Acetamide Electrosynthesis from CO2 and Nitrite in Water.

Renewable electricity driven electrocatalytic CO2 reduction reaction (CO2 RR) is a promising solution to carbon neutralization, which mainly generate simple carbon products. It is of great importance to produce more valuable C-N chemicals from CO2 and nitrogen species. However, it is challenging to co-reduce CO2 and NO3 - /NO2 - to generate aldoxime an important intermediate in the electrocatalytic C-N coupling process. Herein, we report the successful electrochemical conversion of CO2 and NO2 - to acetamide for the first time over copper catalysts under alkaline condition through a gas diffusion electrode. Operando spectroelectrochemical characterizations and DFT calculations, suggest acetaldehyde and hydroxylamine identified as key intermediates undergo a nucleophilic addition reaction to produce acetaldoxime, which is then dehydrated to acetonitrile and followed by hydrolysis to give acetamide under highly local alkaline environment and electric field. Moreover, the above mechanism was successfully extended to the formation of phenylacetamide. This study provides a new strategy to synthesize highly valued amides from CO2 and wastewater.

Discovery of sertraline and its derivatives able to combat drug-resistant gastric cancer cell via inducing apoptosis.

Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug - sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC50 value of 18.73 µM. To understand the structure-activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC50 value of the best compound was improved to 5.2 µM. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.

Recent advances in the contribution of circRNAs to cisplatin chemotherapy resistance in cancers.

Worldwide, cancer is a serious threat to the health of citizens of every country, with the incidence and mortality increasing year by year. Cisplatin is the first-line anticancer drug commonly used in clinics and is widely used for the treatment of solid tumors including lung, gastric, liver, bladder, and ovarian cancer. Although cisplatin-based chemotherapy has a high clinical response efficacy, patients will inevitably develop drug resistance after repeated use, leading to severe restrictions of its application. Circular RNAs (circRNAs) are a promising class of non-coding RNAs capable of promoting or suppressing cancer via functioning as miRNAs sponges. Recently, an increasing amount of evidence shows that circRNAs are closely related to the cisplatin resistance of cancers. Therefore, standing at the perspective of the cisplatin chemotherapy resistance, this paper reviews the research progress of circRNAs related to cisplatin resistance of various cancers.

Autocorrected preconditioning regularization inversion algorithm for an atmospheric turbulence profile.

Atmospheric turbulence profiles have great significance for adaptive optics, astronomical observations, laser propagation in atmospheres, and free space optical communications. The two-aperture differential scintillation method is a recent approach for analyzing remote-sensing atmospheric turbulence profiles that utilizes active beacons to make it suitable for different measurement situations. The relationship between differential scintillation and atmospheric turbulence profiles can be modeled using the Fredholm integral equation. To address this ill-posed integration problem, the discrete forward observation equation is first analyzed to obtain better integration intervals and measurement intervals needed for inversion. Then an autocorrected preconditioning conjugate gradient normal residual (PCGNR) algorithm is proposed to acquire atmospheric turbulence profiles. The algorithm contains a developed autocorrection strategy that incorporates incremental differences, adaptive thresholds, and weighted averages to correct for artefacts and marginal errors that arise from the PCGNR method. Compared with other regularized methods, the proposed autocorrected PCGNR method is more accurate and robust in the presence of noise.

Codelivery of Ponatinib and SAR302503 by Active Bone-Targeted Polymeric Micelles for the Treatment of Therapy-Resistant Chronic Myeloid Leukemia.

Point mutations in the BCR-ABL1 domain and primitive chronic myelogenous leukemia (CML) cells existing in the bone marrow environment insensitive to tyrosine kinase inhibitors (TKIs) have become two major challenges in the CML therapy. In this study, combined TKI ponatinib and JAK2 inhibitor SAR302503 short-term treatment effectively suppressed growth and promoted apoptosis of BaF3/T315I cells in cytokine-containing medium in vitro. SAR302503 prevented cytokine-dependent resistance to ponatinib via inhibition of JAK2/STAT5 phosphorylation. Codelivery of ponatinib and SAR302503 by active bone-targeted polymeric micellar formulation greatly increased the drug accumulation in medullary cavity. The therapeutic efficacy of bone-targeted formulation was demonstrated in BaF3/T315I cells inoculated murine model with no dose-limited toxicity detectable in health mice. Thus, the intravenous injectable bone-homing ponatinib and SAR302503 micellar formulation represents a promising strategy for the treatment of therapy-resistant CML.

Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice.

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.

Coronary In-Stent Restenosis: Assessment with Corrected Coronary Opacification Difference across Coronary Stents Measured with CT Angiography.

PURPOSE: To determine whether changes in coronary opacification normalized to the aorta (corrected coronary opacification [CCO]) across stents can help identify in-stent restenosis (ISR) severity with use of invasive coronary angiography as the standard of reference. MATERIALS AND METHODS: This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The authors retrospectively analyzed 106 patients (88 men, 18 women; mean age, 59.6 years ± 10.4; age range, 36-84 years) who had previously undergone stent implantation within 3 months of coronary computed tomographic (CT) angiography. Attenuation values in the coronary lumen were measured proximal and distal to the stents and normalized to the descending aorta. The CCO difference across the stent was compared with the severity of ISR. One-way analysis of variance least significant difference was used for comparison. RESULTS: A total of 141 stents were assessed. Seventy-six stents were normally patent, 18 had ISR of less than 50%, 28 had ISR of 50%-99%, and 19 were fully occluded. The median CCO differences in the four groups were 0.078, 0.163, 0.346, and 0.606, respectively. There was no significant difference between stents with an ISR of at least 50% and those with total occlusion (P = .056), although the other groups had significant differences at pairwise comparison (P < .01 for all). For stents smaller than 3 mm in diameter, the median CCO differences in the four groups were 0.086, 0.136, 0.390, and 0.471, respectively. The CCO differences across normal stents and stents with ISR of less than 50% were significantly less than those across stents with an ISR of at least 50% and those with total occlusion (P < .01 for all). There were no significant differences between stents with no ISR and those with an ISR of less than 50% (P = .821) and between stents with an ISR of at least 50% and those with an ISR of 100% (P = .836). CONCLUSION: The CCO difference across coronary stents is related to ISR severity in obstructive ISR in stents smaller than 3 mm in diameter.

Cat favus caused by Microsporum incurvatum comb. nov.: the clinical and histopathological features and molecular phylogeny.

Favus is a distinctive form of infection that is caused by exclusively dermatophytes. Its clinical presentation is characterized by scutula, which are concave, thick fungal crusts. The best-known examples of human scalp favus are caused by Trichophyton schoenleinii and those of mouse favus are caused by T. quinckeanum. However, other dermatophytes, such as T. violaceum, T. verrucosum, Microsporum audouinii, M. gallinae, M. gypseum, and M. canis, have been reported sporadically to cause favic lesions. Favus on cats has rarely been mentioned in the literature, and the pathogens with which it has been associated are, for the most part, unknown. Here, we examine four cat favus cases, focusing on clinical presentations and histopathological features. In all cases the etiologic agent was identified as M. incurvatum based on its morphological characteristics and sequences of internal transcribed spacers (ITS) of nuclear ribosomal DNA. Phylogenetic analysis using the neighbor-joining method, which is based on ITS, showed that these four isolates belonged to two strains of M. incurvatum; one strain was a new combination from the basionym Nannizzia incurvata.

Predictive factors of thyroid cancer in patients with Graves' disease.

BACKGROUND: The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. METHODS: This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. RESULTS: Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. CONCLUSIONS: Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System.

Background: Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited. Objective: This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals. Results: FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT). Conclusions: There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscular-related adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events.

Role of Exosomal Non-Coding RNA in the Tumour Microenvironment of Genitourinary System Tumours.

In recent years, genitourinary system tumors are common in people of all ages, seriously affecting the quality of life of patients, the pathogenesis and treatment of these diseases are constantly being updated and improved. Exosomes, with a lipid bilayer that enable delivery of their contents into body fluids or other cells. Exosomes can regulate the tumor microenvironment, and play an important role in tumor development. In turn, cellular and non-cellular components of tumor microenvironment also affect the occurrence, progression, invasion and metastasis of tumor. Non-coding RNAs have been shown to be able to be ingested and released by exosomes, and are seen as a potential tool in cancer diagnosis and treatment. Here, we summarize the effect of non-coding RNAs of exosome contents on the tumor microenvironment of genitourinary system tumor, expound the significance of non-coding RNAs of exosome in the occurrence, development, diagnosis and treatment of cancers.

[Clinical outcome of patients undergoing emergent coronary artery bypass grafting following failed percutaneous coronary intervention in stent era].

OBJECTIVE: To explore clinical outcomes of patients undergoing emergent coronary artery bypass grafting (CABG) following failed percutaneous coronary intervention (PCI) in the stent era. METHODS: Eleven patients who underwent emergent CABG following failed PCI from January, 2002 to December 2010 were enrolled. The in-hospital follow-up included cardiac deaths, Q-wave myocardial infarction, kidney failure, and cerebrovascular events. The clinical end-point of out-hospital follow-up was the major adverse cardiac events including death, myocardial infarction, and target lesion revascularization. RESULTS: The patients were (61 ± 5) years old. Coronary angiography showed 5 patients had triple vessel lesions. There were 9 target lesions on left anterior descending artery. There were 3 (27.3%) severe calcified, 4 (36.4%) chronic total occlusion, and 4 (36.4%) diffused long lesions. Reasons for emergent CABG were dissection (n = 5, 45.5%), perforation (n = 3, 27.3%), failure to sufficient predilation (n = 1, 9.1%), acute closure (n = 1, 9.1%) and stent loss (n = 1, 9.1%). The average duration of follow-up was (47 ± 33) months. During in-hospital follow-up, there were 1 (9.1%) cardiac death and 2 (18.2%) Q wave myocardial infarction. During follow-up after hospital discharge, 1 patient (9.1%) died of kidney failure, and there was no rehospitalization due to cardiac events. CONCLUSIONS: Emergent CABG after failed PCI often happened in patients with complex coronary lesions. The long term outcome of patients requiring emergent CABG after failed PCI was favorable in this cohort.

The osteogenic niche-targeted arsenic nanoparticles prevent colonization of disseminated breast tumor cells in the bone.

Up to 70% of patients with late-stage breast cancer have bone metastasis. Current treatment regimens for breast cancer bone metastasis are palliative with no therapeutic cure. Disseminated tumor cells (DTCs) colonize inside the osteogenic niches in the early stage of bone metastasis. Drug delivery into osteogenic niches to inhibit DTC colonization can prevent bone metastasis from entering its late stage and therefore cure bone metastasis. Here, we constructed a 50% DSS6 peptide conjugated nanoparticle to target the osteogenic niche. The osteogenic niche was always located at the endosteum with immature hydroxyapatite. Arsenic-manganese nanocrystals (around 14 nm) were loaded in osteogenic niche-targeted PEG-PLGA nanoparticles with an acidic environment-triggered arsenic release. Arsenic formulations greatly reduced 4T1 cell adhesion to mesenchymal stem cells (MSCs)/preosteoblasts (pre-OBs) and osteogenic differentiation of osteoblastic cells. Arsenic formulations also prevented tumor cell colonization and dormancy via altering the direct interaction between 4T1 cells and MSCs/pre-OBs. The chemotactic migration of 4T1 cells toward osteogenic cells was blocked by arsenic in mimic 3D osteogenic niche. Systemic administration of osteogenic niche-targeted arsenic nanoparticles significantly extended the survival of mice with 4T1 syngeneic bone metastasis. Our findings provide an effective approach for osteogenic niche-specific drug delivery and suggest that bone metastasis can be effectively inhibited by blockage of tumor cell colonization in the bone microenvironment.

Dexmedetomidine Preserves Activity of Neurons in Primary Somatosensory Cortex Compared to Propofol and Ketamine.

General anesthesia has been shown to induce significant changes in the functional connectivity of the cerebral cortex. However, traditional methods such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) lack the spatial resolution to study the effects of general anesthesia on individual cortical neurons. This study aimed to use high-resolution two-photon imaging, which can provide single-neuron resolution, to investigate the characteristics of consciousness under general anesthesia. We used C57BL/6J and Thy1-GCamp6s mice and found that at similar levels of sedation, as measured by EEG, dexmedetomidine did not significantly inhibit the spontaneous activity of neuronal somata in the S1 cortex, but preserved the frequency of calcium events in neuronal spines. In contrast, propofol and ketamine dramatically inhibited the spontaneous activity of both neuronal somata and spines. The S1 cortex still responded to whisker stimulation under dexmedetomidine anesthesia, but not under propofol or ketamine anesthesia. Our results suggest that dexmedetomidine anesthesia has unique neuronal properties associated with its ability to facilitate easy awakening in the clinic. These findings provide insights into the development of more effective strategies for monitoring consciousness during general anesthesia.

[Association between side effects of oral anti-diabetic drugs and self-reported mental health and quality of life among patients with type 2 diabetes].

OBJECTIVE: To examine the association between the side effects of oral anti-diabetic drugs (OAD) and self-reported mental health and quality of life among patients with type 2 diabetes mellitus (T2DM). METHODS: An observational, cross-sectional multicenter study with a retrospective medical chart review was conducted at 16 medical centers from around China. The T2DM patients were followed-up and treated with OAD alone prior to the index visit from January to September 2007. All subjects were ≥30 years old at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Health-related quality of life was measured by the EuroQol-5D (EQ-5D) and Hypoglycemia Fear Survey (HFS)-II. RESULTS: The symptoms of hypoglycemia were reported by 41.8% (n=203) of participants, and 19.2% (n=93) experienced weight gain. For those reporting hypoglycemia, the scores were higher for HFS-II [7.00 (2.00-19.00) vs 0.00 (0.00-7.00), P<0.01] and lower for EQ-5D (0.90±0.12 vs 0.93±0.13, P=0.003) than those without hypoglycemic symptoms. According to the multivariate linear regression analysis, the symptoms of hypoglycemia were positively correlated with HFS-II (ß=5.78, P<0.01) and negatively with EQ-5D (ß=-0.04, P<0.05) after adjusting for patient and disease characteristics. CONCLUSION: There is a high possibility of hypoglycemic risks among T2DM patients on OAD therapy. The self-reported hypoglycemia is associated with health-related quality of life and hypoglycemic fear. They may have an impact on the long-term prognosis.

[The in-hospital outcome and predictors of major adverse cardiac events after transradial intervention in patients with coronary artery disease].

OBJECTIVE: The purpose of this study is to evaluate the in-hospital clinical outcome of patients with coronary artery disease who underwent transradial intervention (TRI) and analyze the predictors of clinical outcome. METHODS: From May 2004 to May 2009, there were 16 281 patients who underwent transradial intervention, as well as 5388 patients who underwent transfemoral intervention (TFI) at our institution. The clinical characteristics, procedural characteristics, and in-hospital clinical adverse events were compared between TRI and TFI groups. Multivariable logistic regression analysis was performed to determine predictors of in-hospital major adverse cardiac events (composite of death, myocardial infarction, or target lesion revascularization) of TRI. RESULTS: The annulations time was significantly longer for TRI than TFI (P < 0.01), fluoroscopy time, amount of contrast agent and procedural success rate (95.5% for TRI and 96.2% for TFI) were similar between the two groups. However, the rates of vascular complications (0.1% for TRI group and 1.3% for TFI group, P < 0.01), incidence of in-hospital major adverse cardiac events (1.6% vs. 3.8%, P < 0.01) and in-hospital death (0.2% vs. 0.4%, P < 0.01) were all significantly lower in TRI group compared with TFI group. The following characteristics were identified as independent multivariate predictors of in-hospital major adverse cardiac events of TRI: age ≥ 65 (OR: 1.98, 95%CI: 1.50 - 2.61, P < 0.01), prior myocardial infarction (OR: 2.14, 95%CI: 1.63 - 2.82, P < 0.01), use of drug-eluting stent (DES) (OR: 0.68, 95%CI: 0.47 - 0.98, P = 0.04), dissection during procedure (OR: 4.08, 95%CI: 2.28 - 7.33, P < 0.01), left main lesion (OR: 2.12, 95%CI: 1.09 - 4.13, P = 0.03), number of implanted stents (OR: 1.25, 95%CI: 1.09 - 1.43, P < 0.01), and total stented length (OR: 1.01, 95%CI: 1.00 - 1.02, P = 0.03). CONCLUSIONS: In this large single-centre patient cohort, the transradial intervention is superior to transfemoral intervention in terms of in-hospital safety and efficacy. Age ≥ 65, prior myocardial infarction, use of DES, dissection during procedure, left main lesion, number of implanted stents and total stented length were identified as independent multivariate predictors of in-hospital major adverse cardiac events of TRI.

Charging effects of SiO2 thin film on Si substrate irradiated by penetrating electron beam.

In this work, the charging effect and induced conductivity of SiO2 thin films on Si substrate irradiated by penetrating electron beam (e-beam) are investigated based on numerical calculation and experiment. The numerical model is performed by considering the electron scattering, trapping, drift, diffusion and recombination, and solved by the Monte Carlo and finite difference method. The results show that, under e-beam irradiation, due to emission of secondary electrons (SEs) from the surface, the net charge density is positive near the surface, but negative inside the film. The net charge density and resulting negative charging intensity decrease under e-beam irradiation because of high electron mobility. With e-beam irradiation, the free electrons drift and diffuse to the meter and thus the sample current increases. Meanwhile, the transmission current remains unchanged due to the weak charging intensity. With the increasing beam energy, the transmission current increases to the beam current. The sample current and the induced current gain reach the maximum at the beam energy of 15 keV. The sample current and the induced conductivity at the steady state increase linearly with beam current. The induced current gain increases with the rising positive bias voltage. The influence of film parameters on the charge effect is also analyzed.

[Comparison of outcomes after transradial intervention in patients of different age groups].

OBJECTIVE: To compare the in-hospital clinical outcome of patients with coronary artery disease in different age groups [< 65 years (younger), 60 to 79 years (older), and ≥ 80 years (octogenarians)] underwent transradial intervention (TRI) so asto analyze the predictors of adverse events. METHOD: From May 2004 to May 2009, a total of 16 293 patients underwent transradial intervention at our institution. The in-hospital outcome for patients in different age groups after TRI was investigated. Multivariable logistic regression analysis was performed to determinate the predictors of in-hospital major adverse cardiac events (MACE) (composed of death, myocardial infarction or target vessel revascularization). RESULTS: Angiographic success rates were not different (97.5%, 97.4%, 98.1%, P > 0.05) between 3 groups. However, the rates of procedural complications became progressively higher with age group (0.8%, 1.2%, 4.0%, P < 0.01). In-hospital MACE (1.3% vs 2.2% vs 7.5%, P < 0.01) and mortality (0.1% vs 0.3% vs 2.9%, P < 0.01) increased incrementally with age group. Aad it was associated with a significant decrement of DES (92.0%, 89.6%, 57.3%, P < 0.01). The following characteristics were identified as independent multivariate predictors of in-hospital major adverse cardiac events: age ≥ 80 (OR 6.26, 95%CI: 3.33 to 11.74; P < 0.01), prior myocardial infarction (OR 2.19, 95%CI: 1.66 to 2.88; P < 0.01), left main lesion (OR 2.02, 95%CI: 1.04 to 3.91; P = 0.04), age of 65 to 79 (OR 1.83, 95%CI: 1.37 to 2.43; P < 0.01), number of implanted stents (OR 1.31, 95%CI: 1.15 to 1.50; P < 0.01), total stented length (OR 1.01, 95%CI: 1.01 to 1.02; P = 0.03), and use of DES (OR 0.59, 95%CI: 0.39 to 0.89; P = 0.01). CONCLUSIONS: The younger and older patients undergoing TRI have a more favorable in-hospital outcome. However the octogenarians has a substantially higher risk of in-hospital MACE.

Docetaxel-Loaded Chitosan-Cholesterol Conjugate-Based Self-Assembled Nanoparticles for Overcoming Multidrug Resistance in Cancer Cells.

Cholesteryl hemisuccinate (CHS)-conjugated chitosan (CS)-based self-assembled nanoparticles (NPs) were developed for enhancing the intracellular uptake of docetaxel in multidrug resistance (MDR)-acquired cancer cells. CHS-CS was successfully synthesized and self-aggregation, particle size, zeta potential, drug entrapment efficiency, and in vitro drug release of docetaxel-loaded CHS-CS NPs were tested. The optimized NPs had a mean hydrodynamic diameter of 303 nm, positive zeta potential of 21.3 mV, and spherical shape. The in vitro release of docetaxel from the optimized CHS-CS NPs in different pH medium (pH 6.0 and 7.4) revealed that the release was improved in a more acidic condition (pH 6.0), representing a tumor cell's environment. The superior MDR-overcoming effect of docetaxel-loaded CHS-CS NPs, compared with docetaxel solution, was verified in anti-proliferation and cellular accumulation studies in MDR-acquired KBV20C cells. Thus, CHS-CS NPs could be potentially used for overcoming the MDR effect in anticancer drug delivery.

Dual oligopeptides modification mediates arsenic trioxide containing nanoparticles to eliminate primitive chronic myeloid leukemia cells inside bone marrow niches.

Chronic myeloid leukemia (CML) is one type of hematopoietic stem cell diseases. Although BCR-ABL1 tyrosine kinase inhibitors are remarkably effective in inducing remission in chronic phase patients, they are not curative in a majority of patients due to their failure to eradicate residual CML stem/progenitor cells, which reside in bone marrow niches. Here, we presented novel dual oligopeptides-conjugated nanoparticles and demonstrated their effective delivery of arsenic trioxide in bone marrow niches for the elimination of primitive CML cells. We encapsulated As-Ni transitional metal compounds into polymeric nanoparticles based on the reverse micelle rationale. The loading density and stability of arsenic trioxide in nanoparticles were improved. In vitro experiments demonstrated that dual oligopeptides conjugated nanoparticles could deliver arsenic trioxide into bone marrow niches including endosteal niches and vascular niches. The colony-forming activity of CML cells was remarkably restrained in the presence of metaphyseal bone fragments pre-incubated with bone marrow niche targeted arsenic nanoparticles. The in vitro vascular niche model suggested that CML cell proliferation was also successfully inhibited through a tight contact with HUVECs, which were pre-treated using niche-targeted arsenic nanoparticles. This bone marrow niche targeted delivery strategy has a potential usage for the treatment of CML and other malignant hematologic disorders originated from the bone marrow.