Removal of Aquatic Cadmium Ions Using Thiourea Modified Poplar Biochar

Removal of aquatic cadmium ions using biochar is a low-cost method, but the results are usually not satisfactory. Modified biochar, which can be a low-cost and efficient material, is urgently required for Cd-polluted water and soil remediation. Herein, poplar bark (SB) and poplar sawdust (MB) were used as raw materials to prepare modified biochar, which is rich in N- and S- containing groups, i.e., TSBC-600 and TMBC-600, using a co-pyrolysis method with thiourea. The adsorption characteristics of Cd2+ in simulated wastewater were explored. The results indicated that the modification optimized the surface structure of biochar, Cd2+ adsorption process by both TSBC-600 and TMBC-600 was mainly influenced by the initial pH, biochar dosage, and contact time, sthe TSBC-600 showed a higher adsorption capacity compared to TMBC-600 under different conditions. The Langmuir adsorption isotherm model and pseudo-second-order kinetic model were more consistent with the adsorption behavior of TSBC-600 and TMBC-600 to Cd2+, the maximum adsorption capacity of TSBC-600 and TMBC-600 calculated by the Langmuir adsorption isotherm model was 19.998 mg/g and 9.631 mg/g, respectively. The modification method for introducing N and S into biochar by the co-pyrolysis of biomass and thiourea enhanced the removal rate of aquatic cadmium ions by biochar

In situ nanozyme-amplified NIR-II phototheranostics for tumor-specific imaging and therapy

The discovery of near-infrared-II (NIR-II) tumor phototheranostics holds a great promise for use in nanomedicine on account of its enhanced penetration depth, high spatial resolution, and noninvasiveness. However, contemporary "always on" phototherapeutic agents often have many undesirable side effects that hinder their clinical trial progress. To overcome this dilemma, an in situ nanozyme-amplified chromogenic nanoreactor by loading 3,3′,5,5′-tetramethylbenzidine (TMB) and ultrasmall PtAu nanoparticles into a metal-organic framework is developed for specific tumor theranostics, leaving normal tissues unharmed. As an intelligent photoacoustic diagnostic agent, the as-constructed nanoreactor remains silent until they enter the tumor site (H2O2-activated and acid-enhanced conditions) and turns on photoacoustic signal to render a preoperative tumor diagnosis. As a nanozyme, the special microenvironment of the tumor tissue is used to initiate its catalytic damage by reactive oxygen species for chemodynamic therapy (CDT). More importantly, the TMB is oxidized, and the subsequent photothermal therapy (PTT) can be realized, leading to an optimal combination of CDT and PTT to concurrently fight obstinate cancers. The present “all-in-one” phototheranostics utilize nanozyme-augmented NIR-II agents for specific tumor ablation, which are promising for further development of intelligent nanozymes in the tumor therapy.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Submitted/Accepted versionThis work was supported by the National Key Research and Development Program of China (2018YFE0206900), the National Natural Science Foundation of China (21778020, 81927807, 31750110464, and 31950410755), the Sci-Tech Innovation Foundation of Huazhong Agricultural University (2662018PY024), the National Key R&D Program of China (2016YFD0500706), and Science and Technology Major Project of Guangxi (Gui Ke AA18118046). This work was also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081) and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)

ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor beta Signaling through a Direct Interaction with Smad3

A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-beta signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-beta signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-beta -induced G(1) cell cycle arrest and TGF-beta -induced cell migration. This study identifies and characterizes a novel repressor of TGF-beta signaling

An Individually Controlled Multitined Expandable Electrode Using Active Cannula‐Based Shape Morphing for On‐Demand Conformal Radiofrequency Ablation Lesions

Being minimally invasive and highly effective, radiofrequency ablation (RFA) is widely used for small‐sized malignant tumor treatment. However, in clinical practice, a large number of tumors are found in irregular shape, while the current RFA devices are hard to control the morphologic appearance of RFA lesions on demand, which usually ends up with unnecessarily excessive tissue ablation and subsequently often brings irreversible damage to the organs’ functions. Herein, active cannulas for each of the individually controlled subelectrodes to achieve an on‐demand shape morphing and thus conformal RFA lesion are introduced. The target shape as well as the length of inserted subelectrodes can be precisely controlled by tuning the active stylets and cannulas. What's more, owing to independent movement and energy control of each subelectrodes, the electrode is shown to be not only efficient enough to accomplish accurate trajectory control to target tissue in a single insertion, but also adaptive enough to ablate target tissues with diverse morphologic appearances and locations. On‐demand conformal ablation of target tissue is demonstrated as well under the guidance of ultrasound imaging with the device. Potentially, the RFA electrode is a promising minimally invasive treatment of malignant tumors in future clinical practice. An interactive preprint version of the article can be found at: https://www.authorea.com/doi/full/10.22541/au.164019293.38729522

Polarization of tumor-associated macrophages promoted by vitamin C-loaded liposomes for cancer immunotherapy

While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treatment, it is of benefit to only a subset of patients because of the tumor immunosuppressive microenvironment. Herein, we report that the specified delivery of vitamin C at the tumor site by responsive lipid nanoparticles can efficiently induce oxidative toxicity and the polarization of M1 macrophages, promoting the infiltration of activating cytotoxic T lymphocytes in the tumor microenvironment for intensive immune checkpoint blocking therapy. Both in vitro and in vivo assays demonstrate successful vitamin C-induced polarization of M2 macrophages to M1 macrophages. In vivo transcriptome analysis also reveals the activation mechanism of vitamin C immunity. More importantly, the combination approach displays much better immune response and immune process within the tumor microenvironment than clinical programmed cell death ligand 1 (Anti-PD-L1) alone. This work provides a powerful therapeutic application of vitamin C to amplify Anti-PD-L1 immunotherapy in cancer treatment, which brings hope to patients with clinically insensitive immunity.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)This work was supported by the National Key Research and Development Program of China (2018YFE0206900 and 2016YFD0500706), the National Natural Science Foundation of China (21778020, 81927807, 31750110464, and 31950410755), the Sci-Tech Innovation Foundation of Huazhong Agricultural University (2662018PY024), and Science and Technology Major Project of Guangxi (Gui Ke AA18118046). This work is also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081) and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)

Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways

<div><p>The effects of vitamin K2 on apoptosis in a variety of cancer cells have been well established in previous studies. However, the apoptotic effect of vitamin K2 on bladder cancer cells has not been evaluated. The aim of this study is to examine the apoptotic activity of Vitamin K2 in bladder cancer cells and investigate the underlying mechanism. In this study, Vitamin K2 induced apoptosis in bladder cancer cells through mitochondria pathway including loss of mitochondria membrane potential, cytochrome C release and caspase-3 cascade. Furthermore, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK was detected in Vitamin K2-treated cells and both SP600125 (an inhibitor of JNK) and SB203580 (an inhibitor of p38 MAPK) completely abolished the Vitamin K2-induced apoptosis and loss of mitochondria membrane potential. Moreover, the generation of reactive oxygen species (ROS) was detected in bladder cancer cells, upon treatment of vitamin K2 and the anti-oxidant N-acetyl cysteine (NAC) almost blocked the Vitamin K2-triggered apoptosis, loss of mitochondria membrane potential and activation of JNK and p38 MAPK. Taken together, these findings revealed that Vitamin K2 induces apoptosis in bladder cancer cells via ROS-mediated JNK/p38 MAPK and Mitochondrial pathways.</p></div

Electrochemical Biosensor Employing Bi₂S₃ Nanocrystals-Modified Electrode for Bladder Cancer Biomarker Detection

Bladder cancer is a kind of malignant tumor with high incidence in the urinary system, complex pathogenic causes, and the high recurrence rate. Biosensors capable of rapid, on site, and accurate bladder cancer diagnosis method continue to be lacking. Here, the electrochemical biosensor for detecting cytokeratin 18 (CK18, bladder cancer biomarker) was constructed based on the chemically modified electrode (CME). The work electrode (WE) was modified by bismuth sulfide semiconductor nanocrystals (Bi2S3 NCs), and then immobilized with CK18 antibodies and blocking agents to complete the electrode preparation. The results indicated that the interface of a flexible carbon electrode with Bi2S3 NCs film was steady with reliable charge transfer capability. With the large specific area and quantum size effect, the proposed sensor could detect CK18 antigen protein with an ultralow detection limit of 1.87 fM (fmol L−1) and wide linear dynamic range of 1–1000 pg mL−1, respectively. Detecting results could be read in less than 30 s with the portable, planar flexible CME. The sensitive and specific electrochemical biosensor possessed the characteristics of rapidity, ease-of-use, and non-invasive detection, indicating the application prospect in the early screening of bladder cancer and other diseases

ROS mediated the mitochondria dysfunction and regulated activation of JNK/p38 in vitamin K2-triggered apoptosis of human bladder cancer T24 cells.

<p>(A). T24 cells were treated with 5mM antioxidant NAC for 1 hour prior to the treatment with or without 100 μM vitamin K2 for 24 hours, then the mitochondria membrane potential was assessed using the Rhodamine 123 dye by flow cytometry. (B). The expression of Bax, Puma and Bcl-2 were changed after treatment with 100 μM vitamin K2 for 24 hours in the present or absent of 5mM antioxidant N-acetyl cysteine (NAC) to human bladder cancer T24 cells. (C). T24 cells were treated 40 μM SP600125(SP) for 1 hour before treatment of 100 μM vitamin K2 for 24 hours, mitochondria membrane potential was evaluated using Rhodamine 123 dye by flow cytometry. (D). T24 cells were treated 10 μM SB203580(SB) for 1 hour before treatment of 100 μM vitamin K2 for 24 hours, mitochondria membrane potential was evaluated using Rhodamine 123 dye by flow cytometry. (E). T24 cells were treated with 5mM NAC for 1 hour before exposure to 100 μM vitamin K2 for 24 hours, then the total proteins were isolated from the cells and activation of JNK/p38 were determined by western blots. ** P<0.01 and *** P<0.001.</p