Two‐photon supramolecular assembly with near‐infrared (NIR) fluorescence emission is constructed from tetraphenylethene derivative possessing methoxyl and vinyl pyridine salt (TPE‐2SP), cucurbit8uril ...(CB8), and β‐cyclodextrin modified hyaluronic acid (HA‐CD). The obtained experimental results indicate that the TPE‐2SP exhibits a very weak fluorescence emission at 650 nm, and then complexes with cucurbit7uril (CB7) to form 1:2 supramolecular pseudorotaxane with an enhanced NIR fluorescence emission at 660 nm. Compared with CB7, CB8 can assemble with TPE‐2SP to be two‐axial netlike pseudopolyrotaxane, resulting in close packing to increase TPE‐2SP fluorescence emission with a redshift of 30 nm. Interestingly, TPE‐2SP/CB8 continues to assemble with cancer cell targeting agent HA‐CD into nanoparticles, leading to assembling‐induced further enhancement of NIR emission. Surprisingly, supramolecular nanoparticles have the two‐photon character, and are successfully applied to mitochondrial targeting imaging. This supramolecular assembly system, with two‐photon absorption and assembly‐induced enhanced NIR luminescence properties, opens new way for biological targeted imaging.
Due to host–guest induced emission by cucurbit8uril, supramolecular nanosquares display near‐infrared emission in aqueous solution. Further assembling with cancer cell targeting agent, β‐cyclodextrin modified hyaluronic acid (HA‐CD) into supramolecular nanoparticles leads to assembling‐induced enhancement of NIR emission dramatically. Furthermore, supramolecular nanoparticles can be applied for two‐photon mitochondrial targeted NIR imaging.
Objective
This study intended to establish a droplet digital PCR (dd‐PCR) for monitoring minimal residual disease (MRD) in patients with BCR/ABL (P210)‐positive chronic myeloid leukemia (CML), ...thereby achieving deep‐level monitoring of tumor load and determining the efficacy for guided clinically individualized treatment.
Methods
Using dd‐PCR and RT‐qPCR, two cell suspensions were obtained from K562 cells and normal peripheral blood mononuclear cells by gradient dilution and were measured at the cellular level. At peripheral blood (PB) level, 61 cases with CML‐chronic phase (CML‐CP) were obtained after tyrosine kinase inhibitor (TKI) treatment and regular follow‐ups. By RT‐qPCR, BCR/ABL (P210) fusion gene was undetectable in PB after three successive analyses, which were performed once every 3 months. At the same time, dd‐PCR was performed simultaneously with the last equal amount of cDNA. Ten CML patients with MR4.5 were followed up by the two methods.
Results
At the cellular level, consistency of results of dd‐PCR and RT‐qPCR reached R2 ≥ 0.99, with conversion equation of Y = 33.148X1.222 (Y: dd‐PCR results; X: RT‐qPCR results). In the dd‐PCR test, 11 of the 61 patients with CML (18.03%) tested positive and showed statistically significant difference (P < .01). In the follow‐up of 10 CML patients who were in MR4.5. All patients were loss of MR4.0, and 4 were tested positive by dd‐PCR 3 months earlier than by RT‐qPCR.
Conclusion
In contrast with RT‐qPCR, dd‐PCR is more sensitive, thus enabling accurate conversion of dd‐PCR results into internationally standard RT‐qPCR results by conversion equation, to achieve a deeper molecular biology‐based stratification of BCR/ABL(P210) MRD. It has some reference value to monitor disease progression in clinic.
The use of antibiotics may accelerate the development of antibiotic resistance genes (ARGs) and bacteria which shade health risks to humans and animals. The emerging of ARGs in the water environment ...is becoming an increasing worldwide concern. Hundreds of various ARGs encoding resistance to a broad range of antibiotics have been found in microorganisms distributed not only in hospital wastewaters and animal production wastewaters, but also in sewage, wastewater treatment plants, surface water, groundwater, and even in drinking water. This review summarizes recently published information on the types, distributions, and horizontal transfer of ARGs in various aquatic environments, as well as the molecular methods used to detect environmental ARGs, including specific and multiplex PCR (polymerase chain reaction), real-time PCR, DNA sequencing, and hybridization based techniques.
Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the ...hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury‐preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury‐preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up‐regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury‐preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair.
Cover Image for this issue: doi: 10.1111/jnc.14741
To most closely replicate the complex microenvironment in injured brain, we used extract of traumatic brain tissue to preconditioning umbilical cord mesenchymal stem cells (MSCs) in vitro, and stereotaxically injected these secretome into dentate gyrus of hippocampus in a rat severe Traumatic brain injury (TBI) model. We observed that traumatically preconditioning secretome could significantly further promote the differentiation, migration and maturation of newborn cells in dentate gyrus, and finally improved the cognitive function after TBI. Our study utilized the injury‐preconditioning secretome to inducibly amplify the neurogenesis and cognitive recovery, which can offers a novel and safer candidate for nerve repair.
Open Science: This manuscript was awarded with the Open Materials Badge
For more information see: https://cos.io/our-services/open-science-badges/
Cover Image for this issue: doi: 10.1111/jnc.14741
Coronavirus disease 2019 (COVID-19) is an important and urgent threat to global health. Inflammation factors are important for COVID-19 mortality, and we aim to explore whether the baseline levels of ...procalcitonin (PCT), C-reaction protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are associated with an increased risk of mortality in patients with COVID-19. A retrospective study was conducted and a total of 76 patients with confirmed COVID-19 were included between January 17, 2020 to March 2, 2020, of these cases, 17 patients were dead. After adjusting covariates, PCT (≥ 0.10 ng/mL) and CRP (≥ 52.14 mg/L) exhibited independent increasing risks of mortality were used hazard ratio (HR) of 52.68 (95% confidence interval CI: 1.77-1571.66) and 5.47 (95% CI: 1.04-28.72), respectively. However, NRL (≥ 3.59) was not found to be an independent risk factor for death in our study. Furthermore, the elevated PCT levels were still associated with increasing risk of mortality in the old age group (age ≥ 60 y), and in the critically severe and severe patients after adjustment for complications. Thu Baseline levels of PCT and CRP have been addressed as independent predictors of mortality in patients with COVID-19.
Titanium dioxide (TiO2) nanoparticles (NPs) have been widely used in industrial and consumer products. Comprehensive and accurate detection, characterization, and quantification of TiO2 NPs are ...important for understanding the specific property, behavior, fate, and potential risk of TiO2 NPs in natural and engineered environments. This review provides a summary of recent analytical studies of TiO2 NPs and their aggregation, coagulation, flocculation, sedimentation, stabilization under a wide range of conditions and processes. Much attention is paid on sample preparation prior to an analytical procedure, analysis of particle size, morphology, structure, state, chemical composition, surface properties, etc., via measurements of light scattering and zeta potential, microscopy, spectroscopy, and related techniques. Recently, some advanced techniques have also been explored to characterize TiO2 NPs and their behaviors in the environment. Many issues must be considered including distinction between engineered TiO2 NPs and their naturally occurring counterparts, lack of reference materials, interlaboratory comparison, when analyzing low concentrations of TiO2 NPs and their behaviors in complex matrices. No “ideal” technique has emerged as each technique has its own merits, biases, and limitations. Multi-method approach is highlighted to provide in-depth information. Improvements of analytical method for determination of TiO2 NPs have been recommended to be together with exposure modelers and ecotoxicologists for maximum individual and mutual benefit. Future work should focus on developing analytical technology with the advantages of being reliable, sensitive, selective, reproducible, and capable of in situ detection in complicated sample system.
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•Essential to assess behavior of TiO2 NPs in natural and engineered environment.•Challenging to determine TiO2 NPs at low concentrations in complex matrices.•Efforts to characterize TiO2 NPs in aggregate, coagulate, flocculate, sediment.•Important to stabilize TiO2 NP to control particle fate, effect, and application.•More advanced methods in need to investigate TiO2 NPs in complex matrices.
Abstract
Exposing and stabilizing undercoordinated platinum (Pt) sites and therefore optimizing their adsorption to reactive intermediates offers a desirable strategy to develop highly efficient ...Pt-based electrocatalysts. However, preparation of atomically controllable Pt-based model catalysts to understand the correlation between electronic structure, adsorption energy, and catalytic properties of atomic Pt sites is still challenging. Herein we report the atomically thin two-dimensional PtTe
2
nanosheets with well-dispersed single atomic Te vacancies (Te-SAVs) and atomically well-defined undercoordinated Pt sites as a model electrocatalyst. A controlled thermal treatment drives the migration of the Te-SAVs to form thermodynamically stabilized, ordered Te-SAV clusters, which decreases both the density of states of undercoordinated Pt sites around the Fermi level and the interacting orbital volume of Pt sites. As a result, the binding strength of atomically defined Pt active sites to H intermediates is effectively reduced, which renders PtTe
2
nanosheets highly active and stable in hydrogen evolution reaction.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
An implementable algorithm for solving nonsmooth nonconvex constrained optimization is proposed by combining bundle ideas, proximity control, and the exact penalty function. We construct two kinds of ...approximations to nonconvex objective function; these two approximations correspond to the convex and concave behaviors of the objective function at the current point, which captures precisely the characteristic of the objective function. The penalty coefficients are increased only a finite number of times under the conditions of Slater constraint qualification and the boundedness of the constrained set, which limit the unnecessary penalty growth. The given algorithm converges to an approximate stationary point of the exact penalty function for constrained nonconvex optimization with weakly semismooth objective function. We also provide the results of some preliminary numerical testing to show the validity and efficiency of the proposed method.
Nanocarrier-based drug delivery systems hold impressive promise for biomedical application because of their excellent water dispersibility, prolonged blood circulation time, increased drug ...accumulation in tumors, and potential in combination therapeutics. However, most nanocarriers suffer from low drug-loading efficiency, poor therapeutic effectiveness, potential systematic toxicity, and unstable metabolism. As an alternative, carrier-free nanodrugs, completely formulated with one or more drugs, have attracted increasing attention in cancer therapy due to their advantage of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug-loading. In recent years, carrier-free nanodrugs have contributed to progress in a variety of therapeutic modalities. In this review, different common strategies for carrier-free nanodrugs preparation are first summarized, mainly including nanoprecipitation, template-assisted nanoprecipitation, thin-film hydration, spray-drying technique, supercritical fluid (SCF) technique, and wet media milling. Then we describe the recently reported carrier-free nanodrugs for cancer chemo-monotherapy or combination therapy. The advantages of anti-cancer drugs combined with other chemotherapeutic, photosensitizers, photothermal, immunotherapeutic or gene drugs have been demonstrated. Finally, a future perspective is introduced to highlight the existing challenges and possible solutions toward clinical application of currently developed carrier-free nanodrugs, which may be instructive to the design of effective carrier-free regimens in the future.
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