Piperidine is a crucial pharmacophore and a special scaffold in the realm of drug discovery. Its flexibility increases the molecule's capability to bind to the receptor. The piperidine-containing compounds are distinguished by their remarkable activity, and are increasingly becoming a vital category of pesticides. In this review, the research progress of piperidines in the discovery of pesticides was updated according to their active characteristics. The structure-activity relationships (SARs), and mechanisms of action of piperidine-containing compounds were also discussed. This article is meant to enable readers to quickly understand piperidines, while providing ideas for creating piperidines with novel structures and unique mechanisms of action.

Background Osteosarcoma (OS) is a highly metastatic primary bone malignancy, and the treatment options remain inadequate. Hence, exploring innovative natural medications is required. Prunetin (PRU) is an isoflavone that has been a proven anticancer agent in numerous cancer cell lines. However, the activity of PRU against OS remains uncertain. Materials and Methods Here, we studied the anticancer activity of PRU (20 and 25 µM) on human OS cells MG-63 and investigated its latent mechanism. The PRU activity of MG-63 cells cytotoxicity, intracellular ROS, metastasis, apoptosis, anti-apoptotic proteins, MAPK/STAT-3, and AKT signaling pathways was assessed by MTT assay, DCFH-DA, DAPI, PI, AO/EB, cell adhesion, and RT-PCR analysis. Findings unveiled that PRU could constrain MG-63 cell viability and adhesion through elevated intracellular ROS and elicited apoptosis. Results Likewise, PRU (20 and 25 µM) avert the MG-63 cell proliferation, which stimulates apoptosis by the enhancement of Bax and caspases, while it diminishes Bcl-2 in a dose-dependent way. Furthermore, PRU could reduce Pin-1, and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that PRU alleviates MG-63 cell proliferation and metastasis via ROS-mediated apoptosis, which triggers MAPKs/STAT3 and AKT pathways, suggesting that PRU is a promising natural remedy for OS. In order to comprehend the therapeutic target for cancer, we assessed the effect of PRU on the expression of Pin1, which is thought to be over-expressed in many human malignancies. According to our findings, PRU specifically suppressed Pin1 expression to reduce the expression of Akt, STAT3, P38, JNK, P65, and IL-6. We evaluated the impact of PRU on the expression of Pin1, which is allegedly over-expressed in many human malignancies, to better understand the therapeutic target for cancer. Researchers state that PRU inhibited the expression of Akt, STAT3, P38, JNK, P65, and IL-6 in particular, by suppressing Pin1 expression. Conclusion Together, these results suggest that PRU may be an effective treatment for bone cancer in people by preventing Pin1 expression.

Cell surface receptors play a key role in intracellular signaling, and their overexpression and activation are among the drivers of multiple diseases. Selective inhibition of cell surface receptors is important for regulating intracellular signaling pathways and cell behavior. Here, we design engineered aptamers to selectively inhibit receptor function. In this strategy, the aptamer specifically recognizing the extracellular structural domain of the EGFR, was conjugated to an adamantane moiety through linking arms of various lengths in order to obtain better performances toward EGFR. These interactions inhibit EGFR dimerization, thereby impeding the activation of downstream signaling pathways. It is shown that the adamantane-modified aptamers exhibit superior inhibition of downstream effector proteins relative to the unmodified aptamers. The optimal inhibitory effect was observed with a linker arm of 40 T-base in length. Notably, the best-performing adamantane-modified aptamer specifically binds to A549 cells with a dissociation constant (22.6 +/- 4.5 nM) that is approximately 4-fold lower than that of the parent EGFR aptamer (94.4 +/- 21.9 nM). We further combine the use of the adamantane-modified aptamer with that of genistein, a natural isoflavone compound with EGFR tyrosine kinase inhibition activity, to enhance the inhibitory effect on EGFR and its downstream signaling employing a synergistic action. This study is expected to provide a versatile approach for the improvement of existing aptamers obtaining increased selective inhibition of cell surface receptors.

This review is dedicated to offering a new perspective on using DNA nanostructures to explore the progress of cell–cell communication.

New coccine (NC), as a kind of common colorant, has been frequently used in our daily life. Herein, the fluorescent composite (PNTs@C6) prepared by the hydrophobic non-covalent interaction between peptide nanotubes and coumarin 6 (C6) was designed for the determination of NC. Due to the activation of C6 by peptide nanotubes, the composite exhibits strong green fluorescence emission, which can be selectively quenched by NC through the inner filter effect. Therefore, a new fluorescent method based on the PNTs@C6 composite for NC detection was constructed. Under optimal conditions, the fluorescence quenching of the sensor exhibits a good linear relationship with the concentration of NC in the range of 0.01-10 μM and the limit of detection is 3.6 nM. Furthermore, the strategy shows simplicity, rapid response and high selectivity and has been successfully applied to the detection of NC in food samples.

Herein, 2-mercapto-5-benzimidazolesulfonate acid sodium salt dihydrate (MBZS)-protected gold-silver bimetallic nanoclusters, named MBZS-AuAg NCs, were synthesized. Interestingly, we found that MBZS-AuAg NCs solutions can exhibit different fluorescence color changes under sulfide stimulation. A series of modern analytical testing techniques were used to explore the interaction mechanism between MBZS-AuAg NCs and sulfide. Sulfide ions can not only cause MBZS-AuAg NCs to exhibit rich fluorescence color changes similar to those of a chameleon but also have four linear relationships between the response intensity and sulfide concentration. A wide-range sulfide fluorescence sensing platform was constructed based on four linear segments with different fluorescence color responses. This sensing platform can be directly used for the determination of S2- with a detection limit as low as 11 nM. The portable test paper based on MBZS-AuAg NCs can realize the visual and rapid detection of gaseous hydrogen sulfide with a detection limit of 100 ppb (v/v). The wide detection range of the proposed method not only allows it to be used as an alternative method for sulfide detection in environmental samples but also has potential applications in the rapid detection and early warning of hydrogen sulfide gas in industrial and mining scenarios.

One-pot means was performed for the rapid preparation of copper nanoclusters (Cu NCs), which were employed as a fluorescence system for the sensitive apigenin measurement in pharmaceutical samples. Herein, CuCl2 aqueous solution was reduced to Cu NCs through ascorbic acid and the Cu NCs were protected through trypsin under 65 celcius for 4 h. The entire preparation process was rapid, facile and environmentally friendly. The trypsincapped Cu NCs were demonstrated through ultraviolet-visible spectroscopy, fluorescence spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and fluorescence lifetime, respectively. The Cu NCs revealed blue fluorescence with emission wavelength around 465 nm under the excitation wavelength of 380 nm. The fluorescence weakening feature of Cu NCs with apigenin was observed. On this basis, a facile and sensitive turn-off fluorescent nanoprobe for the sensing of apigenin in real samples was developed. The logarithm of relative fluorescence intensity revealed a good linear relationship with apigenin contents from 0.5 & mu;M to 300 & mu;M with the detection limit of 0.079 & mu;M. The Cu NCs-based fluorescent nanosensor have been employed to measure the apigenin amounts in real samples such as medical saline, bovine and human serum. The results revealed excellent potential of this Cu NCs-based fluorescent nanoprobe for the convention computation of apigenin amounts in real samples.

Designing single-atom nanozymes with densely exposed metal atom active sites and enhancing catalytic activity to detect pollutants remain a serious challenge. Herein, we reported a single-atom nanozyme with layered stacked Fe/Cu dual active sites (Fe/Cu-NC SAzyme) synthesized via hydrothermal and hightemperature pyrolysis using folic acid as a template. Compared with Fe-NC and Cu-NC SAzyme, Fe/Cu-NC SAzyme has higher peroxidase-like activity, which indicates that the doping of synthesized Fe/Cu bimetals can improve the catalytic activity and that the atomic loading of Fe and Cu in Fe/Cu-NC is 5.5 wt% and 2.27 wt%, respectively. When S 2 - is added to the Fe/Cu-NC catalytic system, a high-sensitivity and high-selectivity S 2 - colorimetric sensing platform can be established, with a wide linear range (0.09- 6 mu mol/L) and a low detection limit (30 nmol/L), which can be used to detect S 2 - in environmental water samples. What's more, the Fe/Cu-NC SAzyme can activate peroxymonosulfate (PMS) to degrade 99.9% of rhodamine B (RhB) within 10 min with a degradation kinetics of 0.5943 min -1 . This work details attractive applications in Fe/Cu-NC SAzyme colorimetric sensing and dye degradation. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Drug resistance is a worldwide health care crisis which impedes disease treatment and increases financial burden, especially for its multifactorial nature and high complexity. Herein, we developed a multiparametric approach to visualize and detect drug resistance in living cancer cells, through the combination of DNAtemplated covalent protein labeling strategy and fluorescent resonance energy transfer technique. Gefitinib resistance in non-small cell lung cancer caused by mesenchymal-epidermal transition factor (Met) overexpression and hyperactivation was investigated as a proof-of-concept. Unlike the traditional single-factor investigation, the proposed approach evaluated the contribution of three important parameters towards the resistance, including the changes of Met expression level, the homodimerization of Met with itself and the heterodimerization of Met with epidermal growth factor receptor (EGFR). A multiple regression model based on these three parameters was tentatively established for evaluation of the resistance level of laboratory-developed resistant cells and evaluation of the resistance level of patient-derived cells. Such an approach facilitates a quick identification of a drug resistance, to evaluate not only the resistance level but also the resistance mechanism.

Benefiting from superior programmable performance and flexible design of DNA technologies, a variety of single-molecule RNA fluorescence imaging methodologies have been reported. However, the multiplexing capability is restricted owing to the spectral overlap of fluorophores. To overcome this limitation, some inspiring multiplex imaging strategies have been developed, but in practice, it remains challenging to achieve convenient and rapid imaging in live cells due to complex designs and additional pretreatments to increase cell permeability. Here, we report an activatable fluorescence-encoded nanoprobe (AFENP) strategy, through which fluorescence-encoded functional modules for qualitative analysis and activated nucleic acid assemblies functional modules for quantitative testing enable simple multiplexed RNA imaging in single live cells. As a proof of principle, by two distinguishable fluorophores (fluorescein and rhodamine B) and their seven distinctly differentiated intensity levels, self-assembled AFENP enables simplified and quick simultaneous in situ detection and imaging of seven types of targets in live single cells because the fluorescent quantitative signal is activated only in the presence of target avoiding the washing procedures and additional pretreatment to increase cell permeability is undesired. We expect that this practical single-cell analysis platform will be adopted for multiple gene expression analysis and imaging in live cells on account of its simplicity and multiplex capability.

The construction of highly sensitive detection methods for hydroquinone (HQ) in environment and cosmetics is of great significance for environmental protection and human health. In this work, a novel detection method for HQ was successfully developed by constructing a metal-organic framework mimic enzyme colorimetric sensor (Mn/Fe-MOF@Pd1.0) with excellent peroxidase-like activity, which was synthesized by doping manganese ions into Fe-MOF by introducing bimetallic active centers, thereby improving the peroxidase-like activity of Fe-MOF, and the acid resistance and stability of Mn/Fe-MOF were improved by supporting palladium (Pd NPs). It is proven that Mn/Fe-MOF@Pd1.0 promoted the decomposition of hydrogen peroxide (H2O2) to generate active species, therefore, oxidized chromogenic substrate discoloration. On this basis, the detection of HQ based on the Mn/Fe-MOF@Pd1.0 colorimetric sensor was constructed, in which the limit of detection (LOD) was 0.09 mu M in the linear range of 0.3-30 mu M. Furthermore, Mn/Fe-MOF@Pd1.0 was successfully used for detecting HQ in hy-droquinone whitening cream and actual water samples. The successful synthesis of Mn/Fe-MOF@Pd1.0 may provide new insights for further study of the enzyme-like activity of metal-organic framework composites, and the constructed facile and sensitive sensor system could broaden the application prospects of HQ detection.

Substrate materials with high sensitivity and storage stability are crucial for the practical analytical application of surface-enhanced Raman scattering (SERS) techniques. In this work, a SERS-active substrate (Si/Au@Ag/ZIF-67) was fabricated with a metal-organic framework (ZIF-67) on a plasmonic surface (Si/Au@Ag) via self-assembly. The as-prepared material combined the properties of the abundant hotspots of the Au@Ag nanoparticles and the excellent adsorption performance of ZIF-67 for organic molecules. The synergy leads to high sensitivity of the composite substrate with a low detection limit for 4-aminothiophenol (a typical Raman reporter molecule) down to 2.0 × 10-9 M and the analytical enhancement factor (AEF) of the SERS substrate is 3.4 × 106. Moreover, the substrates exhibited good repeatability, high reproducibility, and reliable stability due to the MOF coating. The SERS signal was stable after 60 days of storage at room temperature. Ultimately, the optimal Si/Au@Ag/ZIF-67 was applied as a SERS sensor to analyze thiram, and the results showed a linear concentration range from 10-7 to 10-5 M with good linearity (R2 = 0.9934). The recoveries of thiram in spiked apple juice were in the range of 95.7-102.3%, with relative standard deviations less than 4.3%. These results predict that the proposed SERS substrates may hold great potential for the detection of environmental and food pollution in practical applications.

Single-atom catalysts with atomically dispersed sites have been widely used as nanozymes for colorimetric sensing because their tunable M-N-x active centers are similar to those of natural enzymes. However, their low metal atom loading leads to insufficient catalytic activity and affects the sensitivity of colorimetric sensing, which limits their further applications. Herein, multi-walled carbon nanotubes (MWCNs) are selected as carriers to reduce the aggregation of ZIF-8 and improve the electron transfer efficiency of nanomaterials. Meanwhile, MWCN/FeZn-NC single-atom nanozymes with excellent peroxidase-like activity were prepared by pyrolysis on ZIF-8 doped with a second metal Fe. Based on the excellent peroxidase activity of MWCN/FeZn-NCs, a dual-functional colorimetric sensing platform for Cr(vi) and 8-hydroxyquinoline was established. The detection limits of the dual-function platform are 40 nM for Cr(vi) and 55 nM for 8-hydroxyquinoline. This work provides a highly sensitive and selective strategy for the detection of Cr(vi) and 8-hydroxyquinoline in hair care products, which has great application prospects in the field of pollutant detection and control.

Receptor dimerization is an essentialmechanism for theactivationof most receptor tyrosine kinases by ligands. Thus, regulating thenanoscale spatial distribution of cell surface receptors is significantfor studying both intracellular signaling pathways and cellular behavior.However, there are currently very limited methods for exploring theeffects of modulating the spatial distribution of receptors on theirfunction by using simple tools. Herein, we developed an aptamer-baseddouble-stranded DNA bridge acting as "DNA nanobridge",which regulates receptor dimerization by changing the number of bases.On this basis, we confirmed that the different nanoscale arrangementsof the receptor can influence receptor function and its downstreamsignals. Among them, the effect gradually changed from helping toactivate to inhibiting as the length of DNA nanobridge increased.Hence, it can not only effectively inhibit receptor function and thusaffect cellular behavior but also serve as a fine-tuning tool to getthe desired signal activity. Our strategy is promising to provideinsight into the action of receptors in cell biology from the perspectiveof spatial distribution.

Specific discrimination of cancer from inflammation and normal tissue at the same time simply and sensitively, is of great significance for the diagnosis of cancer and the improvement of patient survival. Hence, we present the design of a targeted supramolecular fluorescent nanoprobe (SFNP) and modulate its supramolecular interaction between different functional modules via host-guest chemistry for identification of lung adenocarcinoma cancer from inflammation. Aptamer-targeted SFNP (SFNP-Aptamer) for recognition of human lung adenocarcinoma A549 cells and folate-targeted SFNP (SFNP-Folate) for folate receptor recognition of activated macrophages in inflamed lesions, can be facilely fabricated just by modulating inter-module interactions. The supramolecular ensemble composed of SFNP-Aptamer and SFNP-Folate can not only specifically distinguish lung adenocarcinoma A549 cells, activated macrophages and normal cells, but also successfully distinguish lung adenocarcinoma tissue, inflammatory tissue and normal tissue in tumor-adjacent tissue sections. So the supramolecular ensemble may have potential application for cancer inflammation diagnosis.

Ferritin plays an important role in regulating the homeostasis of iron in cells by storing/releasing iron. Current methods usually explored the determination of iron content, but in-situ imaging of the iron storage/release from ferritin in cells cannot be achieved. Hence, an engineered self-assembled biomimetic-compartmented nanoprobe (APO@CDs) has been constructed. The protein shell of APO (apoferritin) acted as ion channel module to control iron ions entering/exiting ferritin cavity; the inner core of CDs (carbon dots) acted as signal module for iron ions response. Compared with CDs, the response sensitivity and specificity to iron ions (Fe3+) have been improved by using APO@CDs, and the cytotoxicity was significantly reduced. Additionally, compared with cells containing APO@CDs alone, the normalized fluorescence gray value of Fe3+-treated cells was significantly decreased (0.275), indicating that Fe3+ has effectively entered the ferritin. Furtherly, that of Fe3+-treated cells incubated with deferoxamine (DFO) was significantly enhanced (0.712), showing that Fe3+ was released from ferritin under the mediation of DFO. The results demonstrate that APO@CDs can be successfully applied to in-situ imaging of iron storage/release from ferritin in cells, providing a potential platform for the in-situ dynamic study of the iron storage/release in biomedical field.

Inspired by natural enzymes, artificial enzymes have been widely studied due to their ease of mass production, robustness to harsh environments and high stability. In this work, a peptide nanotube/hemin composite (KL@hemin) as an artificial enzyme was prepared by immobilizing hemin onto self-assembled peptide nanotubes (PNTs). The successful loading of hemin was determined by a series of characterizations. The multiple noncovalent interactions between the PNTs and hemin endow KL@hemin with strong stability. Subsequent enzyme activity tests showed that the prepared KL@hemin exhibited enhanced peroxidase activity. Further experiments indicate that PNTs as carriers can not only protect hemin from dimerization to maintainenzyme activity but also increase the affinity of hemin to the substrate for faster binding and accelerate mass transfer, thus promoting the whole catalytic process. Coupled with a peroxidase-catalyzed chromogenic system, a colorimetric method for dopamine detection was constructed based on KL@hemin. The strategy shows high sensitivity and selectivity and has been applied to the determination of dopamine in dopamine injection and meat samples.

Tiopronin (TPN) protected gold-silver bimetallic nanoclusters (TPN-AuAg NCs) were synthesized in an aqueous medium by a one-pot method. The synthesized TPN-AuAg NCs are spherical with an average diameter of 1.75 +/- 0.5 nm and can emit bright fluorescence in the red spectral range (E-m = 670 nm). Based on the "on-off-on" process of the nanoclusters' fluorescence, a fluorescent probe for sequential detection of Fe3+ and ascorbic acid (AA) was proposed. After adding Fe3+ ions into the TPN-AuAg NCs solution, a composite Fe3+@TPN-AuAg NCs could be formed. Due to the internal filtering effect (IFE) between Fe3+ and TPN-AuAg NCs, the fluorescence of the nanoclusters was quenched. Subsequently, when AA was continuously added to the fluorescence quenching system, based on the reduction effect of AA on Fe3+ in the complex, the fluorescence of Fe3+@TPN-AuAg NCs could be sensitively turned on. The detection limits of the fluorescence titration measurements calculated using the equation 3 sigma/k, were 150 nM (Fe3+) and 60 nM (AA), respectively. The proposed method has been successfully applied to detect Fe3+ and AA in human serum samples.

In this work, sulfur quantum dots (TPA-SQDs) protected by terephthalic acid as a stabilizer were synthesized using a one-pot method. When excited at 310 nm, the synthesized TPA-SQDs solution emitted strong blue fluorescence at 428 nm, and the absolute quantum yield was as high as 85.99%. The proposed SQDs can be used as a fluorescent probe to specifically quench tartrazine (TZ), showing a good linear relationship (R-2 = 0.996) at TZ concentrations of 0.1-20 mu M, with a detection limit of 39 nM. By analysing the fluorescence lifetime, UV-Vis absorption spectrum and zeta potential of the assay system, it can be speculated that the fluorescence quenching mechanism of TZ on TPA-SQDs is the inner filter effect (IFE). The proposed method was applied to the detection of TZ in vitamin water and orange juice, and the results were consistent with the determination results by highperformance liquid chromatography. The recoveries and relative standard deviations were 93.2-102.6% and 1.34-2.88%, respectively, which provided an alternative method for the determination of TZ in beverages or other food samples.

This study aimed to evaluate the image quality and diagnostic value of compressed sensing-sensitivity encoding (CS-SENSE) accelerated 3-dimensional (3D) T2-weighted turbo spin-echo (T2W TSE) sequence in patients with rectal cancer compared with conventional 3D and 2-dimensional (2D) sequences. A total of 54 patients who underwent the above three sequences were enrolled. Two radiologists independently reviewed the image quality using an ordinal 5-point Likert scale. The quantitative measurement was performed to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The diagnostic value was assessed using TN staging, extramural vascular invasion and mesorectal fascia status. Friedman and McNemar’s tests were applied for comparative analysis. Forty-two patients were successfully included. Compared with 3D and 2D sequences, the CS-SENSE 3D sequence speeded up by 39