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In the tumor microenvironment (TME), the cross-talk between tumor cells and hepatic stellate cells (HSCs) could facilitate tumor drug resistance and metastasis, leading to poor prognosis in the patients with hepatocellular carcinoma (HCC). Herein, blocking the cross-talk would be an effective antitumor strategy. In this study, nanoscale dual-ligand-modified multifunctional liposomes (CMDLs) were prepared for the codelivery of curcumin and metformin. To mimic a real TME, the "HSC + HCC" cell cocultured model and "m-HSC–HCC" coimplanted model were established to evaluate the antitumor effect in vitro and in vivo, respectively. These models have been proven to be more efficient for antitumor analysis than tumor cells alone. Compared to free drugs, CMDLs well strengthened drug internalization and drug retention in vitro. Notably, the combined drug formulations, especially CMDLs, exhibited a greater proapoptotic effect than single treatment groups. Furthermore, the in vivo antitumor studies showed that CMDLs exhibited low extracellular matrix deposition, less tumor angiogenesis, and superior anti-HCC efficacy than the other groups in both subcutaneous H22 cells and "m-HSC + H22" coimplanted mice models. The antitumor mechanisms revealed that the combination therapy based on the nanoscale CMDLs could not only inhibit the activation of HSCs by blocking the TGF-β/Smad2 pathway but also block tumor metastasis by reversing epithelial mesenchymal transformation of HCC, which provides a promising approach for anti-HCC therapy. [ABSTRACT FROM AUTHOR]

Nanozymes exhibiting remarkable antioxidant capabilities represent an effective therapeutic approach for ulcerative colitis (UC). This study synthesized the MnNi@PVP nanoenzyme through high-temperature pyrolysis and the NaCl template method, which exhibited multienzyme activity comprising glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). This study investigated the therapeutic effect of MnNi@PVP on colitis caused by sodium dextran sulfate (DSS). The findings indicated that MnNi@PVP notably decreased the disease activity index (DAI) score, which encompasses weight loss, colon shortening, and histopathological changes. MnNi@PVP showed effectiveness in addressing oxidative damage and suppressing the levels of proinflammatory markers, such as tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin (IL)-6, by inactivating the TLR4 pathway and macrophages. In addition, MnNi@PVP demonstrated the ability to repair tight junction proteins (occludin and ZO-1) and restore the intestinal barrier. The transcriptome sequencing demonstrated that MnNi@PVP could regulate inflammatory factor expression pathways and immune processes. Additionally, negatively charged MnNi@PVP can selectively bind to inflamed colonic tissues through electrostatic interactions, endowing it with targeted reparative capabilities at the location of intestinal inflammation. The MnNi@PVP, which possesses the reactive oxygen and nitrogen species (RONS) clearance capability examined in this section, is expected to provide the basis for the targeted repair of intestinal function.

To determine the protective mechanism of puerarin against nonalcoholic steatohepatitis (NASH), the pharmacodynamic effects of puerarin on NASH were evaluated by using zebrafish, cells, and mice. Western blotting, flow cytometry, immunofluorescence, and qRT-PCR were used to detect the effects of puerarin on RAW264.7 autophagy and polarization. Key target interactions between autophagy and polarization were detected using immunoprecipitation. Puerarin regulated the M1/M2 ratio of RAW 264.7 cells induced by LPS + INF-γ. Transcriptomics revealed that PAI-1 is a key target of puerarin in regulating macrophage polarization. PAI-1 knockout reduced the number of M1-type macrophages and increased the number of M2-type macrophages. Puerarin regulated PAI-1 and was associated with macrophage autophagy. It increased p-ULK1 expression in macrophages and activated autophagic flux, reducing the level of PAI-1 expression. Stat3/Hif-1α and PI3K/AKT signaling pathways regulated the number of macrophage polarization phenotypes, reducing liver lipid droplet formation, alleviating liver structural abnormalities, decreasing the number of cytoplasmic vacuoles, and decreasing the area of blue collagen in NASH mice. Puerarin is a promising dietary component for NASH alleviation.

In this work, CuO/Fe 2 O 3 nanozymes with high peroxidase-like activity were synthesized by using hydrothermal and calcination methods. The high-resolution transmission electron microscopy (HRTEM) proved that the heterogeneous interface of CuO/Fe 2 O 3 was the main reason for the high enzyme-like activity. Strong interactions of CuO and Fe 2 O 3 were successfully verified by X-ray absorption near-edge structure (XANES) characterization. Experiments and density functional theory (DFT) calculations were also used to explain the increased enzyme activity. The heterogeneous interface acted as the main active center, facilitating the electron transfer from CuO to Fe 2 O 3 . A colorimetric and intelligent sensing system was constructed based on deep learning. Using the peroxidase-like activity of CuO/Fe 2 O 3 , a platform for glufosinate pesticides and chlortetracycline hydrochloride (CTC) with the signal "on-off-on" changes were established. The limit of detection (LOD) of glufosinate and CTC was 28 and 0.69 μM, respectively. It was successfully applied in the detection of environmental water and soil. This study can provide an intelligent detection method for environmental monitoring.

Although the application of nanozymes has been widely studied, it is still a huge challenge to develop highly active and multifunctional nanozyme catalysts with a wider application prospect. Co 3 O 4 /CoFe 2 O 4 hollow nanocubes (HNCs) with oxygen vacancies were proposed in this study, which had a porous oxide heterostructure with CoFe 2 O 4 as the core and Co 3 O 4 as the shell. The Co 3 O 4 /CoFe 2 O 4 HNCs had three enzyme activities: peroxidase-like, oxidase-like, and catalase-like. Combining XPS depth profiling with density functional theory (DFT), the catalytic mechanism of peroxidase-like activity was explored in depth, which was mainly originated from ·OH produced by the synergistic effect between the outer oxygen and inner oxygen and electron transfer between Co and Fe. A colorimetry/smartphone dual sensing platform was designed based on the peroxidase-like activity. Especially, a multifunctional intelligent sensing platform based on deep learning-YOLO v3 algorithm-assisted smartphone was constructed to realize real-time and rapid in situ detection of l-cysteine, norfloxacin, and zearalenone. Surprisingly, the detection limit of norfloxacin was low at 0.015 μM, which was better than that of the newly published detection method in the field of nanozymes. Meanwhile, the detection mechanism of l-cysteine and norfloxacin was successfully investigated by in situ FTIR. In fact, it also showed outstanding applications in detecting l-cysteine in the food environment and norfloxacin in drugs. Furthermore, Co 3 O 4 /CoFe 2 O 4 HNCs also could degrade 99.24% of rhodamine B, along with good reusability even after 10-cycle runs. Therefore, this work provided an in-depth understanding of the synergistic effect between the outer and inner oxygen in the reaction mechanism and an efficient method for establishing a deep-learning-assisted intelligent detection platform. In addition, this research also offered a good guideline for the further development and construction of nanozyme catalysts with multienzyme activities and multifunctional applications.

An optical monitoring device combining a smartphone with a polychromatic ratiometric fluorescence-colorimetric paper sensor was developed to detect Hg 2+ and S 2- in water and seafood. This monitoring included the detection of food deterioration and was made possible by processing the sensing data with a machine learning algorithm. The polychromatic fluorescence sensor was composed of blue fluorescent carbon quantum dots (CDs) (BU-CDs) and green and red fluorescent CdZnTe quantum dots (QDs) (named GN-QDs and RD-QDs, respectively). The experimental results and density functional theory (DFT) prove that the incorporation of Zn can improve the stability and quantum yield of CdZnTe QDs. According to the dynamic and static quenching mechanisms, GN-QDs and RD-QDs were quenched by Hg 2+ and sulfide, respectively, but BU-CDs were not sensitive to them. The system colors change from green to red to blue as the concentration of the two detectors rises, and the limits of detection (LOD) were 0.002 and 1.488 μM, respectively. Meanwhile, the probe was combined with the hydrogel to construct a visual sensing intelligent test strip, which realized the monitoring of food freshness. In addition, a smartphone device assisted by multiple machine learning methods was used to text Hg 2+ and sulfide in real samples. It can be concluded that the fabulous stability, sensitivity, and practicality exhibited by this sensing mechanism give it unlimited potential for assessing the contents of toxic and hazardous substances Hg 2+ and sulfide.

Due to the lack of a general descriptor to predict the activity of nanomaterials, the current exploration of nanozymes mainly depended on trial-and-error strategies, which hindered the effective design of nanozymes. Here, with the help of a large number of Ni-O-Co bonds at the interface of heterostructures, a prediction descriptor was successfully determined to reveal the double enzyme-like activity mechanisms for Ni/CoMoO 4 . Additionally, DFT calculations revealed that interface engineering could accelerate the catalytic kinetics of the enzyme-like activity. Ni-O-Co bonds were the main active sites for enzyme-like activity. Finally, the colorimetric signal and intelligent biosensor of Ni/CoMoO 4 based on deep learning were used to detect organophosphorus and ziram sensitively. Meanwhile, the in situ FTIR results uncovered the detection mechanism: the target molecules could block Ni-O-Co active sites at the heterostructure interface leading to the signal peak decreasing. This study not only provided a well design strategy for the further development of nanozymes or other advanced catalysts, but it also designed a multifunctional intelligent biosensor platform. Furthermore, it also provided preferable ideas regarding the catalytic mechanism and detection mechanism of heterostructure nanozymes.

Pt/SiO 2 -Al 2 O 3 catalysts were prepared by the traditional impregnation method (IM) and the strong electrostatic adsorption (SEA) process. Differences in particle size, surface chemical state, Pt adsorption site, ammonia oxidation activity, and thermal stability of Pt species were studied systematically. For the fresh catalyst of Pt/SiO 2 -Al 2 O 3 -IM (Pt/SiO 2 -Al 2 O 3 -IM-fresh), Pt species were dispersed unselectively on SiO 2 -Al 2 O 3 , and the large average size (6.6 nm) of Pt species could be observed in a bimodal distribution (ranges of 5.5-6.5 and 8.5-9.5 nm). After the hydrothermal treatment, the Pt size of the aged catalyst (Pt/SiO 2 -Al 2 O 3 -IM-aged) increased significantly, especially Pt particles on SiO 2 showed obvious agglomeration and some even increased to 40 nm. Conversely, for the catalyst prepared through the SEA process, Pt species of Pt/SiO 2 -Al 2 O 3 -SEA-fresh were selectively absorbed on Al 2 O 3 , the Pt particle size was in the range of 1.5-6.0 nm, and the average particle size was only 2.7 nm. After hydrothermal aging, Pt species did not show obvious agglomeration (the average particle size was 3.2 nm). Above all, Pt/SiO 2 -Al 2 O 3 -SEA presented better catalytic activity and thermal stability than Pt/SiO 2 -Al 2 O 3 -IM, i.e., the temperatures of 50% NH 3 conversion for the fresh and aged Pt/SiO 2 -Al 2 O 3 -SEA catalysts were 216 and 223 °C, respectively, much lower than those for Pt/SiO 2 -Al 2 O 3 -IM-fresh (228 °C) and Pt/SiO 2 -Al 2 O 3 -IM-aged (250 °C)., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

An amino-controlled regiodivergent asymmetric synthesis of CF 3 -containing spiro-pyrrolidine-pyrazolone compounds is described. With alkaloid-derived squaramide as catalyst, the 1,3-dipolar cycloaddition of α,β-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While the cyclohexanediamine-derived squaramide was employed, the reaction afforded a series of structure isomers through a switched umpolung reaction.

A simple and efficient protocol for silver-promoted direct C-H phosphonation of 1-naphthylamine derivatives with H-phosphonates was described. This reaction proceeded smoothly for 1-naphthylamine derivatives at the C4 site, providing a facile and efficient route to 4-phosphonated 1-naphthylamine derivatives. This phosphonation could tolerate a diverse type of functional groups at the pyridinyl and naphthyl moieties. Further functionalization of the phosphonated product was also explored at the C2 and C8 sites, such as fluoridation, methylation, methoxylation, and amination. In addition, DFT studies of the reaction intermediate showed that the most electrophilic reactive site is at the C4 site in the naphthyl ring.

We report here for the first time a novel difluoromethylated ketimine building block condensed by thioisatin and difluoroethylamine, offering efficient access to a broad range of enantioenriched products bearing difluoroethylamine units (27 examples, ≤98% yield, >99% ee) in the presence of quinine-derived squaramide. Further transformation of the intermediate would generate a variety of versatile functional blocks like α-difluoromethyl amines, β-amino acid, and β-diamine with retention of the enantiomeric excess at the difluoromethyl-bound carbon.

NH 3 emissions were limited strictly because of the threat for human health and sustainable development. Pt/Al 2 O 3 and Pt/CeZrO 2 were prepared by the impregnation method. Differences in surface chemical states, reduction ability, acid properties, morphological properties, reaction mechanisms, and ammonia oxidation activity were studied. It indicated that Pt species states were affected by different metal-support interactions. The homogeneously dispersed Pt species over Pt/Al 2 O 3 exposed Pt(111) because of weak metal-support interactions; there even existed an obvious interface between Pt and Al 2 O 3 . While obscure even an overlapped interface was observed over Pt/CeZrO 2 , resulting in the formation of PtO because of the oxygen migration from CeZrO 2 to Pt species (confirmed by CO-FTIR, the cycled H 2 -TPR and transmission electron microscopy results). It was noteworthy that different reaction mechanisms were induced by different states of Pt species; NH was the key intermediate species for ammonia oxidation reaction over Pt/Al 2 O 3 , but two kinds of intermediates, N 2 H 4 and HNO, were observed for Pt/CeZrO 2 . It consequently resulted in the obvious distinction of the NH 3 -SCO catalytic performance; the light-off temperatures of NH 3 over Pt/Al 2 O 3 and Pt/CeZrO 2 were 231 and 275 °C, respectively, while the maximum N 2 selectivity (65%) was obtained over Pt/CeZrO 2 , it was obviously better than that over Pt/Al 2 O 3 .

Hydrogen peroxide (H 2 O 2 )-generating enzymes (HGEs) are potentially useful for tumor therapy, but the potential is limited by the challenge in regulating H 2 O 2 production. Herein, we present site-specific in situ growth of a cationic polymer poly( N, N'-dimethylamino-2-ethyl methacrylate) (PDMA) from the N-terminus of glucose oxidase (GOX) to generate a site-specific and cationic GOX-PDMA conjugate with well-retained activity and enhanced stability to regulate H 2 O 2 generation for cancer starvation and H 2 O 2 therapy. Notably, the efficiency of endocytosis of the conjugate was 4-fold higher than that of free GOX. As a result, relative to free GOX, the conjugate showed 1.5-fold increased cytotoxicity, 2-fold enhanced tumor retention, and 5-fold increased tolerability after intratumoral injection. Importantly, a single intratumoral injection of the conjugate completely abolished colon tumors without detectable side effects, whereas free GOX was ineffective and systemically toxic. This chemistry may provide a new, simple, general, and efficient solution to regulate H 2 O 2 production and thereby to dramatically improve the antitumor efficacy of HGEs while reducing side effects.

The T-1000 liquid metal terminator, which can transform and self-repair, represents a dream for decades that robots can fundamentally change our daily life. Until now, some large-scale liquid metal machines have been developed. However, there is no report on nanoscaled liquid metal machines and their biomedical applications. We describe here a shape-transformable and fusible rodlike swimming liquid metal nanomachine, based on the biocompatible and transformable liquid metal gallium. These nanomachines were prepared by a pressure-filter-template technology, and the diameter and length could be controlled by adjusting the nanoporous templates, filter time, and pressure. The as-prepared liquid gallium nanomotors display a core-shell nanorod structure composed of a liquid gallium core and solid gallium oxide shell. Upon exposure to an ultrasound field, the generated acoustic radiation force in the levitation plane can propel them to move autonomously. The liquid metal nanomachine can actively seek cancer cells and transform from a rod to a droplet after drilling into cells owing to the removal of gallium oxide layers in the acidic endosomes. These transformed nanomachines could fuse together inside cells and photothermally kill cancer cells under illumination of near-infrared light. Such acoustically propelled shape-transformable rodlike liquid metal nanomachines have great potential for biomedical applications.

Nicotine is a major toxic alkaloid in wastes generated from tobacco production and cigarette manufacturing. In the present work, a nicotine-degrading bacterial strain was isolated from tobacco powdery waste. The isolate was identified as Pseudomonas sp. S-1 based on morphology, physiology, and 16S rRNA gene sequence. Suitable conditions of isolate S-1 for nicotine degradation were pH 7.0 and 30 °C. Catabolic intermediates of nicotine were isolated with preparative-HPLC and characterized with LC-HRMS and NMR. The catabolic pathways of nicotine were involved in dehydrogenation, oxidation, hydrolysis, and hydroxylation. Interestingly, nicotine catabolism in strain S-1 undergoes a new pyrrolidine pathway that differs from the other three catabolic pathways in bacterial species. This work sheds light on catabolic diversity of nicotine and heteroaromatics.

We report a magnetically actuated peanut-shaped hematite colloid motor that can not only move in a rolling or wobbling mode in fluids but also perform single cell manipulation and patterning in a noncontact way. The peanut motor in a rolling mode can reach a maximal velocity of 10.6 μm s -1 under a rotating magnetic field of 130 Hz and 6.3 mT and achieve a more precisely controllable motion in predefined tracks. While in a wobbling mode, the motor reaches a maximal velocity of 14.5 μm s -1 under a conical rotating magnetic field of 80 Hz and 6.3 mT and can climb over steep slopes to adapt the motor for more complex environments. The fluid flow simulation results reveal that the difference between two movement modes mostly comes from the distribution discrepancy of the flow fields near the motors. Through the integration of the rolling and wobbling movement, these peanut motors can autonomously transport and release cells to a predefined site and thus form complex cell patterns without a physical contact. Such magnetically actuated peanut colloid motors afford a biofriendly technique for manipulation and patterning of cells, cell measurements, and intracellular communication investigations.

The assembly of gold nanoparticles (AuNPs) to AuNP assemblies is of interest for cancer therapy and imaging. Herein we introduce a new and general paradigm, thermally triggered AuNP assembly, for the development of novel intelligent platforms for cancer photothermal therapy (PTT) and multimodal imaging. Site-specific conjugation of a thermally sensitive elastin-like polypeptide (ELP) to AuNPs yields thermally sensitive ELP-AuNPs. Interestingly, ELP-AuNPs can in situ form AuNP assemblies composed of short necklace-like gold nanostructures at elevated temperatures and thus show strong near-infrared light absorption and high photothermal effect. These thermally responsive properties of ELP-AuNPs enable simultaneous photothermal/photoacoustic/X-ray computed tomographic imaging and PTT of melanoma after single intratumoral injection of ELP-AuNPs. The thermally triggered assembly of a variety of nanoparticles with optical, electronic, and magnetic properties into nanoparticle assemblies may open new ways for the establishment of intelligent platforms for various applications in biomedicine.