The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.

Curcumin has been reported to possess antitumor activity with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. In order to overcome these limitations and discover novel small molecules with potential antitumor activity, 29 curcumin mimics were synthesized, which were confirmed by 1H NMR and HR-MS, and their cytotoxic property was evaluated against five human cancer cell lines in vitro. Compounds 16, 18 and 19 exhibited good cytotoxic property, their IC50 value were even below 5 micromol x L(-1) to some cancer cell lines, 5-9 times better than curcumin.

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.

Hypertrophic obstructive cardiomyopathy(HOCM)is a hereditary cardiac disorder characterized primarily by septal hypertrophy and left ventricular outflow tract obstruction.Traditional therapeutic modalities,such as medications and surgeries,do not yield satisfactory outcomes in a subset of patients.The advancements have been made in novel treatments,including new drugs and percutaneous intramyocardial septal radiofrequency ablation(PIMSRA),still need further observation to obtain long-term efficacy and safety.In recent years,stereotactic body radiation therapy(SBRT)has emerged as an innovative non-invasive approach for treating HOCM.Studies indicate that SBRT allows for precise targeting of the hypertrophied septal region,causing both direct and indirect damage to targeted myocardial cells.This can alleviate left ventricular outflow tract obstruction and myocardial ischemia,fulfilling the therapeutic objective.For those with HOCM who neither respond well to medications nor are surgical candidates,SBRT offers a potential new therapeutic alternative.However,the latent risks of radiation therapy persist,such as the onset of radiation-induced heart disease(RIHD).The preliminary investigations guarantee the safety and feasibility of SBRT in HOCM management,an increased volume of clinical studies and prolonged follow-up data are essential to evaluate its real efficacy and potential hazards.In addition,research regarding the therapeutic mechanisms of SBRT for HOCM,optimal dosages and treatment durations,indications and contraindications,prevention of complications,and enhancing the precision of radiation therapy,still needs to be further exploration,to determine the best therapeutic strategies.

Large-scale genetic manipulation of the genome refers to the genetic modification of large fragments of DNA using knockout, integration and translocation. Compared to small-scale gene editing, large-scale genetic manipulation of the genome allows for the simultaneous modification of more genetic information, which is important for understanding the complex mechanisms such as multigene interactions. At the same time, large-scale genetic manipulation of the genome allows for larger-scale design and reconstruction of the genome, and even the creation of entirely new genomes, with great potential in reconstructing complex functions. Yeast is an important eukaryotic model organism that is widely used because of its safety and easiness of manipulation. This paper systematically summarizes the toolkit for large-scale genetic manipulation of the yeast genome, including recombinase-mediated large-scale manipulation, nuclease-mediated large-scale manipulation, de novo synthesis of large DNA fragments and other large-scale manipulation tools, and introduces their basic working principles and typical application cases. Finally, the challenges and developments in large-scale genetic manipulation are presented.
DNA ; Gene Editing ; Genetic Engineering ; Saccharomyces cerevisiae/genetics* ; Translocation, Genetic

OBJECTIVE To analyze the influential factors for clinical efficacy of polymyxin B combined with other antibiotics in the treatment of carbapenem-resistant Acinetobacter baumannii （CRAB） pulmonary infection. METHODS A retrospective analysis was conducted on the clinical data of patients with CRAB pulmonary infection in our hospital from May 2021 to October 2024. Information such as age， gender， admitting department， infection status， underlying medical conditions， mechanical ventilation time， combination anti-infective treatment regimens， and the Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE-Ⅱ） score 24 h before medication was compiled. Based on the effectiveness of the treatment， patients were divided into treatment-effective group and treatment-ineffective group. Univariate analysis and multivariate Logistic regression analysis were employed to identify independent factors influencing clinical efficacy. RESULTS A total of 156 patients were included， and 108 patients were treated effectively， with an effective rate of 69.23%. The results of univariate analysis indicated that there were statistically significant differences between 2 groups in terms of the duration of mechanical ventilation time， APACHE-Ⅱ score 24 h before medication， the number of complication types， the proportion of abnormal coagulation function， anti-infective treatment course， and hospital stay before medication （P＜0.05）. The results of multivariate Logistic regression analysis showed that APACHE-Ⅱ score≥15 points 24 h before medication [OR＝2.965， 95%CI （1.284， 6.845）， P＝0.020]， mechanical 20251606） ventilation time≥10 d [OR＝3.577， 95%CI （1.185， 10.793）， P＝0.037] and hospital stay≥14 d before medication [OR＝2.422， 95%CI （1.036， 5.654）， P＝0.041] were independent 15120420253@139.com risk factors， and anti-infective treatment course＞7 d was a protective factor [OR＝0.445， 95%CI （0.221， 0.895）， P＝0.043]. CONCLUSIONS This study shows that the effective rate of polymyxin B combined with other antibiotics in the treatment of CRAB pulmonary infection is less than 70%. The mechanical ventilation time≥10 d， APACHE-Ⅱ score≥15 points 24 h before medication， and hospital stay≥14 d before medication may lead to treatment failure， whereas anti-infective treatment course＞7 d may be associated with treatment success.

Childhood is a critical period for growth and development, and the oral microbiota, as the second most diverse microbial community in the human body, plays a pivotal role in maintaining children's health. Recent studies have demonstrated that dysbiosis of the oral microbiota not only contributes to oral diseases such as dental caries and periodontitis but may also influence the development of children's skeletal, nervous, digestive, cardiovascular, and immune systems through mechanisms involving inflammatory responses, metabolic regulation, and cross-organ communication networks. This review systematically examines the role of the oral microbiota in childhood growth and development and, guided by the core principles of the "active health" model, proposes multiple intervention strategies—including probiotics, xylitol, and mouthwashes—to optimize children's health through early oral microbiota modulation.

Oral health is closely related to systemic health. Common chronic oral diseases, periodontitis and periapical inflammation for example, not only affect the health of oral soft and hard tissues including the alveolar bone and gums, but may also cause changes in systemic conditions such as chronic low-grade inflammation, elevated oxidative stress levels, and dysbiosis of the microbiota. These changes in systemic health can exacerbate the progression of obesity. Therefore, through proactive oral health interventions such as maintaining good oral hygiene habits, modifying dietary structures, and undergoing oral examinations, it is possible to effectively prevent and alleviate inflammatory oral diseases, and actively intervene in obesity. This article delves into the impact of inflammatory oral diseases on obesity and their underlying mechanisms, defines the concept of "oral proactive healthcare", and systematically summarizes their preventive and therapeutic effects on inflammatory oral diseases, thereby demonstrating the potential of improving obesity through proactive oral health strategies.

To evaluate the correlation between ultrasound ossification ratio(OR) and exercise intensity among adolescents.