Detection and Identification of Pesticides in Fruits Coupling to an Au-Au Nanorod Array SERS Substrate and RF-1D-CNN Model Analysis.

In this research, a method was developed for fabricating Au-Au nanorod array substrates through the deposition of large-area Au nanostructures on an Au nanorod array using a galvanic cell reaction. The incorporation of a granular structure enhanced both the number and intensity of surface-enhanced Raman scattering (SERS) hot spots on the substrate, thereby elevating the SERS performance beyond that of substrates composed solely of an Au nanorod. Calculations using the finite difference time domain method confirmed the generation of a strong electromagnetic field around the nanoparticles. Motivated by the electromotive force, Au ions in the chloroauric acid solution were reduced to form nanostructures on the nanorod array. The size and distribution density of these granular nanostructures could be modulated by varying the reaction time and the concentration of chloroauric acid. The resulting Au-Au nanorod array substrate exhibited an active, uniform, and reproducible SERS effect. With 1,2-bis(4-pyridyl)ethylene as the probe molecule, the detection sensitivity of the Au-Au nanorod array substrate was enhanced to 10-11 M, improving by five orders of magnitude over the substrate consisting only of an Au nanorod array. For a practical application, this substrate was utilized for the detection of pesticides, including thiram, thiabendazole, carbendazim, and phosmet, within the concentration range of 10-4 to 5 × 10-7 M. An analytical model combining a random forest and a one-dimensional convolutional neural network, referring to the important variable-one-dimensional convolutional neural network model, was developed for the precise identification of thiram. This approach demonstrated significant potential for biochemical sensing and rapid on-site identification.

Injectable, Adhesive Albumin Nanoparticle-Incorporated Hydrogel for Sustained Localized Drug Delivery and Efficient Tumor Treatment.

Injectable hydrogels are receiving increasing attention as local depots for sustained anticancer drug delivery. However, most current hydrogel-based carriers lack tissue-adhesive ability, a property that is important for the immobilization of drug-loaded systems at tumor sites to increase local drug concentration. In this study, we developed a paclitaxel (PTX)-loaded injectable hydrogel with firm tissue adhesion for localized tumor therapy. PTX-loaded bovine serum albumin (BSA) nanoparticles (PTX@BN) were prepared, and the drug-loaded hydrogel was then fabricated by cross-linking PTX@BN with o-phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) via a condensation reaction between OPA and the amines in BSA. The hydrogel showed firm adhesion to various organs and tumor tissues ex vivo due to the condensation reaction of unreacted OPA groups and amines in the tissues. The PTX-loaded nanocomposite hydrogels sustained PTX release over 30 days following the Korsmeyer-Peppas model and exhibited notable inhibition activities against mouse C26 colon and 4T1 breast cancer cells in vitro. Following peritumoral injection into mice with C26 or 4T1 tumors, the PTX@BN-loaded hydrogel significantly enhanced the antitumor efficacy and prolonged animal survival time compared to free PTX solutions with low systemic toxicity. Therefore, the adhesive, PTX-loaded nanocomposite hydrogels have the potential for efficient localized tumor therapy.

Circulating Transforming Growth Factor-ß1 Levels in Preeclamptic Women: a Meta-analysis.

Transforming growth factor (TGF)-ß1, an angiogenic factor in the maternal circulation, has been suggested to be related to preeclampsia. However, the findings from previous studies were inconsistent. Thus, we conducted a meta-analysis to assess the difference in circulating TGF-ß1 levels between women with preeclampsia and normal pregnancies. Twenty-four studies including 1748 women with PE and 1404 women with normal pregnancy were included in our study. The results showed that circulating TGF-ß1 levels were not different before the time of active disease (standardized mean differences, - 0.46 [95% CI, - 0.16 to 0.15]; P = 0.000). At the time of active disease, women with preeclampsia (n = 1207) had higher circulating TGF-ß1 levels than normotensive controls (n = 912; standardized mean differences, 0.94 [95% CI, 0.52 to 1.35]; P = 0.000). Circulating TGF-ß1 levels were higher in both early-onset/severe and late-onset/mild types of preeclampsia. No publication biases were found. We conclude that preeclamptic women have higher circulating TGF-ß1 than those with normal pregnancy at the time of preeclampsia diagnosis.

Visual monitoring of the mitochondrial pH changes during mitophagy with a NIR fluorescent probe and its application in tumor imaging.

Mitophagy, a mitochondria-selective autophagy process, plays critical roles in maintaining intracellular homeostasis by removing the damaged mitochondria and recycling the nutrients in a lysosome-dependent manner. Mitophagy process could result in the changes of mitochondrial pH. So fluorescent probes for detecting mitochondrial pH during mitophagy are highly needed for exploring the functions of mitochondria. Herein, a series of near-infrared pH probes were designed based on the rhodamine framework. The probes showed high sensitivity for pH with the tunable pKa from 4.74 to 6.54. Particularly, for probe 5 (with the pKa of 6.54), a linear relationship between fluorescence intensity and pH in the range of 5.6-7.2 was observed, which was suitable for mitochondrial pH detection. The probe displayed excellent mitochondria-targeting ability. It was applied to monitor pH changes during mitophagy caused by starvation. Besides, in vivo non-invasive visualization of tumor pH variations was achieved via the fluorescence imaging in the near-infrared region. We anticipate that the probe may be a useful tool for revealing essential information about mitophagy-related research and clinical tumor diagnosis.

The novel sandwich composite structure: a new detection strategy for the ultra-sensitive detection of cyclotrimethylenetrinitramine (RDX).

This study presents a novel sandwich composite structure that was designed for the ultra-sensitive detection of cyclotrimethylenetrinitramine (RDX). Au nanorod arrays (Au NRAs) were prepared and bound to 10-7M 6-MNA as adsorption sites for RDX, while Au nanorods (Au NRs) were modified using 10-5M 6-MNA as SERS probes. During detection, RDX molecules connect the SERS probe to the surface of the Au NRAs, forming a novel type of Au NRAs-RDX-Au NRs 'sandwich' composite structure. The electromagnetic coupling effect between Au NRs and Au NRAs is enhanced due to the molecular level of the connection spacing, resulting in new 'hot spots'. Meanwhile, Au NRAs and Au NRs have an auto-enhancement effect on 6-MNA. In addition, the presence of charge transfer in the formed 6-MNA-RDX complex induced chemical enhancement. The limits of detection of RDX evaluated by Raman spectroscopy using 6-MNA were as low as 10-12mg ml-1(4.5 × 10-15M) with good linear correlation between 10-12and 10-8mg ml-1(correlation coefficientR2 = 0.9985). This novel sandwich composite structure accurately detected RDX contamination in drinking water and on plant surfaces in an environment with detection limits as low as 10-12mg ml-1and 10-8mg ml-1.

A novel hydrazone-based fluorescent "off-on-off" probe for relay sensing of Ga3+ and PPi ions.

A novel hydrazone-based fluorescent probe (E)-3-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4H-chromen-4-one (BTC) has been rationally designed and synthesized. BTC can subsequently detect Ga3+ and PPi ions through the absorption and emission off-on-off response with high specificity. Importantly, fluorescent probe BTC can well discriminate Ga3+ from Al3+ and In3+. The association constant (K) was calculated as 2.06 × 104M-1, and the limit of detection (LOD) was calculated as 4.88 × 10-2µM. Competitive binding studies also illustrated good results of the probe BTC towards Ga3+. Job's plot and HRMS results substantiated the 1:1 stoichiometry between BTC and Ga3+ ion. The interaction binding mode of BTC with Ga3+ was proposed by HRMS, 1H NMR spectral titration, UV-vis absorption and fluorescence spectral measurements. The combination of the restraint of the photo-induced electron transfer (PET) process and the chelation enhanced fluorescence (CHEF) process is responsible for the fluorescence enhancement of this probe. The in situ chelated BTC-Ga3+ could further monitor pyrophosphate ion (PPi) by demetallization process with quenching fluorescence emission. Additionally, the BTC and BTC-Ga3+ showed good cell permeability and could detect Ga3+ and PPi ions in onioninner epidermal cells, respectively.

A near-infrared fluorescent probe based on the hemicyanine skeleton for the detection of hydrogen peroxide in vivo.

As a member of the reactive oxygen species, hydrogen peroxide (H2O2) plays critical roles in oxidative stress and cell signaling. Intracellular abnormal levels of H2O2 production are closely related to many diseases. Therefore, the real-time monitoring of H2O2 in the cells is important. In this work, we designed a novel fluorescent probe (Mito-H2O2) for the specific detection of H2O2 based on the hemicyanine skeleton, with bright near-infrared fluorescence emission. Mito-H2O2 displayed fast response, excellent water-solubility and great fluorescence intensity enhancement after the addition of H2O2. Furthermore, Mito-H2O2 has been successfully applied to image both of the exogenous and endogenous H2O2 in cells and mice with negligible cytotoxity.

A 'sandwich' structure for highly sensitive detection of TNT based on surface-enhanced Raman scattering.

Ultra-sensitive detection of 2,4,6-trinitrotoluene (TNT) plays an important role in society security and human health. The Raman probe molecule p-aminothiophenol (PATP) can interact with TNT in three ways to form a TNT-PATP complex. In this paper, a 'sandwich' structure was developed to detect TNT with high sensitivity. Au nano-pillar arrays (AuNPAs) substrates modified by low-concentration PATP through Au-S bonds were acted as capture probe for TNT. Meanwhile, Ag nano-particles (AgNPs) modified by PATP at higher concentration were employed as tags for surface-enhanced Raman scattering (SERS). The formation of the TNT-PATP complex is not only the means by which AuNPAs substrates recognize and capture TNT, but also links the SERS tags to TNT, forming an AuNPAs-TNT-AgNPs 'sandwich' structure. The Raman signal of PATP was greatly enhanced mainly because novel 'hot spots' formed between the AuNPAs and AgNPs of the 'sandwich' structure. The Raman signal of PATP was further amplified by the chemical enhancement effect induced by the TNT-PATP complex formation. Based on this mechanism, the limit of detection (LOD) of TNT was determined from the Raman signal of PATP. The LOD reached 10-9 mg/mL (4.4 × 10-12 M), much lower than that suggested by the US Environmental Protection Agency (88 nM). Moreover, TNT was selectively detected over several TNT analogues 2,4-dinitrotoluene (DNT), p-nitrotoluene (NT) and hexogen (RDX). Finally, the 'sandwich' structure was successfully applied to TNT detection in environmental water and sand.

Cell membrane camouflaged cerium oxide nanocubes for targeting enhanced tumor-selective therapy.

Anticancer therapies with profound efficacy but negligible toxicity are a fundamental pursuit that has been made humanly possible through either targeting or tumor-selective therapeutic (TST) approaches. Herein, we developed a targeting-enhanced tumor-selective cancer therapy aimed at integrating the two approaches by preparing cerium oxide (CeO2) nanocubes with glucose oxidase (GOx) modified on the cube surface and cancer cell membrane (CCM) camouflaged outside. The immune escape and homotypic binding of camouflaged CCM enable targeted delivery of the resultant CeO2-GOx@CCM nanoparticles mostly into cancer tissue, while its acidic environment (pH < 6.6) activated a cascade reaction, in which the glucose was first catalyzed by GOx into H2O2 and then by CeO2 into highly cytotoxic ˙OH killing cancer cells. In the case of off-targeting, when very few CeO2-GOx@CCM nanoparticles were accidentally delivered into normal tissue, its neutral pH environment (pH = 7.4) triggered a protective reaction, in which the H2O2 generated was catalyzed by CeO2 into non-toxic H2O and O2. Both in vitro and in vivo results demonstrated that this targeting-enhanced TST achieved the most remarkable antitumor performance with negligible toxic side effects.

A fast and versatile cross-linking strategy via o-phthalaldehyde condensation for mechanically strengthened and functional hydrogels.

Fast and catalyst-free cross-linking strategy is of great significance for construction of covalently cross-linked hydrogels. Here, we report the condensation reaction between o-phthalaldehyde (OPA) and N-nucleophiles (primary amine, hydrazide and aminooxy) for hydrogel formation for the first time. When four-arm poly(ethylene glycol) (4aPEG) capped with OPA was mixed with various N-nucleophile-terminated 4aPEG as building blocks, hydrogels were formed with superfast gelation rate, higher mechanical strength and markedly lower critical gelation concentrations, compared to benzaldehyde-based counterparts. Small molecule model reactions indicate the key to these cross-links is the fast formation of heterocycle phthalimidine product or isoindole (bis)hemiaminal intermediates, depending on the N-nucleophiles. The second-order rate constant for the formation of phthalimidine linkage (4.3 M-1 s-1) is over 3000 times and 200 times higher than those for acylhydrazone and oxime formation from benzaldehyde, respectively, and comparable to many cycloaddition click reactions. Based on the versatile OPA chemistry, various hydrogels can be readily prepared from naturally derived polysaccharides, proteins or synthetic polymers without complicated chemical modification. Moreover, biofunctionality is facilely imparted to the hydrogels by introducing amine-bearing peptides via the reaction between OPA and amino group.

A Domain-Guided Noise-Optimization-Based Inversion Method for Facial Image Manipulation.

A style-based architecture (StyleGAN2) yields outstanding results in data-driven unconditional generative image modeling. This work proposes a Domain-guided Noise-optimization-based Inversion (DNI) method to perform facial image manipulation. It works based on an inverse code that includes: 1) a novel domain-guided encoder called Image2latent to project the image to StyleGAN2 latent space, which can reconstruct an input image with high-quality and maintain its semantic meaning well; 2) a noise optimization mechanism in which a set of noise vectors are used to capture the high-frequency details such as image edges, further improving image reconstruction quality; and 3) a mask for seamless image fusion and local style migration. We further propose a novel semantic alignment evaluation pipeline. It evaluates the semantic alignment with an inverse code by using different attribute boundaries. Extensive qualitative and quantitative comparisons show that DNI can capture rich semantic information and achieve a satisfactory image reconstruction. It can realize a variety of facial image manipulation tasks and outperform state of the art.

A hydrazone-based spectroscopic off-on probe for sensing of basic arginine and lysine.

A simple probe BHN based on naphthol and benzothiazole is reported for detecting of arginine (Arg) and lysine (Lys) with high selectivity and sensitivity. The BHN in aqueous solution upon reacting with Arg or Lys induced a visible color change from colorless to yellow. The probe BHN can also be employed for fluorescence turn-on sensing of Arg and Lys with the limits of detection (LOD) of 5.20 × 10-2 µM and 3.69 × 10-2 µM, respectively. The naked eye colorimetric and fluorimetric detecting is lack of sensitive to other common amino acids including Gly, Ala, Ser, Pro, Val, Thr, Cys, Leu, Ile, Asn, Asp, Glu, Gln, Met, His, and Phe. The sensing mechanism has been proposed by pH investigation and 1H NMR spectra.

Derivation of a human induced pluripotent stem cell (hiPSC) line (PUMCSMi001-A) from peripheral blood mononuclear cells of one healthy female donor.

Human induced pluripotent stem cells (hiPSCs) are valuable models for studying the molecular pathogenesis of inherited diseases and key tools for cell therapy. We derived peripheral blood mononuclear cells (PBMCs) isolated from a 30-year-old healthy female donor using integration-free Sendai virus to generate a hiPSC line, PUMCSMi001-A, which can serve as a control for the studies of pathogenesis of cardiovascular disease and drug screening. Quality assessment confirmed that the cell line PUMCSMi001-A expressed pluripotency genes, had normal karyotype and differentiation potential into three layers in vivo.

Fabrication of Ag@Au (core@shell) nanorods as a SERS substrate by the oblique angle deposition process and sputtering technology.

Gold (Au) and silver (Ag) are the main materials exhibiting strong Surface-Enhanced Raman Scattering (SERS) effects. The Ag nano-rods (AgNRs) and Au nano-rods (AuNRs) SERS substrates prepared using the technology of the oblique angle deposition (OAD) process have received considerable attention in recent years because of their rapid preparation process and good repeatability. However, AgNR substrates are unstable due to the low chemical stability of Ag. To overcome these limitations, an Ag@Au core-shell nano-rod (NR) array SERS substrate was fabricated using the OAD process and sputtering technology. Moreover, simulation analysis was performed using finite-difference time-domain calculations to evaluate the enhancement mechanism of the Ag@Au NR array substrate. Based on the simulation results and actual process conditions, the Ag@Au core-shell NR array substrate with the Au shell thickness of 20 nm was studied. To characterize the substrate's SERS performance, 1,2-bis(4-pyridyl)ethylene (BPE) was used as the Raman probe. The limit of detection of BPE could reach 10-12 M. The Ag@Au NR array substrate demonstrated uniformity with an acceptable relative standard deviation. Despite the strong oxidation of the hydrogen peroxide (H2O2) solution, the Ag@Au NR array substrate maintains good chemical stability and SERS performance. And long-term stability of the Ag@Au NR substrate was observed over 8 months of storage time. Our results show the successful preparation of a highly sensitive, repeatable and stable substrate. Furthermore, this substrate proves great potential in the field of biochemical sensing.

Rapid and selective visualization of mitochondrial hypochlorite by a red region water-soluble fluorescence probe.

Hypochlorite (-OCl) has long been recognized as an effective microbicidal agent in immune system. Herein, we report the design, preparation and spectral characteristics of a -OCl fluorescent probe (FI-Mito). The probe exhibited remarkable fluorescence turn-on signal in the red region upon -OCl titration with the detection limit as low as 0.9 nM. FI-Mito displayed specific response for -OCl in completely aqueous solution. Meanwhile, the introduction of quaternized pyridine realized mitochondria-targeting ability. FI-Mito was further applied to monitor the generation of endogenous -OCl in the mitochondria of macrophage cells and mice. Therefore, it was established that FI-Mito may serve as a useful molecular tool for -OCl detection in vivo.

Selective sensing of PPi by fluorogenic Al(III)-probe complex in aqueous medium.

A newly designed Schiff base probe JN has been synthesized. It is highly selective and sensitive towards Al3+ in nearly 100% aqueous medium by exhibiting a dramatic "turn-on" fluorescence response at 495 nm (λex = 450 nm). The sensing mechanism of JN towards Al3+ ions was proposed as the combination of PET, ICT, ESIPT, and CHEF processes according to spectra studies and theory calculations. The in situ generated mononuclear Al(III) complex JN-Al3+ could sequentially detect PPi ions by turn-off fluorescence response. The selectivity and sensitivity of the JN-Al3+ complex towards PPi ions are based on demetalization process. Interestingly, the fact that Al3+ can bind with 1, 2, or 3 PPi has been revealed by HRMS study. The probes JN and JN-Al3+ complexes were able to capture Al3+ and PPi ions, respectively, as demonstrated by fluorescence imaging of the adult zebrafish and onion inner epidermal cells samples.

Selective monitoring ATP using a fluorogenic Al(III)-probe complex in aqueous medium.

A simple commercially available probe 8-hydroxyjulolidine-9-aldehyde (HJ) has been developed as a turn-on fluorescent probe specifically for Al3+ and characterized systemically. The probe HJ for Al3+ ion exhibits strong green fluorescence under ultraviolet light. The HJ acted as an OFF-ON-OFF type fluorescent probe for Al3+ and ATP in nearly 100% aqueous media. The 1:1 binding stoichiometry between probe and Al3+ has been established from Job's plot and HRMS studies. The limit of detection for Al3+ ion is found to be 5.75 × 10-8 M. The large association constant between HJ and Al3+ ion is 1.05 × 105 M-1. Detailed insights of probe-metal interaction mechanisms have been studied by the density functional theory (DFT) as well as the time dependent-DFT (TDDFT) calculations. Moreover, benefiting from the water solubility and biocompatibility of the probe HJ and its HJ-Al3+ complex, they have also been successfully applied to detect Al3+ and ATP by bioimaging in onion epidermal cells and adult zebrafish respectively.

A near-infrared rhodamine-based lysosomal pH probe and its application in lysosomal pH rise during heat shock.

Heat shock is a potentially fatal condition characterized by high body temperature (>40 °C), which may lead to physical discomfort and dysfunctions of organ systems. Acidic pH environment in lysosomes can activate enzymes, thus facilitating the degradation of proteins in cellular metabolism. Owing to the lack of a practical research tool, it remains difficult to exploit relationship between heat shock and lysosome. Herein, a NIR lysosomal pH chemosensor (NRLH) was developed. One typical lysosome-locating group, morpholine, was incorporated into NRLH. The fluorescence intensity showed pH-dependent characteristics and responded sensitively to pH fluctuations in the pH range of 3.0-5.5. NRLH with a pKa of 4.24 displayed rapid response and high selectivity for H+ among common species. We also demonstrated NRLH was capable of targeting lysosomes. Importantly, NRLH was applied in cellular imaging and the data revealed that lysosomal pH increased but never decreased during the heat shock. Therefore, NRLH may act as an effective molecular tool for exploring the mechanisms of heat-related pathology in bio-systems.

Fabrication of Au Nanorods by the Oblique Angle Deposition Process for Trace Detection of Methamphetamine with Surface-Enhanced Raman Scattering.

Oblique angle deposition (OAD) is a simple, low cost, effective, and maskless nanofabrication process. It can offer a reliable method for the mass fabrication of uniform metal nanorods which can be used as the surface-enhanced Raman scattering (SERS) substrate with an excellent enhancing performance. Up to now, Ag nanorods SERS substrates have been extensively studied. However, Ag is chemically active and easy to oxidize under atmospheric conditions. Comparatively, Au is chemically stable and has better biocompatibility than Ag. In this paper, we in detail, studied the electromechanical (EM) field distribution simulation, fabrication, and application of Au nanorods (AuNRs) on trace detection of methamphetamine. According to the finite-difference time-domain (FDTD) calculation results, the maximum EM intensity can be obtained with the length of AuNRs to be 800 nm and the tilting angle of AuNRs to be 71° respectively. The aligned Au nanorod array substrate was fabricated by the OAD process. The two key process parameters, deposition angle, and deposition rate were optimized by experiments, which were 86° and 2 Å/s, respectively. Using 1,2-bis (4-pyridyl) ethylene (BPE) as the probe molecule, the limit of detection (LOD) was characterized to be 10-11 M. The AuNRs were also used to detect methamphetamine. The LOD can be down to M (i.e., 14.92 pg/ml), which meet the requirements of the on-site rapid detection of the methamphetamine in human urine (500 ng/ml).

Enhancement of ultralow-intensity NIR light-triggered photodynamic therapy based on exo- and endogenous synergistic effects through combined glutathione-depletion chemotherapy.

Although photodynamic therapy (PDT), which uses a photosensitizer (PS) to generate toxic reactive oxygen species (ROS) upon laser irradiation to kill cancer cells, has been widely applied, the relatively high laser intensity required causes photodamage to healthy neighboring cells and limits its success. Furthermore, glutathione (GSH, an antioxidant) is overexpressed in cancer cells, which can scavenge the generated ROS, thus lowering PDT efficacy. Herein, ultralow-intensity near-infrared (NIR) light-triggered PDT was developed and enhanced through combined GSH-depletion chemotherapy (Chemo) based on exo- and endogenous synergistic effects. Highly emissive upconversion nanoparticles (UCNPs) were prepared and coated with a solid silica shell, which was used to encapsulate the PS rose bengal and bond the drug camptothecin with a disulfide-bond linker. The combination of highly emissive UCNPs and a matchable PS with an optimized loading dosage enabled ROS to be generated for PDT even upon 808 nm laser irradiation with ultralow intensity (0.30 W cm-2). According to the American National Standard, this laser intensity is below the maximum permissible exposure of skin (MPE, 0.33 W cm-2). Once the prepared nanoparticles endocytosed and encountered intracellular GSH, the disulfide-bond linker was cleaved by GSH, leading to drug release and GSH depletion. PDT was therefore simultaneously enhanced through the exogenous synergic effect of Chemo (namely, the "1 + 1 > 2" therapeutic effect) and the endogenous synergic effect as a result of GSH depletion. It was proven both in vitro and in vivo that this novel dual-synergistic Chemo/PDT system exhibits remarkable therapeutic efficacy with minimal photodamage to healthy neighboring cells.