With the rapid development of engineered nanomaterials for various applications, in vivo toxicological studies for evaluating the potential hazardous effects of nanomaterials on environmental and ...human safety are in urgent need. Zebrafish has long been considered as the “gold standard” for biosafety assessments of chemicals and pollutants due to its high fecundity, cost-effectiveness, well-characterized developmental stages, optical transparency, and so forth. Thus, zebrafish holds great potential for high-throughput nanotoxicity screening. In this review, we summarize the in vivo toxicological profiles of different nanomaterials, including Ag nanoparticles (NPs), CuO NPs, silica NPs, polymeric NPs, quantum dots, nanoscale metal–organic frameworks, etc, in zebrafish and focus on how the physicochemical properties (e.g., size, surface charge, and surface chemistry) of these nanomaterials influence their biosafety. In addition, we also report the recent advances of the in vivo delivery of nanopharmaceuticals using zebrafish as the model organism for therapeutic assessment, biodistribution tracking, and the controlled release of loaded drugs. Limitations and special considerations of zebrafish model are also discussed. Overall, zebrafish is expected to serve as a high-throughput screening platform for nanotoxicity and drug delivery assessment, which may instruct the design of safe nanomaterials and more effective nanomedicines.
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Systematically dissecting the molecular basis of the cell surface as well as its related biological activities is considered as one of the most cutting-edge fields in fundamental sciences. The advent ...of various advanced cell imaging techniques allows us to gain a glimpse of how the cell surface is structured and coordinated with other cellular components to respond to intracellular signals and environmental stimuli. Nowadays, cell surface-related studies have entered a new era featured by a redirected aim of not just understanding but artificially manipulating/remodeling the cell surface properties. To meet this goal, biologists and chemists are intensely engaged in developing more maneuverable cell surface labeling strategies by exploiting the cell's intrinsic biosynthetic machinery or direct chemical/physical binding methods for imaging, sensing, and biomedical applications. In this review, we summarize the recent advances that focus on the visualization of various cell surface structures/dynamics and accurate monitoring of the microenvironment of the cell surface. Future challenges and opportunities in these fields are discussed, and the importance of cell surface-based studies is highlighted.
We present a comprehensive review on the advancements in cell surface modification strategies and their applications in cell surface-localized imaging and sensing.
Developing a universal nanoplatform for efficient delivery of various drugs to target sites is urgent for overcoming various biological barriers and realizing combinational cancer treatment. ...Nanogels, with the advantages of both hydrogels and nanoparticles, may hold potential for addressing the above issue. Here, a dual‐responsive nanogel platform (HPC nanogel) is constructed using β‐cyclodextrin‐conjugated hyaluronic acid (HA‐βCD), polyethyleneimine (PEI), and cisplatin. HA‐βCD and PEI compose the skeleton of the nanogel, and cisplatin molecules provide the junctions inside the skeleton, thus affording a multiple interactions‐based nanogel. Besides, HA endows the nanogel with hyaluronidase (HAase)‐responsiveness, and cisplatin guarantees the glutathione (GSH)‐responsive ability, which make the nanogel a dual‐responsive platform that can degrade and release the loaded drugs when encountering HAase or GSH. Additionally, the HPC nanogel possesses excellent small‐molecule drug and protein loading and intracellular delivery capabilities. Especially, for proteins, their intracellular delivery via nanogels is not hindered by serum proteins, and the enzymes delivered into cells still maintain their catalytic activities. Furthermore, the nanogel can codeliver different cargoes to achieve “cocktail” chemotherapeutic efficacy and realize combination cancer therapy. Overall, the HPC nanogel can serve as a multifunctional platform capable of delivering desired drugs to treat cancer or other diseases.
A platinum‐coordinated, multiple interactions‐based, and hyaluronidase‐ and glutathione‐responsive nanogel platform is developed for universal drug delivery and combination cancer therapy. The nanogel can encapsulate various small drugs and deliver them into cancer cells regardless of their hydrophilicity/hydrophobicity or charge, efficiently deliver peptides and proteins (including enzymes), and realize both the in vitro and in vivo codelivery of multiple cargoes.
To assess the spectrum of pediatric clinical phenotypes in TJP2 disease, we reviewed records of our seven patients in whom intrahepatic cholestasis was associated with biallelic TJP2 variants (13; 12 ...novel) and correlated clinical manifestations with mutation type. The effect of a splicing variant was analyzed with a minigene assay. The effects of three missense variants were analyzed with protein expression in vitro. Our patients had both remitting and persistent cholestasis. Three exhibited growth retardation. Six responded to treatment with cholestyramine, ursodeoxycholic acid, or both. Two had cholecystolithiasis. None required liver transplantation or developed hepatocellular or cholangiocellular malignancy. None manifested extrahepatic disease not attributable to effects of cholestasis. The variant c.2180‐5T>G resulted in exon 15 skipping with in‐frame deletion of 32 amino acid residues in TJP2. The three missense variants decreased but did not abolish TJP2 expression. Patients with truncating or canonical splice‐site variants had clinically more severe disease. TJP2 disease in children includes a full clinical spectrum of severity, with mild or intermittent forms as well as the severe and minimal forms hitherto described. Biallelic TJP2 variants must be considered in children with clinically intermittent or resolved intrahepatic cholestasis.
The overlapping peaks of the target chemical exchange saturation transfer (CEST) solutes and other unknown CEST solutes affect the quantification results and accuracy of the chemical exchange ...parameters-the fractional concentration,
, exchange rate,
, and transverse relaxation rate,
-for the target solutes. However, to date, no method has been established for assessing the overlapping peaks. This study aimed to develop a method for quantifying the
,
, and
values of a specific CEST solute, as well as assessing the overlap between the CEST peaks of the specific solute(s) and other unknown solutes. A simplified
model was proposed, assuming linear approximation of the other solutes' contributions to
. A CEST data acquisition scheme was applied with various saturation offsets and saturation powers. In addition to fitting the
,
, and
values of the specific solute, the overlapping condition was evaluated based on the root mean square error (RMSE) between the trajectories of the acquired and synthesized data. Single-solute and multi-solute phantoms with various phosphocreatine (PCr) concentrations and pH values were used to calculate the
and
of PCr and the corresponding RMSE. The feasibility of RMSE for evaluating the overlapping condition, and the accurate fitting of
and
in weak overlapping conditions, were verified. Furthermore, the method was employed to quantify the nuclear Overhauser effect signal in rat brains and the PCr signal in rat skeletal muscles, providing results that were consistent with those reported in previous studies. In summary, the proposed approach can be applied to evaluate the overlapping condition of CEST peaks and quantify the
,
, and
values of specific solutes, if the weak overlapping condition is satisfied.
A novel and efficient CP bond formation reaction of diarylphosphine oxides with aryl iodides was achieved by combining nickel catalysis and visible‐light‐induced photoredox catalysis. This ...dual‐catalytic reaction showed a broad substrate scope, excellent functional group tolerance, and afforded the corresponding products in good to excellent yields. Compared with the previously reported use of photoredox/nickel dual catalysis in the construction of CC bonds, the methodology described herein was observed to be the first to allow for C‐heteroatom bond formation.
Dual catalysis: A novel and efficient CP bond formation reaction of diarylphosphine oxides with aryl iodides was achieved by combining nickel catalysis and visible‐light‐induced photoredox catalysis (see scheme). This dual‐catalytic reaction showed a broad substrate scope, excellent functional‐group tolerance, and afforded the corresponding products in good to excellent yields. Compared with previously reported photoredox/nickel dual catalytic systems, this methodology is the first to allow for Cheteroatom bond formation.
One hallmark of cancer cells is aberrant glucose metabolism. By desperately consuming glucose, cancer cells grow quickly and form a hypoxic core in the tumor, which severely limits the efficacy of ...oxygen‐dependent therapeutic strategies. Herein, a cell metabolism regulation strategy is adopted to reallocate cell respiration substrates for fueling the processes for cancer therapy by constructing a metabolism nanoregulator (denoted as ATO/GOx PLP). To be specific, a protoporphyrin IX (PpIX, the intermembrane‐translocatable accessory)‐doped liposome is employed for direct intracellular delivery of GOx and atovaquone (ATO, a mitochondrial complex III inhibitor). The PpIX‐doped liposome can efficiently avoid the cargo leakage in blood circulation. Benefiting from the translocation of PpIX from the liposome to the cancer cell membrane, ATO and GOx can be rapidly released upon encountering the plasma membrane and internalized by the cancer cell. By inhibiting mitochondrial oxidative phosphorylation and regulating mitochondrial function, ATO reduces both oxygen consumption and glucose metabolism, sparing more substrates for GOx to kill cancer cells. As a result, ATO/GOx PLP presents outstanding anticancer efficacies both in vitro and in vivo. In addition, the ATO/GOx PLP exhibits excellent biosafety, showing its clinical translation potential. Overall, this study provides a new approach to achieve efficacious metabolism regulation‐based cancer therapy.
A cell metabolism regulation strategy to reallocate the cell respiration substrates for fueling the glucose oxidase (GOx) catalysis process for cancer therapy is developed by constructing a metabolism nanoregulator. More importantly, it is also demonstrated that the carrier of the nanoregulator, the protoporphyrin IX (PpIX)‐doped liposome, can directly and responsively release the encapsulated cargoes via an interesting PpIX translocation process.
Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA‐induced porcine ...parthenogenetic activation (PA) in early‐stage embryos were investigated. Our results showed that 50 μM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early‐stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early‐stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early‐stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis‐related gene NRF‐1 in porcine PA early‐stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early‐stage embryos by regulating oxidative stress and improving mitochondrial function.
An unprecedented α‐allylation of amines was achieved by combining palladium catalysis and visible‐light photoredox catalysis. In this dual catalysis process, the catalytic generation of allyl radical ...from the corresponding π‐allylpalladium intermediate was achieved without additional metal reducing reagents (redox‐neutral). Various allylation products of amines were obtained in high yields through radical cross‐coupling under mild reaction conditions. Moreover, the transformation was applied to the formal synthesis of 8‐oxoprotoberberine derivatives which show potential anticancer properties.
Double up: The title reaction was accomplished by merging palladium catalysis and visible‐light photoredox catalysis. The catalytic generation of an allyl radical from the corresponding π‐allylpalladium intermediate was realized without additional metal reducing reagents for the first time. Various α‐allylation products of amines were achieved in high yields by radical cross‐coupling under mild reaction conditions. SET=single‐electron transfer.
Transition metal-catalysed asymmetric coupling has been established as a robust tool for constructing complex organic molecules. Although this area has been extensively studied, the development of ...efficient protocols to construct stereogenic centres with excellent regio- and enantioselectivities is highly desirable and remains challenging. Asymmetric transition metal catalysis with light intervention provides a practical alternative strategy to current methods and considerably expands the synthetic utility as a result of abundant feedstocks and mild conditions. This tutorial review comprehensively summarizes the recent advances in transition-metal-catalysed asymmetric coupling reactions with light intervention; in particular, a concise analysis of substrate scope and the mechanistic scenarios governing stereocontrol is discussed.
The advances on transition-metal catalysed asymmetric couplings with light intervention in recent years was summarized in this review. In order to better meet the needs of modern chemistry, further research outlook was also proposed.
