ABSTRACT
Cage-type structures based on coordination and dynamic covalent chemistry have the characteristics of facile and efficient preparation but poor stability. Chemically stable organic cages, generally involving fragment coupling and multi-step reactions, are relatively difficult to synthesize. Herein, we offer a general and modular strategy to customize covalent organic cages with diverse skeletons and sizes. First, one skeleton (S) module with three extension (E) modules and three reaction (R) modules are connected by one- or two-step coupling to get the triangular monomer bearing three reaction sites. Then one-pot Friedel-Crafts condensation of the monomer and linking module of paraformaldehyde produces the designed organic cages. The cage forming could be regulated by the geometrical configuration of monomeric blocks. The S-E-R angles in the monomer is crucial; only 120o (2,4-dimethoxyphen as reaction module) or 60o (2,5-dimethoxyphen as reaction module) angle between S-E-R successfully affords the resulting cages. By the rational design of the three modules, a series of organic cages have been constructed. In addition, the host-guest properties show that the representative cages could strongly encapsulate neutral aromatic diimine guests driven by solvophobic interactions in polar solvents, giving the highest association constant of (2.58 ± 0.18) × 105 M-1.
ABSTRACT
BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.
Subject(s)
Colonic Neoplasms , Humans , Reproducibility of Results , Retrospective Studies , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/surgery , Body Composition , Inflammation/diagnostic imaging , Inflammation/etiology , Nomograms , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , TomographyABSTRACT
Herein, a novel molecule S4, which could form a uniform S4 spherical aggregate in water, was synthesized, and the S4 aggregate was used to load Dox to prepare the S4@Dox nanomedicine. The loading efficiency was 80.0 ± 4.5%. The pH response and slow release of Dox were the typical characteristics of the S4@Dox nanomedicine. In vitro experiments showed that cancer cells could successfully phagocytose S4 aggregates and the S4@Dox nanomedicine. The toxicity of S4 aggregates to MCF-7, HepG2, and H22 cells was low, and the S4@Dox nanomedicine had better antitumor activity and specific targeting, especially to the MCF-7 cells. The antitumor activity in vivo and in the tissue section showed that the S4@Dox nanomedicine could significantly reduce Dox toxicity, effectively induce the apoptosis of cancer cells, and effectively inhibit tumor growth, which showed that the nanomedicine had better antitumor activity.
Subject(s)
Nanoparticles , beta-Cyclodextrins , Humans , Drug Carriers , Doxorubicin/pharmacology , Serum Albumin, Human , beta-Cyclodextrins/pharmacology , MCF-7 Cells , Hydrogen-Ion Concentration , Drug LiberationABSTRACT
Tantalum aluminum carbide (Ta4AlC3) phase ceramic (MAX) material has attracted much attention because of its high conductivity, high strength, corrosion resistance, and good optical properties. However, there are too few reports on lasers with Ta4AlC3-based saturable absorbers (SAs). We prepared and characterized a Ta4AlC3-based SA whose nonlinear absorption performances were achieved at a 2 µm waveband range and which was used in a passively Q-switched (PQS) Tm:YAP laser. In the PQS mode, a maximum average output power of 0.78 W was achieved with the central output wavelength of 1991.86 nm from a PQS Tm:YAP laser, corresponding to a pulse duration of 926 ns at 143.8 kHz.
ABSTRACT
CircRNAs play vital roles in biological system mainly through binding RNA-binding protein (RBP), which is essential for regulating physiological processes in vivo and for identifying causal disease variants. Therefore, predicting interactions between circRNA and RBP is a critical step for the discovery of new therapeutic agents. Application of various deep-learning models in bioinformatics has significantly improved prediction and classification performance. However, most of existing prediction models are only applicable to specific type of RNA or RNA with simple characteristics. In this study, we proposed an attractive deep learning model, MSTCRB, based on transformer and attention mechanism for extracting multi-scale features to predict circRNA-RBP interactions. Therein, K-mer and KNF encoding are employed to capture the global sequence features of circRNA, NCP and DPCP encoding are utilized to extract local sequence features, and the CDPfold method is applied to extract structural features. In order to improve prediction performance, optimized transformer framework and attention mechanism were used to integrate these multi-scale features. We compared our model's performance with other five state-of-the-art methods on 37 circRNA datasets and 31 linear RNA datasets. The results show that the average AUC value of MSTCRB reaches 98.45 %, which is better than other comparative methods. All of above datasets are deposited in https://github.com/chy001228/MSTCRB_database.git and source code are available from https://github.com/chy001228/MSTCRB.git.
ABSTRACT
The metastasis is a major reason for the poor prognosis of the patients with prostate cancer (PC). Currently, androgen deprivation therapy (ADT) is the basic method for the treatment of PC regardless of surgery or drug treatments. However, ADT therapy is generally not recommended for patients with advanced/metastatic PC. Herein, we report for the first time a long non-coding RNA (lncRNA)-PCMF1 which promotes the progression of Epithelial-Mesenchymal Transition (EMT) in PC cells. Our data demonstrated that PCMF1 in metastatic PC tissues increased significantly compared to non-metastatic specimens. Mechanism research showed that PCMF1 could competitively bind to hsa-miR-137 instead of the 3' -Untranslated Region (UTR) of Twist Family BHLH Transcription Factor 1 (Twist1) by acting as an endogenous miRNA sponge. Furthermore, we found that silence of PCMF1 effectively blocked the EMT in PC cells by indirectly suppressing Twist1 protein mediated by hsa-miR-137 at post-transcriptional level. In summary, our research shows that PCMF1 promotes the EMT of PC cells by causing the functional inactivation of hsa-miR-137 on Twist1 protein, which is an independent risk factor of PC. PCMF1 knockdown combined with hsa-miR-137 expression is a promising PC-targeted therapy. Furthermore, PCMF1 is also expected to act as a useful marker for predicting malignant changes and assessing the prognosis of PC patients.
Subject(s)
MicroRNAs , Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , RNA, Long Noncoding/genetics , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism , Epithelial-Mesenchymal Transition/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Androgen Antagonists , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Movement/geneticsABSTRACT
Bacterial drug resistance is becoming increasingly serious, and it is urgent to develop effective antibacterial drugs. Antimicrobial peptides (AMPs), as potential candidates against bacteria, have a broad prospect for development. Herein, a series of AMPs with biological characteristics (net positive charge, amphiphilicity, and α-helix), an AXA motif recognized by membrane bound serine protease type I signal peptidases (SPase I), an FLPII motif to reduce hemolysis, and a monosaccharide motif to improve the stability and activity were designed and synthesized, and among which, the glycolipidpeptide GLP6 (glycosylated LP6 lipopeptide) had excellent antibacterial and immunomodulatory activity, good stability and biocompatibility, and excellent biofilm eradication and membrane penetrating activity. The positively charged spherical aggregates formed by self-assembly of GLP6 could encapsulate tetracycline (TC) to form GLP6@TC with a sustained-release effect, which could enhance the sensitivity of bacteria to the antibiotic and realize combined sterilization. The results of acute peritonitis and bacterial keratitis showed that GLP6@TC had a good combined antibacterial effect and the ability to inhibit interleukin-2 (IL-2), which could significantly reduce the inflammatory response while treating bacterial infection, and it had great potential for application. The results of computer molecular docking showed the AXA motif could effectively bind to SPase I, which was consistent with the results of biological experiments. In general, the study could provide a perspective for the design of AMPs and combined antibacterial therapy.
Subject(s)
Anti-Infective Agents , Antimicrobial Cationic Peptides , Molecular Docking Simulation , Antimicrobial Cationic Peptides/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria , Microbial Sensitivity TestsABSTRACT
Pseudomyxoma peritonei, a rare condition consisting of intraperitoneal mucinous tumors and ascites, most commonly arises from mucinous tumors of the appendix. Very rarely, mucinous deposits arise in the retroperitoneum without intraperitoneal involvement. This has been termed pseudomyxoma extraperitonei. It is a rare and poorly understood condition that is heterogeneous in its clinical behavior, and only a few cases presenting as localized disease in the retroperitoneum have been reported. In this paper, we report the first case of pseudomyxoma extraperitonei presenting as a simple renal hilar mass and mimicking a tumor of renal origin in a horseshoe-kidney patient. The patient underwent isthmusectomy and nephrectomy. Immunohistochemical staining suggested appendiceal origin. She remained alive without adjuvant therapy postoperatively, and no evidence of recurrence was present for 25 months.