latin Square design with a 2 x 2 factorial arrangement of treatments across four 24-d periods. The experimental diets were: 1) CON (basal total mixed ration), 2) 3-NOP (60 mg/kg DM), 3) TAN (3% of DM), and 4) 3-NOP + TAN. Spot samples of urine, feces, and gas emissions (via GreenFeed) were collected at the end of each period 8 times over 3 days. No 3-NOP x TAN x Breed interactions were observed for DM intake (DMI), milk production, or enteric gas emissions, except for CH4 yield (g/kg DMI) and CO2 production. Breed influenced DMI, milk production, and component yields, with HF cows consuming 3.7 kg/d more DMI, producing 9.3 kg/d more milk, and achieving greater feed efficiency and higher milk component yields than BS cows. Milk yield and energy-corrected milk (ECM) tended to increase in HF but tended to decrease in BS cows by 3-NOP. Cows fed TAN had 1 kg/d lower DMI with the tendency for 3-NOP x TAN showed greater reduction when TAN was fed alone, but milk yield, ECM, and feed efficiency remained unchanged. Cows fed TAN exhibited 18% lower milk urea nitrogen (N) concentration and 23.0% lower urinary N but 36.7% greater fecal N excretions as a percentage of daily N intake. A 3-NOP x Breed interaction was observed in CH4 production (g/d), with a 21.7% reduction in HF, and a 13.0% reduction in BS. Similarly, there were 3-NOP x Breed tendencies in CH4 yield and intensity (g/kg ECM), with reductions in HF cows of 21.8% and 23.4%, respectively, compared to 11.0% and 10.8% in BS cows. In conclusion, there were no synergistic or additive effects between 3-NOP and TAN on enteric CH4 mitigation. The enteric CH4 emission mitigating effect of 3-NOP was more pronounced in HF cows than in BS cows. Further research is needed to understand breed-specific responses and to optimize CH4 mitigation strategies for inclusion in national greenhouse gas inventories. ImplicationsThis study demonstrated that the feed additive 3-nitrooxypropanol reduces enteric methane emissions in dairy cows, with a greater reduction observed in Holsteins (22%) compared to Brown Swiss (13%) cows. While combining 3-NOP with Acacia mearnsii tannin extract did not further reduce methane. Feeding Acacia mearnsii extract decreased nitrogen excretion, potentially reducing environmental nitrogen pollution from manure. Neither additive substantially impacted milk production; however, 3-nitrooxypropanol tended to increase milk yield in Holsteins while reducing it in Brown Swiss. Overall, this study suggests that enteric methane mitigation efficacy of dietary strategies for different cattle breeds should be further investigated.

animal behavior and cognition↗

bioRxiv2024

UniversalEPI: Harnessing Attention Mechanisms to Decode Chromatin Interactions in Rare and Unexplored Cell Types

Enhancer-promoter interactions (EPIs) play a central role in gene regulation, but experimental techniques such as Hi-C for mapping these interactions remain costly and labor-intensive. Computational methods have been developed to predict EPIs in silico from DNA sequence and chromatin information; however, there are major challenges with the generalizability and accuracy of predictions by existing methods across cell types and conditions unseen during model training. We developed and validated UniversalEPI, an attention-based deep ensemble model that predicts EPIs up to 2 Mb apart using only DNA sequence and chromatin accessibility (ATAC-seq) data. Unlike models that reconstruct full Hi-C contact maps, UniversalEPI focuses on biologically relevant, sparse chromatin interactions between accessible regulatory elements. It generalizes across both bulk and single-cell ATAC-seq-derived pseudo-bulk datasets, delivering state-of-the-art performance while using fewer input modalities than existing approaches. By modeling predictive uncertainty, UniversalEPI enables statistically robust differential analysis of chromatin interactions across conditions. We demonstrate its utility by tracking dynamic EPIs during human macrophage activation and identifying regulatory differences between cancer cell states in esophageal adenocarcinoma. By providing precalculated Hi-C predictions for 157 ENCODE datasets, UniversalEPI expands the scope and applicability of in silico 3D genome modeling for studying gene regulation in development and disease.

genomics↗

bioRxiv2024

The transcription factor GABPA is a master regulator of naive pluripotency

The establishment of naive pluripotency is a continuous process starting with the generation of inner cell mass (ICM) which then differentiating into epiblast (EPI). Recent studies have revealed key transcription factors (TFs) for ICM formation, but which TFs initiate EPI specification remains unknown. Here, using a targeted rapid protein degradation system, we show that GABPA is not only a regulator of major ZGA, but also a master EPI specifier required for naive pluripotency establishment by regulating 47% of EPI genes during E3.5 to E4.5 transition. Chromatin binding dynamics analysis suggests that GABPA controls EPI formation at least partly by binding to the ICM gene promoters occupied by the pluripotency regulators TFAP2C and SOX2 at E3.5 to establish naive pluripotency at E4.5. Our study not only uncovers GABPA as a master pluripotency regulator, but also supports the notion that mammalian pluripotency establishment requires a dynamic and stepwise multi-TFs regulatory network.

developmental biology↗

bioRxiv2024

HumanTestisDB: A Comprehensive Atlas of Testicular Transcriptomics and Cellular Interactions

Advances in single-cell technology have enabled the detailed mapping of testicular cell transcriptomes, which is essential for understanding spermatogenesis. However, the fragmented nature of age-specific data from various literature sources has hindered comprehensive analysis. To overcome this, the Human Testis Database (HumanTestisDB) was developed, consolidating multiple human testicular sequencing datasets to address this limitation. Through extensive investigation, 38 unique cell types were identified, providing a detailed perspective on cellular variety. Furthermore, the database systematically categorizes samples into eight developmental stages, offering a structured framework to comprehend the temporal dynamics of testicular development. Each stage features comprehensive maps of cell-cell interactions, elucidating the complex communication network inside the testicular microenvironment at particular developmental stages. Moreover, by facilitating comparisons of interactions among various cell types at different stages, the database permits examining alterations that transpire during critical transitions in spermatogenesis. HumanTestisDB, available at https://shalab.njmu.edu.cn/humantestisdb, offers vital insights into testicular transcriptomics and interactions, serving as an essential resource for advancing research in reproductive biology.

cell biology↗

bioRxiv2024

The microbiome diversifies N-acyl lipid pools - including short-chain fatty acid-derived compounds

N-acyl lipids are important mediators of several biological processes including immune function and stress response. To enhance the detection of N-acyl lipids with untargeted mass spectrometry-based metabolomics, we created a reference spectral library retrieving N-acyl lipid patterns from 2,700 public datasets, identifying 851 N-acyl lipids that were detected 356,542 times. 777 are not documented in lipid structural databases, with 18% of these derived from short-chain fatty acids and found in the digestive tract and other organs. Their levels varied with diet, microbial colonization, and in people living with diabetes. We used the library to link microbial N-acyl lipids, including histamine and polyamine conjugates, to HIV status and cognitive impairment. This resource will enhance the annotation of these compounds in future studies to further the understanding of their roles in health and disease and highlight the value of large-scale untargeted metabolomics data for metabolite discovery.

bioinformatics↗

bioRxiv2024

Differential Regulation of Large-scale Chromosome Conformations in Osteoblasts and Osteosarcoma

Correct chromosome organization in the cell nucleus is essential for genome function. However, dynamics and regulations of large-scale chromosomal conformations beyond single compartments at larger than ten megabases in vivo in single cells remain largely unknown. Here we use CRISPR-Sirius, a high-resolution and high-sensitivity real-time imaging technique, to directly visualize distinctions in large-scale chromosomal conformations between live osteosarcoma (OS) cells and osteoblasts, suggesting extensive chromatin reorganization during cell transformation. A surprising discovery is that chromosome 19 long arm is primarily extended in osteoblasts and maintained by H3K27me3. Extended chromosome conformation has been reported in fly and mouse but not in human cells yet. However, in OS cells, chromosome 19 primarily folded into collapsed conformations, which reshape in minutes and are regulated by the chromosome architectural proteins CTCF and cohesin in the presence of H3K27ac. Changes in chromosome conformations by knocking down the cohesin subunit RAD21 resulted in altered gene expression, including proto-oncogenes. Transcription inhibition by a small molecule inhibitor did not have detectable effects on large-scale chromosome conformation, suggesting that local transcription events have limited effects on large-scale chromosomal architecture. Our results provide unique insights into the complex regulatory mechanisms of endogenous large-scale chromosome organization in normal and transformed osteogenic tissues. One-sentence summaryRegulations of chromosome territory organization in normal and cancer bone cells visualized by CRISPR-based live-cell imaging.

cell biology↗

bioRxiv2024

CIGB-300 reverses chemo-resistance in MDR1-transfected lung squamous cancer cells

BackgroundInhibition of ABC transporter protein activity is considered to be the most effective method to reverse multidrug resistance (MDR). In this study, we evaluated the MDR reversal potential of CIGB-300, a potent CK2 kinase inhibitor. MethodsABCB1 overexpressing lung adenocarcinoma NCI-H226 cells were constructed using lentivirus, and the expression of ABCB1 gene and protein was detected by real-time fluorescence quantitative PCR and Western blotting. MTT assay was used to assess the cytotoxicity and MDR reversal effect of CIGB-300.The effect of CIGB-300 on ABCB1 expression was determined by Western Blotting. Cell surface expression and subcellular localization of ABCB1 were examined by Flow Cytometry and Immunofluorescence Staining. Rh123 efflux and accumulation were measured by Fluorescent Enzyme Labeler and Flow Cytometry. ResultsCIGB-300 significantly increased the sensitivity of drug-resistant cells overexpressing the ABCB1 drug efflux pump (NCI-H226-ABCB1), while it had no effect on their parental cell lines. At the same time, its mechanism of action may be related to the inhibition of ABCB1 expression, which was dose-dependent, Moreover, in addition, we demonstrated that CIGB-300 reduced the expression of NFKB and CDC37 proteins. ConclusionsOur study elucidated that CIGB-300 reverses ABCB1-mediated MDR by inhibiting ABCB1 protein expression or intracellular signaling and provides a potential therapeutic strategy to improve tumor chemosensitivity.

cancer biology↗

bioRxiv2024

FoldMark: Protecting Protein Generative Models with Watermarking

Proteins are the principal architects of life, fueling advances in bioengineering, drug discovery, and synthetic biology. The integration of generative AI with computational protein science has revolutionized protein design while also posing dual-use risks, such as enabling the creation of pandemic-capable proteins that require strong biosecurity safeguards. Here, we introduce FoldMark, a first-of-its-kind watermarking strategy leveraging distributional and evolutionary principles tailored for protein generative models, balancing watermark capacity and structural quality. FoldMark achieves over 95% watermark bit accuracy at 32 bits with minimal impact on structural quality (>0.9 scTM scores) for leading models including AlphaFold3, ESMFold, RFDiffusion, and RFDiffusionAA. For user tracing, FoldMark can successfully trace up to 1 million users. To validate FoldMark in wet lab, we applied it to structure-based design of EGFP and CRISPR-Cas13, showing wildtype-level function (98% fluorescence, 95% editing efficiency) and >90% watermark detection, demonstrating its practical utility for safeguarding AI-driven protein research.

bioinformatics↗

bioRxiv2024

Activating p53Y220C with a Mutant-Specific Small Molecule

TP53 is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compound TRanscriptional Activator of p53 (TRAP-1) due to its ability to engage mutant p53 and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription. Treatment of p53Y220C expressing pancreatic cell lines with TRAP-1 results in rapid upregulation of p21 and other p53 target genes and inhibits the growth of p53Y220C-expressing cell lines. Negative control compounds that are unable to form a ternary complex do not have these effects, demonstrating the necessity of chemically induced proximity for the observed pharmacology. This approach to activating mutant p53 highlights how chemically induced proximity can be used to restore the functions of tumor suppressor proteins that have been inactivated by mutation in cancer.

cancer biology↗

bioRxiv2024

Iridescent structural coloration in a crested Cretaceous enantiornithine bird from Jehol Biota

A combination of sectioning and microscopy techniques, along with the application of finite-difference-time-domain modeling on a fossil feather, results in the novel estimation of the range of iridescent colors from the fossilized melanosome type and organization preserved in the elongate head crest feathers of a new Cretaceous enantiornithine bird. The densely packed rod-like melanosomes are estimated to have yielded from red to deep blue iridescent coloration of the head feathers. The shape and density of these melanosomes also may have further increased the feathers structural strength. This occurrence on a likely male individual is highly suggestive of both a signaling function of the iridescent crest, and a potential behavioral role in adjusting the angle of light incidence to control the display of this iridescent structural coloration.

evolutionary biology↗

bioRxiv2024

All-trans retinoic acid-mediated ADAR1 degradation synergizes with PD-1 blockade to suppress pancreatic cancer

As a double-stranded RNA-editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically "cold" into "hot" tumors susceptible to immune checkpoint blockade.

cancer biology↗

bioRxiv2024

Physics-Informed Ellipsoidal Coordinate Encoding Implicit Neural Representation for high-resolution volumetric wide-field microscopy

Wide-field fluorescence microscopy through axial scanning provides a simple way for volumetric imaging of cellular and intracellular activities, but the optical transfer function (OTF) of wide-field microscopy suffers from axial frequency deficiencies, leading to strong interference from out-of-focus fluorescence signals and reduced imaging quality. Richardson-Lucy (RL) deconvolution and its variants are commonly employed to reduce inter-plane signal interference of wide-field microscopy. However, these methods are still affected by the "missing cone" issue inherent in the OTF, compromising both the axial resolution and optical sectioning capability. Existing deep learning methods could realize high-fidelity 3D image stack restoration, but relying on high-quality paired datasets or specific assumptions about sample distributions. Here, we propose a novel method named physics-informed ellipsoidal coordinate encoding implicit neural representation (PIECE-INR), to tackle the challenges of background signal interference and resolution loss in axial scanning image stacks using the wide-field microscopy. In PIECE-INR, we integrate the wide-field fluorescence imaging model with the self-supervised INR network for high-fidelity reconstruction of 3D fluorescence data without the need of additional ground truth data for training. We further design a novel ellipsoidal coordinate encoding based on the systems OTF constraints and incorporate implicit priors derived from the physical model as the loss function into the reconstruction process. Our approach enables block-wise reconstruction of large-scale images by using localized physical information. We demonstrate state-of-the-art performance of our PIECE-INR method in volumetric imaging of live HeLa cells, large-volume C. elegans whole-embryo, and mitochondrial dynamics.

cell biology↗

bioRxiv2024

Gene encoding CC-NBS-LRR protein on rye chromosome 1RS confers wheat stripe rust resistance

Stripe rust, a globally widespread disease, stands as one of the most significant threats to wheat cultivation. The 1BL/1RS translocation, renowned for its robust resistance to both rust and powdery mildew, has historically played an important role in wheat breeding and production. The gene for resistance to stripe rust on the 1RS is known as Yr9 and plays an important role in the production of wheat, but over the course of long-term breeding had lost its resistance due to the evolution of stripe rust towards greater and greater virulence. In this paper, we cloned the stripe rust resistance gene, Yr9, from triticale by genetic mapping approach. The Yr9 encodes a typical nucleotide-binding leucine-rich repeat (NLR) protein. Both transgenic and overexpression of Yr9 in highly stripe rust susceptible wheat varieties conferred complete resistance to the stripe rust races CYR17 and partial resistance to the stripe rust races CYR32, CYR33, and CYR34. In addition, the Yr9 allele in the 1BL/1RS translocation line also showed the same level of resistance to stripe rust. Both two alleles loses resistance when deployed in the field or inoculated with mixed physiological races collected from the field. Our findings provide valuable insights for breeders to strategically incorporate disease resistance genes and provides a foundation for further understanding how pathogenic bacteria might evolve to evade recognition via NLR type proteins. SignificanceThe 1BL/1RS translocation between wheat and rye is the most successful case of exogenous gene application in plant genetic improvement and has been used in wheat breeding for over 50 years. Here we report the cloning of a stripe rust resistance gene Yr9 located on rye chromosome 1RS using a triticale population. The Yr9 encodes a coiled-coil nucleotide-binding site leucine-rich repeat (CC-NBS-LRR) protein that show complete resistance to the stripe rust races CYR17 and partial resistance to the stripe rust races CYR32, CYR33, and CYR34, albeit demonstrating susceptibility under field conditions. Our findings position Yr9 as an ideal candidate gene to study the mechanism of inactivation of disease resistance genes as a result of pathogen evolution.

genetics↗

bioRxiv2024

Proteolysis-targeting vaccines (PROTAVs) for robust tumor combination immunotherapy

Protein/peptide subunit vaccines are promising to promote the tumor therapeutic efficacy of immune checkpoint blockade (ICB). However, current protein/peptide vaccines elicit limited antitumor T cell responses, leading to suboptimal therapeutic efficacy. Here, we present proteolysis-targeting vaccines (PROTAVs) that facilitate antigen proteolytic processing and cross-presentation to potentiate T cell responses for robust ICB combination immunotherapy of melanoma. PROTAVs are modular conjugates of protein/peptide antigens, E3 ligase-binding ligands, and linkers. In antigen-presenting cells (APCs), PROTAVs bind to E3 ligases to rapidly ubiquitinate PROTAV antigens, facilitating antigen proteolytic processing by proteasome, and thereby promoting antigen cross-presentation to T cells and potentiating CD8+ T cell responses. We developed a melanoma PROTAV using a tandem peptide of trivalent melanoma-associated antigens. Co-delivered by lipid nanoparticles (LNPs) with bivalent immunostimulant adjuvants, this PROTAV promotes the quantity and quality of melanoma-specific CD8+ T cells in mice. Further, combining PROTAV and ICB ameliorates the immunosuppressive melanoma microenvironment. As a result, PROTAV and ICB combination enhances melanoma complete regression rates and eradicated 100% large BrafV600E melanoma without recurrence in syngeneic mice. PROTAVs hold the potential for robust tumor combination immunotherapy.

bioengineering↗

bioRxiv2024

A sensitive red/far-red photoswitch for controllable gene therapy in mouse models of metabolic diseases

Red light optogenetic systems are in high demand for the precise control of gene expression for gene- and cell-based therapies. Here, we report a red/far-red light-inducible photoswitch (REDLIP) system based on the chimeric photosensory protein FnBphP (Fn-REDLIP) or PnBphP (Pn-REDLIP) and their interaction partner LDB3, which enables efficient dynamic regulation of gene expression with a timescale of seconds without exogenous administration of a chromophore in mammals. We used the REDLIP system to establish the REDLIP-mediated CRISPR-dCas9 (REDLIPcas) system, enabling optogenetic activation of endogenous target genes in mammalian cells and mice. The REDLIP system is small enough to support packaging into adeno-associated viruses (AAVs), facilitating its therapeutic application. Demonstrating its capacity to treat metabolic diseases, we show that an AAV-delivered Fn-REDLIP system achieved optogenetic control of insulin expression to effectively lower blood glucose levels in type 1 diabetes model mice and control an anti-obesity therapeutic protein (thymic stromal lymphopoietin, TSLP) to reduce body weight in obesity model mice. REDLIP is a compact and sensitive optogenetic tool for reversible and non-invasive control that can facilitate basic biological and biomedical research.

synthetic biology↗

bioRxiv2024

Mechanism of NPC1L1 mediated 27-hydroxycholesterol metabolisms in the occurrence and development of osteoporosis

Cholesterol metabolism is closely related to the occurrence and development of osteoporosis, but the exact mechanism remains unclear. Niemann-Pick C1-like 1 (NPC1L1) is one of the key cholesterol transporter proteins, however, there are few reports on the functions of NPC1L1 besides regulating cholesterol transport, let alone bone homeostasis. Our preliminary research indicated that NPC1L1 may play a negative regulatory role in osteogenic differentiation. In this study, using in vitro osteogenic differentiation experiment and mouse osteoporosis model, we showed here that NPC1L1 expression was downregulated during osteogenesis, and NPC1L1 knockdown significantly enhanced osteogenic differentiation ability of osteoblasts and delayed progress of osteoporosis. Mechanistically, through RNA sequencing, NPC1L1 was found regulate cholesterol metabolism rather than transportation. It increased 27-Hydroxycholesterol (27-OHC) level through activating 27-hydroxylase (Cyp27a1), resulting in 27-OHC accumulation in osteoblasts and inhibition of osteogenesis. Moreover, C/EBP was proved mediated NPC1L1 promotes production of 27-OHC by Cyp27a1. These findings reveal that NPC1L1 inhibits osteogenesis and promotes osteoporosis via regulate cholesterol metabolism. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/615783v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@11a62bforg.highwire.dtl.DTLVardef@148fb9aorg.highwire.dtl.DTLVardef@7e486eorg.highwire.dtl.DTLVardef@c53116_HPS_FORMAT_FIGEXP M_FIG NPC1L1 inhibits osteogenic differentiation and promotes the progression of OP through the C/EBP/Cyp27a1/27-OHC axis. C_FIG

molecular biology↗