Dual Agents Research Articles

Nonuniform sliding-window reconstruction for accelerated dual contrast agent quantification with MR fingerprinting

ObjectiveMR fingerprinting (MRF) can enable preclinical studies of cell tracking by quantifying multiple contrast agents simultaneously, but faster scan times are required for in vivo applications. Sliding window (SW)-MRF is one option for accelerating MRF, but standard implementations are not sufficient to preserve the accuracy of T2*, which is critical for tracking iron-labelled cells in vivo.PurposeTo develop a SW approach to MRF which preserves the T2* accuracy required for accelerated concentration mapping of iron-labelled cells on single-channel preclinical systems.MethodsA nonuniform SW was applied to the MRF sequence and dictionary. Segments of the sequence most sensitive to T2* were subject to a shorter window length, preserving the T2* sensitivity. Phantoms containing iron-labelled CD8+ T cells and gadolinium were used to compare 24× undersampled uniform and nonuniform SW-MRF parameter maps. Dual concentration maps were generated for both uniform and nonuniform MRF and compared.ResultsLin’s concordance correlation coefficient, compared to gold standard parameter values, was much greater for nonuniform SW-MRF than for uniform SW-MRF. A Wilcoxon signed-rank test showed no significant difference between nonuniform SW-MRF and gold standards. Nonuniform SW-MRF outperformed the uniform SW-MRF concentration maps for all parameters, providing a balance between T2* sensitivity of short window lengths, and SNR of longer window lengths.ConclusionsNonuniform SW-MRF improves the accuracy of matching compared to uniform SW-MRF, allowing higher accelerated concentration mapping for preclinical systems.

Thermosensitive hydrogel with programmed dual-octenidine release combating biofilm for the treatment of apical periodontitis.

The utilization of intracanal medicaments is an indispensable procedure in root-canal treatment. However, the conventional intracanal medicaments still need improvement regarding antimicrobial efficacy and ease of clinical operation. To address the above issues, OCT/PECT@OCT + ALK composite hydrogel characterized by programming sequential release of dual antimicrobial agents has been proposed. Thanks to the self-assemble ability of amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), dual hydrophilic and hydrophobic antimicrobial agents could be easily encapsulated in the hydrogel system and tailored for sequential drug release for a better antibiofilm effect. The hydrophilic octenidine (Octenidine dihydrochloride, OCT-HCl) is encapsulated in the hydrophilic part of hydrogel for instantaneous elevating the drug concentration through bursting release, and the hydrophobic octenidine (Octenidine, OCT) is further loaded into the PECT nanoparticles to achieve a slower and sustained-release profile. Additionally, calcium hydroxide (Ca(OH)2) was incorporated into the system and evenly dispersed among PECT nanoparticles to create an alkaline (ALK) environment, synergistically enhancing the antibiofilm effect with higher efficiency and prolonged duration. The antibiofilm effect has been demonstrated in root-canal models and apical periodontitis rats, exhibiting superior performance compared to clinically used Ca(OH)2 paste. This study demonstrates that OCT/PECT@OCT + ALK composite thermosensitive hydrogel is a potential intracanal medicament with excellent antibiofilm effect and clinical operability.

Advanced combination therapy: is it the best way to break the therapeutic ceiling?

Current therapeutic strategies for inflammatory bowel disease (IBD) have reached a plateau in the rates of response and/or remission achieved with a single therapeutic agent. Consequently, the advanced combination therapy (ACT) strategy has emerged as a novel treatment concept for IBD. ACT involves the use of two different targeted therapies, whether biologic or small molecules, with the primary goal of overcoming the therapeutic plateau. Real-world evidence is accumulating among patients undergoing ACT, especially those dealing with concurrent IBD and extraintestinal manifestations or grappling with medically refractory IBD. The recently conducted VEGA study, a randomized clinical trial, has provided crucial insights by demonstrating that the short-term combination of dual biological agents can lead to superior disease control compared to single agents in patients diagnosed with ulcerative colitis (UC). This suggests that ACT holds promise as a therapeutic option to enhance disease control effectively. However, there is still limited evidence of ACT in UC patients who have proven refractory to biologic therapy and patients with Crohn's disease. This review aims to discuss whether ACT represents the optimal approach for overcoming the therapeutic ceiling in IBD.

Natural product-inspired [3 + 2] cycloaddition-based spirooxindoles as dual anticancer agents: synthesis, characterization, and biological evaluation by in vitro and in silico methods.

Breast and colorectal cancers are the most common tumors, with high recurrence and low survival rates. We designed and synthesized a series of spirooxindole pyrrolidinyl derivatives, which were further evaluated for anti-proliferative activity using MDA-MB-468 and HCT 15 cell lines. The best inhibitor of this class, compound 6f, showed a very good inhibition potency, both on the MDA-MB-468 and HCT 15 cells as confirmed by molecular docking and molecular dynamic studies that predicted its binding mode into the active site of the targets. In summary, this study provided a new anti-proliferative derivative 6f which is worthy of further research.

Chitosan dual gel-like functionalized with flavonoid extract and cinnamaldehyde oil using dual cross-linking agents: Characterization, antioxidant, and antimicrobial effects

This study evaluated antioxidant and antimicrobial properties of chitosan gel (Cs-gel) functionalized with cinnamaldehyde oil (CN) and orange peel-derived flavonoid extract (Fs) using the ionic-gelation method. Results showed that the encapsulation efficiencies of CCF-9 and CCN were 83.14 ± 3.34 and 80.56 ± 1.17%, respectively. The interaction of CN or Fs on Cs-gel indicates the presence of H-bonding formation, as observed by UV–vis spectroscopy, Fourier transform infrared spectrophotometry (FTIR), and Raman-spectroscopy showed a good corroboration with Surflex-dock findings. Scanning electron microscopy also showed the integration that occurred between Cs and both ligands, which was further supported with X-ray diffraction and X-Ray photoelectron spectroscopy spectra. The textural properties of CCF-5 gel showed high hardness, chewiness, and gumminess values, indicating that the integration of Fs and CN altered the microstructure of Cs-gel. Chotison-functionalized based gels exhibited higher antioxidant abilities against DPPH and ABTS free radicals than Cs-gel. The CCF-9 gel showed a good inhibition value of 29.91 ± 1.22 and 93.61 ± 2.12% against Penicillium expansum and Alternaria westerdijkiae, respectively. Additionally, CCF-9 inhibition zones against Staphylococcus aureus, Escherichia coli, and Bacillus cerues were 28.65 ± 0.05, 27.69 ± 0.04, and 26.16 ± 0.02 mm, respectively. These findings demonstrated the potential antioxidant and antimicrobial effects of functionalized chitosan gel indicating its potential as a bioactive additive for food preservation.

Intraluminal Thrombus of the Extracranial Cerebral Arteries in Acute Ischemic Stroke: Manifestations, Treatment Strategies, and Outcome.

Intraluminal thrombus (ILT) of the cervical arteries is an uncommon finding that can lead to acute or recurrent ischemic stroke. Currently, antithrombotic therapy in the form of antiplatelet and/or anticoagulation is considered the mainstay of treatment, but evidence of which one has a better outcome is lacking. A retrospective cohort study included 28 patients diagnosed with acute stroke or transient ischemic attack with ILT of the extracranial arteries from 2013 to 2022. The primary efficacy outcome was assessed as recurrent stroke, and the primary safety outcome was assessed as hemorrhagic complications. Secondary outcomes were assessed as the resolution of thrombi by CT angiography (CTA) and clinical improvement by the Modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS). Out of 28 patients, more than half (57.1%; n = 16) were males with a mean age of 57.8 ± 9.5 years and an average BMI of 26.9 ± 4.5 kg/m2. As initial treatment, twenty-four patients received anticoagulation and four received antiplatelet agents. Recurrent strokes were found in four patients (14.29%), and all were initially treated with anticoagulation. One patient in the anticoagulation group had a significant retroperitoneal hemorrhage. None of the patients in the antiplatelets group had a recurrent stroke or bleeding event. Initial treatment with antiplatelet agents significantly improved the NIHSS on day 7 (P = 0.017). A significant improvement in NIHSS on day 90 was observed in the anticoagulant group (P = 0.011). In the follow-up CTA performed on 24 patients, 18 (75%) showed complete resolution (3 out of 3 (100%) in the antiplatelet group and 15 out of 21 (71.43%) in the anticoagulant group). Initial treatment with anticoagulants improves neurologic outcomes in patients with ILT-induced acute ischemic stroke but carries the risk of recurrent stroke and bleeding. However, initial treatment with dual antiplatelet agents appears to have comparable efficacy without sequelae, particularly in atherosclerosis-induced ILT.

Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections.

Poor responses to medical care and the failure of pharmacological treatment for many high-frequency diseases, such as cancer and viral infections, have been widely documented. In this context, numerous metal-based substances, including cisplatin, auranofin, various gold metallodrugs, and ruthenium complexes, are under study as possible anticancer and antiviral agents. The two Ru(III) and Ru(II) complexes, namely, BOLD-100 and RAPTA-C, are presently being studied in a clinical trial and preclinical studies evaluation, respectively, as anticancer agents. Interestingly, BOLD-100 has also recently demonstrated antiviral activity against SARS-CoV-2, which is the virus responsible for the COVID-19 pandemic. Over the last years, much effort has been dedicated to discovering new dual anticancer-antiviral agents. Ru-based complexes could be very suitable in this respect. Thus, this review focuses on the most recent studies regarding newly synthesized Ru(II) complexes for use as anticancer and/or antiviral agents.

Dual targeting agent Thiotert inhibits the progression of glioblastoma by inducing ER stress-dependent autophagy

Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro. Furthermore, Thiotert disrupted the thioredoxin (Trx) system while causing cellular DNA damage, which in turn caused endoplasmic reticulum (ER) stress-dependent autophagy. Knockdown of ER stress-related protein ATF4 in U251 cells inhibited ER stress-dependent autophagy caused by Thiotert to some extent. Orthotopic transplantation experiments further showed that Thiotert had the same anti-GBM activity and mechanism as in vitro. Conclusively, these results suggest that Thiotert induces ER stress-dependent autophagy in GBM cells by disrupting redox homeostasis and causing DNA damage, which provides new insight for the treatment of GBM.

Enhancement of optical and radiation shielding properties in calcium–magnesium silicate bioactive glasses through Na2O and P2O5 additives

The present study investigates the influence of Na2O/MgO and P2O5/SiO2 substitutions on the structure and protective properties of bioactive glasses composed of 32CaO–19MgO–0.5P2O5–0.5CaF2–48SiO2 (mole %). The glass samples are prepared using the conventional melt-quenching method. Optical analyses, including refractive index (n), molar refraction (Rm), and cationic polarizability (αm), are calculated and discussed to examine structural modifications. Raman spectroscopy is employed for detailed structural analysis. The effects of compositional changes on the protective parameters are thoroughly investigated by theoretically determining mass attenuation using the newly developed Phy-X/PSD software and XCOM programs, which are then experimentally confirmed at three selected radioactive isotope energies. Experimental measurements of mass attenuation coefficient follow the sequence: MACG1 > MACG2 > MACG3 > MACG4. Raman spectroscopy results indicate that the glass network primarily consists of silicate and phosphate species as the main structural units. An increase in the molar ratio of Na2O and P2O5 improves the radiation shielding effectiveness of the samples. Among them, sample G5, with the lowest SiO2 and MgO content, exhibits the best shielding characteristics due to its high density and molar fraction of Na2O and P2O5. A correlation between microhardness and protective effectiveness is also established. The obtained results support the potential use of these glasses as dual agents for both radiation shielding and medical devices simultaneously.

Computational probing of tavaborole-graphene oxide dual therapeutic agent against the onychomycosis fungal infections

In this study, the density functional theory (DFT) simulations was applied to investigate the adsorption of tavaborole (TAV) antifungal drug on the graphene oxide (GO) surface. All possible positions for TAV molecule adsorption on the GO surface were explored to find out which one is energetically favorable. The DFT calculations show that the adsorption energy (Ead) for most stable TAV@GO complex system is highly negative (−28.23 kcal mol−1) which verifies that the adsorption of TAV molecule onto the GO structure is energetically appropriate. The various electronic structure analyses such as frontier molecular orbital (FMO), HOMO-LUMO gap (Eg), dipole moment (DM), chemical potential (µ), global hardness (η), global electrophilisity (ω), and molecular electrostatic potential (MEP) were performed for individual TAV molecule, GO surface and TAV/GO complex system. Moreover, the existence of non-covalent interactions between TAV molecule and GO structure were monitored through natural bond orbital (NBO), non-covalent interactions (NCI), 3D color-filled isosurface presentation, and charge-decomposition analysis (CDA). Due to the significant stability of TAV@GO complex as well as verified antifungal activity of both individual TAV molecule and GO structure, we hope that TAV@GO complex system can act as a promising antifungal binary drug against the onychomycosis infections.

Jelly snakes to reduce early postoperative vomiting in children after adenotonsillectomy: The randomized controlled snakes trial

BackgroundDespite the use of dual antiemetic agents, postoperative nausea and vomiting (PONV) occurs in an unacceptably large number of patients post-tonsillectomy. There has been increased interest in alternative and non-pharmacological treatments for PONV e.g., chewing gum. We investigated if chewing a large confectionary jelly snake had prophylactic antiemetic effects postoperatively in young children. MethodsProspective, open-label randomised controlled trial of 240 patients, 2–16 years. Patients administered a confectionary jelly snake to chew postoperatively were compared with a control group. The primary outcome was the number of episodes of vomiting within 6 h of the operation on an intention-to-treat basis. Secondary outcomes: incidence of nausea, vomiting at 6 and 24 h, rescue antiemetic use, acceptability, delayed discharge. Results233 patients were randomised to receive the confectionary snake (snake group, 118) or standard care (control group, 115). The number of vomiting episodes in 6 h was similar between groups on an intention-to-treat basis, with 39 episodes across 22 (19%) patients in the control group and 31 across 19 (16%) patients in the snake group (p = 0.666). From post anaesthetic care unit until 24 h there was no difference in doses of antiemetics or delayed discharge due to PONV. A secondary as per protocol analysis did not change this result. ConclusionsChewing of confectionery jelly snakes within one hour of waking following adenotonsillectomy with vapour-maintained anaesthesia and two prophylactic antiemetics did not further reduce the incidence of early vomiting. Registrationprospective registration at the Australia and New Zealand Clinical Trials Registry (ACTRN12618000637246).

Pediatric Patients with Tracheostomies and Its Multifacet Association with Lower Airway Infections: An 8-Year Retrospective Study in a Large Tertiary Center.

Background: Lower respiratory tract infections frequently complicate the care of children with chronic tracheostomies. Pediatric patients have significantly more risk to have tracheostomy infections than adults. Better understanding of modifiable risk factors for pulmonary exacerbations may improve the care of technology-dependent children. Methods: A retrospective single-center cohort study conducted on children with tracheostomy and chronic home ventilator to determine the incidence of pulmonary exacerbations leading to hospitalizations, emergency room (ER) visits, and antibiotic prescriptions. Oral and nebulized antibiotic prescriptions were collected and correlated to the type of exacerbation. Results: Gram-negative enteric organisms were the most common microbes seen in the lower airways, with Pseudomonas aeruginosa cultured in 86% of the subjects. P. aeruginosa presence predicted a 4-fold increased rate of pulmonary-related hospitalization. In pediatric patients with chronic respiratory failure, 64% of readmissions were pulmonary or tracheostomy related. When compared to standard care subjects on dual agent, alternating monthly nebulized antibiotic therapy (for chronic pseudomonas colonization) experienced 41% fewer hospitalizations [incidence rate ratios (IRR) 0.59 (0.18), P = 0.08], 46% fewer ER visits [IRR 0.56 (0.16), P = 0.04], and 41% fewer pulmonary-related ER visits [IRR 0.59 (0.19), P = 0.94]. Discussion: Children who require artificial airways are at an increased risk for bacterial bronchopulmonary infections. Most notable risk factors for hospitalization in tracheostomized children included neurologic impairment, dysphagia, aspiration, gastrotomy tube dependence, and gastroesophageal reflux disease. Pathogenic microbes such as P. aeruginosa species, certain gram-negative bacteria, candida, and yeast also predicted increased hospitalizations. Use of nebulized antibiotics prophylaxis in a subset of patients predicted lower rates of hospitalization or ER visits. More studies are needed to assess whether there is increased antimicrobial resistance with this strategy, and whether the benefits persist in the long-term nebulized antibiotics utilization.

INNV-21. EXTENDED SURVIVAL OF RECURRENT ANAPLASTIC OLIGODENDROGLIOMA PATIENT WITH GOOD FUNCTIONAL STATUS ON LONG TERM PEMBROLIZUMAB AND BEVACIZUMAB THERAPY - A CASE REPORT

Abstract INTRODUCTION Anaplastic oligodendroglioma (AO) is a rare high-grade glioma. Standard of care include resection, radiotherapy followed by chemotherapy. However, effective treatment for recurrent AO is limited. Here we report pembrolizumab (Pembro) + bevacizumab (Bev) therapy for recurrent AO. CASE A 55-year-old male had a brain mass discovered on MRI in 2012 and received no treatment until resection in 2014. He underwent second tumor resection in late 2016 and pathology demonstrated an AO, WHO grade 3. He received radiation followed by PCV regimen in 2017. Ten months later in March 2018, he had tumor progression on PCV. Temozolomide was started. Two months later, Bev (10 mg/kg) was initiated in May 2018 due to further progression. After 12 months of Bev therapy, in mid-2019, Pembro was added due to new and enlarged lesions on MRI. After 18 months of q-3-week Bev (10mg/kg) + Pembro, Bev was on hold in December 2020 due to multiple TIAs. Single agent Pembro was continued for 6 months until April 2021 when his brain MRI showed increased enhancement. Then q-3-week Bev was resumed at a reduced dose (7.5mg/kg). These dual agents continued for 14 months until June 2022 when Bev dose was further reduced to 5mg/kg due to side effect. Bev was on hold again in December 2022 due to high Urine Protein/Creatinine ratio. Single agent Pembro was continued until May 2023 when lower dose Bev (2.5mg/kg) was resumed after MRI showed one subcentimeter new lesion. The small lesion is stable again on q-3-week 2.5 mg/kg Bev+Pembro. The patient has been clinically functional on Bev+Pembro treatment. DISCUSSION Four years of adjuvant pembrolizumab and tailored dose of bevacizumab have resulted in long term repeated stabilization of recurrent AO. The dose and duration of bevacizumab use need to be tailored to minimize adverse effects and to maintain positive effects.

Changes of hospital-level variation in use of optimal medical treatment for long-term follow-up from a multi-level methodological approach

Abstract Background Contemporary guidelines documented that optimal medical therapy (OMT) should be prescribed to improve clinical outcome in patients with acute myocardial infarction (AMI). However, the changes of hospital-level variations in prescription rates of OMT for long-term follow-up are unknown. Purpose We aimed to investigate (1) impact of hospital-level variation on the use of each medication and OMT and (2) changes of hospital-level variation in prescription rates of individual medical therapy and OMT during the follow-up. Methods We examined hospital medications of 13,516 AMI patients without documented contraindications to antiplatelet agents, β-blockers (BB), angiotensin-converting enzyme inhibitors (ACE) /angiotensin II receptor blockers (ARB), or statins from the Korean Acute Myocardial Infarction Registry (KAMIR) – National Institute of Health (NIH) database. OMT was defined as use of all 4 indicated medications. Hierarchical generalized linear mixed models estimated hospital-level variation in prescription rates of OMT and each medication after adjustment for patient-level factors. Variation was explored with a median rate ratio (MRR), which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Results The prescription rates of OMT and each effective cardiac medications are presented in Figure. There were substantial decreases in the prescription rates for OMT (from 66.7% to 51.6%) and dual antiplatelet agents (from 99.1% to 50.4%) for 2 years follow-up. After adjustment for patient-level covariates, hospital-level MRR for OMT was 1.47 at discharge, indicating an 47% likelihood that 2 random hospitals would differ in treating identical AMI patients. As the prescription rates of OMT and each effective cardiac medications decreased, adjusted hospital-level MRR for OMT (from 1.47 to 1.22), BB therapy (from 1.35 to 1.15), ACE/ARB therapy (from 1.68 to 1.16), and statin therapy (from 1.19 to 1.06) decreased for 2-year follow-up, whereas MRR for dual antiplatelet therapy increased at 1 year (MRR; 1.61) and 2 years (MRR; 1.63) follow-up (Figure). Among patient-level factors, age >70 years, Killip class>2, obesity, hypertension, previous coronary artery disease, renal dysfunction, reduced ejection fraction, percutaneous coronary intervention was independently associated with the use of OMT. Conclusion Hospital-level variations in the use of OMT and each effective cardiac medications were observed at discharge, but weakened overtime, except for use of dual antiplatelet therapy.

Self-assembly of PEG-PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing.

Refractory diabetic wounds are associated with high incidence, mortality, and recurrence rates and are a devastating and rapidly growing clinical problem. However, treating these wounds is difficult owing to uncontrolled inflammatory microenvironments and defective angiogenesis in the affected areas, with no established effective treatment to the best of our knowledge. Herein, we optimized a dual functional therapeutic agent based on the assembly of LL-37 peptides and diblock copolymer poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS). The incorporation of PEG-PPS enabled responsive or controlled LL-37 peptide release in the presence of reactive oxygen species (ROS). LL-37@PEG-PPS nanomicelles not only scavenged excessive ROS to improve the microenvironment for angiogenesis but also released LL-37 peptides and protected them from degradation, thereby robustly increasing angiogenesis. Diabetic wounds treated with LL-37@PEG-PPS exhibited accelerated and high-quality wound healing in vivo. This study shows that LL-37@PEG-PPS can restore beneficial angiogenesis in the wound microenvironment by continuously providing angiogenesis-promoting signals. Thus, it may be a promising drug for improving chronic refractory wound healing.

Dual Biologic Therapy for Refractory Crohn's Disease With Perforation in a Patient Declining Surgical Intervention

ABSTRACT Dual biologic therapy can improve clinical, biomarker, and endoscopic outcomes in selected patients with refractory Crohn's disease in whom multiple biologics had failed. We presented a patient with refractory Crohn's disease who was admitted for terminal ileal perforation, massive bloody stool, shock, and disseminated intravascular coagulation. He refused further surgical resection because of the fear of short bowel syndrome. He was successfully treated with dual biologic therapy, antimicrobial agents, and percutaneous needle decompressions. Dual biologic treatment could be a viable option for patients with refractory Crohn's disease with complications in selected critical conditions who refuse surgery.

OSSP-PTA: An Online Stochastic Stepping Policy for PTA on Reinforcement Learning

DC analysis is essential and still quite challenging in large-scale nonlinear circuit simulation. Pseudo transient analysis (PTA) is a widely-used and has great potential solver in the industry. However, the PTA convergence and simulation efficiency is still seriously affected by its stepping policy. This paper proposes an online stochastic stepping policy (OSSP) for PTA based on deep reinforcement learning (DRL). To achieve better policy evaluation and stronger stepping exploration ability, the dual soft Actor-Critic agents work with the proposed valuation splitting and online momental scaling, enabling our OSSP to intelligently encode PTA iteration status and online further adjust forward and backward time-step size for unseen test circuits without human intervention and domain knowledge, trained solely by RL from self-search. Our public sample buffer and priority sampling are also introduced to overcome the sparsity and imbalance of sample data. Numerical examples demonstrate that the proposed OSSP achieves a significant efficiency speedup (up to 47.0X less NR iterations) and convergence enhancement on unseen test circuits compared with the previous iter-based and SER-based stepping methods, in just one stepping iteration.

Surface-Modified Electrospun Glass Nanofibers from Silane Treatment and Their Use for High-Performance Epoxy-Based Nanocomposite Materials.

As a new and promising reinforcing filler, electrospun glass nanofibers (EGNFs) have attracted attention in the field of polymer composite materials. However, the reinforcing effectiveness of surface-modified EGNFs using different silane coupling agents in epoxy resin is still not quite clear. In this research, a series of silane coupling agents with increasing chain lengths in the order of methyl trimethoxysilane (MTMS), (3-aminopropyl) triethoxysilane (APTES), (3-glycidyloxypropyl) trimethoxysilane (GPTMS), and dual silane coupling agent APTES-GPTMS were employed to carry out surface treatment on the EGNFs. The pristine and silane functionalized EGNFs were then incorporated into epoxy resin as reinforcing fillers at low loading levels, i.e., 0.25 wt.%, 0.5 wt.%, and 1 wt.%, and the mechanical properties of the resultant epoxy nanocomposites, including strength, stiffness, ductility, and toughness, were evaluated. A commercial product of glass nanoparticles (GNPs) was used as a control to compare the reinforcing effectiveness of the EGNFs and the GNPs. This study revealed that the EGNFs could provide significant reinforcing and toughening effects at ultra-low loading (0.25 wt.%) in epoxy nanocomposite materials. Furthermore, surface modification of the EGNFs with silane coupling agents with long chain lengths, e.g., by using dual silane coupling agents, APTES-GPTMS, could enhance the interfacial bonding between the EGNFs and the epoxy matrix and further increase the mechanical performance of the EGNF-reinforced epoxy nanocomposite materials. Through this research, we realized epoxy nanocomposite materials with much-improved mechanical properties, i.e., 37%, 24%, 18%, 57% improvement in strength, stiffness, ductility, and toughness, respectively, with respect to those of the cured neat epoxy material with an ultra-low loading (0.25 wt.%) of APTES-GPTMS-EGNFs. Our research paves the road for developing lighter and stronger epoxy nanocomposite materials with EGNFs.

One-Pot Synthesis of Bioinspired Peptide-Decorated Apatite Nanoparticles for Nanomedicine.

Hybrid organic-inorganic bio-inspired apatite nanoparticles (NPs) are attractive for biomedical applications and especially in nanomedicine. Unfortunately, their applications in nanomedicine are limited by their broad particle size distributions and uncontrolled drug loading due to their multistep synthesis process. Besides, very few attempts at exposing bioactive peptides on apatite NPs are made. In this work, an original one-pot synthesis of well-defined bioactive hybrid NPs composed of a mineral core of bioinspired apatite surrounded by an organic corona of bioactive peptides is reported. Dual stabilizing-bioactive agents, phosphonated polyethylene glycol-peptide conjugates, are prepared and directly used during apatite precipitation i) to form the organic corona during apatite precipitation, driving the size and shape of resulting hybrid NPs with colloidal stabilization and ii) to expose peptide moieties (RGD or YIGSR sequences) at the NPs periphery in view of conferring additional surface properties to enhance their interaction with cells. Here, the success of this approach is demonstrated, the functionalized NPs are fully characterized by Fourier-transform infrared, Raman, X-ray diffraction, solid and liquid state NMR, transmission electron microscopy, and dynamic light scattering, and their interaction with fibroblast cells is followed, unveiling a synergistic proliferative effect.

Review of the Application of Dual Drug Delivery Nanotheranostic Agents in the Diagnosis and Treatment of Liver Cancer.

Liver cancer has high incidence and mortality rates and its treatment generally requires the use of a combination treatment strategy. Therefore, the early detection and diagnosis of liver cancer is crucial to achieving the best treatment effect. In addition, it is imperative to explore multimodal combination therapy for liver cancer treatment and the synergistic effect of two liver cancer treatment drugs while preventing drug resistance and drug side effects to maximize the achievable therapeutic effect. Gold nanoparticles are used widely in applications related to optical imaging, CT imaging, MRI imaging, biomarkers, targeted drug therapy, etc., and serve as an advanced platform for integrated application in the nano-diagnosis and treatment of diseases. Dual-drug-delivery nano-diagnostic and therapeutic agents have drawn great interest in current times. Therefore, the present report aims to review the effectiveness of dual-drug-delivery nano-diagnostic and therapeutic agents in the field of anti-tumor therapy from the particular perspective of liver cancer diagnosis and treatment.