Programmable DNA Scaffolds Enable Orthogonal Engineering of Cell Membrane-Based Nanovesicles for Therapeutic Development.

Cell membrane-based nanovesicles (CMNVs) play pivotal roles in biomolecular transportation in living organisms and appear as attractive bioinformed nanomaterials for theranostic applications. However, the current surface-engineering technologies are limited in flexibility and orthogonality, making it challenging to simultaneously display multiple different ligands on the CMNV surface in a precisely controlled manner. Here, we developed a DNA scaffold-programmed approach to orthogonally engineer CMNVs with versatile ligands. The designed DNA scaffolds can rapidly anchor onto the CMNV surface, and their unique sequences and hybridized properties enable independent control of the loading of multiple different types of biomolecules on the CMNVs. As a result, the orthogonal engineering of CMNVs with a renal targeted peptide and a therapeutic protein at controlled ratios demonstrated an enhanced renal targeting and repair potential in vivo. This study highlights that a DNA scaffold-programmed platform can provide a potent means for orthogonal and flexible surface engineering of CMNVs for diverse therapeutic purposes.

An Investigation into PVA Fiber Modified with SiO2 for Improving Mechanical Properties of Oil-Well Cements.

In this paper, we conduct a comprehensive investigation into PVA fiber modified with SiO2 to improve the mechanical properties of oil-well cements. Specifically, SiO2 was coated onto the surface of polyvinyl alcohol fiber (PVAF) as its silicon source via a sol-gel process by using tetraethyl orthosilicate (TEOS), while hydrochloric acid and ammonia were respectively used as the catalyst in the sol (hydrolysis) and the gel (condensation) processes. The PVAF microstructure was then characterized with the scanning electron microscope (SEM), while the effects of the modified PVAF on both mechanical and rheological properties of oil-well cements were examined. Due to the fact that SiO2 can be uniformly coated onto the PVAF surface, such modified PVAF can slightly improve the rheology of the cement slurry, while the raw PVAF exhibits poor dispersion at a high dosage. Compared with those of cement stone without PVAF after curing for 28 days at 60 °C, the flexural strength, compressive strength, and elastic modulus of the cement stone incorporated with the modified PVAFs were enhanced by 37.7%, 66.1%, and 50.0%, respectively. The SEM test (EDX) test, XRD test, and thermogravimetric test prove that the SiO2 coating on the PVAF surface can promote the hydration of cement clinker and can react with Ca(OH)2 to generate CSH gel. The SiO2 grafted onto the surface of PVAFs can improve the bond strength at the fiber/cement matrix interface, thus improving the mechanical properties of cement stone.

Effect of Chemical Composition of Metal-Organic Crosslinker on the Properties of Fracturing Fluid in High-Temperature Reservoir.

To investigate the effect of the chemical composition of a metal-organic crosslinker on the performances of fracturing fluid in high-temperature conditions, four zirconium (Zr) crosslinkers and one aluminum-zirconium (Al-Zr) crosslinker with a polyacrylamide were used. The crosslinkers possessed the same Zr concentration, but they differed in component amounts and the order of the addition of the crosslinker components, leading to different chemical compositions in the crosslinkers. The fracturing fluids prepared by different tested crosslinkers were compared in terms of properties of rheological behavior, sand-carrying ability, microstructure, and gel breaking characteristics. The results showed that the fracturing fluids prepared by zirconium lactic acid, ethanediamine, and sorbitol crosslinkers offered the slowest viscosity development and highest final viscosity compared to the zirconium lactic acid crosslinker and the zirconium lactic acid and ethanediamine crosslinker. The zirconium sorbitol, lactic acid, and ethanediamine crosslinker exhibited a faster crosslinking rate and a higher final viscosity than the zirconium lactic acid, ethanediamine, and sorbitol crosslinker; the crosslinker showed crosslinking density and crosslinking reactivity, resulting in more crosslinking sites and a higher strength in the fracturing fluid. The Al-Zr-based crosslinker possessed better properties in temperature and shear resistance, viscoelasticity, shear recovery, and sand-carrying ability than the Zr-based crosslinker due to the synergistic crosslinking effect of aluminum and zirconium ions. The tertiary release gelation mechanism of the Al-Zr-based fracturing fluid achieved a temperature resistance performance in the form of continuous crosslinking, avoiding the excessive crosslinking dehydration and reducing viscosity loss caused by early shear damage. These results indicated that the chemical compositions of metal-organic crosslinkers were important factors in determining the properties of fracturing fluids. Therefore, the appropriate type of crosslinker could save costs without adding the additional components required for high-temperature reservoirs.

Subtype-WGME enables whole-genome-wide multi-omics cancer subtyping.

We present an innovative strategy for integrating whole-genome-wide multi-omics data, which facilitates adaptive amalgamation by leveraging hidden layer features derived from high-dimensional omics data through a multi-task encoder. Empirical evaluations on eight benchmark cancer datasets substantiated that our proposed framework outstripped the comparative algorithms in cancer subtyping, delivering superior subtyping outcomes. Building upon these subtyping results, we establish a robust pipeline for identifying whole-genome-wide biomarkers, unearthing 195 significant biomarkers. Furthermore, we conduct an exhaustive analysis to assess the importance of each omic and non-coding region features at the whole-genome-wide level during cancer subtyping. Our investigation shows that both omics and non-coding region features substantially impact cancer development and survival prognosis. This study emphasizes the potential and practical implications of integrating genome-wide data in cancer research, demonstrating the potency of comprehensive genomic characterization. Additionally, our findings offer insightful perspectives for multi-omics analysis employing deep learning methodologies.

Microalgae-loaded biocompatible alginate microspheres for tissue repair.

Hydrogel-based microcarriers have demonstrated effectiveness in wound repair treatments. The current research focus is creating and optimizing active microcarriers containing natural ingredients capable of conforming to diverse wound shapes and depths. Here, microalgae (MA)-loaded living alginate hydrogel microspheres were successfully fabricated via microfluidic electrospray technology, to enhance the effectiveness of wound healing. The stable living alginate hydrogel microspheres loaded with photoautotrophic MA were formed by cross-linking alginate with calcium ions. The combination of MA-loaded living alginate microspheres ensures high biocompatibility and efficient oxygen release, providing strong support for wound healing. Concurrently, vascular endothelial growth factor (VEGF) has been successfully introduced into the microspheres, further enhancing the comprehensive effectiveness of wound treatment. Covering the rat's wound with these MA-VEGF-loaded alginate microspheres further substantiated their significant role in promoting collagen deposition and vascular generation during the wound closure processes. These results confirm the outstanding value of microalgae-loaded live alginate hydrogel microspheres in wound healing, paving the way for new prospects in future clinical treatment methods.

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis.

Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7Δmye) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7Δmye mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.

Deciphering cuproptosis-related signatures in pediatric allergic asthma using integrated scRNA-seq and bulk RNA-seq analysis.

OBJECTIVE: Allergic asthma (AA) is common in children. Excess copper is observed in AA patients. It is currently unclear whether copper imbalance can cause cuproptosis in pediatric AA. METHODS: The datasets about pediatric AA (GSE40732 and GSE40888) were obtained from Gene Expression Omnibus (GEO) database. The expression of cuproptosis-related genes (CRGs) and immune cell infiltration in pediatric AA samples were analyzed. Single-cell RNA sequencing (scRNA-seq) data (GSE193816) were used to evaluate the expression patterns of CRGs in AA. The identification of differentially expressed genes within clusters was conducted using weighted gene co-expression network analysis. Subsequently, disease progression and cuproptosis-related models were screened using random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and general linear model (GLM) algorithms. RESULTS: Four CRGs were notably increased in pediatric AA samples. CD4+ T cells, macrophages and mast cells exhibited a lower cuproptosis score in AA samples, indicating that these immune cells may be closely associated with cuproptosis in AA development. Co-expression network of CRGs in AA was constructed. AA samples were divided into two cuprotosis clusters. Following construction of four machine-learning models, SVM model exhibited the highest efficacy of prediction in the testing set (AUC = 0.952). SVM model containing five important variables can be used for prediction of AA. CONCLUSION: This work provided a machine learning model containing five important variables, which may have good diagnostic efficiency for pediatric AA.

Cadmium Exposure was Associated with Sex-Specific Thyroid Dysfunction: Consistent Evidence from Two Independent Cross-Sectional Studies Based on Urinary and Blood Cadmium Measurements.

Population-based studies on the association between cadmium (Cd) exposure and thyroid function are limited and have shown conflicting results. Two independent cross-sectional studies using different Cd biomarkers were carried out in six rural areas with different soil Cd levels in China. Thyroid dysfunction was defined based on levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4). Multivariable linear regression, multiple logistic regression, and restrictive cubic splines models were used to estimate the association between Cd and thyroid dysfunction. For both of the two independent studies, higher Cd levels were observed to be associated with lower TSH levels and higher risk of thyroid dysfunction. The negative relationship between urinary Cd and TSH was found in both total participants (ß = - 0.072, p = 0.008) and males (ß = - 0.119, p = 0.020) but not in females; however, the negative relationship between blood Cd and TSH was only found in females (ß = - 0.104, p = 0.024). Higher urinary Cd was associated with higher risk of thyroid dysfunction (OR = 1.77, p = 0.031), while higher blood Cd was associated with higher risk of thyroid dysfunction (OR = 1.95, p = 0.011). Results from the two independent cross-sectional studies consistently suggested that higher Cd levels were associated with sex-specific thyroid dysfunction.

Study on the Inhibition Mechanism of Hydration Expansion of Yunnan Gas Shale using Modified Asphalt.

Drilling fluids play an essential role in shale gas development. It is not possible to scale up the use of water-based drilling fluid in shale gas drilling in Yunnan, China, because conventional inhibitors cannot effectively inhibit the hydration of the illite-rich shale formed. In this study, the inhibition performance of modified asphalt was evaluated using the plugging test, expansion test, shale recovery experiment, and rock compressive strength test. The experimental results show that in a 3% modified asphalt solution, the expansion of shale is reduced by 56.3%, the recovery is as high as 97.8%, water absorption is reduced by 24.3%, and the compression resistance is doubled compared with those in water. Moreover, the modified asphalt can effectively reduce the fluid loss of the drilling fluid. Modified asphalt can form a hydrophobic membrane through a large amount of adsorption on the shale surface, consequently inhibiting shale hydration. Simultaneously, modified asphalt can reduce the entrance of water into the shale through blocking pores, micro-cracks, and cracks and further inhibit the hydration expansion of shale. This demonstrates that modified asphalt will be an ideal choice for drilling shale gas formations in Yunnan through water-based drilling fluids.

Nutrient availability regulates the secretion and function of immune cell-derived extracellular vesicles through metabolic rewiring.

Extracellular vesicle (EV)-based immunotherapeutics have emerged as promising strategy for treating diseases, and thus, a better understanding of the factors that regulate EV secretion and function can provide insights into developing advanced therapies. Here, we report that nutrient availability, even changes in individual nutrient components, may affect EV biogenesis and composition of immune cells [e.g., macrophages (Mφs)]. As a proof of concept, EVs from M1-Mφ under glutamine-depleted conditions (EVGLN-) had higher yields, functional compositions, and immunostimulatory potential than EVs from conventional GLN-present medium (EVGLN+). Mechanistically, the systemic metabolic rewiring (e.g., altered energy and redox metabolism) induced by GLN depletion resulted in up-regulated pathways related to EV biogenesis/cargo sorting (e.g., ESCRT) and immunostimulatory molecule production (e.g., NF-κB and STAT) in Mφs. This study highlights the importance of nutrient status in EV secretion and function, and optimizing metabolic states and/or integrating them with other engineering methods may advance the development of EV therapeutics.

Preparation and Performance Evaluation of Ionic Liquid Copolymer Shale Inhibitor for Drilling Fluid Gel System.

An inhibitor that can effectively inhibit shale hydration is necessary for the safe and efficient development of shale gas. In this study, a novel ionic liquid copolymer shale inhibitor (PIL) was prepared by polymerizing the ionic liquid monomers 1-vinyl-3-aminopropylimidazolium bromide, acrylamide, and methacryloyloxyethyl trimethyl ammonium chloride. The chemical structure was characterized using fourier transform infrared spectroscopy (FT-IR) and hydrogen-nuclear magnetic resonance (H-NMR), and the inhibition performance was evaluated using the inhibition of slurrying test, bentonite flocculation test, linear expansion test, and rolling recovery test. The experimental results showed that bentonite had a linear expansion of 27.9% in 1 wt% PIL solution, 18% lower than that in the polyether amine inhibitor. The recovery rate of shale in 1 wt% PIL was 87.4%. The ionic liquid copolymer could work synergistically with the filtrate reducer, reducing filtration loss to 7.2 mL with the addition of 1%. Mechanism analysis showed that PIL adsorbed negatively charged clay particles through cationic groups, which reduced the electrostatic repulsion between particles. Thus, the stability of the bentonite gel systems was destroyed, and the hydration dispersion and expansion of bentonite were inhibited. PIL formed a hydrophobic film on the surface of clay and prevented water from entering into the interlayer of clay. In addition, PIL lowered the surface tension of water, which prevented the water from intruding into the rock under the action of capillary force. These are also the reasons for the superior suppression performance of PIL.

The mitochondria‒paraspeckle axis regulates the survival of transplanted stem cells under oxidative stress conditions.

Rationale: Stem cell-based therapies have emerged as promising tools for tissue engineering and regenerative medicine, but their therapeutic efficacy is largely limited by the oxidative stress-induced loss of transplanted cells at injured tissue sites. To address this issue, we aimed to explore the underlying mechanism and protective strategy of ROS-induced MSC loss. Methods: Changes in TFAM (mitochondrial transcription factor A) signaling, mitochondrial function, DNA damage, apoptosis and senescence in MSCs under oxidative stress conditions were assessed using real-time PCR, western blotting and RNA sequencing, etc. The impact of TFAM or lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) knockdown or overexpression on mitochondrial function, DNA damage repair, apoptosis and senescence in MSCs was also analyzed. The effect of mitochondrion-targeted antioxidant (Mito-TEMPO) on the survival of transplanted MSCs was evaluated in a mouse model of renal ischemia/reperfusion (I/R) injury. Results: Mitochondrial ROS (mtROS) bursts caused defects in TFAM signaling and overall mitochondrial function, which further impaired NEAT1 expression and its mediated paraspeckle formation and DNA repair pathways in MSCs, thereby jointly promoting MSC senescence and death under oxidative stress. In contrast, targeted inhibition of the mtROS bursts is a sufficient strategy for attenuating early transplanted MSC loss at injured tissue sites, and coadministration of Mito-TEMPO improved the local retention of transplanted MSCs and reduced oxidative injury in ischemic kidneys. Conclusions: This study identified the critical role of the mitochondria‒paraspeckle axis in regulating cell survival and may provide insights into developing advanced stem cell therapies for tissue engineering and regenerative medicine.

Emerging role of extracellular vesicles in veterinary practice: novel opportunities and potential challenges.

Extracellular vesicles are nanoscale vesicles that transport signals between cells, mediating both physiological and pathological processes. EVs facilitate conserved intercellular communication. By transferring bioactive molecules between cells, EVs coordinate systemic responses, regulating homeostasis, immunity, and disease progression. Given their biological importance and involvement in pathogenesis, EVs show promise as biomarkers for veterinary diagnosis, and candidates for vaccine production, and treatment agents. Additionally, different treatment or engineering methods could be used to boost the capability of extracellular vesicles. Despite the emerging veterinary interest, EV research has been predominantly human-based. Critical knowledge gaps remain regarding isolation protocols, cargo loading mechanisms, in vivo biodistribution, and species-specific functions. Standardized methods for veterinary EV characterization and validation are lacking. Regulatory uncertainties impede veterinary clinical translation. Advances in fundamental EV biology and technology are needed to propel the veterinary field forward. This review introduces EVs from a veterinary perspective by introducing the latest studies, highlighting their potential while analyzing challenges to motivate expanded veterinary investigation and translation.

Construction and optimization of representative actual driving cycles based on the improved autoencoder.

In this study, much work has been performed to accurately and efficiently develop representative actual driving cycles. Electric vehicle road tests were conducted and the associated data were gathered based on the manual driving method, and the Changsha Driving Cycle Construction (CS-DCC) method was proposed to achieve systematical construction of a representative driving cycle from the original data. The results show that the refined data exhibit greater stability and a smoother pattern in contrast to the original data after noise reduction by five-scale wavelet analysis. The Gaussian Kernel Principal Component Analysis (KPCA) algorithm is chosen to reduce the dimensionality of the characteristic matrix, and the number of principal components is selected as 5 with a cumulative contribution rate of 85.99%. The average error of the characteristic parameters between the optimized drive cycle and the total data is further reduced from 13.6 to 6.1%, with a reduction ratio of 55.1%. Meanwhile, the constructed driving cycle has prominent local characteristics compared with four standard driving cycles, demonstrating the necessity of constructing an actual driving cycle that reflects localized driving patterns. The findings present a powerful application of artificial intelligence in advancing engineering technologies.

The application prospect and challenge of the alternative methanol fuel in the internal combustion engine.

In the context of global carbon neutrality, the internal combustion engines aim to further reduce the carbon emission and improve the fuel economy for the transportation sector. Methanol is treated as a renewable, reliability, and applicability energy, which also shows some superior physicochemical properties compared to the traditional fossil fuels. However, some challenges such as cold start issue, low fuel economy, high unregulated emissions need to address before the methanol widely applies in the engines. This article comprehensively reviews the physicochemical properties and production processes of the methanol, the cold start issue of the methanol engine, and emission and combustion characteristics of the methanol engine for evaluating its potential effect of emission reduction and energy saving in the transportation sector. In addition, different optimization strategies and advanced technologies are proposed and comprehensively discussed in this paper for addressing the issues of the cold start, combustion and emissions of the methanol engines in the real application. Finally, the conclusions and prospects of the methanol engine are presented for promoting its application in the transportation sector and further reducing the carbon emission in the near future, thereby achieving the carbon peak and carbon neutrality in the China.

Injectable Multifunctional Composite Hydrogel as a Combination Therapy for Preventing Postsurgical Adhesion.

Postsurgical adhesion (PA) is a common and serious postoperative complication that affects millions of patients worldwide. However, current commercial barrier materials are insufficient to inhibit diverse pathological factors during PA formation, and thus, highly bioactive materials are needed. Here, this work designs an injectable multifunctional composite hydrogel that can serve as a combination therapy for preventing PA. In brief, this work reveals that multiple pathological events, such as chronic inflammatory and fibrotic processes, contribute to adhesion formation in vivo, and such processes can not be attenuated by barrier material (e.g., hydrogel) alone treatments. To solve this limitation, this work designs a composite hydrogel made of the cationic self-assembling peptide KLD2R and TGF-ß receptor inhibitor (TGF-ßRi)-loaded mesenchymal stem cell-derived nanovesicles (MSC-NVs). The resulting composite hydrogel displays multiple functions, including physical separation of the injured tissue areas, antibacterial effects, and local delivery and sustained release of anti-inflammatory MSC-NVs and antifibrotic TGF-ßRi. As a result, this composite hydrogel effectively inhibited local inflammation, fibrosis and adhesion formation in vivo. Moreover, the hydrogel also exhibits good biocompatibility and biodegradability in vivo. Together, the results highlight that this "all-in-one" composite hydrogel strategy may provide insights into designing advanced therapies for many types of tissue injury.

PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway.

Thyroid cancer is the most common endocrine malignancy worldwide. Although significant progress has been made in understanding the genetic and molecular alterations that drive thyroid cancer, the mechanisms underlying thyroid tumor progression remain unclear. In this study, we explored the involvement of Plastin-3 (PLS3) in the progression of papillary thyroid cancer and elucidated the underlying molecular mechanisms. We first analyzed clinical samples from papillary thyroid cancer patients and found that PLS3 expression was significantly upregulated in tumor tissues compared to adjacent normal tissues. Moreover, high PLS3 expression was associated with advanced tumor stage and poor prognosis. Further in vitro and in vivo experiments showed that PLS3 could promote the proliferation, migration, and invasive behavior of papillary thyroid cancer cells, while PLS3 knockdown suppressed these processes. Mechanistically, we found that PLS3 promoted papillary thyroid cancer progression by activating the Notch signaling pathway. Specifically, PLS3 upregulated the expression of Notch receptors (Notch1) and downstream target gene (Hes1) in papillary thyroid cancer cells. In summary, our findings collectively indicate that PLS3 plays a pivotal role in driving the progression of papillary thyroid cancer and holds promise as a viable therapeutic target for the treatment of this disease.

Identification and characteristic analysis of semi-natural habitats in China's economically developed areas: New insights to inform cultivated land system ecological conservation.

Identifying and characterizing semi-natural habitats (SNHs) are important to the ecological conservation of cultivated land systems and implementing China's ecological civilization strategy. This study revealed the concept and characteristics of SNHs in Chinese cultivated land systems regarding human activities, resource types, and spatial landscape patterns. The resource quantity, landscape quality, and spatial distribution of SNHs in Southern Jiangsu's cultivated land system were analyzed by constructing the identification model of "land use/land cover type-cultivated land use intensity-spatial landscape pattern". The results showed that the area of SNHs in Southern Jiangsu's cultivated land system was 25.35%, significantly influenced by cultivated land intensification and expansion. The higher the cultivated land use intensity, the lower the quantity of SNHs, and the proportion of SNHs in the intensive-use pattern was only 2.97%. 68.18% of the SNHs in Southern Jiangsu were water, and habitats for important species, such as woodland, grassland, wetlands, and bare land, were scarce. A small patch area, high landscape fragmentation, poor landscape richness and diversity, and low connectivity accompanied increased cultivated land use intensity. From the extensive to intensive utilization, the spatial spread of SNHs from low-value aggregation to high-value scatter areas, with hotspot areas of cultivated land use intensity and SNHs existing only in a small part of Nanjing and Changzhou. This study provides a scientific reference for the rehabilitation and restoration of SNHs in the context of the ecological transformation of land use. It promotes the sustainable intensification of cultivated land systems. It also provides new ideas for linking ecological and urban spaces to form a stable and systematic national ecological safety network.

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Integration of multiple terminology bases: a multi-view alignment method using the hierarchical structure.

MOTIVATION: In the medical field, multiple terminology bases coexist across different institutions and contexts, often resulting in the presence of redundant terms. The identification of overlapping terms among these bases holds significant potential for harmonizing multiple standards and establishing unified framework, which enhances user access to comprehensive and well-structured medical information. However, the majority of terminology bases exhibit differences not only in semantic aspects but also in the hierarchy of their classification systems. The conventional approaches that rely on neighborhood-based methods such as GCN may introduce errors due to the presence of different superordinate and subordinate terms. Therefore, it is imperative to explore novel methods to tackle this structural challenge. RESULTS: To address this heterogeneity issue, this paper proposes a multi-view alignment approach that incorporates the hierarchical structure of terminologies. We utilize BERT-based model to capture the recursive relationships among different levels of hierarchy and consider the interaction information of name, neighbors, and hierarchy between different terminologies. We test our method on mapping files of three medical open terminologies, and the experimental results demonstrate that our method outperforms baseline methods in terms of Hits@1 and Hits@10 metrics by 2%. AVAILABILITY AND IMPLEMENTATION: The source code will be available at https://github.com/Ulricab/Bert-Path upon publication.