Phospholipid-inspired alkoxylation induces crystallization and cellular uptake of luminescent COF nanocarriers.

The porous nature and structural variability of covalent organic frameworks (COFs) make them preferred for drug loading and delivery applications. However, most COF materials suffer from poor luminescent properties and inefficiency for cell uptake. Herein, we experimentally demonstrate the crucial role of long alkoxy chains in the synthesis of crystalline COF nanostructures with high cellular uptake efficiency. After luminescence integration through band engineering, the semiconducting COF exhibits an optical bandgap of 2.05 eV, an emission wavelength of 632 nm, a high quantum yield of 37 %, and excellent fluorescence stability (100 % at 3 h). Such excellent optical properties of the designed COF nanocarriers enable quantitative evaluations of cellular uptake and visual tracking of drug delivery. It was demonstrated that the cellular uptake efficiency was enhanced by orders of magnitude for the COF after the introduction of long n-octyloxy chains, which firstly delivered the anticancer camptothecin (CPT) to cell lysosomes, and then underwent "endo/lysosomal escape" to induce cell apoptosis. In vivo assay evidenced a significant enhancement in the therapeutic effect with a 96 % inhibition of tumor growth after 14 days of treatment. This progress sheds light on designing cutting-edge drug delivery nanosystems based on COF materials with integrated diagnostic and therapeutic functions.

Combined pollution characteristics and ecological risks of multi-pollutants in Poyang Lake.

Poyang Lake, the largest freshwater lake in China, faced severe ecological degradation in the past decade. Combined pollution of multi-pollutants may be one of the contributing factors. However, the characteristics of combined pollution and the ecological risks are still not clear. In this study, we used Polar Organic Chemical Integrative Sampler (POCIS), In Situ Bioassay Passive Sampling Device (ISBPSD) and conventional sampling methods, to study the toxic pollutants levels and the combined biological toxicity effects. The results showed that high levels of organochlorine pesticides (OCPs, averaged 162 ng/g) and polycyclic musk (PCM, averaged 53.6 ng/g) residues, as well as some metals such as nickel (Ni), lead (Pb) concentrations exceeded the relevant standard level in the sediment. The risk of combined pollution in the water was relatively low, but high risk was found in the sediments. According to the ISBPSD studies, the survival rates of species in the water and sediments were only 10.0-45.0% and 1.67-11.7% respectively, which was much lower than that reported in other typical basins of China. OCPs, PCMs, and certain metals such as Pb and Ni may be the key toxic pollutants causing biological toxicity effects in Poyang Lake.

Red-Fluorescent Covalent Organic Framework Nanospheres for Trackable Anticancer Drug Delivery.

Covalent organic frameworks (COFs) have emerged as promising drug carriers due to their structural variability, inherent porosity, and customizable functions. However, most COFs used in drug delivery suffer from low cellular bioavailability and poor luminescence properties. In this study, we designed a series of size-tunable, crystalline, and red-fluorescent COF nanospheres (COFNSs) for trackable anticancer drug delivery. The semiconducting COFNSs were prepared by condensations of 1,3,5-triformylbenzene (TFB) with various dihydrazide blocks through the Schiff-base reaction, resulting in red emission at 647 nm and excellent fluorescence stability (∼100% for 1 h). Such fluorescence property allowed for systematic investigation of the cellular endocytosis pathway of COFNSs, visualization of drug delivery, and observation of the cell apoptosis process. The COFNSs exhibited high cell viability (>90%), a loading capacity of 183 wt % for the anticancer drug camptothecin (CPT), and significant enhancement in inhibiting 4T1 cancers both in vitro and in vivo as the CPT nanocarrier. This progress presents a valuable approach to design COF nanocarriers with integrated fluorescent and drug delivery functions.

Flower-like porous BCN assembled by nanosheets for paclitaxel delivery.

Developing smart drug delivery systems has become a feasible solution to overcome the challenges in cancer chemotherapeutics. In this work, porous boron carbon nitride (ZBCN) nanomaterials with flower-like structures assembled with BCN nanosheets were synthesized by using ZIF-L as a template. The rich hydroxyl groups on the BCN surfaces make it highly dispersible and stable in aqueous solutions. Additionally, ZBCN exhibits stable photoluminescence properties that can be utilized for cellular uptake and tracking of drug delivery. Furthermore, the flower-like ZBCN structure contributes to a large specific surface area of up to 340 m2 g-1 and a pore volume of 1.03 cm3 g-1; and the presence of rich macropores results in a high drug loading capacity of 116 wt% for paclitaxel. In vitro and in vivo anticancer experiments demonstrated that ZBCN exhibits excellent performance in delivering anticancer drugs, with in vivo tumor inhibition of 58%. This study presents a novel template method for preparing porous BCN nanomaterials, offering a promising platform for high-performance anticancer drug delivery.

A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014-2022).

Background: The REFLECT phase-III trial has demonstrated the efficacy of lenvatinib in improving the overall survival of advanced hepatocellular carcinoma (HCC) patients, comparable to sorafenib. The rapidly evolving landscape of hepatocellular carcinoma therapy presents new avenues for lenvatinib. This study aims to provide a scientometric analysis of publications and predict research hotspots in this field. Methods: Relevant publications were sourced from the Web of Science Core Collection (WoSCC) database up until November 2022. The bibliometrix tool in R was employed for scientometric analysis and visualization. Results: A total of 879 publications from 2014 to 2022 were obtained from WoSCC that met the established criteria. These studies involved 4,675 researchers from 40 countries, with an average annual growth rate of 102.5%. The highest number of publications was from Japan, followed by China, Italy, and the United States. The largest proportion of studies, 14.0% (n = 123), was contributed by FUDAN UNIV. The studies were published in 274 journals, with CANCERS (n = 53) being the top journal, followed by FRONTIERS IN ONCOLOGY (n = 51) and HEPATOLOGY RESEARCH (n = 36). The top ten journals accounted for 31.5% of the 879 studies. The most prolific authors were Kudo M (n = 51), Hiraoka A (n = 43), and Tsuji K (n = 38). A total of 1,333 keywords were analyzed, with the present research hotspots being "immune checkpoint inhibitors," "prognosis," and "pd-1." Co-occurrence clustering analysis revealed the top keywords, authors, publications, and journals. Strong collaboration was identified in the field. Conclusion: This scientometric and visual analysis provides a comprehensive summary of the published articles on lenvatinib in HCC during 2014-2022, highlighting the research hotspots, knowledge domain, and frontiers. The results can provide insights into future research directions in this field.

All-Organic PTFE Coated PVDF Composite Film Exhibiting Low Conduction Loss and High Breakdown Strength for Energy Storage Applications.

Plastic film capacitors are widely used in pulse and energy storage applications because of their high breakdown strength, high power density, long lifetime, and excellent self-healing properties. Nowadays, the energy storage density of commercial biaxially oriented polypropylene (BOPP) is limited by its low dielectric constant (~2.2). Poly(vinylidene fluoride) (PVDF) exhibits a relatively high dielectric constant and breakdown strength, making it a candidate material for electrostatic capacitors. However, PVDF presents significant losses, generating a lot of waste heat. In this paper, under the guidance of the leakage mechanism, a high-insulation polytetrafluoroethylene (PTFE) coating is sprayed on the surface of a PVDF film. The potential barrier at the electrode-dielectric interface is raised by simply spraying PTFE and reducing the leakage current, and then the energy storage density is increased. After introducing the PTFE insulation coating, the high-field leakage current in the PVDF film shows an order of magnitude reduction. Moreover, the composite film presents a 30.8% improvement in breakdown strength, and a 70% enhancement in energy storage density is simultaneously achieved. The all-organic structure design provides a new idea for the application of PVDF in electrostatic capacitors.

Boron Dopants in Red-Emitting B and N Co-Doped Carbon Quantum Dots Enable Targeted Imaging of Lysosomes.

Lysosomes are of great significance to cell growth, metabolism, and survival, as they independently maintain acidity and regulate various balances in cells. Therefore, it is essential to develop advanced probes for lysosome visualization and live tracking. Herein, a type of lysosome-targeting probe based on boron (B) and nitrogen (N) co-doped carbon quantum dots (B/N-CQDs) is presented, which exhibits red emission at 618 nm, high quantum yield (28%), and excellent fluorescence stability (97% at 1 h). These B/N-CQDs are prepared by a novel and green solid-state reaction and purified using a simple extraction process without additional chemical modifications. It is found that the boron dopants in the structure play a crucial role in the resultant lysosome-specific targeting property through borate esterification between boronic acid groups in the sample and diol structures in glycoproteins. This can be applied as a powerful tool for cell apoptosis, necrosis, and endosomal escape tracking. This work not only offers a new concept for targeted subcellular probe designs via chemical doping but also demonstrates the feasibility of these tools for analyzing complex cellular physiological activities.

Design of size uniform and controllable covalent organic framework nanoparticles for high-performance anticancer drug delivery.

Covalent organic frameworks (COFs) receive much attention in biomedicine because of their unique adsorption, optical and biological properties, as well as highly variable structures. However, preparation of nanosized COFs with uniform and controllable size is still a challenge. Herein, we develop a facile interfacial method to prepare the COF nanoparticles (COFNPs) with the uniform size of 30-50 nm from p-benzoquinone (BQ) and 4-[1,2,2-tris(4-aminophenyl)ethenyl]aniline (TPEA) by Michael addition. The TPEA-BQ COFNPs show positive zeta potential and effectively load the hydrophobic anticancer drug camptothecin (CPT) with the capacity of up to 127wt%, and remarkably improved the CPT dispersibility in water due to the retention of quinone structure. In vitro assay reveals CPT@ TPEA-BQ significantly reduced cell viability to 29% after 24 h incubation, much lower than that of free CPT (51%) at the same concentration of 10 µg mL-1. Further in vivo experiment confirms the high anticancer drug delivery performance of the designed TPEA-BQ COFNPs. After 20 days of injection treatment, the CPT loaded in TPEA-BQ COFNPs inhibits the tumor growth by 60%, much higher than that of free CPT group (23%). This work demonstrates the feasibility to design advanced drug delivery systems based on highly structure-tunable COF system.

Self-cleaning MnZn ferrite/biochar adsorbents for effective removal of tetracycline.

A renewable tri-metallic spinel decorated biochar adsorbent (MZF-BC) was fabricated by a facile hydrothermal method and to remove tetracycline. The physicochemical properties of MZF-BC were well studied. MZF-BC with a hybrid pore structure of mesopores (~7.6 nm) and macropores (~50 nm) has the maximum tetracycline adsorption capacity reaching 142.4 mg g-1. Through the study of adsorption kinetics, isotherms and key influencing factors, it was found that MZF-BC adsorption on tetracycline was primarily multi-layer effect with the initial adsorption behavior of pore filling associated with hydrogen bonding and π-π stacking. Furthermore, the MZF-BC performs excellent regeneration ability by driving Fenton-like catalysis as the self-cleaning process in the liquid phase. This study contributes to a new insight into the in-situ regeneration of biochar-based adsorbents after adsorbing organic pollutants in pharmaceutical wastewater treatment.

Enantioselective Domino Reaction of 3-Vinylindole and p-Quinone Methides Enabled by Chiral Imidodiphosphoric Acids: Asymmetric Synthesis of Multisubstituted 3-Indolyl Cyclopenta[b]indoles.

The development of a stereoselective method for the rapid assembly of structurally complex molecules remains fascinating and challenging in synthetic organic chemistry. Here, we report an enantioselective domino reaction between 3-vinylindole and p-quinone methide for the preparation of 3-indolyl cyclopenta[b]indoles containing multiple chiral centers. Chiral imidodiphosphoric acids enable this cascade asymmetric process, delivering a series of products with excellent yields (≤99%), enantioselectivities (≤99%), and diastereoselectivities (≤20:1 dr).

An integrated pan-cancer analysis of TFAP4 aberrations and the potential clinical implications for cancer immunity.

Studies have shown that transcription factor activating enhancer binding protein 4 (TFAP4) plays a vital role in multiple types of cancer; however, the TFAP4 expression profile is still unknown, as is its value within the human pan-cancer analysis. The present study comprehensively analysed TFAP4 expression patterns from 33 types of malignancies, along with the significance of TFAP4 for prognosis prediction and cancer immunity. TFAP4 displayed inconsistent levels of gene expression across the diverse cancer cell lines, and displayed abnormal expression within most malignant tumours, which closely corresponded to overall survival. More importantly, the TFAP4 level was also significantly related to the degree of tumour infiltration. TFAP4 was correlated using gene markers in tumour-infiltrating immune cells and immune scores. TFAP4 expression was correlated with tumour mutation burden and microsatellite instability in different cancer types, and enrichment analyses identified TFAP4-associated terms and pathways. The present study comprehensively analysed the expression of TFAP4 across 33 distinct types of cancers, which revealed that TFAP4 may possibly play a vital role during cancer formation and development. TFAP4 is related to differing degrees of immune infiltration within cancers, which suggests the potential of TFAP4 as an immunotherapy target in cancers. Our study demonstrated that TFAP4 plays an important role in tumorigenesis as a prognostic biomarker, which highlights the possibility of developing new targeted treatments.

Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study.

Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan-Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types.

Asymmetric Synthesis of 1,1,1-Triarylethanes by Chiral Imidodiphosphoric Acid Catalyzed Nucleophilic Addition of Pyrrole and Indoles to 3-Vinylindoles.

Chiral imidodiphosphoric acids were employed as efficient catalysts in the enantioselective addition reaction of pyrrole and indoles to 3-vinylindoles. A series of optically active 1,1,1-triarylethmanes bearing quaternary stereocenters were synthesized in excellent yields (up to 99% yield) and enantioselectivities (up to 98% ee). Gram-scale reactions of 1i and 2a as well as 1o and 5a demonstrated the synthetic utility of this methodology. Control experiments showed that the formation of a double H-bond between the catalyst and substrates is necessary for an excellent outcome.

Magnetic Nature of the CrIII-LnIII Interactions in [CrIII2LnIII3] Clusters with Slow Magnetic Relaxation.

Two 3d-4f hetero-metal pentanuclear complexes with the formula {[CrIII2LnIII3L10(OH)6(H2O)2]Et3NH} [Ln=Tb (1), Dy (2); HL=pivalic acid, Et3N=triethylamine] have been produced. The metal core of each cluster is made up of a trigonal bipyramid with three LnIII ions (plane) and two CrIII ions (above and below) held together by six µ3-OH bridges. Also reported with this series is the diamagnetic CrIII-YIII analogue (3). Fortunately, we successfully prepared AlIII-LnIII analogues with the formula {[AlIII2LnIII3L10(OH)6(H2O)2]Et3NH⋅H2O} [Ln=Tb (4), Dy (5)], containing diamagnetic AlIII ions, which can be used to evaluate the CrIII-LnIII magnetic nature through a diamagnetic substitution method. Subsequently, static (dc) magnetic susceptibility studies reveal dominant ferromagnetic interactions between CrIII and LnIII ions. Dynamic (ac) magnetic susceptibility studies show frequency-dependent out-of-phase (χ'') signals for [CrIII2TbIII3] (1), [CrIII2DyIII3] (2), and [AlIII2DyIII3] (5), which are derived from the single-ion behavior of LnIII ions and/or the CrIII-LnIII ferromagnetic interactions.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling.

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling / 中国天然药物

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling / 中国天然药物

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

A survey of eMedia-delivered interventions for schizophrenia used in randomized controlled trials.

BACKGROUND: Randomized trials evaluating electronic Media (eMedia) delivery of interventions are increasingly frequent in mental health. Although a number of reviews have reported efficacy of these interventions, none has reviewed the type of eMedia interventions and quality of their description. We therefore decided to conduct a survey of eMedia-delivered interventions for schizophrenia. METHODS: We surveyed all relevant trials reliably identified in the Cochrane Schizophrenia Group's comprehensive register of trials by authors working independently. Data were extracted regarding the size of the trial, interventions, outcomes and how well the intervention was described. RESULTS: eMedia delivery of interventions is increasingly frequent in trials relevant to the care of people with schizophrenia. The trials varied considerably in sample sizes (mean =123, median =87, range =20-507), and interventions were diverse, rarely evaluating the same approaches and were poorly reported. This makes replication impossible. Outcomes in these studies are limited, have not been noted to be chosen by end users and seem unlikely to be easy to apply in routine care. No study reported on potential adverse effects or cost, end users satisfaction or ease of use. None of the papers mentioned the use of CONSORT eHealth guidelines. CONCLUSION: There is a need to improve reporting and testing of psychosocial interventions delivered by eMedia. New trials should comply with CONSORT eHealth guidance on design, conduct and reporting, and existing CONSORT should be updated regularly, as the field is constantly evolving.

The ferromagnetic [Ln2Co6] heterometallic complexes.

Four 3d-4f heterometallic complexes with the formula, {[Ln2Co6(OH)4(L1)6(L2)8(CH3CN)2]·nCH2Cl2} (Ln = Dy (1), n = 0.5; Ho (2), n = 1; Gd (3), n = 1; Y (4), n = 1; HL1 = 6-chloro-2-pyridinol, HL2 = pivalic acid), were synthesized. Single-crystal X-ray diffraction analyses revealed that complexes 1-4 consisted of a [Ln2Co6] core, featuring a Ln-Ln edge-sharing double-trigonal-bipyramid configuration. The magnetic susceptibilities revealed ferromagnetic coupling within complexes 1 and 2, and complex 1 displayed slow relaxation of magnetization.

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.