A machine learning approach to predicting dry eye-related signs, symptoms and diagnoses from meibography images.

Purpose: To use artificial intelligence to identify relationships between morphological characteristics of the Meibomian glands (MGs), subject factors, clinical outcomes, and subjective symptoms of dry eye. Methods: A total of 562 infrared meibography images were collected from 363 subjects (170 contact lens wearers, 193 non-wearers). Subjects were 67.2 % female and were 54.8 % Caucasian. Subjects were 18 years of age or older. A deep learning model was trained to take meibography as input, segment the individual MG in the images, and learn their detailed morphological features. Morphological characteristics were then combined with clinical and symptom data in prediction models of MG function, tear film stability, ocular surface health, and subjective discomfort and dryness. The models were analyzed to identify the most heavily weighted features used by the algorithm for predictions. Results: MG morphological characteristics were heavily weighted predictors for eyelid notching and vascularization, MG expressate quality and quantity, tear film stability, corneal staining, and comfort and dryness ratings, with accuracies ranging from 65 % to 99 %. Number of visible MG, along with other clinical parameters, were able to predict MG dysfunction, aqueous deficiency and blepharitis with accuracies ranging from 74 % to 85 %. Conclusions: Machine learning-derived MG morphological characteristics were found to be important in predicting multiple signs, symptoms, and diagnoses related to MG dysfunction and dry eye. This deep learning method illustrates the rich clinical information that detailed morphological analysis of the MGs can provide, and shows promise in advancing our understanding of the role of MG morphology in ocular surface health.

Multitasking Integrated Metasurface for Electromagnetic Wave Modulation with Reflection, Transmission, and Absorption.

Accommodating multiple tasks within a tiny metasurface unit cell without them interfering with each other is a significant challenge. In this paper, an electromagnetic (EM) wave modulation metasurface capable of reflection, transmission, and absorption is proposed. This multitasking capability is achieved through a cleverly designed multi-layer structure comprising an EM Wave Shield Layer (ESL), a Polarization Modulation Layer (PML), and a Bottom Plate Layer (BPL). The functionality can be arbitrarily switched by embedding control materials within the structure. Depending on external excitation conditions, the proposed metasurface can realize reflection-type co-planar polarization to cross-polarization conversion, transmission-type electromagnetically induced transparency-like (EIT-like) modes, and broadband absorption. Notably, all tasks operate approximately within the same operating frequency band, and their performance can be regulated by the intensity of external excitation. Additionally, the operating principle of the metasurface is analyzed through impedance matching, an oscillator coupling model, and surface current distribution. This metasurface design offers a strategy for integrated devices with multiple functionalities.

Surface PD-1 expression in T cells is suppressed by HNRNPK through an exonic splicing silencer on exon 3.

OBJECTIVE: Immunotherapy targeting programmed cell death 1 (PDCD1 or PD-1) and its ligands has shown remarkable promise and the regulation mechanism of PD-1 expression has received arising attention in recent years. PDCD1 exon 3 encodes the transmembrane domain and the deletion of exon 3 produces a soluble protein isoform of PD-1 (sPD-1), which can enhance immune response by competing with full-length PD-1 protein (flPD-1 or surface PD-1) on T cell surface. However, the mechanism of PDCD1 exon 3 skipping is unclear. METHODS: The online SpliceAid program and minigene expression system were used to analyze potential splicing factors involved in the splicing event of PDCD1 exon 3. The potential binding motifs of heterogeneous nuclear ribonucleoprotein K (HNRNPK) on exon 3 predicted by SpliceAid were mutated by site-directed mutagenesis technology, which were further verified by pulldown assay. Antisense oligonucleotides (ASOs) targeting the exonic splicing silencer (ESS) on PDCD1 exon 3 were synthesized and screened to suppress the skipping of exon 3. The alternative splicing of PDCD1 exon 3 was analyzed by semiquantitative reverse transcription PCR. Western blot and flow cytometry were performed to detect the surface PD-1 expression in T cells. RESULTS: HNRNPK was screened as a key splicing factor that promoted PDCD1 exon 3 skipping, causing a decrease in flPD-1 expression on T cell membrane and an increase in sPD-1 expression. Mechanically, a key ESS has been identified on exon 3 and can be bound by HNRNPK protein to promote exon 3 skipping. Blocking the interaction between ESS and HNRNPK with an ASO significantly reduced exon 3 skipping. Importantly, HNRNPK can promote exon 3 skipping of mouse Pdcd1 gene as well. CONCLUSIONS: Our study revealed a novel evolutionarily conserved regulatory mechanism of PD-1 expression. The splicing factor HNRNPK markedly promoted PDCD1 exon 3 skipping by binding to the ESS on PDCD1 exon 3, resulting in decreased expression of flPD-1 and increased expression of sPD-1 in T cells.

Design, synthesis and antiproliferative evaluation of tetrahydro-ß-carboline histone deacetylase inhibitors bearing an aliphatic chain linker.

The use of histone deacetylase inhibitors (HDACis) is an effective approach for cancer treatment. In this work, a series of hydroxamic acid-based HDACis with a tetrahydro-ß-carboline core and aliphatic linker have been designed and synthesized. The optimal compound 13d potently inhibited HDAC1 and showed good antiproliferative activity against different tumor cell lines in vitro. Molecular docking of 13d was conducted to rationalize the high binding affinity for HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for solid tumors.

Multipath-controlled bidirectional metasurface for multitasking polarization regulation and absorption.

In the design of metasurfaces, integrating multiple tasks into a single small unit cell and achieving regulation through various paths pose a serious challenge. In this paper, a multipath-controlled bidirectional metasurface (MCBM) is designed to achieve polarization regulation, perfect absorption and total reflection as multitasking functions. The findings demonstrate that under different excitation conditions, when co-planar polarized terahertz (THz) waves are incident normally on the metasurface, the MCBM can convert co-planar polarization to cross-polarization, co-planar polarization to circular polarization wave in reflection mode, and co-planar polarization to cross-polarization in transmission, respectively. When co-planar polarized THz waves are incident from the back side of the metasurface, the tasks of MCBM change to broadband perfect absorption, total reflection, and transmission co-planar polarization to cross-polarization conversion. Remarkably, all operating frequency bands of these tasks are very approximate. Additionally, the multitasking functions can be switched by altering the excitation conditions, and their performance can be regulated through multipath controls, such as the temperature, voltage, and polarization status. Our design provides an effective strategy for multipath-controlled multitasking integrated devices in the THz band.

Re-exploration of tetrahydro-ß-carboline scaffold: Discovery of selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting and neuroprotective activities.

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.

Jiawei Kongsheng Zhenzhong Pill: marker compounds, absorption into the serum (rat), and Q-markers identified by UPLC-Q-TOF-MS/MS.

Background: The Jiawei Kongsheng Zhenzhong pill (JKZP), a Chinese herbal prescription comprised of eight Chinese crude drugs, has been historically employed to treat neurological and psychological disorders. Nevertheless, the ambiguous material basis severely hindered its progress and application. Purpose: The current study aimed to establish a rapid analytical method for identifying the chemical components of the JKZP aqueous extract and the components absorbed into the rat serum to investigate the quality markers (Q-markers) responsible for the neuroprotective effects of JKZP. Methods: The qualitative detection of the chemical components, prototype components, and metabolites of the aqueous extracts of JKZP, as well as the serum samples of rats that were administered the drug, was performed using the ultra-performance liquid chromatography- quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) technology. This analysis combined information from literature reports and database comparisons. Moreover, the study was conducted to anticipate the potential Q-markers for the neuroprotective effects of JKZP based on the "five principles" of Q-marker determination. Results: A total of 67 compounds and 111 serum components (comprising 33 prototypes and 78 metabolites) were detected and identified. Combining the principles of quality transmission and traceability, compound compatibility environment, component specificity, effectiveness, and measurability, the study predicted that five key compounds, namely, senkyunolide H, danshensu, echinacoside, loganin, and 3,6'-disinapoyl sucrose, may serve as potential pharmacological bases for the neuroprotective effects of JKZP. Conclusion: To summarize, the UPLC-Q-TOF-MS/MS technique can be employed to rapidly and accurately identify compounds in JKZP. Five active compounds have been predicted to be the Q-markers for the neuroprotective effects of JKZP. This discovery serves as a reference for improving quality, advancing further research and development, and utilizing Chinese herbal prescriptions.

Exploration the mechanism of Shenling Baizhu San in the treatment of chronic obstructive pulmonary disease based on UPLC-Q-TOF-MS/MS, network pharmacology and in vitro experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. AIM OF THE STUDY: The objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. MATERIALS AND METHODS: First, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. RESULTS: A total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. CONCLUSIONS: The mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.

Protocol for preparation of LiCl-based ultra-hygroscopic curdlan heat exchanger for dehumidification.

Desiccant-coated heat exchangers provide a practical solution for the efficient removal of moisture from the air. Here, we present a protocol to synthesize an ultra-hygroscopic polymer to develop a LiCl loaded in curdlan hydrogel (LiCl@Cur)-coated heat exchanger for deep dehumidification. We describe steps for preparing the curdlan gel solution, hydrogel, LiCl solution, and LiCl@Cur. We then detail procedures for preparing curdlan-coated and LiCl@Cur-coated heat exchangers. The coated heat exchanger described in this protocol has a maximum dehumidification capacity of 12 g/kg. For complete details on the use and execution of this protocol, please refer to Pan et al. (2023).1.

[Research progress on Huangqi Guizhi Wuwu Decoction and predictive analysis of quality markers].

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

Mechanism of Yushenhuoxue prescription in treating endometriosis based on network pharmacology and the effect on the TNF pathway.

Endometriosis is a common disease in the field of gynaecology, exhibiting clinical manifestations such as dysmenorrhoea, pelvic masses, and infertility, affecting 2-10% of women of reproductive age worldwide. Currently, the acceptance rate of hormonal drugs in patients is low and certain side effects exist. In this study, based on network pharmacology, it was found that the Yushenhuoxue (YSHX) formula could potentially affect endometriosis through the TNF signalling pathway. Clinical studies indicated that YSHX demonstrated the ability to reduce the vas score of dysmenorrhoea, resulting in a significant down-regulation of serum ca125 and inflammatory factors (IL-6, IL-1ß, TNF-α). In vivo studies showed that stem cell mice in the YSHX group exhibited significantly reduced lesion volumes than those in the model group. Serum levels of IL-1ß and IL-6 were significantly decreased. Moreover, the phosphorylation levels of NF-κB p65 and the expression of TNF-α protein were significantly decreased. In vitro studies have shown that YSHX inhibits the proliferation, invasion, and migration of endometriotic cells. This study partially verified that YSHX contributed to the treatment of endometriosis by regulating the TNF signalling pathway and improving the inflammatory state of endometriosis.

Tetrahydro-ß-carboline derivatives as potent histone deacetylase 6 inhibitors with broad-spectrum antiproliferative activity.

A series of tetrahydro-ß-carboline (THßC)-based hydroxamic acids were rationally designed and synthesized as novel selective HDAC6 inhibitors (sHDAC6is) by the application of scaffold hopping strategy. Several THßC analogues were highly potent (IC50 < 5 nM) and selective against HDAC6 enzyme and exhibited good antiproliferative activity against human multiple myeloma (MM) cell. Molecular docking interpreted the structure activity relationship (SAR). Target engagement of HDAC6 was confirmed in RPMI-8226 cells using the WB assay. In vitro, (1S, 3R)-1-(4-chlorophenyl)-N-(4-(hydroxycarbamoyl)benzyl)-2,3,4,9-tetrahydro-1H-pyrido[3, 4-b]indole-3-carboxamide (14g) showed potent broad antiproliferative activity against various tumors including leukemia, colon cancer, melanoma, and breast cancer cell lines, better than ACY-1215. Moreover, 14g also showed good pharmacokinetics properties in mice via oral administration.

Research on Xiaoyao Powder in the treatment of depression based on epigenetics and quality markers.

Depression has become one of the most common public health issues around the world, and the incidence has been increasing in recent years. A large amount of clinical investigations have proven that the treatment of depression is difficult. The prognosis is poor, and the fatality rate is high. At present, western medicine is the preferred treatment for depression, but it often causes adverse clinical reactions such as dry mouth, blurred vision, and memory loss, etc. The herbal compound Xiaoyao Powder is a traditional medicine for soothing the liver and relieving depression, strengthening the spleen, and nourishing the blood. It can reduce adverse reactions. It is effective in treating depression. In this study, we elucidate the function of Xiaoyao Powder in anti-depression from the perspective of clinical application and pharmacological mechanisms such as regulating epigenetic and chemical quality markers to provide empirical and experimental theoretical results that contribute to developing future depression therapy with Xiaoyao Powder.

Multifunctional-hierarchical flexibility metasurfaces for multispectral compatible camouflage of microwave, infrared and visible.

The prevalent use of multispectral detection technology makes single-band camouflage devices ineffective, and the investigation of technology for camouflage that combines multispectral bands becomes urgent. The multifunctional-hierarchical flexibility metasurfaces (MHFM) for multispectral compatible camouflage of microwave, infrared, and visible, is proposed, fabricated, and measured. MHFM is primarily composed of an infrared shielding layer (IRSL), a radar absorbing layer (RAL), and a visible color layer (VCL). Among them, IRSL can block thermal infrared detection, and RAL can efficiently absorb microwave band electromagnetic (EM) waves. The VLC can display black (below 28°C), purple (28°C∼31°C), green (31°C∼33°C), and yellow (above 33°C) at different temperatures to achieve visible camouflage. Simulation results show that MHFM can achieve absorption higher than 90% in the 2.9∼13.9 GHz microwave band. Theoretically, the emissivity of MHFM in the infrared spectral range 3∼14 µm is less than 0.34. In addition, the MHFM consists of high-temperature-resistant materials that can be used normally at temperatures up to 175°C, providing excellent high-temperature stability. The measurement results show that the camouflage performance of the MHFM is in excellent agreement with the proposed theory. This study proposes a new method for multispectral camouflage that has broad engineering applications.

A workflow to visualize vertebrate eyes in 3D.

PURPOSE: To establish a workflow to visualize the surgical anatomy in 3D based on histological data of eyes of experimental animals for improving the planning of complex surgical procedures. METHODS: Four C57BL/6J wild-type(wt) mouse eyes, three Brown Norway rat eyes and four Chinchilla Bastard rabbit eyes were enucleated and processed for standard histology with serial sections and hematoxylin and eosin staining. Image stacks were processed to obtain a representation of the eye anatomy in 3D. In addition, virtual image stacks and 3D point clouds were generated by processing sagittal sections of eyes with stepwise 180° rotation and projection around the eye axis to construct a rotationally symmetric 3D model from one single sagittal section. RESULTS: Serial sections of whole eyes of mice, rats and rabbits showed significant artifacts interfering with a practical image stack generation and straightforward 3D reconstruction despite the application of image registration techniques. A workflow was established to obtain a 3D image of the eye based on virtual image stacks and point cloud generation by rotation of a single sagittal section of the eye around the symmetry axis. By analyzing the tissue shrinkage during histological processing true biometric reconstructions of the eyes were feasible making the resulting model usable for 3D modeling and simulation, e.g. for planning of complex surgical procedures in different species. CONCLUSION: Because serial sections of the eye with standard histological protocols yielded too many artifacts for a straightforward 3D visualization we reconstructed a pseudorealistic 3D model based on virtual image stacks and point cloud generation calculated from a single sagittal section of the eye. Such a model detailing microscopic structures of the whole eye will allow for a specific planning of surgical procedures in small animal eyes in order to prevent surgical complications in a very early stage of an experiment and it will support the design and development of complex intraocular implants. It will therefore be helpful in surgical teaching and improve laboratory animal welfare by an expected reduction of experimental animal numbers. Further processing including integration of mechanical tissue properties is needed to convert these 3D models into a practical virtual reality teaching and simulation platform for eyes of several species.

A Porcine DNMT1 Variant: Molecular Cloning and Generation of Specific Polyclonal Antibody.

DNA methyltransferase 1 (DNMT1), the first-identified DNA methyltransferase in mammals, has been well studied in the control of embryo development and somatic homeostasis in mice and humans. Accumulating reports have demonstrated that DNMT1 plays an important role in the regulation of differentiation and the activation of immune cells. However, little is known about the effects of porcine DNMT1 on such functional regulation, especially the regulation of the biological functions of immune cells. In this study, we report the cloning of DNMT1 (4833 bp in length) from porcine alveolar macrophages (PAMs). According to the sequence of the cloned DNMT1 gene, the deduced protein sequence contains a total of 1611 amino acids with a 2 amino acid insertion, a 1 amino acid deletion, and 12 single amino acid mutations in comparison to the reported DNMT1 protein. A polyclonal antibody based on a synthetic peptide was generated to study the expression of the porcine DNMT1. The polyclonal antibody only recognized the cloned porcine DNMT1 and not the previously reported protein due to a single amino acid difference in the antigenic peptide region. However, the polyclonal antibody recognized the endogenous DNMT1 in several porcine cells (PAM, PK15, ST, and PIEC) and the cells of other species (HEK-293T, Marc-145, MDBK, and MDCK cells). Moreover, our results demonstrated that all the detected tissues of piglet express DNMT1, which is the same as that in porcine alveolar macrophages. In summary, we have identified a porcine DNMT1 variant with sequence and expression analyses.

The prognostic value of deep earlobe creases in patients with acute ischemic stroke.

Background and purpose: Data on earlobe crease (ELC) among patients with acute ischemic stroke (AIS) are limited. Here, we determined the frequency and characteristics of ELC and the prognostic effect of ELC among AIS patients. Methods: A total of 936 patients with acute AIS were enrolled during the period between December 2018 and December 2019. The patients were divided into those without and with ELC, unilateral and bilateral ELC, and shallow and deep ELC, according to the photographs taken of the bilateral ears. Logistic regression models were used to estimate the effect of ELC, bilateral ELC, and deep ELC on poor functional outcomes at 90 days (a modified Rankin Scale score ≥2) in AIS patients. Results: Among the 936 AIS patients, there were 746 (79.7%) patients with ELC. Among patients with ELC, there were 156 (20.9%) patients with unilateral ELC and 590 (79.1%) with bilateral ELC and 476 (63.8%) patients with shallow ELC and 270 (36.2%) with deep ELC. After adjusting for age, sex, baseline NIHSS score, and other potential covariates, patients with deep ELC were associated with a 1.87-fold [odds ratio (OR) 1.87; 95% confidence interval (CI), 1.13-3.09] and 1.63-fold (OR 1.63; 95%CI, 1.14-2.34) increase in the risk of poor functional outcome at 90 days in comparison with those without ELC or shallow ELC. Conclusion: ELC was a common phenomenon, and eight out of ten AIS patients had ELC. Most patients had bilateral ELC, and more than one-third had deep ELC. Deep ELC was independently associated with an increased risk of poor functional outcome at 90 days.

Enhancer RNA IRS2e is essential for IRS2 expression and the oncogenic properties in oral squamous cell carcinoma.

The crucial roles of enhancer RNAs (eRNAs) in the regulation of gene expression in human diseases have drawn wider and wider attention in recent years. However, the specific expression profile and function of eRNAs are still rarely discussed in oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSC). In this study, we aimed to investigate the expression and function of an uncharacterized eRNA, insulin receptor substrate 2 enhancer RNA (IRS2e), in OSCC. We found that IRS2e was overexpressed in HNSC and its overexpression was positively correlated with a poor prognosis. The downregulation of IRS2e by short hairpin RNA significantly inhibited cell growth and induced cellular apoptosis and cell-cycle arrest in OSCC cells. Furthermore, the ablation of IRS2e inhibited tumor growth in vivo. Mechanically, IRS2e is essential for the expression of insulin receptor substrate 2 (IRS2), an oncogene nearby IRS2e in chromosome 13. Altogether, our study demonstrated that IRS2e is a novel oncogenic eRNA required for oncogene IRS2 expression in OSCC.

Circ_0001667 accelerates breast cancer proliferation and angiogenesis through regulating CXCL10 expression by sponging miR-6838-5p.

BACKGROUND: An increasing number of circular RNAs (circRNAs) have been shown to play an important role in the tumorigenesis of breast cancer. The aim of this study was to investigate the expression and function of circ_0001667 and its potential molecular mechanisms in breast cancer. METHODS: The expression levels of circ_0001667, miR-6838-5p and CXC chemokine ligand 10 (CXCL10) in breast cancer tissues and cells were detected by quantitative real-time PCR. Cell counting kit-8 assay, EdU assay, flow cytometry, colony formation and tube formation assays were used to detect cell proliferation and angiogenesis. The binding relationship between miR-6838-5p and circ_0001667 or CXCL10 was predicted using the starBase3.0 database and verified by dual-luciferase reporter gene assay, RIP and RNA pulldown. Animal experiments were performed to assess the function of circ_0001667 knockdown on breast cancer tumor growth. RESULTS: Circ_0001667 was highly expressed in breast cancer tissues and cells, and its knockdown inhibited proliferation and angiogenesis of breast cancer cells. Circ_0001667 sponged miR-6838-5p, and inhibition of miR-6838-5p reversed the inhibitory effect of silencing circ_0001667 on proliferation and angiogenesis of breast cancer cells. MiR-6838-5p targeted CXCL10, and overexpression of CXCL10 reverses the effect of miR-6838-5p overexpression on breast cancer cell proliferation and angiogenesis. In addition, circ_0001667 interference also reduced breast cancer tumor growth in vivo. CONCLUSION: Circ_0001667 is involved in breast cancer cell proliferation and angiogenesis through regulation of the miR-6838-5p/CXCL10 axis.

The Application of Pyrrolo[2, 3-d]pyrimidine Scaffold in Medicinal Chemistry from 2017 to 2021.

The application of privileged structures in drug design is an effective strategy, which usually leads to innovative hits/leads and successful structural optimization. Pyrrolo[2, 3- d]pyrimidine are such a scaffold which are frequently used in many clinical drugs. The biocompounds bearing pyrrolo[2, 3-d]pyrimidine skeleton show different pharmacological effects such as anti-neurodegenerative, anti-inflammatory, antibacterial, and antitumor activities. In this article, we reviewed the representative structures and biological characteristics of reported synthetic pyrrolo[2, 3-d]pyrimidine compounds from 2017 to 2021. The linked diseases and targets were also mentioned briefly. This work might provide a reference for the subsequent drug discovery based on pyrrolo[2, 3-d]pyrimidine scaffold.