Abstract In our research on novel anticancer agents, a series of N 6 ‐hydrazone purine derivatives were designed and synthesized by analysis of a pharmacophore model for ATP‐competitive inhibitors. The activities screening results showed that N 6 ‐hydrazone purine derivatives 21 and 26 not only showed potential antiproliferative activity against the A549 and MCF‐7 cell lines comparable to Vandetanib as a positive control but also had moderate antiplatelet aggregation activity. In order to investigate the possible targets, a molecular docking study was carried out on the fourteen kinases associated with anticancer and antiplatelet aggregation activities. The results indicated that compounds 21 and 26 had the potential activity to target VEGFR‐2, PI3Kα, EGFR, and HER2 kinases. The inhibition of the kinases assay showed that compound 26 could target VEGFR‐2, PI3Kα, and EGFR (IC 50 = 0.822, 3.040 and 6.625 μM). All results indicated that compound 26 will be an encouraging framework as potential new multi‐target anticancer agent with potential antiplatelet aggregation activity.
The outbreaks caused by RNA and DNA viruses, such as SARS-CoV-2 and monkeypox, pose serious threats to human health. The RLR and cGAS-STING pathways contain major cytoplasmic sensors and signaling transduction axes for host innate antiviral immunity. In physiological and virus-induced pathological states, the activation and inactivation of these signal axes are tightly controlled, especially post-translational modifications (PTMs). E3 ubiquitin ligases (E3s) are the direct manipulator of ubiquitin codons and determine the type and modification type of substrate proteins. Therefore, members of the E3s family are involved in balancing the host’s innate antiviral immune responses, and their functions have been extensively studied over recent decades. In this study, we overviewed the mechanisms of different members of three E3s families that mediate the RLR and cGAS-STING axes and analyzed them as potential molecular targets for the prevention and treatment of virus-related diseases.
Tooth extraction commonly leads to postoperative wound bleeding, bacterial infection, and even the occurrence of dry socket. Therefore, developing a biomedical material with favorable antibacterial and excellent hemostatic properties to prevent the post-extraction dry socket is necessary. Herein, quaternary ammonium chitosan/ carboxymethyl starch/alginate (ACQ) sponges are developed
Highly pathogenic coronaviruses have caused significant outbreaks in humans and animals, posing a serious threat to public health. The rapid global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in millions of infections and deaths. However, the mechanisms through which coronaviruses evade a host’s antiviral immune system are not well understood. Liquid–liquid phase separation (LLPS) is a recently discovered mechanism that can selectively isolate cellular components to regulate biological processes, including host antiviral innate immune signal transduction pathways. This review focuses on the mechanism of coronavirus-induced LLPS and strategies for utilizing LLPS to evade the host antiviral innate immune response, along with potential antiviral therapeutic drugs and methods. It aims to provide a more comprehensive understanding and novel insights for researchers studying LLPS induced by pandemic viruses.
The cover image is based on the RESEARCH ARTICLE Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS-induced pro-inflammatory responses through NF-кB, MAPK, and PI3K-Akt signaling pathways in alveolar epithelial type II cells by Tian Feng et al., https://doi.org/10.1002/ptr.6499.
BACKGROUND Internet-based cognitive behavior therapy (ICBT) may provide an accessible alternative to face-to-face treatment, but the evidence base in adolescents is limited. OBJECTIVE We conducted a systematic review and meta-analysis to evaluate the effectiveness of ICBT in treating depression in adolescents. METHODS Four electronic databases were searched on April 19, 2022. Randomized controlled trials (RCTs) evaluating the effectiveness of ICBT for depression in adolescents were included. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook Version 5.1.0. We used the GRADE approach to assess the certainty of the evidence. RevMan 5.4 was used for meta-analysis. RESULTS A total of 12 RCTs involving 1139 patients were included. Compared with the control group, our meta-analysis results demonstrated that ICBT significantly decreased the depression scores of adolescents (SMD = −0.63, 95% CI: [−0.90, −0.37], p < .05). In addition, no significant differences were found in the patient’s anxiety and QoL scores. (SMD = −0.63, 95% CI: [−0.90, −0.37], p < .05; SMD = 0.12, 95% CI: [−0.10, 0.34], p > .05). CONCLUSIONS Very low certainty evidence demonstrated that ICBT may be a promising treatment, especially in reducing depression in adolescents. CLINICALTRIAL PROSPERO registration: CRD42021277562
Early onset sepsis (EOS) remains a potentially fatal newborn condition, especially in very preterm infants. Data on the pathogen distribution and antibiotic susceptibility patterns of EOS among very preterm infants are scarce but essential for the choice of empirical antibiotic administration. We sought to assess the epidemiologic characteristics and antibiotic susceptibility patterns of pathogens causing EOS among a cohort of very preterm infants in China.This prospective, observational study included a cohort of infants born at a gestational age (GA) less than 32 weeks of 32 newborn intensive care units (NICUs) in China between January 1, 2018 and December 31, 2020. EOS was defined by isolation of pathogenic species from blood culture within 72 h of birth.A total of 108 EOS cases (18.4 per 1000 admissions) were identified among 5865 very preterm infants. Incidence of EOS increased with the decrease of GA and birthweight. Escherichia coli (n = 44, 40.7%) was the most common pathogen, followed by Klebsiella spp. (n = 10, 9.3%). The distribution and proportion of pathogenic bacteria varied significantly by GA. E. coli and Klebsiella spp. showed high resistance to ampicillin and third-generation cephalosporins, while they showed good susceptibility to carbapenem antibiotics and piperacillin-tazobactam.Our data demonstrated that pathogens causing neonatal EOS showed high rates of resistance to ampicillin and third-generation cephalosporins. This raised questions about the best empirical antibiotic choice for preterm infants suspected of having EOS in low- and middle-income countries (LMICs).
Abstract The present work aims to study the mechanical performance of glass fiber reinforced polybutylene terephthalate (GF/PBT) composite materials used for high-pressure casing under different thermal aging temperatures. Both tensile and three-point bending tests are conducted on the thermally aged GF/PBT samples. Meanwhile, the stress analysis is performed using the finite element method, and the tensile fracture morphology and mode are observed using a scanning electron microscope. The findings reveal a decline in both tensile and bending strengths of GF/PBT as the aging temperature rises. It is worth noting that the elastic modulus of the composite samples remained relatively unaffected by thermal aging. The thermally aged materials exhibit brittle fracture, which directly affects the bonding performance between glass fibers and PBT matrix.
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