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Through vicinal difunctionalization of nitriles, a successful, innovative strategy for the synthesis of N-alkyl amidines is developed. This methodology capitalizes on commercially available nitriles, alcohols, and sulfonamides. The activation of alcohols by trifluoromethanesulfonic anhydride (Tf2O) plays a pivotal role throughout the entire reaction process. In comparison to existing amidine synthesis methods, this strategy showcases notable advantages, including the avoidance of toxic and hazardous azides, the exclusion of transition metal catalysts, and the use of mild reaction conditions. Importantly, this methodology provides an effective approach for late-stage modification of complex molecules and drugs, holding promise for the construction of molecular libraries in drug discovery. [ABSTRACT FROM AUTHOR]

Environment-benign one-pot three-component cycloadditions of diazo compounds, nitrosoarenes and vinyl pyrimidines, or vinyl purines, or vinyl imidazoles, or vinyl triazoles or vinyl indole have been developed. This catalyst- and additive-free strategy could efficiently introduce the isoxazolidine skeleton into nucleoside analogues, oxazole molecules and indole derivatives to provide diverse classes of isoxazolidinyl pyrimidine nucleoside analogues, isoxazolidinyl purine nucleoside analogues, isoxazolidinyl imidazoles, isoxazolidinyl triazoles and isoxazolidinyl indole with moderate to good yields for most substrates. [ABSTRACT FROM AUTHOR]

N-Nitrosamines, nitroso compounds with strong carcinogenic effects on humans, have been frequently detected in natural waters. In agricultural areas, there is typically a lack of drinking water treatment processes and distribution systems. As a result, residents often consume groundwater as drinking water which may contain N-nitrosamines, necessitating the investigation of the occurrence, sources, and carcinogenic risk of N-nitrosamines within the groundwater of agricultural areas. This study identified eight N-nitrosamines in groundwater and river water in the Jianghan Plain, a famous agricultural region in central China. N-Nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosomorpholine (NMOR), N-nitrosopyrrolidine (NPYR), and N-nitrosodi-n-butylamine (NDBA) were detected in groundwater, with NDMA being the main compound detected (up to 52 ng L−1). Comparable concentrations of these N-nitrosamines were also found in river water. From laboratory experiments, we found a tremendous potential for the formation of N-nitrosamines in groundwater. Principal component analysis and multiple linear regression analysis results showed that the primary sources of N-nitrosamines in groundwater were the uses of nitrogen fertilizers and pesticides carrying specific N-nitrosamines such as NPYR. The average total carcinogenic risk values of detected N-nitrosamines were higher than the acceptable risk level (10−5), suggesting a potential carcinogenic risk of groundwater. Further research is urgently needed to minimize N-nitrosamine levels in the groundwater of agricultural areas, particularly in those where pesticides and fertilizers are heavily used. [ABSTRACT FROM AUTHOR]

In contrast to the demand for freshwater that is increasing continuously due to population growth and economic growth, the availability of freshwater resources is decreasing rapidly due to environmental pollution and climate change. Solar-powered desalination is an eco-friendly and efficient way to produce freshwater. Herein, a facile method based on the Rayleigh–Bénard convection was developed to synthesize hierarchical nanomaterials–hydrogel evaporators. The SnSe nanosheets were encapsulated in poly(hydroxyethyl 2-methacrylate) hydrogel, and the resultant thin, porous SnSe–hydrogel composite layer was seamlessly integrated into the hydrogel matrix. Under one-sun irradiation, the SnSe–hydrogel evaporator demonstrated a high water-evaporation rate (2.20 kg m−2 h−1) and high energy conversion efficiency (91.70%). Moreover, the evaporator not only had excellent long-term mechanical properties, but also demonstrated excellent ion-rejection rates during a long-term seawater evaporation test, which indicated the potential application of the evaporator to sustainable solar-powered desalination in the offing or on ocean-going vessels. Our results provide a route for the synthesis of functional nanocomposite hydrogels for solar-powered water purification, sensing, biomedical, and other fields. [ABSTRACT FROM AUTHOR]

Tumor-derived exosomes have been recognized as promising biomarkers for early-stage cancer diagnosis, tumor prognosis monitoring and individual medical treatment. However, it is a huge challenge to separate exosomes from trace biological samples in clinics for disease diagnosis. Herein, we propose a simple, quick, and label-free method for isolating circulating exosomes from serum of patients. The strategy synergistically integrates chitosan electrostatic-adsorption, micro-patterned substrates, and microfluidic shuttle flow control to enable the capture/release of circulating exosomes in a simple manner. Using this microchip, we can isolate exosomes from trace samples (10 μl) with relative purity over 90% and high RNA recovery ratio over 84% within 15 minutes, which is impossible for traditional ultracentrifugation methods. We then validate the application of the microchip using 24 serum samples from clinical breast cancer and breast fibroma patients. The isolated exosomes are subjected to miRNA sequencing and RT-PCR, followed by pathway prediction analysis. The results showed that exosomes were relevant to the invasion and metastasis of breast cancer cells and hsa-miR-18a-3p might have the potential to become a new biomarker for distinguishing breast cancer from breast fibroma (AUC = 0.83, P value = 0.019). This established method is simple, quick and easy to operate with integration. And it may pave a new way for clinical research on exosomes and tumor relevant diagnosis. [ABSTRACT FROM AUTHOR]

Most cancer cells employ overexpression of glucose transports (GLUTs) to satisfy glucose demand ("Sweet Tooth") for increased aerobic glycolysis rates. GLUT1, one of the most widely expressed GLUTs in numerous cancers, was identified as a prognosis-related biomarker of gastric cancer via tissue array analysis. Herein, a "Sweet Tooth"-oriented SN38 prodrug delivery nanoplatform (Glu-SNP) was developed for targeted gastric cancer therapy. For this purpose, a SN38-derived prodrug (PLA-SN38) was synthesized by tethering 7-ethyl-10-hydroxycamptothecin (SN38) to biocompatible polylactic acid (PLA) with the appropriate degree of polymerization (n = 44). The PLA-SN38 conjugate was further assembled with glycosylated amphiphilic lipid to obtain glucosamine-decorated nanoparticles (Glu-SNP). Glu-SNP exhibited potent antitumor efficiency both in vitro and in vivo through enhanced cancer cell-specific targeting associated with the overexpression of GLUT1, which provides a promising approach for gastric cancer therapy. [ABSTRACT FROM AUTHOR]

The poor predictive power of existing preclinical models has spurred efforts to develop human-relevant models for accurate assessment of drug safety. In this work, we developed a multi-organoids-on-a-chip system derived from human induced pluripotent stem cells (hiPSCs), which allows for the assessment of the cardiac safety of an antidepressant drug, following liver metabolism in vitro. This liver-heart organoids-on-chip device contains compartmentalized chambers separated by a porous membrane, which permits the co-culture of 3D human liver organoids in the upper multi-well chamber and cardiac organoids in the bottom micropillar array simultaneously. The co-cultured liver and heart organoids on chip maintained good viability and human organ-specific functions respectively, including the synthesis of albumin and urea of liver organoids, and the beating function of cardiac organoids. In particular, the liver organoids displayed proper metabolic capabilities with high expression of CYP450 enzyme genes. Clomipramine, a widely used antidepressant drug, can be metabolized into an active metabolite (desmethylclomipramine) through the hepatic CYP450 enzymes of liver organoids on chip identified by mass spectrometry. After exposure to 1 μM clomipramine in the liver chamber for 24 h and 48 h, the co-cultured heart organoids in the bottom layer showed significantly reduced cell viability, impaired functions of cardiac beating and calcium flux, indicating the hepatic metabolism-dependent cardiotoxicity induced by clomipramine. By combining stem cell biology and microengineered technology, this proposed hiPSC-derived multi-organoids-on-a-chip system can reflect human organ-specific functions, as well as the complex process of drug metabolism and responses at the multi-organ level. It may provide a novel platform for the assessment of drug effectiveness and safety in vitro. [ABSTRACT FROM AUTHOR]

Lithium is a critical strategic metal for world economy development and is used in various fields, such as daily life, aviation, medicine, chemical industry, etc. Crown ethers can adsorb Li+ from a mixed ionic solution based on the size matching effect and synergistic effects of functional groups. The selective adsorption properties with Li+, Na+, Mg2+ and the interaction between crown ethers and metal ions were analyzed to guide the design of crown ethers with high selectivity for Li+. The geometric structural characteristics of 1,8-dihydroxyl-4,4,5,5-tetramethylbenzo-14-crown-4 (CE) and complexes with Li+, Na+, and Mg2+ metal ions were investigated using density functional theory modeling (DFT) at the M062X/def2SVP, def2TZVP level. The nature and strength of the interactions were analyzed by atoms in molecules (AIM) topological analysis and symmetry-adapted perturbation theory (SAPT) energy decomposition analysis. The results showed that the interaction strength of CE with metal ions followed the order: CE-Mg2+ > CE-Li+ > CE-Na+. The interaction energies can be separated into four kinds: electrostatics, exchange, induction, and dispersion. The stability of these complexes was mainly driven by electrostatics and induction. According to the analysis results of reduced density gradient (RDG), the metal ions mainly interacted with the oxygen atoms on the ring and did not interact with the hydroxyl groups directly. CE was synthesized and the extraction rates of Mg2+ and Li+ were better than that of Na+. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived islet cells provide promising resources for diabetes studies, cell replacement treatment and drug screening. Recently, hPSC-derived organoids have represented a new class of in vitro organ models for disease modeling and regenerative medicine. However, rebuilding biomimetic human islet organoids from hPSCs remains challenging. Here, we present a new strategy to engineer human islet organoids derived from human induced pluripotent stem cells (hiPSCs) using an organ-on-a-chip platform combined with stem cell developmental principles. The microsystem contains a multi-layer microfluidic device that allows controllable aggregation of embryoid bodies (EBs), in situ pancreatic differentiation and generation of heterogeneous islet organoids in parallel under perfused 3D culture in a single device. The generated islet organoids contain heterogeneous islet-specific α and β-like cells that exhibit favorable growth and cell viability. They also show enhanced expression of pancreatic β-cell specific genes and proteins (PDX1 and NKX6.1) and increased β-cell hormone specific INS gene and C-peptide protein expressions under perfused 3D culture conditions compared to static cultures. In addition, the islet organoids exhibit more sensitive glucose-stimulated insulin secretion (GSIS) and higher Ca2+ flux, indicating the role of biomimetic mechanical flow in promoting endocrine cell differentiation and maturation of islet organoids. This islet-on-a-chip system is robust and amenable to real-time imaging and in situ tracking of islet organoid growth, which may provide a promising platform for organoid engineering, disease modeling, drug testing and regenerative medicine. [ABSTRACT FROM AUTHOR]

Pd–Cu alloys with adjustable morphologies were synthesized and examined as nanocatalysts for electro-oxidation of ethylene glycol. The Cu2+ can effectively adjust the morphology of the Pd–Cu alloys. The as-prepared super-branched Pd–Cu alloys exhibit a greatly enhanced catalytic activity toward ethylene glycol electro-oxidation, because the super-branched structure creates abundant surface active sites and a suitable electronic landscape benefiting from alloying Pd with Cu. [ABSTRACT FROM AUTHOR]

Liver organoids derived from human pluripotent stem cells (PSCs) represent a new type of in vitro liver model for understanding organ development, disease mechanism and drug testing. However, engineering liver organoids with favorable functions in a controlled cellular microenvironment remains challenging. In this work, we present a new strategy for engineering liver organoids derived from human induced PSCs (hiPSCs) in a 3D perfusable chip system by combining stem cell biology with microengineering technology. This approach enabled formation of hiPSC-based embryoid bodies (EBs), in situ hepatic differentiation, long-term 3D culture and generation of liver organoids in a perfusable micropillar chip. The generated liver organoids exhibited favorable growth and differentiation of hepatocytes and cholangiocytes, recapitulating the key features of human liver formation with cellular heterogeneity. The liver organoids in perfused cultures displayed improved cell viability and higher expression of endodermal genes (SOX17 and FOXA2) and mature hepatic genes (ALB and CYP3A4) under perfused culture conditions. In addition, the liver organoids showed a marked enhancement of hepatic-specific functions, including albumin and urea production and metabolic capabilities, indicating the role of mechanical fluid flow in promoting the functions of the liver organoids. Moreover, the liver organoids exhibited hepatotoxic response after exposure to acetaminophen (APAP) in a dose- and time-dependent manner. The established liver organoid-on-a-chip system may provide a promising platform for engineering stem cell-based organoids with applications in regenerative medicine, disease modeling and drug testing. [ABSTRACT FROM AUTHOR]

CdTe films were electrochemically deposited from an alkaline solution with the assistance of nitrilotriacetic acid (NTA) and tetramethylammonium hydroxide (TMAH). CdTe film prepared at the complexing ratio of 14 : 1 was well-crystallized and highly (111)-oriented; after annealing, it was free of voids with good interface contact. The deposition is demonstrated to occur via UPD mechanism. TMAH prevented the introduction of alkaline metal ions into CdTe films. This provides a novel approach for depositing CdTe films at the lower temperature. [ABSTRACT FROM AUTHOR]

This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h−1, resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications. [ABSTRACT FROM AUTHOR]

Optical materials play a momentous role in anti-counterfeiting field, such as authentication, currency and security. The development of tunable optical properties and optical responses to a range of external stimuli is quite imperative for the growing demand of optical anti-counterfeiting technology. Metal halide perovskites have attracted much attention of researchers due to their excellent optical properties. In addition, co-doping methods have been gradually applied to the research of metal halide perovskites, by which more abundant luminescence phenomena can be introduced into the host perovskite. Herein, the ns 2 ions of bismuth (Bi 3+ ) and antimony (Sb 3+ ) ions co-doped zero-dimensional Cs 2 SnCl 6 metal halide with an excitation-wavelength-dependent emission phenomenon is synthesized as an efficient multimodal luminescent material, the luminescence of which is tunable and covers a wide region of color. What's more, a dynamic dual-emission phenomenon is captured when the excitation wavelength changes from 320 nm to 420 nm for Cs 2 SnCl 6 :Bi 0.08 Sb 0.12 crystals. Moreover, the Bi 3+ and Sb 3+ doped metal halide material shows great enhancement in solvent resistance and thermal stability compared to the pristine Cs 2 SnCl 6 . The admirable stability and distinguishable photoluminescence (PL) phenomenon of this all-inorganic metal halide has great potential to be applied in optical anti-counterfeiting technology. Furthermore, the co-doping method can accelerate the discovery of new luminescence phenomena in original metal halide perovskites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Twelve new Cephalotaxus alkaloids (1-12) and nine known analogues (13-21) were isolated and identified from the twigs and leaves of Cephalotaxus sinensis. The structures of the new compounds (1-12) were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Cephalosine H (8) is the third example of an alkaloid containing the cephalolancine skeleton. Cephalosines J and K (10 and 11) are the rare natural Δ(2)1-alkene-6-hydroxyl homoerythrina-type alkaloids isolated from the Cephalotaxus genus. The racemization of cephalotaxine-type alkaloids is discussed. Alkaloids 6, 7, 11, 16, 18 and 19 exhibited broad and potent cytotoxicities against five human cancer cell lines, with IC 50 values ranging from 0.053 to 10.720 μM, highlighting these compounds as promising leads for the development of new antitumor agents.

The complicated synthesis and undesirable biocompatibility of nanomaterials hinder the synergistic photothermal/photodynamic therapy for bacterial infections. Herein, we develop a one-step preparation method of 2D AuPd alloy nanosheets as imaging-guided photonic nano-antibiotics. 2D AuPd alloy nanosheets with an extremely small thickness (∼1.5 nm) exhibit prominent photothermal effects ( η = 76.6%), excellent ROS generation, strong photoacoustic signals and desirable biocompatibility. AuPd nanosheets can eliminate 100% of representative Gram-positive ( Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli ) when irradiated using an 808 nm laser at 1 W cm -2 for 5 minutes. After being modified with a bacterial targeting peptide, under the guidance of photoacoustic imaging, AuPd nanosheets achieve promising synergistic photothermal/photodynamic therapeutic efficacy in treating Staphylococcus aureus infected mice. This work expands the biomedical application of 2D noble metal nanomaterials to the field of photonic nano-antibiotics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)