Design, Synthesis and Insecticidal Activity of Novel meta-Diamide Compounds Containing Pyridine Rings.

In order to discover new meta-diamide compounds with good activity and novel structure, 15 related compounds were designed and synthesized by the bioisosterism principle with cyproflanilide as the lead compound. The insecticidal activities of these compounds against Plutella xylostella and Tetranychus cinnabarinus were tested, and the results of biological activity test showed that some compounds had more than 90 % insecticidal activity against Plutella xylostella at 1 mg/L and Tetranychus cinnabarinus at 100 mg/L. Especially, N-(2-bromo-6-(difluoromethoxy)-4-(perfluoro propan-2-yl)phenyl)-6-(isonicotinamido)picolinamide against Tetranychus cinnabarinus at 10 mg/L was 100 %, which was better than that of cyproflanilide. Molecular docking studies suggested that N-(2-bromo-6-(difluoromethoxy)-4-(perfluoropropan-2-yl)phenyl)-6-(4-cyano-2-methylbenzamido)picolinamide had a closely combined with the Plutella xylostella 3RHW (a glutamate-gated chloride channel). This study provides an avenue for designing and synthesizing a new generation of more effective pesticides.

Design, synthesis, and evaluation of new 2-oxoquinoline arylaminothiazole derivatives as potential anticancer agents.

A series of novel 2-oxoquinoline derivatives containing arylaminothiazole were designed and synthesized as potential antitumor agents. The synthesized compounds were evaluated for their in vitro cytotoxicity activity against HeLa, NCI-H460, T24 and SKOV3 cancer cell lines using MTT assay. Among them, compound A7 exhibited the most potent activity against the test cancer cell lines, with the IC50 values ranged from 4.4 to 8.7 µM. The results of tubulin polymerization assay showed that compound A7 could inhibit tubulin polymerization in vitro. Meanwhile, molecular docking study revealed that A7 can bind to the colchicine site of tubulin and formed hydrogen bonds with key amino acid residues in the active site. Further mechanism study demonstrated that compound A7 blocked cell cycle arrest at G2/M phase, induced cell apoptosis and depolarized mitochondria of HeLa cells. Collectively, our findings suggest that A7 could serve as a promising lead for the development of more efficient microtubule polymerization inhibitors for cancer therapy.

Temperature-Controlled Divergent Hydroamination Cyclization [2+2]-Cycloaddition Cascade Reactions of Homopropargylic Amines with 2-Butynedioates: Direct Access To Pyrrolo- b-cyclobutene and Dihydro-1 H-azepines.

The diversified temperature-controlled hydroamination cyclization cascade reactions of homopropargylic amines and 2-butynedioates were developed for the construction of various pyrrolo- b-cyclobutenes and dihydro-1 H-azepines, respectively. This reaction actually involved an intramolecular hydroamination cyclization of homopropargylic amines to give the active dihydropyrroles intermediates, which subsequently underwent [2+2]-cycloaddition with 2-butynedioates to generate the pyrrolo- b-cyclobutenes at no more than 120 °C. Alternatively, the dihydro-1 H-azepines were directly produced at 150 °C in the reactions of homopropargylic amines and 2-butynedioates. The application of substrate scope was wide, and the corresponding products were obtained in high to excellent yields.

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents.

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.

Development and trends in research on hypertension and atrial fibrillation: A bibliometric analysis from 2003 to 2022.

BACKGROUND: This study aimed to comprehensively analyze research related to hypertension and atrial fibrillation, 2 common cardiovascular diseases with significant global public health implications, using bibliometric methods from 2003 to 2022. METHODS: From the Web of Science Core Collection database, literature on the theme of hypertension and atrial fibrillation was retrieved. Subsequently, comprehensive bibliometric analyses were conducted across multiple dimensions utilizing software tools such as VOSviewer, Citespace, Pajek, Scimago Graphica, and ClusterProfiler. These analyses encompassed examinations of the literature according to country/region, institution, authors, journals, citation relationships, and keywords. RESULTS: It revealed an increasing interest and shifting focus in research over the years. The analysis covered 7936 relevant publications, demonstrating a gradual rise in research activity regarding hypertension combined with atrial fibrillation over the past 2 decades, with a stable growth trend in research outcomes. Geographically, Europe and the Americas, particularly the United States, have shown the most active research in this field, while China has also gained importance in recent years. Regarding institutional contributions, internationally renowned institutions such as the University of Birmingham and the Mayo Clinic have emerged as core forces in this research direction. Additionally, Professor Lip Gregory, with his prolific research output, has stood out among numerous scholars. The American Journal of Cardiology has become a primary platform for publishing research related to hypertension and atrial fibrillation, highlighting its central role in advancing knowledge dissemination in this field. The research focus has shifted from exploring the pathophysiological mechanisms to investigating the treatment of complications and risk factors associated with hypertension and atrial fibrillation. Future research will focus on in-depth exploration of genetic and molecular mechanisms, causal relationship exploration through Mendelian randomization studies, and the application of machine learning techniques in prediction and treatment, aiming to promote the development of precision medicine for cardiovascular diseases. CONCLUSION: In conclusion, this study provides a comprehensive overview of the developmental trajectory of research on hypertension and atrial fibrillation, presenting novel insights into trends and future research directions, thus offering information support and guidance for research in this crucial field of cardiovascular medicine.

Myocardial Perfusion in ST-Segment Elevation Myocardial Infarction Patients After Percutaneous Coronary Intervention: Influencing Factors and Intervention Strategies.

Aim We aim to explore the factors influencing myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) and evaluate the effects of different intervention strategies on myocardial perfusion improvement. Methods A retrospective analysis was conducted on 300 patients with STEMI who underwent primary percutaneous coronary intervention (PPCI) at our hospital between January 2020 and December 2022. Based on post-procedural coronary angiography results using the thrombolysis in myocardial infarction (TIMI) blood flow grade and myocardial blush grade (MBG), patients were categorized into two groups: the normal perfusion group (TIMI grade 3 or MBG 2-3, n=180) and the impaired perfusion group (TIMI grades 0-2 or MBG 0-1, n=120). The impaired perfusion group was further divided using a random number table into the thrombus aspiration-only group (control group, n=60) and the thrombus aspiration combined with nicorandil group (nicorandil group, n=60). A 1:1 propensity score matching method was employed to adjust for baseline characteristics between the groups. Clinical characteristics, hematological parameters, coronary lesion features, and percutaneous coronary intervention (PCI) technical parameters were compared between the matched groups. Additionally, a multivariate logistic regression analysis was performed to identify independent risk factors influencing myocardial perfusion. Furthermore, the post-procedural myocardial perfusion, cardiac function, and clinical prognosis were compared between the control and nicorandil groups. Results After matching, the baseline characteristics of the two groups were compared. The impaired perfusion group had older age, higher proportion of male patients, higher rates of diabetes and hypertension, longer time from symptom onset to balloon dilation, higher peak cardiac troponin I (cTnI) levels, higher proportion of left main or multivessel involvement, heavier coronary lesion burden, and lower balloon inflation pressure (P<0.05). Multivariate logistic regression analysis revealed that age of ≥65 years (odds ratio {OR}=2.34, 95% confidence interval {CI}=1.23-4.46, P<0.01), time from symptom onset to balloon dilation of ≥6 hours (OR=3.12, 95% CI=1.67-5.83, P<0.01), peak cTnI level of ≥100 ng/mL (OR=4.27, 95% CI=2.18-8.36, P<0.01), left main or multivessel involvement (OR=2.86, 95% CI=1.51-5.41, P<0.01), and balloon inflation pressure of <8 atm (OR=3.45, 95% CI=1.79-6.65, P<0.01) were independent risk factors affecting myocardial perfusion. In the intervention analysis, the nicorandil group showed superior post-procedural TIMI blood flow grade, MBG, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) functional classification compared to the control group (P<0.05). During a six-month follow-up, the nicorandil group had a lower incidence of major adverse cardiovascular events (MACE) compared to the control group (P<0.05). Conclusion Age, time from symptom onset to balloon dilation, peak cTnI level, extent of coronary artery lesions, and balloon inflation pressure were identified as independent risk factors affecting myocardial perfusion in STEMI patients after PCI. Compared to simple thrombus aspiration, thrombus aspiration combined with nicorandil demonstrated better improvement in myocardial perfusion, cardiac function, and clinical outcomes for patients with impaired perfusion.

Exploiting redundancy in large materials datasets for efficient machine learning with less data.

Extensive efforts to gather materials data have largely overlooked potential data redundancy. In this study, we present evidence of a significant degree of redundancy across multiple large datasets for various material properties, by revealing that up to 95% of data can be safely removed from machine learning training with little impact on in-distribution prediction performance. The redundant data is related to over-represented material types and does not mitigate the severe performance degradation on out-of-distribution samples. In addition, we show that uncertainty-based active learning algorithms can construct much smaller but equally informative datasets. We discuss the effectiveness of informative data in improving prediction performance and robustness and provide insights into efficient data acquisition and machine learning training. This work challenges the "bigger is better" mentality and calls for attention to the information richness of materials data rather than a narrow emphasis on data volume.

Prognostic value of serological markers of hepatitis B virus infection in squamous cell cervical cancer.

Objective: The current study aimed to investigate the prognostic value of serological markers of hepatitis B virus (HBV) infection in squamous cell cervical cancer. Methods: Squamous cell cervical cancer patients treated by concurrent chemoradiotherapy from January 2013 to December 2015 at Yunnan Cancer Hospital were retrospectively reviewed. Results: Of a total of 277 patients, 12 (4.33%), 93 (33.57%), 2 (0.72%), 25 (9.02%), and 36 patients (13.00%) were seropositive for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibodies (anti-HBs), hepatitis B envelope antigen (HBeAg), anti-hepatitis B envelope antibodies (anti-HBe), and anti-hepatitis B core antibodies (anti-HBc), respectively. No patients experienced more than mild hepatic adverse events during treatment. The five-year overall survival (OS) rates for patients with anti-HBs positive or negative status were 85.8% and 66.2% (p = 0.039), respectively. No statistically significant difference in the five-year OS rates was observed in HBsAg positive and negative, HBeAg positive and negative, anti-HBe positive and negative, anti-HBc positive and negative patients. The multivariable analysis revealed that anti-HBs positivity was an independent favorable prognostic factor for OS (HR= 0.279; 95%CI: 0.083-0.936; p = 0.039) in patients younger than 50 years. Conclusions: The presence of anti-HBs predicts a superior OS for squamous cell cervical cancer patients aged younger than 50 years.

Genome-wide profiling of chemoradiation­induced changes in alternative splicing in colon cancer cells.

Alternative splicing is a key mechanism that regulates protein diversity and has been found to be associated with colon cancer progression and metastasis. However, the function of alternative splicing in chemoradiation­resistant colon cancer remains elusive. In this study, we constructed a chemoradiation­resistant colon cancer cell line. Through RNA-sequencing of normal and chemoradiation­resistant colon cancer cells (HCT116), we found 818 genes that were highly expressed in the normal HCT116 cells, whereas 285 genes were highly expressed in the chemoradiation-resistant HCT116 (RCR-HCT116) cells. Gene ontology (GO) analysis showed that genes that were highly expressed in the HCT116 cells were enriched in GO categories related to cell cycle and cell division, whereas genes that were highly expressed in the RCR-HCT116 cells were associated with regulation of system processes and response to wounding. Analysis of alternative splicing events revealed that exon skipping was significantly increased in the chemoradiation­resistant colon cancer cells. Moreover, we identified 323 alternative splicing events in 293 genes that were significantly different between the two different HCT116 cell types. These alternative splicing­related genes were clustered functionally into several groups related with DNA replication, such as deoxyribonucleotide metabolic/catabolic processes, response to DNA damage stimulus and helicase activity. These findings enriched our knowledge by elucidating the function of alternative splicing in chemoradiation-resistant colon cancer.

Superelasticity, corrosion resistance and biocompatibility of the Ti-19Zr-10Nb-1Fe alloy.

Microstructure, mechanical properties, superelasticity and biocompatibility of a Ti-19Zr-10Nb-1Fe alloy are investigated. X-ray diffraction spectroscopy and transmission electron microscopy observations show that the as-cast Ti-19Zr-10Nb-1Fe alloy is composed of α' and ß phases, but only the ß phase exists in the as-rolled and as-quenched alloys. The tensile stress-strain tests indicate that the as-quenched alloy exhibits a good combination of mechanical properties with a large elongation of 25%, a low Young's modulus of 59 GPa and a high ultimate tensile stress of 723 MPa. Superelastic recovery behavior is found in the as-quenched alloy during tensile tests, and the corresponding maximum of superelastic strain is 4.7% at the pre-strain of 6%. A superelastic recovery of 4% with high stability is achieved after 10 cyclic loading-unloading training processes. Potentiodynamic polarization and ion release measurements indicate that the as-quenched alloy shows a lower corrosion rate in Hank's solution and a much less ion release rate in 0.9% NaCl solution than those of the NiTi alloys. Cell culture results indicate that the osteoblasts' adhesion and proliferation are similar on both the Ti-19Zr-10Nb-1Fe and NiTi alloys. A better hemocompatibility is confirmed for the as-quenched Ti-19Zr-10Nb-1Fe alloy, attributed to more stable platelet adhesion and small activation degree, and a much lower hemolysis rate compared with the NiTi alloy.

Three-Dimensional BC/PEDOT Composite Nanofibers with High Performance for Electrode-Cell Interface.

There is an increasing need to synthesize biocompatible nanofibers with excellent mechanical and electrical performance for electrochemical and biomedical applications. Here we report a facile approach to prepare electroactive and flexible 3D nanostructured biomaterials with high performance based on bacterial cellulose (BC) nanofibers. Our approach can coat BC nanofibers with poly(3,4-ethylenedioxythiophene) (PEDOT) by in situ interfacial polymerization in a controllable manner. The PEDOT coating thickness is adjustable by the monomer concentration or reaction time during polymerization, producing nanofibers with a total diameter ranging from 30 to 200 nm. This fabrication process also provides a convenient method to tune different parameters such as the average pore size and electrical conductivity on the demands of actual applications. Our experiments have demonstrated that the 3D BC/PEDOT nanofibers exhibit high specific surface area, excellent mechanical properties, electroactive stability, and low cell cytotoxicity. With electrical stimulation, calcium imaging of PC12 neural cells on BC/PEDOT nanofibers has revealed a significant increase in the percentage of cells with higher action potentials, suggesting an enhanced capacitance effect of charge injection. As an attractive solution to the challenge of designing better electrode-cell interfaces, 3D BC/PEDOT nanofibers promise many important applications such as biosensing devices, smart drug delivery systems, and implantable electrodes for tissue engineering.