The combination of DNA nanostructures and materials for highly sensitive electrochemical detection.

Due to the wide range of electrochemical devices available, DNA nanostructures and material-based technologies have been greatly broadened. They have been actively used to create a variety of beautiful nanostructures owing to their unmatched programmability. Currently, a variety of electrochemical devices have been used for rapid sensing of biomolecules and other diagnostic applications. Here, we provide a brief overview of recent advances in DNA-based biomolecular assays. Biosensing platform such as electrochemical biosensor, nanopore biosensor, and field-effect transistor biosensors (FET), which are equipped with aptamer, DNA walker, DNAzyme, DNA origami, and nanomaterials, has been developed for amplification detection. Under the optimal conditions, the proposed biosensor has good amplification detection performance. Further, we discussed the challenges of detection strategies in clinical applications and offered the prospect of this field.

Broadband nanostructured fiber mode convertors enabled by inverse design.

Nanostructured fiber devices enabling mode conversion between arbitrary fiber modes are proposed and numerically validated. The intra-fiber nanostructures are optimized by the inverse design algorithm. We demonstrate a set of designs of nanophotonic fibers that can facilitate high-purity conversion from the fundamental mode to higher-order modes up to 3 orders for both LP and OAM modes inside the fibers. The purity values of the output modes can reach 98% with an ultra-wide operation band exceeding 400 nm around the telecom wavelengths. These devices can be fabricated by technique of thermal drawing of assembled preforms, making them suitable for mass production.

Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: A multi-center real-world retrospective study.

To parallelly compare the efficacy of neoadjuvant immunotherapy (tislelizumab), neoadjuvant chemotherapy (gemcitabine and cisplatin), and neoadjuvant combination therapy (tislelizumab + GC) in patients with muscle-invasive bladder cancer (MIBC) and explore the efficacy predictors, we perform a multi-center, real-world cohort study that enrolls 253 patients treated with neoadjuvant treatments (combination therapy: 98, chemotherapy: 107, and immunotherapy: 48) from 15 tertiary hospitals. We demonstrate that neoadjuvant combination therapy achieves the highest complete response rate and pathological downstaging rate compared with neoadjuvant immunotherapy or chemotherapy. We develop and validate an efficacy prediction model consisting of pretreatment clinical characteristics, which can pinpoint candidates to receive neoadjuvant combination therapy. We also preliminarily reveal that patients who achieve pathological complete response after neoadjuvant treatments plus maximal transurethral resection of the bladder tumor may be safe to receive bladder preservation therapy. Overall, this study highlights the benefit of neoadjuvant combination therapy based on tislelizumab for MIBC.

Vertically Aligned Graphene Prepared by Photonic Annealing for Ultrasensitive Biosensors.

Graphene exhibits excellent physical, electronic, and chemical properties that are highly desirable for biosensing applications. However, most graphene biosensors are based on graphene lying flat on a substrate and therefore do not utilize its maximum specific surface area for ultrasensitive detection. Herein, we report the novel use of photonic annealing on a flexographically printed graphene-ethyl cellulose composite to produce vertically aligned graphene (VAG) biosensors for ultrasensitive detection of algal toxins in drinking water. These VAG structures, which maximized the specific surface area of graphene, were formed by partial removal of the polymeric binder upon applying intense pulsed light on the printed graphene. A label-free and low-cost VAG biosensor based on a non-faradaic electrochemical impedance spectroscopy technique was fabricated. The biosensor exhibited a limit of detection of 1.2 ng/L for microcystin-LR in local tap water. Such an ultrasensitive VAG biosensor is suitable for low-cost mass production using an integrated roll-to-roll flexographic printing with rapid photonic annealing technique.

Recent Advances on Electrochemical Sensors for the Detection of Organic Disinfection Byproducts in Water.

Irreversible organ damage or even death frequently occurs when humans or animals unknowingly drink contaminated water. Therefore, in many countries drinking water is disinfected to ensure removal of harmful pathogens from drinking water. If upstream water treatment prior to disinfection is not adequate, disinfection byproducts (DBPs) can be formed. DBPs can exist as wide variety of compounds, but up until now, only several typical compounds have drinking water standards attributed to them. However, it is apparent that the range of DBPs present in water can comprise hundreds of compounds, some of which are at high enough concentrations to be toxic or potentially carcinogenic. Hence, it becomes increasingly significant and urgent to develop an accessible, affordable, and durable sensing platform for a broader range and more sensitive detection of DBPs. Compared with well-established laboratory detection techniques, electrochemical sensing has been identified as a promising alternative that will provide rapid, affordable, and sensitive DBP monitoring in remote water sources. Therefore, this Review covers current state-of-the-art development (within the past decade) in electrochemical sensing to detect organic DBPs in water, which covered three major aspects: (1) recognition mechanism, (2) electrodes with signal amplification, and (3) signal read-out techniques. Moreover, comprehensive quality assessments on electrochemical biosensors, including linear detection range, limit of detection (LoD) and recovery, have also been summarized.

Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion.

Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components.

Synthesis and Biological Evaluation of Novel Ursolic acid Derivatives as Potential Anticancer Prodrugs.

Ursolic acid (UA) is a natural product which has been shown to possess a wide range of pharmacological activities, in particular those with anticancer activity. In this study, 13 novel ursolic acid derivatives were designed and synthesized in an attempt to further improve compound potency. The structures of the newly synthesized compounds were confirmed using mass spectrometry, infrared spectroscopy, and (1) H NMR. The ability of the UA derivatives to inhibit cell growth was assayed against both various tumor cell lines and a non-pathogenic cell line, HELF. Analysis of theoretical toxicity risks for all derivatives was performed using OSIRIS and indicated that the majority of compounds would present moderate to low risks. Pharmacological results indicated that the majority of the derivatives were more potent growth inhibitors than UA. In particular, 5b demonstrated IC50 values ranging from 4.09 ± 0.27 to 7.78 ± 0.43 µm against 12 different tumor cell lines. Flow cytometry analysis indicated that 5b induced G0/G1 arrest in three of these cell lines. These results were validated by structural docking studies, which confirmed that UA could bind to cyclins D1 (Cyc D1) and cyclin-dependent kinases (CDK6), the key regulators of G0/G1 transition in cell cycle, while the piperazine moiety of 5b could bind with glucokinase (GK), glucose transporter 1 (GLUT1), and ATPase, which are the main proteins involved in cancer cell metabolism. Acridine orange/ethidium bromide staining confirmed that 5b was capable of inducing apoptosis and decreasing cell viability in a dose-dependent manner.

Effect of heterologous bone marrow mononuclear cell transplantation on midpalatal expansion in rats.

The aim of this study was to explore whether bone marrow mononuclear cell (BMMC) transplantation is able to accelerate the bone remodeling induced by midpalatal expansion in rats. A total of 48 male Sprague-Dawley rats (mean weight, 208.36±7.32 g) were divided into control and midpalatal expansion with or without BMMC transplantation groups. Histological and morphological changes were observed in each group. The osteogenic activities and differential potentials of the transplanted BMMCs labeled with bromodeoxyuridine in the midpalatal bone tissue were assessed by osteocalcin expression. The receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to reflect the equilibrium between bone resorption and formation. The results demonstrated that the width of the maxillary dental arch increased distinctly within 2 weeks of midpalatal expansion with BMMC transplantation. The morphology of the midpalatal suture in this group changed significantly; the cartilage was completely replaced by fibrous-like tissue expressing osteocalcin. The palatal bone was reorganized from a cancellous form into a mature compact structure after an additional 2-week relapse period. Immunostaining results indicated that the heterologous transplanted BMMCs survived and differentiated into osteoblasts during the remodeling induced by midpalatal expansion. The RANKL/OPG expression ratio significantly decreased after 2 weeks of midpalatal expansion with BMMC transplantation due to the inhibition of RANKL expression. Heterologous BMMC transplantation appears to accelerate the midpalatal bone remodeling induced by expansion of the rats through increasing the number of osteoprogenitor cells and regulating the RANKL-OPG signaling pathway.

Expression of non-neuronal cholinergic system in maxilla of rat in vivo.

BACKGROUND: Acetylcholine (ACh) is known to be a key neurotransmitter in the central and peripheral nervous systems, which is also produced in a variety of non-neuronal tissues and cell. The existence of ACh in maxilla in vivo and potential regulation role for osteogenesis need further study. RESULTS: Components of the cholinergic system (ACh, esterase, choline acetyltransferase, high-affinity choline uptake, n- and mAChRs) were determined in maxilla of rat in vivo, by means of Real-Time PCR and immunohistochemistry. Results showed RNA for CarAT, carnitine/acylcarnitine translocase member 20 (Slc25a20), VAChT, OCTN2, OCT1, OCT3, organic cation transporter member 4 (Slc22a4), AChE, BChE, nAChR subunits α1, α2, α3, α5, α7, α10, ß1, ß2, ß4, γ and mAChR subunits M1, M2, M3, M4, M5 were detected in rat's maxilla. RNA of VAChT, AChE, nAChR subunits α2, ß1, ß4 and mAChR subunits M4 had abundant expression (2(-ΔCt) > 0.03). Immunohistochemical staining was conducted for ACh, VAChT, nAChRα7 and AChE. ACh was expressed in mesenchymal cells, chondroblast, bone and cartilage matrix and bone marrow cells, The VAChT expression was very extensively while ACh receptor α7 was strongly expressed in newly formed bone matrix of endochondral and bone marrow ossification, AchE was found only in mesenchymal stem cells, cartilage and bone marrow cells. CONCLUSIONS: ACh might exert its effect on the endochondral and bone marrow ossification, and bone matrix mineralization in maxilla.

Expression of non-neuronal cholinergic system in maxilla of rat in vivo

BACKGROUND: Acetylcholine (ACh) is known to be a key neurotransmitter in the central and peripheral nervous systems, which is also produced in a variety of non-neuronal tissues and cell. The existence of ACh in maxilla in vivo and potential regulation role for osteogenesis need further study. RESULTS: Components of the cholinergic system (ACh, esterase, choline acetyltransferase, high-affinity choline uptake, n- and mAChRs) were determined in maxilla of rat in vivo, by means of Real-Time PCR and immunohistochemistry. Results showed RNA for CarAT, carnitine/acylcarnitine translocase member 20 (Slc25a20), VAChT, OCTN2, OCT1, OCT3, organic cation transporter member 4 (Slc22a4), AChE, BChE, nAChR subunits α1, α2, α3, α5, α7, α10, ß1, ß2, ß4, γ and mAChR subunits M1, M2, M3, M4, M5 were detected in rat's maxilla. RNA of VAChT, AChE, nAChR subunits α2, ß1, ß4 and mAChR subunits M4 had abundant expression (2(-ΔCt) > 0.03). Immunohistochemical staining was conducted for ACh, VAChT, nAChRα7 and AChE. ACh was expressed in mesenchymal cells, chondroblast, bone and cartilage matrix and bone marrow cells, The VAChT expression was very extensively while ACh receptor α7 was strongly expressed in newly formed bone matrix of endochondral and bone marrow ossification, AchE was found only in mesenchymal stem cells, cartilage and bone marrow cells. CONCLUSIONS: ACh might exert its effect on the endochondral and bone marrow ossification, and bone matrix mineralization in maxilla.