Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe.

Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.

Carbon Dots with Absorption Red-Shifting for Two-Photon Fluorescence Imaging of Tumor Tissue pH and Synergistic Phototherapy.

Phototherapy exhibits significant potential as a novel tumor treatment method, and the development of highly active photosensitizers and photothermal agents has drawn considerable attention. In this work, S and N atom co-doped carbon dots (S,N-CDs) with an absorption redshift effect were prepared by hydrothermal synthesis with lysine, o-phenylenediamine, and sulfuric acid as raw materials. The near-infrared (NIR) absorption features of the S,N-CDs resulted in two-photon (TP) emission, which has been used in TP fluorescence imaging of lysosomes and tumor tissue pH and real-time monitoring of apoptosis during tumor phototherapy, respectively. The obtained heteroatom co-doped CDs can be used not only as an NIR imaging probe but also as an effective photodynamic therapy/photothermal therapy (PDT/PTT) therapeutic agent. The efficiencies of different heteroatom-doped CDs in tumor treatment were compared. It was found that the S,N-CDs showed higher therapeutic efficiency than N-doped CDs, the efficiency of producing 1O2 was 27%, and the photothermal conversion efficiency reached 34.4%. The study provides new insight into the synthesis of carbon-based nanodrugs for synergistic phototherapy and accurate diagnosis of tumors.

A tumor microenvironment-induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy.

Tumor microenvironment-responsive therapy has enormous application potential in the diagnosis and treatment of cancer. The glutathione (GSH) level has been shown to be significantly increased in tumor tissues. Thus, GSH can be used as an effective endogenous molecule for diagnosis and tumor microenvironment-activated therapy. In this study, we prepared a tumor microenvironment-induced, absorption spectrum red-shifted, iron-copper co-doped polyaniline nanoparticle (Fe-Cu@PANI). The Cu(II) in this nanoparticle can undergo a redox reaction with GSH in tumors. The redox reaction induces a red shift in the absorption spectrum of the Fe-Cu@PANI nanoparticles from the visible to the near-infrared region accompanying with the etching of this nanoparticle, which simultaneously activates tumor photoacoustic imaging and photothermal therapy, thereby improving the accuracy of in vivo tumor imaging and the efficiency of photothermal therapy. The nanoparticle prepared in this study has broad application prospects in the diagnosis and treatment of cancer.

Needle knife therapy plus sodium hyaluronate injection for knee osteoarthritis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a worldwide disease and more and more people are suffered from it. With the increasing number of patients, it brings a huge burden on social economy and security system. There are varieties of methods to cure KOA, such as Traditional Chinese Medicine and surgery. Needle knife therapy plus Sodium hyaluronate Injection is one of the prevalent treatments for KOA. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for the treatment of needle knife therapy plus sodium hyaluronate Injection. METHODS: Randomized controlled trials will be used to compare the effect of needle knife therapy plus sodium hyaluronate injection with needle knife alone for KOA patients. Six studies will be included in this meta-analysis, and the relative risk and weight mean difference with 95% CI for the Lysholm knee score, visual analogue scale, and effective rate will be evaluated by using RevMan 5.3 software. Besides, the bias assessment of the included studies will be evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations, Assessment Development, and Evaluation system will be applied to assess the overall quality of the evidence. RESULTS: From the study we will assess the effectiveness, safety of needle knife therapy plus sodium hyaluronate injection on joint pain relief and functional improvement in patients with KOA. CONCLUSION: The study will provide a new evidence to confirm the effect of needle knife therapy plus sodium hyaluronate injection on KOA, which can further guide the selection of therapy. PROSPERO REGISTRATION NUMBER: CRD42020169602.

Acupuncture for the treatment of ankle sprain: A protocol for a systematic review and meta-analysis: study protocol.

BACKGROUND: Ankle sprain is one of the most common musculoskeletal injuries in our daily life, which may lead to chronic ankle instability, reducing the quality of patients' life and imposing a heavy burden on social medical security system. There are many kinds of methods treating ankle sprain, which can be divided into the conservative treatments and surgical intervention. Acupuncture is one of the conservative treatments for ankle sprain, especially in China. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for acupuncture's effectiveness, safety and cost benefits for the treatment. METHODS: For the acquisition of required data of eligible randomized controlled trials (RCTs), literature search will be undertaken from the following database: PubMed, Embase, Web of Science, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database. Quality assessment of the included studies will be independently performed according to the Cochrane Risk of Bias Tool by 2 investigators and the level of evidence for results will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis will be conducted with Revman 5.3. RESULTS: From the study we will assess the effectiveness, safety and cost benefit of acupuncture on pain relief and functional improvement in patients with ankle sprain. CONCLUSION: The conclusion of this study will provide evidence to ensure the effectiveness, safety and cost benefits of acupuncture on ankle sprain, which can further guide the selection of appropriate interventions. PROSPERO REGISTRATION NUMBER: CRD42018116829.

A Multi-level Memristor Based on Al-Doped HfO2 Thin Film.

Non-volatile memory (NVM) will play a very important role in the next-generation digital technologies, including the Internet of things. The metal-oxide memristors, especially based on HfO2, have been favored by lots of researchers because of its simple structure, high integration, fast operation speed, low power consumption, and high compatibility with advanced (complementary metal oxide silicon) CMOS technologies. In this paper, a 20-level stable resistance states Al-doped HfO2-based memristor is presented. Its cycles endurance, data retention time, and resistance ratio are larger than 103, > 104 s, and > 10, respectively.

Probing the Optical Properties of MoS2 on SiO2/Si and Sapphire Substrates.

As an important supplementary material to graphene in the optoelectronics field, molybdenum disulfide (MoS2) has attracted attention from researchers due to its good light absorption capacity and adjustable bandgap. In this paper, MoS2 layers are respectively grown on SiO2/Si and sapphire substrates by atmospheric pressure chemical vapor deposition (APCVD). Atomic force microscopy, optical microscopy, and Raman and photoluminescence spectroscopy are used to probe the optical properties of MoS2 on SiO2/Si and sapphire substrates systematically. The peak shift between the characteristic A1g and E12g peaks increases, and the I peak of the PL spectrum on the SiO2/Si substrate redshifts slightly when the layer numbers were increased, which can help in obtaining the layer number and peak position of MoS2. Moreover, the difference from monolayer MoS2 on the SiO2/Si substrate is that the B peak of the PL spectrum has a blueshift of 56 meV and the characteristic E12g peak of the Raman spectrum has no blueshift. The 1- and 2-layer MoS2 on a sapphire substrate had a higher PL peak intensity than that of the SiO2/Si substrate. When the laser wavelength is transformed from 532 to 633 nm, the position of I exciton peak has a blueshift of 16 meV, and the PL intensity of monolayer MoS2 on the SiO2/Si substrate increases. The optical properties of MoS2 can be obtained, which is helpful for the fabrication of optoelectronic devices.