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On-DNA carboxylic acids are important synthetic intermediates in the synthesis of DNA-encoded library (DEL) structures. Herein, we report an oxoammonium salt-mediated, room temperature, solution-phase oxidation of DNA-linked primary alcohols into carboxylic acids. This method exhibits a wide substrate scope, encompassing aliphatic, benzylic, and heterobenzylic alcohols, and is compatible with DEL encoding strategies. This advancement facilitates a DEL strategy to utilize unprotected alcohols as inert, masked carboxylic acids and enables access to noncommercial bifunctional carboxyl intermediates to enhance the accessible chemical diversity within DELs.
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Álcoois , DNA , Oxirredução , Estrutura Molecular , Álcoois/química , DNA/química , Ácidos Carboxílicos/química , Sais/químicaRESUMO
DNA-encoded libraries (DELs) are a key technology for identifying small-molecule hits in both the pharmaceutical industry and academia, but their chemical diversity is largely limited to water-compatible reactions to aid in the solubility and integrity of encoding DNA tags. To broaden the DEL chemical space, we present a workflow utilizing DNA-cationic surfactant complexation that enables dissolution and reactions on-DNA in anhydrous organic solvents. We demonstrate its utility by developing DEL-compatible photoredox decarboxylative C(sp2)-C(sp3) coupling under water-free conditions. The workflow is optimized for the 96-well format necessary for large-scale DEL productions, and it enables screening and optimization of DEL-compatible reactions in organic solvents.
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DNA , Interações Hidrofóbicas e Hidrofílicas , Tensoativos , Tensoativos/química , DNA/química , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química , Solventes/químicaRESUMO
A novel interlaminar elastic screw spacer technique was designed to maintain lumbar mobility in treating lumbar degenerative diseases. A validated finite element model of L4/5 was used to establish an ISES-1/2 model and an ISES-1/3 model based on different insertion points, a unilateral fixation model and a bilateral fixed model based on different fixation methods, and a Coflex-F model based on different implants. The elastic rods were used to fix screws. Under the same mechanical conditions, we compared the biomechanical characteristics to investigate the optimal entry point for ISES technology, demonstrate the effectiveness of unilateral fixation, and validate the feasibility of the ISES technique. Compared to ISES-1/3, the ISES-1/2 model had lower intradiscal pressure, facet cartilage stress, and posterior structural stress. Compared to the ISES-BF model, the ISES-UF model had lower intervertebral pressure, larger mobility, and smaller stress on the posterior structures. The ISES model had a similar intervertebral pressure and limitation of extension as the Coflex-F model. The ISES model retained greater mobility and reduced the stress on the facet cartilage and posterior structure compared with the Coflex-F model. Our study suggests that the ISES technique is a promising treatment of lumbar degenerative diseases, especially those with osteoporosis.
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Natural killer group 2D (NKG2D) is a homodimeric activating immunoreceptor whose function is to detect and eliminate compromised cells upon binding to the NKG2D ligands (NKG2DL) major histocompatibility complex (MHC) molecules class I-related chain A (MICA) and B (MICB) and UL16 binding proteins (ULBP1-6). While typically present at low levels in healthy cells and tissue, NKG2DL expression can be induced by viral infection, cellular stress or transformation. Aberrant activity along the NKG2D/NKG2DL axis has been associated with autoimmune diseases due to the increased expression of NKG2D ligands in human disease tissue, making NKG2D inhibitors an attractive target for immunomodulation. Herein we describe the discovery and optimization of small molecule PPI (protein-protein interaction) inhibitors of NKG2D/NKG2DL. Rapid SAR was guided by structure-based drug design and accomplished by iterative singleton and parallel medicinal chemistry synthesis. These efforts resulted in the identification of several potent analogs (14, 21, 30, 45) with functional activity and improved LLE.
Assuntos
Proteínas de Transporte , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Humanos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Proteínas de Transporte/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Ligação Proteica , Células Matadoras Naturais/metabolismo , LigantesRESUMO
BACKGROUND: Spinal osteoporosis is a prevalent health condition characterized by the thinning of bone tissues in the spine, increasing the risk of fractures. Given its high incidence, especially among older populations, it is critical to have accurate and effective predictive models for fracture risk. Traditionally, clinicians have relied on a combination of factors such as demographics, clinical attributes, and radiological characteristics to predict fracture risk in these patients. However, these models often lack precision and fail to include all potential risk factors. There is a need for a more comprehensive, statistically robust prediction model that can better identify high-risk individuals for early intervention. AIM: To construct and validate a model for forecasting fracture risk in patients with spinal osteoporosis. METHODS: The medical records of 80 patients with spinal osteoporosis who were diagnosed and treated between 2019 and 2022 were retrospectively examined. The patients were selected according to strict criteria and categorized into two groups: Those with fractures (n = 40) and those without fractures (n = 40). Demographics, clinical attributes, biochemical indicators, bone mineral density (BMD), and radiological characteristics were collected and compared. A logistic regression analysis was employed to create an osteoporotic fracture risk-prediction model. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model's performance. RESULTS: Factors significantly associated with fracture risk included age, sex, body mass index (BMI), smoking history, BMD, vertebral trabecular alterations, and prior vertebral fractures. The final risk-prediction model was developed using the formula: (logit [P] = -3.75 + 0.04 × age - 1.15 × sex + 0.02 × BMI + 0.83 × smoking history + 2.25 × BMD - 1.12 × vertebral trabecular alterations + 1.83 × previous vertebral fractures). The AUROC of the model was 0.93 (95%CI: 0.88-0.96, P < 0.001), indicating strong discriminatory capabilities. CONCLUSION: The fracture risk-prediction model, utilizing accessible clinical, biochemical, and radiological information, offered a precise tool for the evaluation of fracture risk in patients with spinal osteoporosis. The model has potential in the identification of high-risk individuals for early intervention and the guidance of appropriate preventive actions to reduce the impact of osteoporosis-related fractures.
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Although bone mesenchymal stem cell (BMSC) transplantation has been applied to the treatment of spinal cord injury (SCI), the effect is unsatisfactory due to the specific microenvironment (inflammation and oxidative stress) in the SCI area, which leads to the low survival rate of transplanted cells. Thus, additional strategies are required to improve the efficacy of transplanted cells in the treatment of SCI. Hydrogen possesses antioxidant and anti-inflammatory properties. However, whether hydrogen can enhance the effect of BMSC transplantation in the treatment of SCI has not yet been reported. This study was aimed at investigating whether hydrogen promotes the therapeutic effect of BMSC transplantation in the treatment of SCI in rats. In vitro, BMSCs were cultured in a normal medium and a hydrogen-rich medium to study the effect of hydrogen on the proliferation and migration of BMSCs. BMSCs were treated with a serum-deprived medium (SDM), and the effects of hydrogen on the apoptosis of BMSCs were studied. In vivo, BMSCs were injected into the rat model of SCI. Hydrogen-rich saline (5 ml/kg) and saline (5 ml/kg) were given once a day via intraperitoneal injection. Neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) and CatWalk gait analyses. Histopathological analysis, oxidative stress, inflammatory factors (TNF-α, IL-1ß, and IL-6), and transplanted cell viability were detected at 3 and 28 days after SCI. Hydrogen can significantly enhance BMSC proliferation and migration and tolerance to SDM. Hydrogen and BMSC codelivery can significantly enhance neurological function recovery by improving the transplant cell survival rate and migration. Hydrogen can enhance the migration and proliferation capacity of BMSCs to repair SCI by reducing the inflammatory response and oxidative stress in the injured area. Hydrogen and BMSC codelivery is an effective method to improve BMSC transplantation in the treatment of SCI.
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OBJECTIVE: Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. METHOD: ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. RESULT: The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. CONCLUSION: Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.
Assuntos
Células-Tronco Mesenquimais , Núcleo Pulposo , Diferenciação Celular , Proliferação de Células/genética , Estresse do Retículo Endoplasmático , Animais , Hipóxia CelularRESUMO
NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ+, and CD8+ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.
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Células Matadoras Naturais , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Ligantes , Linfócitos T CD8-Positivos , Ligação ProteicaRESUMO
Artificial Intelligence is revolutionizing many aspects of the pharmaceutical industry. Deep learning models are now routinely applied to guide drug discovery projects leading to faster and improved findings, but there are still many tasks with enormous unrealized potential. One such task is the reaction yield prediction. Every year more than one fifth of all synthesis attempts result in product yields which are either zero or too low. This equates to chemical and human resources being spent on activities which ultimately do not progress the programs, leading to a triple loss when accounting for the cost of opportunity in time wasted. In this work we pre-train a BERT model on more than 16 million reactions from 4 different data sources, and fine tune it to achieve an uncertainty calibrated global yield prediction model. This model is an improvement upon state of the art not just from the increase in pre-train data but also by introducing a new embedding layer which solves a few limitations of SMILES and enables integration of additional information such as equivalents and molecule role into the reaction encoding, the model is called BERT Enriched Embedding (BEE). The model is benchmarked on an open-source dataset against a state-of-the-art synthesis focused BERT showing a near 20-point improvement in r2 score. The model is fine-tuned and tested on an internal company data benchmark, and a prospective study shows that the application of the model can reduce the total number of negative reactions (yield under 5%) ran in Janssen by at least 34%. Lastly, we corroborate the previous results through experimental validation, by directly deploying the model in an on-going drug discovery project and showing that it can also be used successfully as a reagent recommender due to its fast inference speed and reliable confidence estimation, a critical feature for industry application.
RESUMO
DNA-encoded library (DEL) screens have become a key technology to find small molecule binders to biological targets for drug discovery applications. The development of new DNA-compatible chemistries to expand the accessible DEL chemical space is imperative to enhance screen success across broad target classes and modalities. Additionally, reactions that use commonly available building blocks as well as those that enable the fsp3 of library members to be increased would have high impact for accessing diverse drug-like structures. Herein, we report a DNA-compatible Giese-type addition of nonstabilized C-centered radicals generated by the deoxygenation of preactivated alcohols into on-DNA olefins. Although alcohols have been historically underused as a building block class within DEL synthesis, their activation to a xanthate enables Csp3-Csp3 coupling to furnish sp3-rich products. This reaction is compatible with multiple classes of functional groups, does not damage the DNA tag, and is suitable for use in DEL productions.
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Álcoois , Alcenos , Alcenos/química , Alquilação , DNA/química , Oxirredução , Indicadores e ReagentesRESUMO
PURPOSE: The short rod technique (SRT) is a novel method for lumbar pedicle screw placement to reduce surgical trauma and avoid damage to the facet joint and articular surface. The core concept is to change the entry point and angle of the screw on the vertebrae at both ends in the sagittal plane to shorten the length of the longitudinal rods. The purpose of this study is to determine the sagittal screw angle (SSA) and its safe Maximum (MAX) value on each lumbar vertebra for the SRT and to observe the shortening effect on the longitudinal rods. METHODS: A total of 152 healthy adults were investigated by measuring the lumbar spine lateral view images. The SSA and MAX-SSA were measured with SRT as reference to the conventional placement technique method. The distance between the entry points of the proximal and distal vertebrae was measured to compare the changes in the length of the longitudinal rods using the two screw placement techniques. RESULTS: + SSA increased from L1 to L4, and -SSA increased from L2 to L5, in which the -SSA of L2, L3, and L4 were significantly greater than those of + SSA (P < 0.05). + MAX-SSA at L1-L4 was 23.26 ± 3.54°, 23.68 ± 3.37°, 24.12 ± 3.29°, and 24.26 ± 3.42°, respectively. -MAX-SSA at L2-L5 was 36.25 ± 3.26°, 38.26 ± 3.73°, 38.62 ± 3.63° and 37.33 ± 3.31°, respectively. Theoretical reductions by calculation for the 2-segment lumbar pedicles were: L1-2: 9 mm, L2-3: 9.29 mm, L3-4: 6.23 mm, and L4-5: 7.08 mm; And the 3-segment lumbar pedicles were: L1-3: 16.97 mm, L2-4: 16.73 mm, L3-5, and 18.24 mm, respectively. CONCLUSIONS: The application of the SRT to lumbar pedicles is a safe screw placement method that can significantly shorten the length of the used longitudinal rods.
Assuntos
Parafusos Pediculares , Fusão Vertebral , Adulto , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Tomografia Computadorizada por Raios XRESUMO
Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique. Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4-L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement. Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending. Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.
RESUMO
Developing new DNA-compatible reactions is key to expanding the accessible chemical space of DNA-encoded library (DEL) technology. Here we disclose the first report of a DNA-compatible carbonylative Suzuki coupling of DNA-conjugated (hetero)aryl iodides with (hetero)aryl boronic acids to access di(hetero)aryl ketones, a valuable structural motif present within several approved or clinically advanced small molecules. The reported DNA-compatible, Pd(OAc)2-mediated system is mild, uses a robust protocol, has a wide substrate scope for both coupling partners, is suitable for large-scale DEL productions, and provides a source of previously unexplored chemical matter for DEL screens.
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Ácidos Borônicos , Paládio , Ácidos Borônicos/química , Catálise , DNA/química , Cetonas , Paládio/químicaRESUMO
A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) has been developed using a direct-to-biology (D2B) approach with a focus on linker effects. A large number of linker analogs-with varying length, polarity, and rigidity-were rapidly prepared and characterized in four cell-based assays by streamlining time-consuming steps in synthesis and purification. The expansive dataset informs on linker structure-activity relationships (SAR) for in-cell E3 ligase target engagement, degradation, permeability, and cell toxicity. Unexpected aspects of linker SAR was discovered, consistent with literature reports on "linkerology", and the method dramatically speeds up empirical optimization. Physicochemical property trends emerged, and the platform has the potential to rapidly expand training sets for more complex prediction models. In-depth validation studies were carried out and confirm the D2B platform is a valuable tool to accelerate PROTAC design-make-test cycles.
RESUMO
DNA-encoded chemical library (DEL) screens are a powerful hit generation tool in drug discovery, but the diversity of DEL chemical matter is dependent on developing robust reaction conditions that may be used on hundreds to millions of substrate combinations and that are compatible with the platform. Here, we disclose the first report of a general, aqueous, DNA-compatible C-N coupling condition that can now couple aliphatic amines, in addition to (hetero)aromatic amines, with a variety of (hetero)aryl iodides, bromides, and chlorides. The reported BippyPhos-Pd(OAc)2 catalyst system has a wide substrate scope for both coupling partners, is operationally feasible for large scale DEL productions, uses common DEL building block solution stocks, and enables an expansion of DEL-accessible, drug-like chemical space.
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Aminas , Paládio , Brometos , Catálise , DNARESUMO
BACKGROUND: Scoliosis is a type of spinal deformity, which is harmful to a person's health. In severe cases, it can trigger paralysis or death. The measurement of Cobb angle plays an essential role in assessing the severity of scoliosis. PURPOSE: The aim of this paper is to propose an automatic system for landmark detection and Cobb angle estimation, which can effectively help clinicians diagnose and treat scoliosis. METHODS: A novel hybrid framework was proposed to measure Cobb angle precisely for clinical diagnosis, which was referred as W-Transformer due to its w-shaped architecture. First, a convolutional neural network of cascade residual blocks as our backbone was designed. Then a transformer was fused to learn the dependency information between spine and landmarks. In addition, a reinforcement branch was designed to improve the overlap of landmarks, and an improved prediction module was proposed to fine-tune the final coordinates of landmarks in Cobb angles estimation. Besides, the public Accurate Automated Spinal Curvature Estimation (AASCE) MICCAI 2019 challenge was served as data set. It supplies 609 manually labeled spine anterior-posterior (AP) X-ray images, each of which contains a total of 68 landmark labels and three Cobb Angles tags. RESULTS: From the perspective of the AASCE MICCAI 2019 challenge, we achieved a lower symmetric mean absolute percentage error (SMAPE) of 8.26% for all Cobb angles and the lowest averaged detection error of 50.89 in terms of landmark detection, compared with many state-of-the-art methods. We also provided the SMAPEs for the Cobb angles of the proximal-thoracic (PT), the main-thoracic (MT), and the thoracic-lumbar (TL) area, which are 5.27%, 14.59%, and 20.97% respectively, however, these data were not covered in most previous studies. Statistical analysis demonstrates that our model has obtained a high level of Pearson correlation coefficient of 0.9398 ( p < 0.001 $p<0.001$ ), which shows excellent reliability of our model. Our model can yield 0.9489 ( p < 0.001 $p<0.001$ ), 0.8817 ( p < 0.001 $p<0.001$ ), and 0.9149 ( p < 0.001 $p<0.001$ ) for PT, MT, and TL, respectively. The overall variability of Cobb angle measurement is less than 4 ∘ $^\circ$ , implying clinical value. And the mean absolute deviation (standard deviation) for three regions is 3.64 ∘ $^\circ$ (4.13 ∘ $^\circ$ ), 3.84 ∘ $^\circ$ (4.66 ∘ $^\circ$ ), and 3.80 ∘ $^\circ$ (4.19 ∘ $^\circ$ ). The results of Student paired t $t$ -test indicate that no statistically significant differences are observed between manual measurement and our automatic approach ( p $p$ -value is always > $>$ 0.05). Regarding the diagnosis of scoliosis (Cobb angle > $>$ 10 ∘ $^\circ$ ), the proposed method achieves a high sensitivity of 0.9577 and a specificity of 0.8475 for all spinal regions. CONCLUSIONS: This study offers a brand-new automatic approach that is potentially of great benefit of the complex task of landmark detection and Cobb angle evaluation, which can provide helpful navigation information about the early diagnosis of scoliosis.
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Escoliose , Humanos , Redes Neurais de Computação , Radiografia , Reprodutibilidade dos Testes , Escoliose/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagemRESUMO
Implicit authentication mechanisms are expected to prevent security and privacy threats for mobile devices using behavior modeling. However, recently, researchers have demonstrated that the performance of behavioral biometrics is insufficiently accurate. Furthermore, the unique characteristics of mobile devices, such as limited storage and energy, make it subject to constrained capacity of data collection and processing. In this paper, we propose an implicit authentication architecture based on edge computing, coined Edge computing-based mobile Device Implicit Authentication (EDIA), which exploits edge-based gait biometric identification using a deep learning model to authenticate users. The gait data captured by a device's accelerometer and gyroscope sensors is utilized as the input of our optimized model, which consists of a CNN and a LSTM in tandem. Especially, we deal with extracting the features of gait signal in a two-dimensional domain through converting the original signal into an image, and then input it into our network. In addition, to reduce computation overhead of mobile devices, the model for implicit authentication is generated on the cloud server, and the user authentication process also takes place on the edge devices. We evaluate the performance of EDIA under different scenarios where the results show that i) we achieve a true positive rate of 97.77% and also a 2% false positive rate; and ii) EDIA still reaches high accuracy with limited dataset size.
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Identificação Biométrica , Aprendizado Profundo , Computadores de Mão , Marcha , PrivacidadeRESUMO
We report two cholesterol-modified oligonucleotides for use as internal controls for on-DNA reactions during the pooled stages of a DNA-encoded chemical library (DECL) synthesis. As these cholesterol-tagged oligonucleotides are chromatographically separable from normal DECL intermediates, they can be directly monitored by mass spectrometry to track reaction progression within a complex pool of DNA. We observed similar product conversions for reactions on substrates linked to a standard DECL DNA headpiece, to the cholesterol-modified oligonucleotides, and to the cholesterol-modified oligonucleotides while in the presence of pooled DECL synthetic intermediates-validating their use as a representative control. We also highlight an example from a DECL production in which the use of the cholesterol-modified oligonucleotides provided quality control information that guided synthetic decisions. We conclude that the use of cholesterol-modified oligonucleotides as a regular control will significantly improve the quality of DECL productions.
Assuntos
Colesterol/química , Oligonucleotídeos/química , Cromatografia Líquida/métodos , Técnicas de Química Combinatória , Espectrometria de Massas/métodosRESUMO
Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment.