We report the rapid separation and purification of lead halide perovskite quantum dots (QDs) in a nonpolar solvent by using a convenient and efficient differential separation method. Size-selective ...precipitation effectively separates the perovskite QDs from larger aggregates and provides direct evidence for strong quantum confinement in the photoluminescence (PL). Significantly, the size-selected perovskite QDs are readily well-dispersed in a nonpolar solvent and remain stable in ambient air (humidity > 60%) for >20 days. These enable measurement of the electronic band structure of versatile perovskite QDs as a function of size for the first time. Despite a clear blue-shift of the optical bandgap, the lowest unoccupied molecular orbital (LUMO) readily moves towards the vacuum level while the highest occupied molecular orbital (HOMO) changes slightly, in good agreement with that observed in the quantum size effect tuning of quasi-2D perovskites and colloidal semiconductor QDs. The results demonstrate the possibility of utilizing differential centrifugation as a novel method to attain size-dependent tunability for property-specific perovskite-QD based optoelectronic applications.
We introduce differential separation as an efficient method for preparing monodisperse fractions of versatile halide perovskite quantum dots with tunable sizes, enabling investigations of their size-dependent electronic band structure properties.
Cuproptosis, a newly discovered cell death pathway, has shown great potential in cancer treatment. Herein, near‐infrared (NIR) light‐driven nanomotors (CuSiO3@Au‐Pd NMs) are designed for ...cuproptosis‐assisted synergistic therapy with autonomous mobility and improved cellular uptake and tumor penetration. Specifically, the released Cu2+ ions from CuSiO3@Au‐Pd NMs can induce the Fenton‐like reaction, leading to the generation of hydroxyl radicals (·OH), accompanied by the depletion of glutathione within the MCF‐7 cells. Additionally, the designed CuSiO3@Au‐Pd NMs also exhibit excellent photothermal effects, which can further promote the production of ·OH, resulting in intensified oxidative stress and cellular apoptosis. Moreover, the enhanced tumor permeation efficiency and cellular uptake of CuSiO3@Au‐Pd NMs via autonomous movement under self‐thermophoretic forces are proved using 2D cellular experiments and 3D multicellular tumor spheroids. The resultant intracellular accumulation of Cu2+ can induce the oligomerization of lipoylated proteins, leading to cuproptosis, along with the mitochondrial dysfunction pathway. More importantly, both in vitro and in vivo experiments show that CuSiO3@Au‐Pd NMs could penetrate deeply into tumors and exhibit great anticancer efficacy through multimodal therapeutic methods. These findings manifest promising potentials of NIR‐powered Cu‐based NMs with high maneuverability for future smart and synergistic cancer therapy.
This study reports the fabrication of near‐infrared light‐driven and directionally controllable nanomotor (CuSiO3@Au‐Pd) that not only enhances cellular uptake and tumor tissue penetration but also facilitates chemodynamic and photothermal therapy, thereby promoting cell apoptosis. Furthermore, the designed CuSiO3@Au‐Pd can induce the cellular cuproptosis pathway, enabling cuproptosis‐assisted synergistic cancer therapy.
Freestanding 2D nanosheets with many unprecedented properties have been used in a myriad of applications. In this work, 2D copper‐bearing metal‐organic frameworks (MOFs; viz., Cu‐BDC) nanosheets are ...successfully fabricated via a facile and benign methodology through using Cu2O nanocubes (≈60 nm) as a confined metal ion source and 1,4‐benzenedicarboxylic acid (H2BDC) as an organic linker. The Cu2O nanocubes gradually release Cu+ ions which are further oxidized by the dissolved oxygen and serve as nutrients for construction of 2D frameworks. In contrast, the conventional solvothermal synthesis with copper salt exclusively yields bulk Cu‐BDC with edge dimensions of 2–10 µm. Interestingly, the as‐prepared Cu‐BDC nanosheets show ultrathin thickness, oriented growth, and excellent crystallinity, which can be exploited as a platform for the design of a series of 2D‐integrated nanocatalysts by loading various metal nanocrystals such as Au, Ag, Pt, and Ru, with 3‐mercaptopropionic acid as molecular link. In addition, it is found that Cu‐BDC/M composites with highly accessible active sites on the surface exhibit high catalytic activity in several condensation reactions between benzaldehyde and primary amines. The findings offer an alternative strategy for rational design and synthesis of 2D MOF nanosheets and the derived 2D nanocomposites for catalytic applications.
In this work, freestanding 2D Cu‐BDC nanosheets with oriented growth are successfully fabricated through using Cu2O nanocubes as a confined metal ion source. Moreover, Cu‐BDC/M‐integrated nanocatalysts (M = Au, Ag, Pt, and Ru) are prepared and examined in several condensation reactions between benzaldehyde and primary amines.
Metal–organic frameworks (MOFs) have attracted enormous research interest as precursors/templates to prepare catalytic materials. However, the effect of structural isomerism of MOFs on the catalytic ...performance has rarely been studied. In this contribution, two topologically different Ce‐benzene tricarboxylate (Ce‐BTC) based on the same ligands and metal centers (viz., “MOF isomers”) are prepared and used as porous supports to load Pt nanoparticles (NPs), which shows distinct differences in porosities and loading behaviors of Pt. Strikingly, an irreversible framework transformation from tetragonal Ce‐BTC to monoclinic isomer is observed during water soaking treatment. The results give clear evidence that Pt/CeO2 derived from tetragonal Ce‐BTC inclines to produce more Pt0 and smaller Pt NPs, which eventually improve the catalytic performance for CO oxidation (T100 = 80 °C). In situ diffuse reflectance infrared Fourier transform spectroscopy analyses demonstrate that the adsorbed CO–Pt0 is the dominant intermediate for CO oxidation, rather than CO–Ptσ+ at the low temperature. Furthermore, MOF isomers based on the same structural units are also found in other Ln‐MOFs, such as Er‐BTC, Eu‐BTC, Y‐BTC, and Ce/Y‐BTC. Overall, this study affords a fundamental understanding of the effect of MOF structural isomers on the catalytic performance of the derived composites.
A facile method is devised for synthesizing two structural isomers of Ce‐benzene tricarboxylate (BTC) based on the same ligands and metal centers and then the metal–organic framework (MOF) isomers are used as porous supports to load Pt nanoparticles (NPs), which shows distinct differences in porosities, loading behaviors of Pt, and the catalytic performance in CO oxidation reaction.
Gas-involving cancer theranostics have attracted considerable attention in recent years due to their high therapeutic efficacy and biosafety. We have reviewed the recent significant advances in the ...development of stimuli-responsive gas releasing molecules (GRMs) and gas nanogenerators for cancer bioimaging, targeted and controlled gas therapy, and gas-sensitized synergistic therapy. We have focused on gases with known anticancer effects, such as oxygen (O2), carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H2S), hydrogen (H2), sulfur dioxide (SO2), carbon dioxide (CO2), and heavy gases that act via the gas-generating process. The GRMs and gas nanogenerators for each gas have been described in terms of the stimulation method, followed by their applications in ultrasound and multimodal imaging, and finally their primary and synergistic actions with other cancer therapeutic modalities. The current challenges and future possibilities of gas therapy and imaging vis-à-vis clinical translation have also been discussed.
Human cytochrome P450 (CYP) 3A4 is the most abundant hepatic and intestinal phase I enzyme that metabolizes approximately 50% marketed drugs. The crystal structure of bound and unbound CYP3A4 has ...been recently constructed, and a small active site and a peripheral binding site are identified. A recent study indicates that CYP3A4 undergoes dramatic conformational changes upon binding to ketoconazole or erythromycin with a differential but substantial (>80%) increase in the active site volume, providing a structural basis for ligand promiscuity of CYP3A4. A number of important drugs have been identified as substrates, inducers and/or inhibitors of CYP3A4. The ability of drugs to act as inducers, inhibitors, or substrates for CYP3A is predictive of whether concurrent administration of these compounds with a known CYP3A substrate might lead to altered drug disposition, efficacy or toxicity. The substrates of CYP3A4 considerably overlap with those of P-glycoprotein (P-gp). To date, the identified clinically important CYP3A4 inhibitors mainly include macrolide antibiotics (e.g., clarithromycin, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and diltiazem), steroids and their modulators (e.g., gestodene and mifepristone), and several herbal and dietary components. Many of these drugs are also mechanism-based inhibitors of CYP3A4, which involves formation of reactive metabolites, binding to CYP3A4 and irreversible enzyme inactivation. A small number of drugs such as rifampin, phenytoin and ritonavir are identified as inducers of CYP3A4. The orphan nuclear receptor, pregnane X receptor (PXR), have been found to play a critical role in the induction of CYP3A4. The inhibition or induction of CYP3A4 by drugs often causes unfavorable and long-lasting drug-drug interactions and probably fatal toxicity, depending on many factors associated with the enzyme, drugs and the patients. The study of interactions of newly synthesized compounds with CYP3A4 has been incorporated into drug development and detection of possible CYP3A4 inhibitors and inducers during the early stages of drug development is critical in preventing potential drug-drug interactions and side effects. Clinicians are encouraged to have a sound knowledge on drugs that behave as substrates, inhibitors or inducers of CYP3A4, and take proper cautions and close monitoring for potential drug interactions when using drugs that are CYP3A4 inhibitors or inducers.
Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (approximately 2-4%). There is a large ...interindividual variation in the enzyme activity of CYP2D6. The enzyme is largely non-inducible and metabolizes approximately 25% of current drugs. Typical substrates for CYP2D6 are largely lipophilic bases and include some antidepressants, antipsychotics, antiarrhythmics, antiemetics, beta-adrenoceptor antagonists (beta-blockers) and opioids. The CYP2D6 activity ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population. To date, 74 allelic variants and a series of subvariants of the CYP2D6 gene have been reported and the number of alleles is still growing. Among these are fully functional alleles, alleles with reduced function and null (non-functional) alleles, which convey a wide range of enzyme activity, from no activity to ultrarapid metabolism of substrates. As a consequence, drug adverse effects or lack of drug effect may occur if standard doses are applied. The alleles *10, *17, *36 and *41 give rise to substrate-dependent decreased activity. Null alleles of CYP2D6 do not encode a functional protein and there is no detectable residual enzymatic activity. It is clear that alleles *3, *4, *5, *6, *7, *8, *11, *12, *13, *14, *15, *16, *18, *19, *20, *21, *38, *40, *42, *44, *56 and *62 have no enzyme activity. They are responsible for the PM phenotype when present in homozygous or compound heterozygous constellations. These alleles are of clinical significance as they often cause altered drug clearance and drug response. Among the most important variants are CYP2D6*2, *3, *4, *5, *10, *17 and *41. On the other hand, the CYP2D6 gene is subject to copy number variations that are often associated with the UM phenotype. Marked decreases in drug concentrations have been observed in UMs with tramadol, venlafaxine, morphine, mirtazapine and metoprolol. The functional impact of CYP2D6 alleles may be substrate-dependent. For example, CYP2D6*17 is generally considered as an allele with reduced function, but it displays remarkable variability in its activity towards substrates such as dextromethorphan, risperidone, codeine and haloperidol. The clinical consequence of the CYP2D6 polymorphism can be either occurrence of adverse drug reactions or altered drug response. Drugs that are most affected by CYP2D6 polymorphisms are commonly those in which CYP2D6 represents a substantial metabolic pathway either in the activation to form active metabolites or clearance of the agent. For example, encainide metabolites are more potent than the parent drug and thus QRS prolongation is more apparent in EMs than in PMs. In contrast, propafenone is a more potent beta-blocker than its metabolites and the beta-blocking activity during propafenone therapy is more prominent in PMs than EMs, as the parent drug accumulates in PMs. Since flecainide is mainly eliminated through renal excretion, and both R- and S-flecainide possess equivalent potency for sodium channel inhibition, the CYP2D6 phenotype has a minor impact on the response to flecainide. Since the contribution of CYP2D6 is greater for metoprolol than for carvedilol, propranolol and timolol, a stronger gene-dose effect is seen with this beta-blocker, while such an effect is lesser or marginal in other beta-blockers. Concordant genotype-phenotype correlation provides a basis for predicting the phenotype based on genetic testing, which has the potential to achieve optimal pharmacotherapy. However, genotype testing for CYP2D6 is not routinely performed in clinical practice and there is uncertainty regarding genotype-phenotype, gene-concentration and gene-dose relationships. Further prospective studies on the clinical impact of CYP2D6-dependent metabolism of drugs are warranted in large cohorts of subjects.
Summary
Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance ...to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug‐induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P‐glycoprotein (P‐gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.
Summary
Plants form complex interaction networks with diverse microbiomes in the environment, and the intricate interplay between plants and their associated microbiomes can greatly influence ...ecosystem processes and functions. The phyllosphere, the aerial part of the plant, provides a unique habitat for diverse microbes, and in return the phyllosphere microbiome greatly affects plant performance. As an open system, the phyllosphere is subjected to environmental perturbations, including global change, which will impact the crosstalk between plants and their microbiomes. In this review, we aim to provide a synthesis of current knowledge of the complex interactions between plants and the phyllosphere microbiome under global changes and to identify future priority areas of research on this topic.
A novel compact multiple-input multiple-output (MIMO) antenna is proposed with wideband gain enhancement. It consists of two identical antenna elements spacing about half wavelength. First, a 1-to-2 ...Y-shaped power divider with wideband anti-phase outputs is designed to feed two modified Vivaldi radiators. The currents on the two radiating surfaces keep the same direction in a wideband to increase radiation without being canceled. Second, the square-ring unit cell is analyzed to form metasurface, placed in the front of the radiator. It can guide the forward electromagnetic (EM) radiation while reducing the backward radiation. Third, a U-shaped slot is etched between the two modified Vivaldi radiators. It is approximated as an effective electrically small dipole radiator. Such arrangement further effectively enhances the radiation performance in the direction of the main lobe and destructively interferes with the sidelobe radiation. These features make the antenna far-field radiation pattern reshaped. Thereby, the gain is improved in a wide bandwidth. Meanwhile, the MIMO antenna diversity performance is analyzed with low mutual coupling. Wideband gain enhancement contributes to improve the detection capability of the frequency modulated continuous wave (FMCW) radar sensor. As a proof of concept, the proposed MIMO antenna prototype is fabricated. The measured impedance bandwidth ranges from 11.5 to 21.3 GHz 59.76% fractional bandwidth (FBW) with isolation of <inline-formula> <tex-math notation="LaTeX">\ge 24.92 </tex-math></inline-formula> dB. The gain is up to 10.6 dBi, the radiation efficiency is 88.01%-90.02%, and the envelope correlation coefficient (ECC) is <inline-formula> <tex-math notation="LaTeX">\le 0.00122 </tex-math></inline-formula>. Integrated with the transceiver chip fabricated on the 65 nm CMOS process, the proposed MIMO antenna is applied in the FMCW radar sensor. The test system is built up, and the experiments on different breathing conditions are conducted for different human subjects. The proposed MIMO antenna could reduce measurement error, thereby improving measurement accuracy for human respiratory monitoring.
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