Tailor-Made Heterocharged Covalent Organic Framework Membrane for Efficient Ion Separation.

Pore size sieving, Donnan exclusion, and their combined effects seriously affect ion separation of membrane processes. However, traditional polymer-based membranes face some challenges in precisely controlling both charge distribution and pore size on the membrane surface, which hinders the ion separation performance, such as heavy metal ion removal. Herein, the heterocharged covalent organic framework (COF) membrane is reported by assembling two kinds of ionic COF nanosheets with opposite charges and different pore sizes. By manipulating the stacking quantity and sequence of two kinds of nanosheets, the impact of membrane surface charge and pore size on the separation performance of monovalent and multivalent ions is investigated. For the separation of anions, the effect of pore size sieving is dominant, while for the separation of cations, the effect of Donnan exclusion is dominant. The heterocharged TpEBr/TpPa-SO3H membrane with a positively charged upper layer and a negatively charged bottom layer exhibits excellent rejection of multivalent anions and cations (Ni2+, Cd2+, Cr2+, CrO4 2-, SeO3 2-, etc). The strategy provides not only high-performance COF membranes for ion separation but also an inspiration for the engineering of heterocharged membranes.

Rapid PFOS mineralization with peroxydisulfate activation process mediated by N modified Fe-based catalyst.

As the cheap and efficient catalysts, the iron-based catalysts have been considered as one of the most promising catalysts for peroxydisulfate (PDS) activation and the development of high-performance iron-based catalysts are attracting growing attentions. In this work, a magnetic Fe-based catalysts (Fe/NC-1000) was obtained by using Fe modified ZIF-8 as the precursor and used to activate the PDS for the degradation of perfluorooctane sulphonate (PFOS). Morphology and structure analysis showed that the resulted Fe/NC-1000 catalyst was displayed porous spheres (40-60 nm) and mainly composed of Fe0, FeNx and carbon. When Fe/NC-1000 was employed to activate the PDS (0.1 g/L of catalyst dosage, 0.5 g/L of PDS dosage and at initial pH of 4.6), the Fe/NC-1000/PDS system exhibited excellent efficiency (97.9 ± 0.1) % for PFOS (10 mg/L) degradation within 30 min. The quenching tests and EPR results revealed that the Fe/NC-1000/PDS system degraded PFOS primarily through singlet oxygen (1O2) evolution and electron-transfer process. Besides, based on the degradation byproducts determined by LC-MS-MS, the PFOS first occurred de-sulfonation to form PFOA, and then the resulted PFOA underwent stepwise defluorination in the Fe/NC-1000/PDS system. Density Functional Theory (DFT) calculations and electrochemistry tests strongly confirmed that Fe/NC-1000 exhibited high electron transfer efficiency, resulting in promoted performance on activating PDS. Importantly, the results of Ecological Structure-Activity Relationship (ECOSAR) analysis showed that the intermediates were lowly toxic during the PFOS degradation, manifesting a green process for PFOS removal. This study would provide more understandings for the persulfate activation process mediated by Fe-based catalysts for Perfluorinated alkyl substances (PFAS) elimination.

A novel salt-tolerant strain Trichoderma atroviride HN082102.1 isolated from marine habitat alleviates salt stress and diminishes cucumber root rot caused by Fusarium oxysporum.

BACKGROUND: Salt stress threaten the growth of plants, and even aggravate plant disease. In this article, salt-tolerant Trichoderma strain was isolated, and its potential to alleviate salt stress and diminish cucumber root rot caused by Fusarium oxysporum was evaluated. RESULTS: Twenty-seven Trichoderma isolates were isolated from samples of sea muds and algae collected from the South Sea of China. Among these, the isolate HN082102.1 showed the most excellent salt tolerance and antagonistic activity against F. oxysporum causing root rot in cucumber and was identified as T. atroviride. Its antagonism ability may be due to mycoparasitism and inhibition effect of volatile substances. The application of Trichoderma mitigated the adverse effects of salt stress and promoted the growth of cucumber under 100 mM and 200 mM NaCl, especially for the root. When T. atroviride HN082102.1 was applied, root fresh weights increased by 92.55 and 84.86%, respectively, and root dry weights increased by 75.71 and 53.31%, respectively. Meanwhile, the application of HN082102.1 reduced the disease index of cucumber root rot by 63.64 and 71.01% under 100- and 0-mM saline conditions, respectively, indicating that this isolate could inhibit cucumber root rot under salt stress. CONCLUSIONS: This is the first report of salt-tolerant T. atroviride isolated from marine habitat showing antagonistic activity to F. oxysporum, and the results provide evidence for the novel strain T. atroviride HN082102.1 in alleviating salt stress and diminishing cucumber root rot, indicating that T. atroviride strain HN082102.1 can be used as biological control agent in saline alkali land.

The experience of patients with cancer on narrative practice: A systematic review and meta-synthesis.

BACKGROUND: In recent years, narrative practice has been applied in clinical settings to address the relational and psychological concerns that occur in tandem with physical illness. It is an emerging strategy to treat patients as individuals with their own stories, rather than purely based on symptoms. OBJECTIVE: To synthesize the experience of patients with cancer using narrative practice. METHODS: Following a systematic search strategy, a literature search was conducted to identify qualitative studies on the experience of patients with cancer using narrative practice. Nine databases were searched up to April 2018, which included six English databases and three Chinese databases. A meta-synthesis was conducted to synthesize the findings of the included studies. MAIN RESULTS: Seven studies out of 2894 studies were included in this review. Patients with cancer had different preferences on narrative practices. In terms of the impacts of narrative practice on patients with cancer, six themes were identified, which included '(a) reducing the gap between patients and clinicians; (b) healing effect; (c) social connection; (d) facilitating self-reflection, self-recognition and self-realization; (e) risk of negative impacts; and (f) Patients' preference on different approaches of narrative practice'. CONCLUSIONS: Patients with cancer experienced positive effects regarding narrative practice. Although some patients may experience negative effects, narrative practice is a humanized way to provide care for patients with cancer in the clinical settings.

Nanoscale Coordination Polymers for Synergistic NO and Chemodynamic Therapy of Liver Cancer.

Nitric oxide (NO) induces a multitude of antitumor activities, encompassing the induction of apoptosis, sensitization to chemo-, radio-, or immune-therapy, and inhibition of metastasis, drug resistance, angiogenesis, and hypoxia, thus attracting much attention in the area of cancer intervention. To improve the precise targeting and treatment efficacy of NO, a glutathione (GSH)-sensitive NO donor (1,5-bis[(l-proline-1-yl)diazen-1-ium-1,2-diol- O2-yl]-2,4-dinitrobenzene, BPDB) coordinates with iron ions to form the nanoscale coordination polymer (NCP) via a simple precipitation and then partial ion exchange process. The obtained Fe(II)-BNCP shows desirable solubility, biocompatibility, and circulation stability. Quick NO release triggered by high concentrations of GSH in tumor cells improves the specificity of NO release in situ, thus avoiding side effects in other tissues. Meanwhile, under high concentrations of H2O2 in tumors, Fe2+ ions in BPDB-based NCP, named Fe(II)-BNCP, exert Fenton activity to generate hydroxyl radicals (·OH), which is the main contribution for chemodynamic therapy (CDT). In addition, ·O2- generated by the Haber-Weiss reaction of Fe2+ ions with H2O2 can quickly react with NO to produce peroxynitrite anion (ONOO-) that is more cytotoxic than ·O2- or NO only. This synergistic NO-CDT effect has been proved to retard the tumor growth in Heps xenograft ICR mouse models. This work not only implements a synergistic effect of NO-CDT therapy but also offers a simple and efficient strategy to construct a coordination polymer nanomedicine via rationally designed prodrug molecules such as NO donors.

Monitoring of Heparin Activity in Live Rats Using Metal-Organic Framework Nanosheets as Peroxidase Mimics.

Metal-organic framework (MOF) nanosheets are a class of two-dimensional (2D) porous and crystalline materials that hold promise for catalysis and biodetection. Although 2D MOF nanosheets have been utilized for in vitro assays, ways of engineering them into diagnostic tools for live animals are much less explored. In this work, a series of MOF nanosheets are successfully engineered into a highly sensitive and selective diagnostic platform for in vivo monitoring of heparin (Hep) activity. The iron-porphyrin derivative is selected as a ligand to synthesize a series of archetypical MOF nanosheets with intrinsic heme-like catalytic sites, mimicking peroxidase. Hep-specific AG73 peptides as recognition motifs are physically adsorbed onto MOF nanosheets, blocking active sites from nonspecific substrate-catalyst interaction. Because of the highly specific interaction between Hep and AG73, the activity of AG73-MOF nanosheets is restored upon the binding of Hep, but not Hep analogues and other endogenous biomolecules. Furthermore, by taking advantages of biocompatibility and diagnostic property enabled by AG73-MOF nanosheets, the elimination process of Hep in live rats is quantitatively monitored by coupling with microdialysis technology. This work expands the biomedical applications of 2D MOF nanomaterials and provides access to a promising in vivo diagnostic platform.

Enzymatically activated reduction-caged SERS reporters for versatile bioassays.

Here we report a facile strategy for activating reduction caged Raman reporters for surface-enhanced Raman scattering (SERS) with peroxidases. After selecting suitable caged reporters, versatile bioassays were developed. First, the bioassays for bioactive small molecules were developed. Then, the immunoassay was developed for C reactive protein (CRP), a biomarker for cardiovascular diseases.

Performance and mechanistic studies of rapid atenolol degradation through peroxymonosulfate activation by V, Co, and bamboo carbon catalyst.

Developing the Co-based catalysts with high reactivity for the sulfate radical (SO4-·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous attentions. To improve the peroxymonosulfate (PMS) activation process, a novel Co-based catalyst simultaneously modified by bamboo carbon (BC) and vanadium (V@CoO-BC) was fabricated through a simple solvothermal method. The atenolol (ATL) degradation experiments in V@CoO-BC/PMS system showed that the obtained V@CoO-BC exhibited much higher performance on PMS activation than pure CoO, and the V@CoO-BC/PMS system could fully degrade ATL within 5 min via the destruction of both radicals (SO4-· and O2-··) and non-radicals (1O2). The quenching experiments and electrochemical tests revealed that the enhancing mechanism of bamboo carbon and V modification involved four aspects: (i) promoting the PMS and Co ion adsorption on the surface of V@CoO-BC; (ii) enhancing the electron transfer efficiency between V@CoO-BC and PMS; (iii) activating PMS with V3+ species; (iv) accelerating the circulation of Co2+ and Co3+, leading to the enhanced yield of reactive oxygen species (ROS). Furthermore, the V@CoO-BC/PMS system also exhibited satisfactory stability under broad pH (3-9) and good efficiency in the presence of co-existing components (HCO3-, NO3-, Cl-, and HA) in water. This study provides new insights to designing high-performance, environment-friendly bimetal catalysts and some basis for the remediation of antibiotic contaminants with SR-AOPs.

3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair.

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.

Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.

Homocysteine thiolactone (HTL), a toxic metabolite of homocysteine (Hcy) in hyperhomocysteinemia (HHcy), is known to modify protein structure and function, leading to protein damage through formation of N-Hcy-protein. HTL has been highly linked to HHcy-associated cardiovascular and neurodegenerative diseases. The protective role of HTL hydrolases against HTL-associated vascular toxicity and neurotoxicity have been reported. Although several endogeneous enzymes capable of hydrolyzing HTL have been identified, the primary enzyme responsible for its metabolism remains unclear. In this study, three human carboxylesterases were screened to explore new HTL hydrolase and human carboxylesterase 1 (hCES1) demonstrates the highest catalytic activity against HTL. Given the abundance of hCES1 in the liver and the clinical significance of its single-nucleotide polymorphisms (SNPs), six common hCES1 nonsynonymous coding SNP (nsSNPs) variants were examined and characterized for their kinetic parameters. Variants E220G and G143E displayed 7.3-fold and 13.2-fold lower catalytic activities than its wild-type counterpart. In addition, the detailed catalytic mechanism of hCES1 for HTL hydrolysis was computational investigated and elucidated by Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) method. The function of residues E220 and G143 in sustaining its hydrolytic activity of hCES1 was analyzed, and the calculated energy difference aligns well with experimental-derived results, supporting the validity of our computational insights. These findings provide insights into the potential protective role of hCES1 against HTL-associated toxicity, and warrant future studies on the possible association between specific genetic variants of hCES1 with impaired catalytic function and clinical susceptibility of HTL-associated cardiovascular and neurodegenerative diseases.

A dual-emission fluorescent nanocomplex of gold-cluster-decorated silica particles for live cell imaging of highly reactive oxygen species.

A novel nanocomplex displaying single-excitation and dual-emission fluorescent properties has been developed through a crown-like assembly of dye-encapsulated silica particles decorated with satellite AuNCs for live cell imaging of highly reactive oxygen species (hROS), including •OH, ClO(-) and ONOO(-). The design of this nanocomplex is based on our new finding that the strong fluorescence of AuNCs can be sensitively and selectively quenched by these hROS. The nanocomplex is demonstrated to have excellent biocompatibility, high intracellular delivery efficiency, and stability for long-time observations. The results reveal that the nanocomplex provides a sensitive sensor for rapid imaging of hROS signaling with high selectivity and contrast.

Nanoscale MOFs in nanomedicine applications: from drug delivery to therapeutic agents.

Metal-organic frameworks (MOFs) hold great promise for widespread applications in biomedicine and nanomedicine. MOFs are one of the most fascinating nanocarriers for drug delivery, benefiting from their high porosity and facile modification. Furthermore, the tailored components of MOFs can be therapeutic agents for various treatments, including drugs as organic ligands of MOFs, active metal as central metal ions of MOFs, and their combinations as carrier-free MOF-based nanodrug. In this review, the advances in delivery systems and applications as therapeutic agents for nanoscale MOF-based materials are summarized. The challenges of MOFs in clinical translation and the future directions in the field of MOFs therapy are also discussed. We hope that more researchers will focus their attention on advancing and translating MOF-based nanodrugs into pre-clinical and clinical applications.

Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma.

PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover,  the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.

A randomized, controlled single, and multiple ascending dose trial of the safety, pharmacokinetics and pharmacodynamics of SN1011 in healthy subjects.

The purpose of this study was to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SN1011, a novel Bruton tyrosine kinase (BTK) inhibitor, and food effects in healthy subjects. In this phase I trial, subjects received single ascending doses (SADs) of SN1011 (100 to 800 mg), multiple ascending doses (MADs) of SN1011 (200 to 600 mg), or placebo q.d. Additionally, 12 subjects randomly received a single dose of SN1011 600 mg under fasting states and then fed states, vice versa. Safety was assessed per Common Terminology Criteria for Adverse Events version 5.0. Pharmacokinetic parameters were calculated by noncompartmental analysis and BTK receptor occupancy in peripheral blood monocytes was determined. Seventy-one healthy subjects were dosed in five SAD cohorts, three MAD cohorts, and one food effect cohort, with 57 receiving SN1011 and 14 receiving placebo. No serious adverse events (AEs) were reported. There was no correlation between AE occurrences and SN1011 exposure. The three most frequent AEs with SN1011 were increased blood triglycerides, decreased neutrophil count, and decreased leucocyte count. SN1011 exhibited a dose-proportional increase in maximum plasma concentration and area under the time concentration curve following single and multiple dose administrations, with an accumulation ratio of 1.5 to 2.2 after multiple dose administrations. No difference in SN1011 exposure was observed between fed states. BTK receptor occupancy remained above 83% over 24 h after single administration and remained above 80% for the MAD groups for 10 days of continuous q.d. administration. SN1011 was well-tolerated and safe after single or multiple exposures to healthy subjects, supporting further clinical development of SN1011 for treatment of autoimmune diseases.

A real-time rural domestic garbage detection algorithm with an improved YOLOv5s network model.

An increasing number of researchers are using deep learning technology to classify and process garbage in rural areas, and have achieved certain results. However, the existing garbage detection models still have problems such as high complexity, missed detection of small targets, low detection accuracy and poor real-time performance. To address these issues, we train a model and apply it to garbage classification and detection in rural areas. In general, we propose an attention combination mechanism based on the YOLOv5 algorithm to build a better backbone network structure, add a new small object detection layer in the head network to enhance the model's ability to detect small objects, adopt the CIoU loss function to optimize the output prediction bounding box, and choose the Adam optimization algorithm to train the model. Our proposed YOLOv5s-CSS model detects a single garbage image in 0.021 s with a detection accuracy of 96.4%. Compared with the YOLOv5 algorithm and the classic detection algorithm, the improved algorithm has better detection speed and detection accuracy. At the same time, the complexity of the network model is reduced to a certain extent, which can meet the requirements of real-time detection of rural domestic garbage.

hESCs-Derived Early Vascular Cell Spheroids for Cardiac Tissue Vascular Engineering and Myocardial Infarction Treatment.

Transplanting functional cells to treat myocardial infarction (MI), a major disease threatening human health, has become the focus of global therapy. However, the efficacy has not been well anticipated, partly due to the lack of microvascular system that supplies nutrients and oxygen. Here, spheroids of early vascular cells (EVCs) derived from human embryonic stem cells (hESCs), rather than single-cell forms, as transplant "seeds" for reconstructing microvascular networks, are proposed. Firstly, EVCs containing CD34+ vascular progenitor cells are identified, which effectively differentiate into endothelial cells in situ and form vascular networks in extracellular matrix (ECM) hydrogel. Secondly, cardiac microtissues and cardiac patches with well-organized microvasculature are fabricated by three-dimensional (3D) co-culture or bioprinting with EVCs and cardiomyocytes in hydrogel. Notably, in 3D-bioprinted myocardial models, self-assembly vascularization of EVC spheroids is found to be significantly superior to EVC single cells. EVC spheroids are also injected into ischemic region of MI mouse models to explore its therapeutic potential. These findings uncover hESCs-derived EVC spheroids rather than single cells are more accessible for complex vasculature engineering, which is of great potential for cardiac tissue vascular engineering and MI treatment by cell therapy.

One Stone Two Birds: Redox-Sensitive Colocalized Delivery of Cisplatin and Nitric Oxide through Cascade Reactions.

Bio-orthogonal bond-cleavage reactions have been used in cancer therapy for improving the biological specificity of prodrug activation, but the spatiotemporal consistency of reactants is still a huge challenge. Although, in most cases, the cleavage catalysts and caged prodrugs are administrated separately, it is difficult to avoid the reactions in advance before they meet at the tumor site. Herein, we design and construct novel coordinative nanoparticles, integrating two prodrugs A and B as ligands and ferric ions as coordinative centers. After nanoparticles accumulated in tumor through passive targeting, inert Pt(IV) prodrug A is specifically and spontaneously reduced into active Pt(II) cisplatin, which acts as the cleavage catalyst to subsequently initiate the in situ bio-orthogonal depropargylation of B, that is, O 2-propargyl nitric oxide (NO) donor. The unique structure of coordinative nanoparticles ensures the spatiotemporal consistency of reactants (prodrugs A and B) and products (cytotoxic cisplatin and tumoricidal NO) for the bio-orthogonal bond-cleavage reaction, which leads to an improved synergistic therapeutic activity for triple-negative breast cancer (TNBC). This new concept of bio-orthogonal dual-prodrug coordinative nanoparticles may inspire further applications in bio-orthogonal chemistry and drug delivery for combination chemotherapy.

Silk Fibroin-Induced Gadolinium-Functionalized Gold Nanoparticles for MR/CT Dual-Modal Imaging-Guided Photothermal Therapy.

The development of multifunction nanoplatforms integrating accurate diagnosis and efficient therapy is of great significance for the precise treatment of tumors. Gold nanoparticles (AuNPs) possessing hallmark features of computed tomography (CT) imaging and photothermal conversion capability hold great potential in tumor theranostics. In this study, taking the advantages of outstanding biocompatibility, interesting anti-inflammatory and immunomodulatory properties, and abundant amino acid residues of silk fibroin (SF), a multifunctional Gd-hybridized AuNP nanoplatform was constructed using SF as a stabilizer and reductant via a facile one-pot biomimetic method, denoted as Gd:AuNPs@SF. The obtained Gd:AuNPs@SF possessed fascinating biocompatibility and excellent photothermal conversion efficiency. Functionalized with Gd, Gd:AuNPs@SF exhibited super tumor-contrasted imaging performance in magnetic resonance (MR) and CT imaging modalities. Moreover, Gd:AuNPs@SF, with strong NIR absorbance, demonstrated that it could effectively kill tumor cells in vitro, and was also proved to successfully ablate tumor tissues through MR/CT imaging-guided photothermal therapy (PTT) without systemic toxicity in Pan02 xenograft C57BL/6 mouse models. We successfully synthesized Gd:AuNPs@SF for MR/CT dual-mode imaging-guided PTT via a facile one-pot biomimetic method, and this biomimetic strategy can also be used for the construction of other multifunction nanoplatforms, which is promising for precise tumor theranostics.