Quercetin inhibits the epithelial-mesenchymal transition and reverses CDK4/6 inhibitor resistance in breast cancer by regulating circHIAT1/miR-19a-3p/CADM2 axis.

Breast cancer (BC) cells have a high risk of metastasis due to epithelial-mesenchymal transition (EMT). Palbociclib (CDK4/6 inhibitor) is an approved drug for BC treatment. However, the drug resistance and metastasis can impair the treatment outcome of Palbociclib. Understanding the mechanisms of EMT and Palbociclib drug resistance in BC is conducive to the formulation of novel therapeutic strategy. Here, we investigated the role of circHIAT1/miR-19a-3p/CADM2 axis in modulating EMT and Palbociclib resistance in BC. circHIAT1 and CADM2 were down-regulated in BC tissues and cell lines, and miR-19a-3p showed an up-regulation. circHIAT1 could interact with miR-19a-3p and suppress its activity, while miR-19a-3p functioned to negatively regulate CADM2. Forced over-expression of circHIAT1 could impaired the EMT status and migratory ability of BC cells, and this effect was inhibited by miR-19a-3p mimic. In addition, we also generated Palbociclib resistant BC cells, and showed that circHIAT1 and CADM2 were down-regulated in the resistant BC cells while miR-19a-3p showed an up-regulation. Forced circHIAT1 over-expression re-sensitized BC cells to Palbociclib treatment. Quercetin, a bioactive flavonoid, could suppressed the migration and invasion of BC cells, and re-sensitized BC cells to Palbociclib. The anti-cancer effect of quercetin could be attributed to its regulatory effect on circHIAT1/miR-19a-3p/CADM2 axis. In vivo tumorigenesis experiment further revealed that quercetin administration enhanced the anti-cancer effect of Palbociclib, an effect was dependent on the up-regulation of circHIAT1 by quercetin. In summary, this study identified quercetin as a potential anti-cancer compound to reverse Palbociclib resistance and impair EMT in BC cells by targeting circHIAT1/miR-19a-3p/CADM2 axis.

Human cytomegalovirus pUL135 protein affects endothelial cell function via CD2AP in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a kind of pediatric vasculitis, whose pathogenesis has not been elucidated until now. Many scholars believe that KD is one type of infectious diseases in the susceptible groups. However, no recognized pathogens are confirmed. Human cytomegalovirus (HCMV) is a ubiquitous human herpes virus, which can infect varieties of cells including endothelial cells. Studies reported that the viral protein pUL135 is very important for virus replication, reactivation and immune escape. Therefore, we hypothesize that HCMV pUL135 may have a pathogenic effect on KD. METHODS: We first determined pUL135 levels in the serum from KD patients. Next, we examined the effects and mechanisms of pUL135 on endothelial cell proliferation and migration. Finally, we assessed the effect of pUL135 on cardiac inflammation in a KD murine model. RESULTS: Data showed that pUL135 level was significantly increased in the serum from KD patients compared with the healthy and fever controls. And pUL135 expression in endothelial cells remarkably inhibited cell proliferation, migration and tube formation. Moreover, expression of pUL135 obviously affected actin cytoskeleton. Mechanism investigation substantiated that pUL135 mediated endothelial cell dysfunction via regulating CD2AP. Ultimately, we found that HCMV pUL135 aggravated coronary arteritis in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. CONCLUSION: Our findings imply that HCMV pUL135-mediated endothelial dysfunction plays an important role in exacerbating coronary artery injury in KD conditions.

Discovery of a novel pyrido[1,2-a]thiazolo[5,4-d]pyrimidinone derivatives with excellent potency against acetylcholinesterase.

As mimetic compounds of the natural alkaloid mackinazolinone, forty pyrido[1,2-a]thiazolo[5,4-d] pyrimidinone were designed and synthesized from a bioisosterism approach. The structure of these compounds was confirmed through analysis using 1H NMR, 13C NMR, and HRMS techniques. All the compounds were evaluated for their anticholinesterase activities and cytotoxicity on normal cells (293 T) by the Ellman method and methyl thiazolyl tetrazolium (MTT) method in vitro. and the structure-activity relationships (SARs) were summarized. The results showed that most of the compounds effectively inhibited acetylcholinesterase (AChE) in the micromolar range with weak cytotoxicity. Compound 7o exhibited the best inhibitory activity against AChE, displaying an IC50 values of 1.67 ± 0.09 µM and an inhibitory constant Ki of 11.31 µM as a competitive inhibitor to AChE. Molecular docking indicated that compound 7o may bind to AChE via hydrogen bond and π-π stacking. Further molecular dynamics (MD) simulations indicated a relatively low binding free energy (- 27.91 kJ·mol-1) of compound 7o with AChE. In summary, the collective findings suggested that 7o was promising as a potential novel drug candidate worthy of further investigation for the treatment of Alzheimer's disease.

Effect and mechanism of C-terminal cysteine on the properties of HEV p222 protein.

Preliminary investigations have demonstrated that the cysteines located at the C-terminus of HEV ORF2 protein exhibits disulfide bonding capability during virus-like particles (VLPs) assembly. However, the effect and mechanism underlying the pairing of disulfide bonds formed by C627, C630, and C638 remains unclear. The p222 protein encompasses C-terminus and serves as a representative of HEV ORF2 to investigate the specific impacts of C627, C630, and C638. The three cysteines were subjected to site-directed mutagenesis and expressed in prokaryotes; Both the mutated proteins and p222 underwent polymerization except for p222A; Surprisingly, only p222 was observed as abundant spherical particles under transmission electron microscope (TEM); Stability and immunogenicity of the p222 exhibited higher than other mutated proteins; LC/MS/MS analysis identified four disulfide bonds in the p222. The novel findings suggest that the three cysteines contribute to structural and functional properties of ORF2 protein, highlighting the indispensability of each cysteine.

Preschool children's asthma medication: parental knowledge, attitudes, practices, and adherence.

Introduction: As parents or legal guardians primarily care for children with asthma, understanding their knowledge, attitudes, and practices (KAP) barriers to treatment and medication adherence is of essential importance. This study aimed to analyze the KAP toward asthma medication and adherence among preschool-aged asthmatic children's parents and explore the factors influencing adherence. Methods: This cross-sectional study was conducted between February 2023 and April 2023. Parents of preschool children with asthma were asked to complete the questionnaire containing knowledge, attitude, practice dimensions, and demographic characteristics. The Morisky Medication Adherence Scale (MMAS) was used to investigate adherence. Results: A total of 632 valid questionnaires (154 male and 478 female) were included. Parents showed moderate knowledge (9.49 ± 2.86, 63.27%, possible range: 0-15) and moderate attitudes (26.18 ± 2.51, 74.80%, possible range: 7-35) towards asthma medication, while their practices (27.46 ± 5.26, 91.53%, possible range: 6-30) were proactive; however, medication adherence was low (4.84 ± 1.78, total score: 8). The attitude scores (OR = 1.10, 95% CI: 1.01-1.19, P=0.020), practice scores (OR = 1.16, 95%CI: 1.12-1.21, p < 0.001), and smoking (OR = 1.64, 95%CI: 1.14-2.37, p = 0.008) were associated with medication adherence. Discussion: Preschool-aged asthmatic children's parents showed moderate knowledge, attitudes, and proactive practice toward asthma medication. Continuous training and education programs should be provided for parents to improve asthma medication management in preschool children.

Identification of Novel Prognostic Biomarkers for Colorectal Cancer by Bioinformatics Analysis.

BACKGROUND/AIMS: Colorectal cancer (CRC) ranks third among malignancies in terms of global incidence and has a poor prognosis. The identification of effective diagnostic and prognostic biomarkers is critical for CRC treatment. This study intends to explore novel genes associated with CRC progression via bioinformatics analysis. MATERIALS AND METHODS: Dataset GSE184093 was selected from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between CRC and noncancerous specimens. Functional enrichment analyses were implemented for probing the biological functions of DEGs. Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter databases were employed for gene expression detection and survival analysis, respectively. Western blotting and real-time quantitative polymerase chain reaction were employed for detecting molecular protein and messenger RNA levels, respectively. Flow cytometry, Transwell, and CCK-8 assays were utilized for examining the effects of GBA2 and ST3GAL5 on CRC cell behaviors. RESULTS: There were 6464 DEGs identified, comprising 3005 downregulated DEGs (dDEGs) and 3459 upregulated DEGs (uDEGs). Six dDEGs were significantly associated with the prognoses of CRC patients, including PLCE1, PTGS1, AMT, ST8SIA1, ST3GAL5, and GBA2. Upregulating ST3GAL5 or GBA2 repressed the malignant behaviors of CRC cells. CONCLUSION: We identified 6 genes related to CRC progression, which could improve the disease prognosis and treatment.

Dual-channel hypergraph convolutional network for predicting herb-disease associations.

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.

Comparison of triplanar chevron osteotomy with chevron osteotomy in hallux valgus treatment for the prevention of transfer metatarsalgia.

Hallux valgus (HV) is often accompanied by metatarsalgia. This study compared the radiological and clinical outcomes of new triplanar chevron osteotomy (TCO) and chevron osteotomy (CO) in the treatment of HV, especially for patients with plantar callosities and metatarsalgia. In this retrospective analysis, 90 patients (45 patients per group) with mild to moderate HV and plantar callosities were treated with TCO and CO from July 2020 to January 2022. In both procedures, the apex was located in the center of the head of the first metatarsal bone, and the CO was oriented towards the fourth MTPJ at a 60° angle. Plantar-oblique chevron osteotomy was defined as chevron osteotomy and a 20° plantar tilt; TCO was defined as plantar-oblique chevron osteotomy-based metatarsal osteotomy with a 10° tilt towards the metatarsal head. Primary outcome measures included preoperative and postoperative hallux valgus angle, 1 to 2 intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), first metatarsal length (FML), and second metatarsal head height X-ray images; clinical measurements, including visual analogue scale and American Orthopaedic Foot & Ankle Society (AOFAS) scores; changes in callosity grade and area; and changes in the number of people with metatarsalgia. Secondary outcomes included complications, recurrence rates, and cosmetic appearance. The hallux valgus angle, IMA, and DMAA were significantly lower after surgery (P  < .001) in all patients. In the TCO group, the mean FML and second metatarsal head height increased significantly postoperatively (P < .001). The AOFAS and visual analogue scale scores improved postoperatively in both groups (P < .001). All patients experienced satisfactory pain relief and acceptable cosmesis. The plantar callosity areas were smaller postoperatively in both the TCO and CO groups, but the change in the area (Δarea) in the TCO group significantly differed from that in the CO group (P < .001). The number of postoperative patients with metatarsalgia and the plantar callosity grade were both significantly lower in the TCO group than in the CO group after osteotomy (P < .05). TCO prevents dorsal shift of the metatarsal head and preserves and even increases FML, thereby preventing future metatarsalgia in patients. Therefore, compared with CO, TCO has better orthopedic outcomes and is an effective method for treating mild to moderate HV and preventing transfer metatarsalgia.

Profiling mitochondria-polyribosome lncRNAs associated with pluripotency.

Pluripotent stem cells (PSCs) provide unlimited resources for regenerative medicine because of their potential for self-renewal and differentiation into many different cell types. The pluripotency of these PSCs is dynamically regulated at multiple cellular organelle levels. To delineate the factors that coordinate this inter-organelle crosstalk, we profiled those long non-coding RNAs (lncRNAs) that may participate in the regulation of multiple cellular organelles in PSCs. We have developed a unique strand-specific RNA-seq dataset of lncRNAs that may interact with mitochondria (mtlncRNAs) and polyribosomes (prlncRNAs). Among the lncRNAs differentially expressed between induced pluripotent stem cells (iPSCs), fibroblasts, and positive control H9 human embryonic stem cells, we identified 11 prlncRNAs related to stem cell reprogramming and exit from pluripotency. In conjunction with the total RNA-seq data, this dataset provides a valuable resource to examine the role of lncRNAs in pluripotency, particularly for studies investigating the inter-organelle crosstalk network involved in germ cell development and human reproduction.

Correlation between peripheral blood α1-MG, DNMT1 expression, and the severity of diabetic nephropathy renal pathological damage.

To explore the correlation between peripheral blood α1-microglobulin (α1-MG) and monocyte DNA methyltransferase 1 (DNMT1) expression and the severity of renal pathological damage in diabetic nephropathy (DN). The study group comprised 100 patients with DN who underwent treatment at our hospital from January 2022 to January 2023, while the control group consisted of 50 patients with uncomplicated diabetes. The relative expression levels of peripheral blood α1-MG and DNMT1 were compared between the 2 groups of patients. Additionally, the levels of vascular endothelial growth factor (VEGF) were measured, and the diagnostic value of DN was explored using ROC curves. Furthermore, the correlation between the aforementioned indicators and the severity of renal pathological damage in the patients of the study group was analyzed. Compared to the patients in the control group, the patients in the study group showed increased relative expression levels of peripheral blood α1-MG and DNMT1, as well as elevated levels of VEGF (P < .05). The diagnostic value of peripheral blood α1-MG, DNMT1 relative expression levels, and VEGF levels for DN was explored using ROC curves. The AUC values were 0.907, 0.923, and 0.936, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the interstitial fibrosis and tubular atrophy scoring (IFTA) score, showing a positive correlation with r-values of 0.651, 0.710, and 0.628, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the interstitial inflammation score, showing a positive correlation with r-values of 0.771, 0.633, and 0.678, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the glomerular grading, showing a positive correlation with r-values of 0.714, 0.609, and 0.677, respectively (P < .05). The expression levels of peripheral blood α1-MG, DNMT1, and VEGF are significantly elevated in patients with DN. These levels show a positive correlation with the IFTA score, interstitial inflammation score, and glomerular grading, contributing to the diagnosis and assessment of DN.

MSI-XGNN: an explainable GNN computational framework integrating transcription- and methylation-level biomarkers for microsatellite instability detection.

Microsatellite instability (MSI) is a hypermutator phenotype caused by DNA mismatch repair deficiency. MSI has been reported in various human cancers, particularly colorectal, gastric and endometrial cancers. MSI is a promising biomarker for cancer prognosis and immune checkpoint blockade immunotherapy. Several computational methods have been developed for MSI detection using DNA- or RNA-based approaches based on next-generation sequencing. Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play critical roles in the development and progression of cancer. We here developed MSI-XGNN, a new computational framework for predicting MSI status using bulk RNA-sequencing and DNA methylation data. MSI-XGNN is an explainable deep learning model that combines a graph neural network (GNN) model to extract features from the gene-methylation probe network with a CatBoost model to classify MSI status. MSI-XGNN, which requires tumor-only samples, exhibited comparable performance with two well-known methods that require tumor-normal paired sequencing data, MSIsensor and MANTIS and better performance than several other tools. MSI-XGNN also showed good generalizability on independent validation datasets. MSI-XGNN identified six MSI markers consisting of four methylation probes (EPM2AIP1|MLH1:cg14598950, EPM2AIP1|MLH1:cg27331401, LNP1:cg05428436 and TSC22D2:cg15048832) and two genes (RPL22L1 and MSH4) constituting the optimal feature subset. All six markers were significantly associated with beneficial tumor microenvironment characteristics for immunotherapy, such as tumor mutation burden, neoantigens and immune checkpoint molecules such as programmed cell death-1 and cytotoxic T-lymphocyte antigen-4. Overall, our study provides a powerful and explainable deep learning model for predicting MSI status and identifying MSI markers that can potentially be used for clinical MSI evaluation.

Preparation, structural characteristics and antioxidant activity of polysaccharide and its metal chelates from the peel of Dioscorea oppositifolia L.

Two metal chelates of Dioscorea oppositifolia L. peel polysaccharides (DTP) were prepared: iron chelate (DTP-Fe) and zinc chelate (DTP-Zn). The physicochemical properties of the polysaccharide and its metal chelates were assessed by UV-Vis absorption spectroscopy, Fourier-transform infra-red spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Antioxidant activities were evaluated by DPPH, ABTS + and hydroxyl radical scavenging assays. According to ICP-MS, the iron content of DTP-Fe was 9.47%, while the zinc content of DTP-Zn was 4.02%. The antioxidant capacity of DTP-Fe increased with the increase of concentration, and its overall activity was higher than that of DTP and DTP-Zn. This polysaccharide-iron chelate can be developed and utilised as an antioxidant and multifunctional iron supplement. DTP-Zn showed the potential to be a natural antioxidant and zinc supplement food.

Development of a 2 µm Solid-State Laser for Lidar in the Past Decade.

The 2 µm wavelength belongs to the eye-safe band and has a wide range of applications in the fields of lidar, biomedicine, and materials processing. With the rapid development of military, wind power, sensing, and other industries, new requirements for 2 µm solid-state laser light sources have emerged, especially in the field of lidar. This paper focuses on the research progress of 2 µm solid-state lasers for lidar over the past decade. The technology and performance of 2 µm pulsed single longitudinal mode solid-state lasers, 2 µm seed solid-state lasers, and 2 µm high power solid-state lasers are, respectively, summarized and analyzed. This paper also introduces the properties of gain media commonly used in the 2 µm band, the construction method of new bonded crystals, and the fabrication method of saturable absorbers. Finally, the future prospects of 2 µm solid-state lasers for lidar are presented.

Erratum: FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.

[This corrects the article DOI: 10.1016/j.isci.2020.101627.].

Aniline-induced production of aniline-containing polyketides and related bicyclic polyketides by the Yellow River wetland-derived fungus Talaromyces funiculosus.

Introduction and Methods: Silencing gene activation can effectively enrich the diversity of fungal secondary metabolites. Results and Discussion: Cultivation of the Yellow River wetland-derived fungus Talaromyces funiculosus HPU-Y01 with aniline led to the isolation of one new aniline-containing polyketide tanicutone A (1), two new bicyclic polyketides tanicutones B-C (2-3), a new related trienoic acid 8-methyldeca-2,4,6-trienoic acid (5), and a known compound 4. The planar structures and configurations of 1-5 were determined by NMR, MS, and ECD calculations. Compound 2 featured a key aldehyde group and showed promising inhibitory activity against Vibrio parahaemolyticus with a minimum inhibitory concentration (MIC) value of 0.17 µg/mL. This is a rare report of aniline-induced fungal production of tetrahydronaphthone polyketides.

Epidemiological characteristics of respiratory viruses in hospitalized children during the COVID-19 pandemic in southwestern China.

Background: Multinational studies have reported that the implementation of nonpharmaceutical interventions (NPIs) to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission coincided with the decline of other respiratory viruses, such as influenza viruses and respiratory syncytial virus. Objective: To investigate the prevalence of common respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Respiratory specimens of children with lower respiratory tract infections (LRTIs) hospitalized at the Children's Hospital of Chongqing Medical University from January 1, 2018 to December 31, 2021 were collected. Seven common pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A and B (Flu A, Flu B), and parainfluenza virus types 1-3 (PIV1-3), were detected by a multiplex direct immunofluorescence assay (DFA). Demographic data and laboratory test results were analyzed. Results: 1) A total of 31,113 children with LRTIs were enrolled, including 8141 in 2018, 8681 in 2019, 6252 in 2020, and 8059 in 2021.The overall detection rates decreased in 2020 and 2021 (P < 0.001). The detection rates of RSV, ADV, Flu A, PIV-1, and PIV-3 decreased when NPIs were active from February to August 2020, with Flu A decreasing most predominantly, from 2.7% to 0.3% (P < 0.05). The detection rates of RSV and PIV-1 resurged and even surpassed the historical level of 2018-2019, while Flu A continued decreasing when NPIs were lifted (P < 0.05). 2) Seasonal patterns of Flu A completely disappeared in 2020 and 2021. The Flu B epidemic was observed until October 2021 after a long period of low detection in 2020. RSV decreased sharply after January 2020 and stayed in a nearly dormant state during the next seven months. Nevertheless, the detection rates of RSV were abnormally higher than 10% in the summer of 2021. PIV-3 decreased significantly after the COVID-19 pandemic; however, it atypically surged from August to November 2020. Conclusion: The NPIs implemented during the COVID-19 pandemic affected the prevalence and seasonal patterns of certain viruses such as RSV, PIV-3, and influenza viruses. We recommend continuous surveillance of the epidemiological and evolutionary dynamics of multiple respiratory pathogens, especially when NPIs are no longer necessary.

Cellular immunotherapy combined with platinum-based chemotherapy prolongs survival for non-small cell lung cancer patients.

Platinum-based chemotherapy is the primary treatment option for advanced non-small cell lung cancer (NSCLC) patients without a driver gene mutation, but its efficacy is still modest. Through a potential synergistic effect, autologous cellular immunotherapy (CIT) composed of cytokine-induced killer (CIK), natural killer (NK), and T cells might enhance it. NK cells exhibited in vitro cytotoxicity toward lung cancer cells (A549 cells) following platinum therapy. Using flow cytometry, the expression of MICA, MICB, DR4, DR5, CD112, and CD155 on lung cancer cells was assessed. In this retrospective cohort study, there were included 102 previously untreated stage IIIB/IV NSCLC patients ineligible for tyrosine kinase inhibitor (TKI) target therapy who received either chemotherapy alone (n=75) or combination therapy (n=27). The cytotoxicity of NK cells for A549 cells was increased obviously and a time-dependent enhancement of this effect was also observed. After platinum therapy, the levels of MICA, MICB, DR4, DR5, CD112, and CD155 on the surface of A549 cells were increased. In the combination group, the median PFS was 8.3 months, compared to 5.5 months in the control group (p=0.042); the median overall survival was 18.00 months, compared to 13.67 months in the combined group (p=0.003). The combination group had no obvious immune-related adverse effects. The combination of NK cells with platinum showed synergistic anticancer effects. Combining the two strategies increased survival with minor adverse effects. Incorporating CIT into conventional chemotherapy regimens may improve NSCLC treatment. However, additional evidence will require multicenter randomized controlled trials.

Synthesis and Activity of Aurone and Indanone Derivatives.

INTRODUCTION: Based on bioactive group splicing, classical bioisosterism, and the rule of alkene insertion, forty-eight aurone, and indanone derivatives were designed and synthesized. They were evaluated for inhibitory activity against C. albicans, E. coli, and S. aureus. Among them, thirty compounds exhibited moderate to excellent antibacterial activity. METHODS: The maximum circle of inhibition was 18 mm (compounds B15, B16, and E7), and the minimum values of MIC and MBC were respectively 15.625 µM (compounds A5 and D2) and 62.5 µM (compounds A6, A8, and E7). RESULTS: The SAR showed that aurone and indanone derivatives could strongly inhibit the growth of Gram-positive bacteria. The introduction of electron-withdrawing groups or hydroxyl is beneficial to the activity. It was exciting that the 3-phenylallylbenzofuranone and 3-allylindanone skeletons with antimicrobial activity were first reported in this study. Compounds A5 and E7 were selected for molecular docking studies with targets MetRS (PBD: 7WPI) and PBP (PDB: 6C3K) to determine the binding interactions at the active site. CONCLUSION: On this basis, the physicochemical and pharmacological properties of the compounds were predicted and analyzed. The influence of these properties on antimicrobial activity and their implications for subsequent work were discussed. The ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) predictions showed that most of the compounds had good pharmacokinetic profiles and high safety profiles.

Research Progress of Small Molecules as Anti-vitiligo Agents.

Vitiligo is a disease characterized by skin discoloration, and no safe and effective drugs have been developed until now. New drug research and development are imminent. This article reviews the research on small-molecule drugs for vitiligo from 1990 to 2021 at home and abroad. They are classified according to their structures and mechanisms of action, including natural products and derivatives, anti-oxidative stress drugs, immunosuppressants, prostaglandins, etc. The research on their anti-vitiligo activity, structural modification, new dosage forms, clinical trials, and the development trend in new anti-vitiligo drugs are reviewed, which provides important references for the development of new drugs.

Screening and identification of hub-gene associated with brain metastasis in breast cancer.

BACKGROUND: The presence of breast cancer in the brain, also known as brain metastasis (BMS), is the primary reason for a bad prognosis in cases of breast cancer. Breast cancer is the most prevalent malignant tumor seen in women in developing nations. At present, there is no effective method to inhibit brain metastasis of breast cancer. Therefore, it is necessary to conduct a systematic study on BMS of breast cancer, which will not provide ideas and sites for follow-up studies on the treatment and inhibition of BMS. METHODS: In this study, data set GSE43837 was screened from gene expression omnibus database, and then R language tool was used for differential analysis of its expression spectrum, The gene ontology functional enrichment and Kyoto encyclopedia of genes and genomes signal pathway enrichment analyses, as well as the interactive gene retrieval tool for hub-gene analysis, were performed. RESULTS: According to the findings, the primary genes linked to breast cancer brain metastases are those that involve interactions between cytokines and their respective receptors and between neuroactive ligands and their respective receptors. The majority of the gene ontology enrichment took place in the extracellular structural tissues, the extracellular matrix tissues, and the second message-mediated signaling. We were able to identify 8 genes that are linked to breast cancer spreading to the brain. The gene score for matrix metallopeptidase1 (MMP-1) was the highest among them, and the genes MMP10, tumor necrosis factor alpha-inducible protein 8, collagen type I alpha 2 chain, vascular cell adhesion molecule 1, and TNF superfamily member 11 were all connected to 1 another in an interaction way. CONCLUSIONS: There is a possibility that the 8 key genes that were identified in this research are connected to the progression of BMS in breast cancer. Among them, MMP1 is 1 that has the potential to have a role in the diagnosis and treatment of BMS in breast cancer.