Multiple brain abscesses caused by Nocardia farcinica infection after hand injury: A case report and literature review.

RATIONALE: Nocardia infection is commonly regarded as an opportunistic pulmonary pathogen affecting debilitated or immunocompromised individuals. Brain abscesses caused by Nocardia farcinica are rare and pose a diagnostic challenge. Traditional diagnostic techniques for identifying Nocardia species, such as blood culture, microscopy, and pathology, have shown inadequate performance. In the reported case, we applied metagenomic next-generation sequencing (mNGS) to diagnose a case of brain abscess due to N. farcinica. PATIENT CONCERNS: A 66-year-old female developed a brain abscess after sustaining a hand injury. The patient exhibited a gradual change in personality and experienced tremors in her right upper limb for a duration of 1 month. DIAGNOSES: The pathogen responsible for the multiple brain abscesses was identified in the cerebrospinal fluid as N. farcinica through mNGS. INTERVENTIONS: Antibiotic treatment included trimethoprim-sulfamethoxazole, linezolid, amikacin, meropenem, and moxifloxacin. OUTCOMES: The patient's symptoms and signs improved significantly after administration of antibiotics to which the pathogen is known to be sensitive. After 5 months of follow-up, magnetic resonance imaging of the head showed that the abscess was basically cured. The patient lived a normal life with no adverse drug reactions. LESSONS: Nocardia brain infection is characterized by an insidious onset and lacks distinctive clinical and imaging features. mNGS was advantageous for the timely identification and management of Nocardia-associated brain abscess in the present case and obviated the need for invasive brain surgery. Expeditious and precise diagnosis coupled with prompt antibiotic therapy can significantly reduce the mortality rate associated with this condition.

Downregulation of Protease Cathepsin D and Upregulation of Pathologic α-Synuclein Mediate Paucity of DNAJC6-Induced Degeneration of Dopaminergic Neurons.

A homozygous mutation of the DNAJC6 gene causes autosomal recessive familial type 19 of Parkinson's disease (PARK19). To test the hypothesis that PARK19 DNAJC6 mutations induce the neurodegeneration of dopaminergic cells by reducing the protein expression of functional DNAJC6 and causing DNAJC6 paucity, an in vitro PARK19 model was constructed by using shRNA-mediated gene silencing of endogenous DANJC6 in differentiated human SH-SY5Y dopaminergic neurons. shRNA targeting DNAJC6 induced the neurodegeneration of dopaminergic cells. DNAJC6 paucity reduced the level of cytosolic clathrin heavy chain and the number of lysosomes in dopaminergic neurons. A DNAJC6 paucity-induced reduction in the lysosomal number downregulated the protein level of lysosomal protease cathepsin D and impaired macroautophagy, resulting in the upregulation of pathologic α-synuclein or phospho-α-synucleinSer129 in the endoplasmic reticulum (ER) and mitochondria. The expression of α-synuclein shRNA or cathepsin D blocked the DNAJC6 deficiency-evoked degeneration of dopaminergic cells. An increase in ER α-synuclein or phospho-α-synucleinSer129 caused by DNAJC6 paucity activated ER stress, the unfolded protein response and ER stress-triggered apoptotic signaling. The lack of DNAJC6-induced upregulation of mitochondrial α-synuclein depolarized the mitochondrial membrane potential and elevated the mitochondrial level of superoxide. The DNAJC6 paucity-evoked ER stress-related apoptotic cascade, mitochondrial malfunction and oxidative stress induced the degeneration of dopaminergic neurons via activating mitochondrial pro-apoptotic signaling. In contrast with the neuroprotective function of WT DNAJC6, the PARK19 DNAJC6 mutants (Q789X or R927G) failed to attenuate the tunicamycin- or rotenone-induced upregulation of pathologic α-synuclein and stimulation of apoptotic signaling. Our data suggest that PARK19 mutation-induced DNAJC6 paucity causes the degeneration of dopaminergic neurons via downregulating protease cathepsin D and upregulating neurotoxic α-synuclein. Our results also indicate that PARK19 mutation (Q789X or R927G) impairs the DNAJC6-mediated neuroprotective function.

Adult ovarian and sellar region mixed germ cell tumor: a case report and literature review.

Mixed germ cell tumors (mGCTs) involving both the ovaries and sellar region have been rarely reported; thus, they pose significant challenges in clinical management. Our report of a case of a 26-year-old female with left ovarian mGCTs (dysgerminoma + yolk sac tumor) who presented with postoperative headaches and blurred vision contributes new information to the literature on treating mGCTs, which can lead to standardized regimens and sequencing guidelines. A physical examination revealed right temporal hemianopia, and elevated levels of alpha-fetoprotein were detected in serum and cerebrospinal fluid. Magnetic resonance imaging (MRI) of the sellar region revealed a space-occupying lesion. Pathological examination of the tumor after endoscopic transnasal resection confirmed the diagnosis of mGCTs (germinomas + yolk sac tumor). The patient received adjuvant chemotherapy and radiotherapy at reduced dosages. During follow-up, tumor markers remained within normal limits, and there was no evidence of tumor recurrence on sellar region MRI. This case highlights the rarity of the simultaneous occurrence of ovarian and sellar region mGCTs and emphasizes the importance of accurate diagnosis and multidisciplinary management.

Development of Peptide Paratope Mimics Derived from the Anti-ROR1 Antibody and Long-Acting Peptide-Drug Conjugates for Targeted Cancer Therapy.

Antibody-based targeted therapy in cancer faces a challenge due to uneven antibody distribution in solid tumors, hindering effective drug delivery. We addressed this by developing peptide mimetics with nanomolar-range affinity for Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using computational methods. These peptides showed both specific targeting and deep penetration in vitro and in vivo. Additionally, we created peptide-drug conjugates (PDCs) by linking targeting peptides to toxin drugs via various linkers and enhancing their in vivo half-life with fatty side chains for albumin binding. The antitumor candidate II-3 displayed exceptional affinity (KD = 1.72 × 10-9 M), internalization efficiency, anticancer potency (IC50 = 0.015 ± 0.002 µM), and pharmacokinetics (t1/2 = 2.6 h), showcasing a rational approach for designing PDCs with favorable tissue distribution and strong tumor penetration.

Exploring the Mechanism of Cardiorenal Protection with Finerenone Based on Network Pharmacology.

INTRODUCTION: Large prospective trials have demonstrated that finerenone could reduce the risk of cardiovascular death and progression of renal failure among patients with chronic kidney disease associated heart failure and/or type 2 diabetes mellitus (T2DM). The aim of this study was to explore the molecular mechanism of finerenone in the treatment of cardiorenal diseases through network pharmacology. METHODS: The STITH, SwissTargetPrediction, PharmMapper, DrugBank, and ChEMBL databases were used to screen the targets of finerenone. The disease-related targets were retrieved from the DisGeNET, GeneCards, CTD, OMIM, and MalaCards databases. The protein-protein interaction (PPI) network was conducted with STRING database and Cytoscape software. The clusterProfiler R package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The interactions of key targets and finerenone were analyzed by molecular docking in Autodock software. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Histopathology of myocardial and renal tissues was observed by hematoxylin-eosin (HE) staining, and detection of protein expressions was conducted using Western blotting. RESULTS: A total of 111 potential cardiorenal targets of finerenone were identified. The main mechanisms of action may be associated with lipids and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and diabetic cardiomyopathy. The hub targets demonstrated by the PPI network were CASP3, ALB, MMP9, EGFR, ANXA5, IGF1, SRC, TNFRSF1A, IL2, and PPARG, and the docking results suggested that finerenone could bind to these targets with high affinities. HE staining revealed the cardiorenal protection of finerenone on diabetic mice. In addition, the protein expressions of CASP3 and EGFR were increased while ALB was decreased in myocardial and renal tissues in diabetic mice compared with control mice, which were reversed by finerenone. CONCLUSION: This study suggested that finerenone exerts cardiorenal benefits through multiple targets and pathways.

Simultaneous removal of nitrogen, phosphorus, and organic matter from oligotrophic water in a system containing biochar and construction waste iron: Performances and biotic community analysis.

The issue of combined pollution in oligotrophic water has garnered increasing attention in recent years. To enhance the pollutant removal efficiency in oligotrophic water, the system containing Zoogloea sp. FY6 was constructed using polyester fiber wrapped sugarcane biochar and construction waste iron (PWSI), and the denitrification test of simulated water and actual oligotrophic water was carried out for 35 days. The experimental findings from the systems indicated that the removal efficiencies of nitrate (NO3--N), total nitrogen (TN), chemical oxygen demand (COD), and total phosphorus (TP) in simulated water were 88.61%, 85.23%, 94.28%, and 98.90%, respectively. The removal efficiencies of actual oligotrophic water were 83.06%, 81.39%, 81.66%, and 97.82%, respectively. Furthermore, the high-throughput sequencing data demonstrated that strain FY6 was successfully loaded onto the biological carrier. According to functional gene predictions derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the introduction of PWSI enhanced intracellular iron cycling and nitrogen metabolism.

Engineering Nanozymes for Tumor Therapy via Ferroptosis Self-Amplification.

Ferroptosis induction is an emerging strategy for tumor therapy. Reactive oxygen species (ROS) can induce ferroptosis but are easily consumed by overexpressed glutathione (GSH) in tumor cells. Therefore, achieving a large amount of ROS production in tumor cells without being consumed is key to efficiently inducing ferroptosis. In this study, a self-amplifying ferroptosis-inducing therapeutic agent, Pd@CeO2-Fe-Co-WZB117-DSPE-PEG-FA (PCDWD), is designed for tumor therapy. PCDWD exhibits excellent multi-enzyme activities due to the loading of Fe-Co dual atoms with abundant active sites, including peroxidase-like enzymes, catalase-like enzymes, and glutathione oxidases (GSHOx), which undergo catalytic reactions in the tumor microenvironment to produce ROS, thereby inducing ferroptosis. Furthermore, PCDWD can also deplete GSH in tumor cells, thus reducing the consumption of ROS by GSH and inhibiting the expression of GSH peroxidase 4. Moreover, the photothermal effect of PCDWD can not only directly kill tumor cells but also further enhance its own enzyme activities, consequently promoting ferroptosis in tumor cells. In addition, WZB117 can reduce the expression of heat shock protein 90 by inhibiting glucose transport, thereby reducing the thermal resistance of tumor cells and further improving the therapeutic effect. Finally, X-ray computed tomography imaging of PCDWD guides it to achieve efficient tumor therapy.

miR397 regulates cadmium stress response by coordinating lignin polymerization in the root exodermis in Kandelia obovata.

Secondary lignification of the root exodermis of Kandelia obovata is crucial for its response to adversity such as high salinity and anaerobic environment, and this lignification is also effective in blocking cadmium transport to the roots. However, how the differences in lignification of root exodermis at different developmental stages respond to Cd stress and its regulatory mechanisms have not been revealed. In this study, after analyzing the root structure and cell wall thickness using a Phenom scanning electron microscope as well as measuring cadmium content in the root cell wall, we found that the exodermis of young and mature roots of K. obovata responded to Cd stress through the polymerization of different lignin monomers, forming two different mechanisms: chelation and blocking. Through small RNA sequencing, RLM-5'-RACE and dual luciferase transient expression system, we found that miR397 targets and regulates KoLAC4/17/7 expression. The expression of KoLAC4/17 promoted the accumulation of guaiacyl lignin during lignification and enhanced the binding of cadmium to the cell wall. Meanwhile, KoLAC7 expression promotes the accumulation of syringyl lignin during lignification, which enhances the obstruction of cadmium and improves the tolerance to cadmium. These findings enhance our understanding of the molecular mechanisms underlying the differential lignification of the root exodermis of K. obovata in response to cadmium stress, and provide scientific guidance for the conservation of mangrove forests under heavy metal pollution.

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin.

Posterior capsule opacification (PCO) remains the predominant complication following cataract surgery, significantly impairing visual function restoration. In this study, we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery. The model incorporated a threaded structure for accurate positioning and observation, allowing for opening and closing. Utilizing 3D printing technology, a stable external support system was created using resin material consisting of a rigid, hollow base and cover. To replicate the lens capsule structure, a thin hydrogel coating was applied to the resin scaffold. The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques, including calcein-AM/PI staining, rhodamine staining, BODIPY-C11 staining and EdU staining in conjunction with transwell assays. Additionally, the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties, including 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), THZ1, sorbinil, 4-octyl itaconate (4-OI), xanthohumol, zebularine, rapamycin and caffeic acid phenethyl ester, on human lens epithelial cells (HLECs). Confocal microscopy facilitated comprehensive imaging of the PCO model. The results demonstrated that the GelMA 60 5% + PLMA 2% composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels. Moreover, compared to using hydrogel as the material for 3D printing the entire model, applying surface hydrogel spin coating with parameters of 2000 rpm × 2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis. Furthermore, rapamycin, 4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study. Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model, showcasing robust cell viability and regular morphology. In conclusion, the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.

Novel dual-target FAAH and TRPV1 ligands as potential pharmacotherapeutics for pain management.

Dual-acting drugs that simultaneously inhibit fatty acid amide hydrolase (FAAH) and antagonize the transient receptor potential vanilloid 1 (TRPV1) is a promising stronger therapeutic approach for pain management without side effects associated with single-target agents. Here, several series of dual FAAH/TRPV1 blockers were designed and synthesized through rational molecular hybridization between the pharmacophore of classical TRPV1 antagonists and FAAH inhibitors. The studies resulted in compound 2r, which exhibited strong dual FAAH/TRPV1 inhibition/antagonism in vitro, exerted powerful analgesic effects in formalin-induced pain test (phase II, in mice), desirable anti-inflammatory activity in carrageenan-induced paw edema in rats, no TRPV1-related hyperthermia side effect, and favorable pharmacokinetic properties. Meanwhile, the contributions of TRPV1 and FAAH to its antinociceptive effects were verified by target engagement and molecular docking studies. Overall, compound 2r can serve as a new scaffold for developing FAAH/TRPV1 dual-activie ligands to counteract pain.

Biodegradable Monometallic Aluminum as a Biotuner for Tumor Pyroptosis.

Pyroptosis is an effective anti-tumor strategy. However, monometallic pyroptosis biotuners have not been explored until now. Here, we discover for the first time that biodegradable monometallic Al can act as a pyroptosis biotuner for tumor therapy. pH-sensitive Al nanoparticles (Al@P) are obtained by equipping polyethylene glycol-b-(poly(methyl methacrylate)-co-poly(4-vinylpyridine), which can exert their effect at the tumor site without affecting normal cells. The H2 and Al3+ release by Al@P in the acidic environment of tumors disrupts the redox balance and ionic homeostasis in tumor cells, thus generating large amounts of reactive oxygen species (ROS), leading to caspase-1 activation, gasdermin D cleavage, and IL-1ß/LDH release, which induces canonical pyroptotic death. Meanwhile, the prodrug Doxorubicin (Pro-DOX) is successfully loaded onto Al@P (Al@P-P) and can be activated by ROS to release DOX in the tumor cells, thus further improving the tumor-killing efficiency. Ultimately, Al@P-P is degradable and exhibits efficient tumor inhibition.

Synergism Variation between intracellular Glutathione, phycocyanin and SOD in microalgae by carbon quantum dot fluorescence.

Based on the use of CQDs as fluorescent probe and covalent coupling method to detect biological molecules with amino groups, to deeply analysis and detect the metabolism of Microcystis aeruginosa. The metabolic changes of carboxyl biomolecules in Microcystis aeruginosa were analyzed by covalent coupling method, including GSH, phycocyanin and SOD enzyme. The changes of GSH content and its correlation between phycocyanin, SOD were analyzed. The content of phycocyanin and SOD reached the maximum on the 65th day, and GSH was more sensitive to the growth and metabolism of microalgae. GSH plays an important role in reducing the external oxidative damage of microalgae cells. The synthesis of glutathione (GSH), GSH/GSSG mutual transformation, the production of phytochelating peptide (PC), the ASA-GSH cycle, and other physiological processes are interconnected. These interactions are crucial for preserving the antioxidant properties of microalgae and regulating redox-sensitive signal transduction.

Denitrification driven by additional ferrous (Fe2+) and manganous (Mn2+) and removal mechanism of tetracycline and cadmium (Cd2+) by biogenic Fe-Mn oxides.

Zoogloea sp. MFQ7 achieved excellent denitrification of 91.71% at ferrous to manganous ratio (Fe/Mn) of 3:7, pH of 6.5, nitrate concentration of 25 mg L-1 and carbon to nitrogen ratio of 1.5. As the Fe/Mn ratio increasd, the efficiency of nitrate removal gradually decreased, indicating that strain MFQ7 had a higher affinity for Mn2+ than Fe2+. In situ generated biogenic Fe-Mn oxides (BFMO) contained many iron-manganese oxides (MnO2, Mn3O4, FeO(OH), Fe2O3, and Fe3O4) as well as reactive functional groups, which play an significant part in tetracycline (TC) and cadmium (Cd2+) adsorption. The adsorption of TC and Cd2+ by BFMO can better fit the pseudo-second-order and Langmuir models. In addition, multiple characterization results of before and after adsorption indicated that the removal mechanism of BFMO on TC and Cd2+ was probably surface complexation adsorption and redox reactions.

Near-Infrared-Responsive Rare Earth Nanoparticles for Optical Imaging and Wireless Phototherapy.

Near-infrared (NIR) light is well-suited for the optical imaging and wireless phototherapy of malignant diseases because of its deep tissue penetration, low autofluorescence, weak tissue scattering, and non-invasiveness. Rare earth nanoparticles (RENPs) are promising NIR-responsive materials, owing to their excellent physical and chemical properties. The 4f electron subshell of lanthanides, the main group of rare earth elements, has rich energy-level structures. This facilitates broad-spectrum light-to-light conversion and the conversion of light to other forms of energy, such as thermal and chemical energies. In addition, the abundant loadable and modifiable sites on the surface offer favorable conditions for the functional expansion of RENPs. In this review, the authors systematically discuss the main processes and mechanisms underlying the response of RENPs to NIR light and summarize recent advances in their applications in optical imaging, photothermal therapy, photodynamic therapy, photoimmunotherapy, optogenetics, and light-responsive drug release. Finally, the challenges and opportunities for the application of RENPs in optical imaging and wireless phototherapy under NIR activation are considered.

Wireless Photoactivated Targeted Nanosystem for Oncotherapy Via Synergistic Effects of Hyperthermia/Redox Stress Amplification/GSK-3ß Activity Inhibition.

Highly soluble salts and gas mediated therapies are emerging antitumor strategies. However, the therapeutic efficacy remains restricted by difficulty in delivering them to the tumor site and poorly controlled release in deep tissues. Here, an intelligent wireless photoactivated targeted nanosystem is designed for delivering LiCl and H2 to tumors for therapy. LiCl causes cell death by inhibiting the activity of GSK-3ß. H2 selectively interacts with reactive oxygen species in the tumor, leading to redox stress, which induces apoptosis. The significant heat generated by the nanosystem not only kills tumor cells but also accelerates the dissolution of LiCl and the release of H2. The rapid dissolution of LiCl leads to a surge in intracellular osmotic pressure, which further intensifies the redox stress response and enhances the efficiency of therapy. The nanosystem shows efficient tumor therapeutic capability via synergistic effects of hyperthermia/redox stress amplification/GSK-3ß activity inhibition.

Tear inflammatory cytokines as potential biomarkers for myopic macular degeneration.

Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.

Simultaneous removal of phosphorus, zinc, and lead from oligotrophic ecosystem by iron-driven denitrification: Performance and mechanisms.

Based on the current situation of complex pollution caused in surface water by oligotrophic condition and heavy metal release from river and lake bottom sediments. This study aimed to achieve the simultaneous removal of nitrate, phosphorus, Zn2+ and Pb2+ through microbial approach. At nitrate concentration of 4.82 mg L-1, carbon to nitrogen ratio of 1.5, pH of 6.0, and Fe2+ concentration of 5.0 mg L-1, the nitrate removal efficiency of Zoogloea sp. FY-6 reached 95.17%. The addition of pollutants under these conditions resulted in 88.76% removal of total phosphorus at 18 h, and 85.46 and 78.59% removal of Zn2+ and Pb2+ respectively, and there was competition for adsorption between Zn2+ and Pb2+. Extracellular polymers and fluorescence excitation-emission substrates confirmed that Fe2+ reduced heavy metal toxicity through promoting bacterial production of secretions and promotes denitrification as a carbon source. Meanwhile, contaminant removal curves and Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy demonstrated the synchronous removal of Zn2+ and Pb2+ mainly through biological action and the formation of nanoscale iron oxides. Biological-iron precipitation also provided adsorption sites for phosphorus. This research provides the theoretical foundation for applying microorganisms to restore oligotrophic source water (rivers and lakes) containing complex pollutants.

Identification of highly potent 2,4-diarylaminopyrimidine analogs of a typical piperidinyl-4-ol moiety as promising antitumor ALK inhibitors.

In light of the cocrystal structure of ceritinib with anaplastic lymphoma kinase (ALK)WT protein, a series of novel 2,4-diarylaminopyrimidine analogs (L1-L25) bearing a typical piperidinyl-4-ol moiety were designed and synthesized with improved biological and physicochemical properties. Satisfyingly, most compounds demonstrated moderate to excellent antitumor effects with IC50 values below 5 µM on ALK-positive Karpas299 and H2228 cells. In particular, L6 bearing the 1-(6-methoxy-pyridin-2-yl)-4-(morpholinomethyl)piperidinyl-4-ol moiety was detected as the optimal compound against ALK-dependent cell lines of Karpas299 (0.017 µM) and H2228 cells (0.052 µM), in company with encouraging ALK enzyme inhibition (ALKWT , IC50 = 1.8 nM). In addition, L6 was also capable of inhibiting ALK-resistant mutations, including ALKL1196M (3.9 nM) and ALKG1202R (5.2 nM). Remarkably, L6 typically repressed colony formation and migration of H2228 cells in a dose-dependent manner. Meanwhile, acridine orange-ethidium bromide staining analysis indicated that the proapoptotic effect of L6 was better than that of ceritinib at the same concentration (50 nM). Ultimately, the binding patterns of L6 to ALKWT and ALKG1202R were ideally established, which further confirmed the structural basis in accordance with the structure-activity relationship analysis.

Prediction of lymph node status in patients with early-stage cervical cancer based on radiomic features of magnetic resonance imaging (MRI) images.

BACKGROUND: Lymph node metastasis is an important factor affecting the treatment and prognosis of patients with cervical cancer. However, the comparison of different algorithms and features to predict lymph node metastasis is not well understood. This study aimed to construct a non-invasive model for predicting lymph node metastasis in patients with cervical cancer based on clinical features combined with the radiomic features of magnetic resonance imaging (MRI) images. METHODS: A total of 180 cervical cancer patients were divided into the training set (n = 126) and testing set (n = 54). In this cross-sectional study, radiomic features of MRI images and clinical features of patients were collected. The least absolute shrinkage and selection operator (LASSO) regression was used to filter the features. Seven machine learning methods, including eXtreme Gradient Boosting (XGBoost), Logistic Regression, Multinomial Naive Bayes (MNB), Support Vector Machine (SVM), Decision Tree, Random Forest, and Gradient Boosting Decision Tree (GBDT) are used to build the models. Receiver operating characteristics (ROC) curve and area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the performance of the models. RESULTS: Of these 180 patients, 49 (27.22%) patients had lymph node metastases. Five of the 122 radiomic features and 3 clinical features were used to build predictive models. Compared with other models, the MNB model was the most robust, with its AUC, specificity, and accuracy on the testing set of 0.745 (95%CI: 0.740-0.750), 0.900 (95%CI: 0.807-0.993), and 0.778 (95%CI: 0.667-0.889), respectively. Furthermore, the AUCs of the MNB models with clinical features only, radiomic features only, and combined features were 0.698 (95%CI: 0.692-0.704), 0.632 (95%CI: 0.627-0.637), and 0.745 (95%CI: 0.740-0.750), respectively. CONCLUSION: The MNB model, which combines the radiomic features of MRI images with the clinical features of the patient, can be used as a non-invasive tool for the preoperative assessment of lymph node metastasis.

Removal of oxytetracycline from wastewater by biochar modified with biosynthesized iron oxide nanoparticles and carbon nanotubes: Modification performance and adsorption mechanism.

The pollution problem of oxytetracycline (OTC) from wastewater becomes more serious, so an efficient, economical, and green adsorption material is urgently explored. In this study, the multilayer porous biochar (OBC) was prepared by coupling carbon nanotubes with iron oxide nanoparticles synthesized by Aquabacterium sp. XL4 to modify corncobs under medium temperature (600 °C) conditions. The adsorption capacity of OBC could reach 72.59 mg g-1 after preparation and operation parameters were optimized. In addition, various adsorption models suggested that OTC removal resulted from the combined effect of chemisorption, multilayer interaction, and disordered diffusion. Meanwhile, the OBC was fully characterized and exhibited a large specific surface area (237.51 m2 g-1), abundant functional groups, stable crystal structure, high graphitization, and mild magnetic properties (0.8 emu g-1). The OTC removal mechanisms mainly included electrostatic interactions, ligand exchange, π-π bonding reactions, hydrogen bonds, and complexation. pH and coexistence substance experiments revealed that the OBC possesses a wide pH adaptation range and excellent anti-interference ability. Finally, the safety and reusability of OBC were confirmed by repeated experiments. In summary, OBC as a biosynthetic material shows considerable potential for application in the field of purifying new pollution from wastewater.