Inactivation activity and mechanism of pulsed light against Alicyclobacillus acidoterrestris vegetative cells and spores in concentrated apple juice.

Alicyclobacillus acidoterrestris has received much attention due to its unique thermo-acidophilic property and implication in the spoilage of pasteurized juices. The objective of this study was to evaluate the sterilization characteristics and mechanisms of pulsed light (PL) against A. acidoterrestris vegetative cells and spores in apple juice. The results indicated that bacteria cells in apple juice (8-20°Brix) can be completely inactivated within the fluence range of 20.25-47.25 J/cm2, which mainly depended on the soluble solids content (SSC) of juice, and the spores in apple juice (12°Brix) can be completely inactivated by PL with the fluence of 54.00 J/cm2. The PL treatment can significantly increase the leakage of reactive oxygen species (ROS) and proteins from cells and spores. Fluorescence studies of bacterial adenosine triphosphate (ATP) indicated that the loss of ATP was evident. Scanning electron microscopy and confocal laser scanning microscope presented that PL-treated cells or spores had serious morphological damage, which reduced the integrity of cell membrane and led to intracellular electrolyte leakage. In addition, there were no significant negative effects on total sugars, total acids, total phenols, pH value, SSC and soluble sugars, and organic acid content decreased slightly during the PL treatment. The contents of esters and acids in aroma components had a certain loss, while that of alcohols, aldehydes and ketones were increased. These results demonstrated that PL treatment can effectively inactivate the bacteria cells and spores in apple juice with little effect on its quality. This study provides an efficient method for the inactivation of A. acidoterrestris in fruit juice.

Target-Induced AIE Effect Coupled with CRISPR/Cas12a System Dual-Signal Biosensing for the Ultrasensitive Detection of Gliotoxin.

Here, a novel rapid and ultrasensitive aptamer biosensor was designed for target-induced activation of AIE effect and followed by the activation of Crispr Cas12a (LbCpf1)-mediated cleavage to achieve dual-signal detection. The prepared DNA building blocks contain the target aptamer, ssDNA-Fc, and Activator1. In this system, the activation mode was divided into two steps. First, when the target interacts with the aptamers, the DNA building blocks would be disintegrated rapidly, releasing a mass of Ac1, generating ETTC-dsDNA aggregated to produce a fluorescence signal by the AIE effect. Second, with the release of Ac2, LbCpf1-crRNA was activated, which greatly improves the ssDNA-Fc cleavage efficiency to render signal amplification and ultrasensitive detection of the target. Satisfactorily, using this approach to detect gliotoxin, optimal conditions for detection was achieved for reducing the detection time to 55 min, achieving a low detection limit of 2.4 fM and a satisfactory linear in the range of 50 fM to 1 nM, which addressed the shortcoming of a weak electrochemical signal in previous sensors. The water-insoluble AIE material was coupled with DNA to obtain water-soluble ETTC-dsDNA and successfully introduced into the sensor system, with a low detection limit of 5.6 fM. Subsequently, the biosensor combined with handheld electrochemical workstation was successfully applied in the detection of gliotoxin in five actual samples, with a detection range of 32.0 to 2.09 × 108 pM. This strategy not only provides a novel and effective detection platform for mycotoxins in complex food matrices but also opens a promising avenue for various molecules detection in imaging and disease diagnosis.

Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4+CD25+Foxp3+ Tregs-mediated gut microbiome of non-obese mice.

Osteoporosis is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. High-fat diet (HFD)-induced obesity also results in bone loss, which is associated with an imbalanced gut microbiome. However, whether HFD-induced obesity or HFD itself promotes osteoclastogenesis and consequent bone loss remains unclear. In this study, we developed HFD-induced obesity (HIO) and non-obesity (NO) mouse models to evaluate the effect of HFD on bone loss. NO mice were defined as body weight within 5% of higher or lower than that of chow diet fed mice after 10 weeks HFD feeding. NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number. This led to increased bone strength and improved bone microstructure via the microbiome-short-chain fatty acids (SCFAs) regulation. Additionally, endogenous gut-SCFAs produced by the NO mice activated free fatty acid receptor 2 and inhibited histone deacetylases, resulting in the promotion of Treg cell proliferation in the HFD-fed NO mice; thereby, inhibiting osteoclastogenesis, which can be transplanted by fecal microbiome. Furthermore, T cells from NO mice retain differentiation of osteoclast precursors of RAW 264.7 macrophages ex vivo. Our data reveal that HFD is not a deleterious diet; however, the induction of obesity serves as a key trigger of bone loss that can be blocked by a NO mouse-specific gut microbiome.

Au Nanoparticles Functionalized Covalent-Organic-Framework-Based Electrochemical Sensor for Sensitive Detection of Ractopamine.

Ractopamine, as a feed additive, has attracted much attention due to its excessive use, leading to the damage of the human nervous system and physiological function. Therefore, it is of great practical significance to establish a rapid and effective method for the detection of ractopamine in food. Electrochemical sensors served as a promising technique for efficiently sensing food contaminants due to their low cost, sensitive response and simple operation. In this study, an electrochemical sensor for ractopamine detection based on Au nanoparticles functionalized covalent organic frameworks (AuNPs@COFs) was constructed. The AuNPs@COF nanocomposite was synthesized by in situ reduction and was characterized by FTIR spectroscopy, transmission electron microscope and electrochemical methods. The electrochemical sensing performance of AuNPs@COF-modified glassy carbon electrode for ractopamine was investigated using the electrochemical method. The proposed sensor exhibited excellent sensing abilities towards ractopamine and was used for the detection of ractopamine in meat samples. The results showed that this method has high sensitivity and good reliability for the detection of ractopamine. The linear range was 1.2-1600 µmol/L, and the limit of detection (LOD) was 0.12 µmol/L. It is expected that the proposed AuNPs@COF nanocomposites hold great promise for food safety sensing and should be extended for application in other related fields.

A Dual-Signaling Electrochemical Aptasensor Based on an In-Plane Gold Nanoparticles-Black Phosphorus Heterostructure for the Sensitive Detection of Patulin.

Patulin (PAT), a type of mycotoxin existing in foodstuffs, is harmful to food safety and human health. Thus, it is necessary to develop sensitive, selective and reliable analytical methods for PAT detection. In this study, a sensitive aptasensor based on a dual-signaling strategy was fabricated, in which a methylene-blue-labeled aptamer and ferrocene monocarboxylic acid in the electrolyte acted as a dual signal, for monitoring PAT. To improve the sensitivity of the aptasensor, an in-plane gold nanoparticles-black phosphorus heterostructure (AuNPs-BPNS) was synthesized for signal amplification. Due to the combination of AuNPs-BPNS nanocomposites and the dual-signaling strategy, the proposed aptasensor has a good analytical performance for PAT detection with the broad linear range of 0.1 nM-100.0 µM and the low detection limit of 0.043 nM. Moreover, the aptasensor was successfully employed for real sample detection, such as apple, pear and tomato. It is expected that BPNS-based nanomaterials hold great promise for developing novel aptasensors and may provide a sensing platform for food safety monitoring.

Label-free fluorescence aptasensor for the detection of patulin using target-induced DNA gates and TCPP/BDC-NH2 mixed ligands functionalized Zr-MOF systems.

Patulin (PAT) is an unsaturated lactone mycotoxin primarily produced by Penicillium expansum and Aspergillus clavatus. Given the potential health risks and economic losses associated with PAT, the rapid detection of PAT using fluorescent aptasensors is of significant importance in evaluating food safety. However, it easily increases the cost and complexity caused by signal labeling. We combined TCPP/BDC-NH2 mixed ligands functionalized Zr metal-organic frameworks (Zr-MOFmix) and terminated three-stranded DNA gates (ttsDNA gates) to fabricate a label-free fluorescent aptasensor for PAT detection. The Zr-MOFmix system was synthesized via a one-pot strategy and could be used to address the problem of pore size limitation and increase the loading amounts of dyes. TtsDNA gate was integrated into the Zr-MOFmix system to control the release of dyes, exhibiting a high signal-to-background ratio. The single-stranded aptamer region in ttsDNA gate situated away from the surface of the Zr-MOFmix, resulting in a natural release of dyes in the absence of PAT. While binding to PAT resulted in target-induced conformational changes that helped form the hairpin structure of the aptamer. This structure hindered the release of dyes from the pores of Zr-MOFmix, thus reducing the fluorescence signals intensity. The stimuli-responsive DNA-gated material provides a platform for PAT analysis under conditions of a low limit of detection (0.871 pg/mL). Furthermore, the excellent specificity and anti-interference of the fluorescent aptasensor make the system suitable for the analysis of apple juice samples. This label-free strategy is cheaper and simper compared with labeled detection, especially for the development of multi-target-detection.

Metagenomic analysis of microflora structure and functional capacity in probiotic Tibetan kefir grains.

Tibetan kefir grains (TKGs) are distinctive and complex mixtures with protein-lipid-polysaccharide matrices and multiple microorganism species. The objective of this study was to evaluate the microflora composition, probiotic species and functional genes within TKGs. Metagenomic analysis was used to evaluate communities of three TKGs, revealing the presence of 715 species, with Lactobacillus kefiranofaciens as the most dominant species. The relative abundances of acetic acid bacteria and yeast significantly differed among the three TKGs (acetic acid bacteria: p < 0.01; yeast: p < 0.05), and the dominant yeast species also varied across three TKGs. Lactobacillus helveticus was the most abundant listed probiotic species, and its abundance did not significantly differ across three TKGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ko01501 was the most abundant pathway that related to human disease. There are 16 different KOs (KEGG Orthology) in the ko01501 pathway were annotated in TKGs, which helps to resist ß-lactam. This study provided a new insight into the microbial community structures and the presence of probiotic species within TKGs and provides a foundation for further targeted studies.

Inhibitory effects of lactobionic acid on Vibrio parahaemolyticus planktonic cells and biofilms.

Vibrio parahaemolyticus is the primary pathogenic bacteria associated with seafood-borne illnesses. Lactobionic acid (LBA) is an organic acid with multiple biological activities that has recently been a focus of interest as an antibacterial agent. The aim of this study was to investigate the inhibitory effects of LBA on Vibrio parahaemolyticus planktonic cells and biofilms. The minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of LBA against Vibrio parahaemolyticus were both identified as 4 mg/mL. LBA exerted antimicrobial effects against planktonic Vibrio parahaemolyticus cells by damaging their membranes, as revealed by reduced intracellular ATP concentrations, increased protein leakage, abnormal cell morphology and diminished membrane integrity after treatment. At 1/16 × MIC and 1/8 × MIC, LBA inhibited biofilm formation and downregulated the expression of some biofilm-related genes, which was confirmed by crystal violet staining, field-emission scanning electron microscopy (FESEM) observations, and real-time quantitative PCR analysis. Moreover, LBA inactivated Vibrio parahaemolyticus cells within biofilms (on polystyrene and stainless steel surfaces), destroyed biofilm structures on stainless steel surfaces, and also reduced the levels of polysaccharides and proteins in the biofilms. Therefore, LBA is a potential low-cost agent that can be used to control planktonic Vibrio parahaemolyticus and its biofilms.

Comparative Metagenomics Reveals Microbial Communities and Their Associated Functions in Two Types of Fuzhuan Brick Tea.

Fuzhuan brick tea (FBT) is a unique post-fermented tea product, naturally co-fermented by microorganisms, and has gained global popularity due to its potential health benefits for humans. Considerable efforts have been made toward elucidating the microbial diversity within FBT, but an understanding of the underlying FBT community interactions and functions remains poorly studied. Consequently, the microbial communities of two types of FBT, originating from Hunan and Shaanxi provinces, were investigated using comparative shotgun metagenomic sequencing and functional annotations. Metagenomic analysis indicated that two communities shared similar taxonomic and functional attributes. Two samples shared 486 genera, in which Pseudomonas contributed most to the abundant functions within the two samples. The carbohydrate active enzyme functions of the communities primarily comprised GH (32.92%), GT (26.8%), CEs (20.43%), and AAs (18.04%). Furthermore, the overall metabolic pathways encoded by the metagenomes were largely associated with carbohydrate and amino acid metabolism, with nine metabolic pathways that were differential between two groups including penicillin and cephalosporin biosynthesis. Significantly, a total of 35 potential probiotics were inferred, with Pseudomonas putida being the most abundant inferred probiotic (80%) within the FBT communities. This study provides new insights into FBT microbial communities on their potential functions and roles in FBT characteristics.

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis.

Background: Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. Methods: To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Gemcitabine (GEM), a first-line chemotherapeutic drug against PDAC, was loaded in 6PA-modified DGL (PDGL) nanoparticles to afford PDGL-GEM. Then PDGL-GEM was co-precipitated with the autophagy inhibitor chloroquine phosphate (CQ) and calcium phosphate to formulate PDGL-GEM@CAP/CQ. The size and morphology of the resulting "nanobomb" PDGL-GEM@CAP/CQ were characterized, and their uptake into cells, cytotoxicity and ability to inhibit autophagy were analyzed at pH 6.5 and 7.4. The anti-tumor and anti-metastasis effects of the nanobomb were explored on mice carrying Pan 02 pancreatic tumor xenografts or orthotopic tumors. Results: The pH-induced dissolution of calcium phosphate facilitated the release of CQ from the nanobomb and deep penetration of PDGL-GEM. The internalization of PDGL-GEM and subsequent intracellular release of GEM inhibited tumor growth, while CQ downregulated autophagy in tumor cells and fibroblasts. In fact, inhibition of xenograft and orthotopic tumor growth was greater with the complete PDGL-GEM@CAP/CQ than with subassemblies lacking GEM or CQ. More importantly, mechanistic studies in vitro and in vivo suggested that the nanobomb inhibits metastasis by downregulating MMP-2 and paxillin, as well as reducing fibrosis. Conclusion: The pH-sensitive PDGL-GEM@CAP/CQ shows potential for inhibiting proliferation and metastasis of pancreatic cancer through an autophagy-dependent pathway.

Comprehensively enhanced delivery cascade by transformable beaded nanofibrils for pancreatic cancer therapy.

Facing the barriers in each step of the in vivo delivery cascade, the low drug delivery efficiency remains problematic in tumor therapy. Although recently the nanofibril drug delivery systems have shown improved circulation and accumulation compared with nanoparticles, the poor deep penetration and cellular internalization hinder their application, especially for pancreatic cancer with dense stroma. To comprehensively address the hurdles in the delivery cascade, a matrix metalloproteinase 2 (MMP-2) responsive transformable beaded nanofibril, which integrates the merits of nanofibril and small-sized nanoparticles, is established. The beaded nanofibril (GD@PPF) is prepared by conjugating gemcitabine-loaded small-sized nanoparticles (GD) with fibrous PEG-PCL (PPF) via GPLGVRG, a substrate peptide of MMP-2. GD@PPF escapes the clearance of the reticuloendothelial system (RES), prolongs the circulation time, and increases the selective accumulation in the tumor as fibrous micelles. Once accumulated in the tumor, small positively-charged GD is released from the beaded nanofibrils in response to MMP-2 overexpression in the stroma of pancreatic cancer, enabling permeation in the dense tumor matrix and cellular internalization, which makes up for the shortcomings of fibrous micelles. Furthermore, the remaining fibrous PPF surround the tumor tightly to impede the efflux of drugs, leading to improved retention. GD@PPF is biocompatible and exhibits excellent antitumor effect in Pan 02 subcutaneous tumor models. Therefore, the MMP-2 responsive transformable beaded nanofibril, which enhances the delivery efficiency in multiple stage of the delivery cascade, presents a promising strategy for pancreatic cancer therapy.

Self-promoted Albumin-Based Nanoparticles for Combination Therapy against Metastatic Breast Cancer via a Hyperthermia-Induced "Platelet Bridge".

It has been a great challenge to simultaneously inhibit the outgrowth of both the primary tumor and metastasis in metastatic cancer treatment. Substantial studies have evidenced that the interaction of platelets and cancer cells supports tumor metastasis, and platelets are considered to have metastasis-targeting property. Inspired by injury-targeting and metastasis-targeting properties of platelets, we constructed a photothermal therapy strategy with activated platelet-targeting albumin-based nanoparticles, PSN-HSA-PTX-IR780, to amplify drug delivery in the primary tumor at mild temperatures and simultaneously inhibit metastasis via a "platelet bridge". Human serum albumin (HSA) was premodified with a P-selectin-targeting peptide (PSN peptide) or IR780 serving as a photosensitizer. Hybrid albumin nanoparticles were assembled via the disulfide reprogramming method and encapsulated paclitaxel (PTX) to formulate PSN-HSA-PTX-IR780. The PSN-modified albumin nanoparticles could bind with upregulated P-selectin on activated platelets and subsequently target cancer cells by using platelets as a "bridge". In addition, nanoparticle-generated hyperthermia induced tissue injury and increased tumor-infiltrating platelets, thereby recruiting more nanoparticles into the tumor in a self-promoted way. In vivo studies showed that the drug accumulation of PSN-HSA-PTX-IR780 was 2.86-fold higher than that of HSA-PTX-IR780 at the optimal temperature (45 °C), which consequently improved the therapeutic outcome. Moreover, PSN-HSA-PTX-IR780 also effectively targets and inhibits lung metastasis by binding with metastasis-infiltrating platelets. Altogether, the self-promoted nanoplatform provides a unique and promising strategy for metastatic cancer treatment with enhanced drug delivery efficacy.

Quantitative analysis of polycyclic aromatic hydrocarbons in soil by infrared spectroscopy combined with hybrid variable selection strategy and partial least squares.

Infrared spectroscopy (IR) combined with multivariate calibration technology can be used as a potential method to quantitative analysis of polycyclic aromatic hydrocarbons (PAHs) in soil, which provides a rapid data support for soil risk assessment. However, IR spectrum contains lots of useless information, its predictive performance is poor. Variable selection is an effective strategy to eliminate irrelevant wavelengths and enhance predictive performance. In this study, IR combined with partial least squares (PLS) was proposed to quantify anthracene and fluoranthene in soil. In order to improve the predictive performance of the PLS calibration model, the synergy interval PLS (siPLS) method was first used for "rough selection" to select feature bands; on this basis, "fine selection" was performed to extract the feature variables. In "fine selection", three different feature variables selection methods, such as successive projection algorithm (SPA), genetic algorithm (GA), and particle swarm optimization (PSO), were compared for their performance in extracting effective variables. The results show that the siPLS-GA calibration model receive a lowest root mean square error (RMSE) and a largest determination coefficient (R2). Results of external validation demonstrate an excellent predictive performance of siPLS-GA calibration model, with the R2 = 0.9830, RMSE = 0.5897 mg/g and R2 = 0.9849, RMSE = 0.4739 mg/g for anthracene and fluoranthene, respectively. In summary, siPLS combined with GA can accurately extract the effective information of the target substance and improve the predictive performance of the PLS calibration model based on IR spectroscopy.

A Non-enzymatic Hydrogen Peroxide Sensor with Enhanced Sensitivity Based on Pt Nanoparticles.

The non-enzymatic electrochemical sensing platform for hydrogen peroxide by using Pt-based nanoparticle was investigated. The characterization of PtNiCo-NPs was done by XRD, TEM, HRTEM, EDS, and XPS. A simple drop-casting technique was used to fabricate the nanomaterial on FTO electrode. The amperometric and cyclic voltammetric results illustrated that PtNiCo-NPs on FTO had excellent electrochemical performance over other mono or bimetallic materials. The catalytic performance for H2O2 sensing based on PtNiCo-NPs possessed a wide linear range from 5 µM to 16.5 mM with a low detection limit of 0.37 µM and a good sensitivity of 1374.4 µA mM-1 cm-2 at a scan rate of 20 mV s-1 (vs. Ag/AgCl). This work presents a new way to produce a ternary nanomaterial for H2O2 sensing with excellent electrochemical performance. In addition, the fabricated nanomaterial showed no interferences for common interfering agents, which indicates the high specificity of the sensor. The PtNiCo-NPs have excellent stability and good reproducibility in real samples.

Simultaneous electrochemical aptasensing of patulin and ochratoxin A in apple juice based on gold nanoparticles decorated black phosphorus nanomaterial.

Simultaneous detection of patulin (PAT) and ochratoxin A (OTA) in food products is in great demand, which can prevent toxins from being exposed to human and animal bodies. However, simultaneous detection of multiple targets still faces a challenge. Herein, we developed a novel electrochemical aptasensor for the simultaneous detection of PAT and OTA in apple juice based on gold nanoparticles decorated black phosphorus (AuNPs-BP) nanomaterial. AuNPs-BP function?/work? as a sensing platform for loading much different electrochemical signal molecules functionalized aptamers. In this context, methylene blue functionalized PAT aptamers (Mb-PAT-aptamers) and ferrocene functionalized OTA aptamers (Fc-OTA-aptamers) have been introduced here to fabricate the aptasensor. Fc close to electrode surface showed a strong signal, whereas Mb was far away from electrode surface so exhibited a weak signal in the absence of OTA and PAT. Two kinds of electrochemical signal changes have been recorded dependent on target of OTA and PAT concentrations. So, simultaneous detection of OTA and PAT is achieved. Under the optimum conditions, using this developed biosensor, PAT and OTA can be quantified at a linearity range of 0.01 × 10-7 µg·mL-1 ~ 0.10 µg·mL-1. In addition, it also has good selectivity, stability and repeatability. For the practical application, it shows promising performance for the simultaneous detection of PAT and OTA in apple juice.

DNA walker-assisted aptasensor for highly sensitive determination of Ochratoxin A.

Ochratoxin A (OTA), a toxic secondary metabolite produced via various fungus, poses a serious threat to the health of human beings and animals. In this paper, an aptasensor for OTA detection based on gold nanoparticles decorated molybdenum oxide (AuNPs-MoOx) nanocomposites, hybridization chain reaction (HCR) and a restriction endonuclease (Nb.BbvCI)-aided walker DNA machine was successfully constructed. In this electrochemical platform, the HCR was also used to embed more electrical signal molecules of methylene blue (MB) on silver nanoparticles (AgNPs) to achieve signal amplification. Under the optimum conditions, after adding OTA and Nb.BbvCI in turn and responding adequately under appropriate conditions, aptamer-DNA (6-DNA) carries the OTA away from the electrode surface, and walker DNA was hybridized autonomously with 5-DNA, releasing a large amount of 5'-DNA with the help of Nb.BBVCI. Finally, the electrochemical signal obtained by differential pulse voltammetry (DPV) was weakened. As an artificial and popular signal amplification technique, the DNA walking machine greatly improved the sensitivity. The proposed biosensor exhibited excellent analytical performance in the range of 0.01-10000 pg mL-1 with a detection limit as low as 3.3 fg mL-1. Furthermore, direct comparison with ultraperformance liquid chromatography (UPLC) indicates excellent agreement to actual samples such as apple juice, orange juice, red wine and serum.

A hybrid of ultrathin metal-organic framework sheet and ultrasmall copper nanoparticles for detection of hydrogen peroxide with enhanced activity.

Here, we design and synthesize a novel 2D Cu-tetrakis(4-carboxyphenyl)porphyrin (TCPP) metal-organic framework (MOF) sheet and ultrasmall Cu5.4O nanoparticle (Cu5.4O USNP) hybrid (Cu-TCPP MOF/Cu5.4O nanocomposite). The graphene-like ultrathin Cu-TCPP MOF sheets offer high surface-to-volume atom ratios and many active sites, which is beneficial for loading more Cu5.4O USNPs. The Cu5.4O USNPs with ultrasmall size (<5 nm) have promising conductivity and excellent enzymatic ability for H2O2. The successfully prepared nanocomposites are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques. The 2D graphene-like ultrathin Cu-TCPP MOF sheets show no H2O2-sensing signals, whereas Cu5.4O USNPs exhibit a clear reduction peak for detection of H2O2. Interestingly, the combination of two kinds of nanomaterials improved the H2O2 sensing ability due to their synergistic effect. The properties of the unmodified electrodes and the Cu-TCPP MOF/Cu5.4O nanocomposite-modified electrodes were systemically studied by cyclic voltammetry (CV), current-time (i-t) response, and square-wave voltammetry (SWV) techniques. The electrochemical sensor for the detection of H2O2 based on the Cu-TCPP MOF/Cu5.4O nanocomposite has a lower detection limit of 0.13 µmol·L-1 and wider linear range of 0.1 × 10-6 ~ 0.59 × 10-3 mol·L-1 and 1.59 × 10-3 ~ 20.59 × 10-3 mol·L-1 when compared with the Cu5.4O USNPs-modified electrode. The electrochemical sensor can be further used to detect H2O2 produced by cells. Graphical abstract The mechanism for sensing H2O2 produced from cells based on a Cu-TCPP MOF/Cu5.4O USNPs nanocomposite-modified electrode.

Synergistic cytotoxicity and co-autophagy inhibition in pancreatic tumor cells and cancer-associated fibroblasts by dual functional peptide-modified liposomes.

Pancreatic ductal adenocarcinoma (PDA) is a highly fatal disease with 5-year survival of ∼8.5%. Nanoplatforms such as nab-paclitaxel and nanoliposomal irinotecan demonstrate superiority and utility in treating different progressions of PDA by prolonging the median overall survival by only a few months. Due to the dense surrounding stroma and the high autophagy in pancreatic cancer, integrin ɑvß3 targeting, acid environmental sensitive, TR peptide-modified liposomal platforms loaded with combined autophagy inhibiting hydroxychloroquine (HCQ), and cytotoxic paclitaxel (PTX) were designed (TR-PTX/HCQ-Lip) to accomplish the aim of synergistically killing tumor cells while inhibiting stroma fibrosis. The results showed that TR peptide-modified liposomes (TR-Lip) have superior targeting and penetrating effects both in vitro and in vivo. TR-PTX/HCQ-Lip efficiently inhibited autophagy in pancreatic cells and surrounding cancer-associated fibroblasts. The synergistic anti-fibrosis roles were also confirmed both in vitro and in vivo, all of which contributes to the enhanced curative effects of TR-PTX/HCQ-Lip in both heterogenetic and orthotopic pancreatic cancer models. STATEMENT OF SIGNIFICANCE: Autophagy plays a significant role in pancreatic ductal adenocarcinoma, especially in activating cancer associated fibroblasts which is also related to collagen generation that promotes the formation of dense stroma, which hinder the cytotoxic drugs to target and kill cancer cells. In this study, we designed integrin ɑvß3 targeting, acid environmental sensitive liposomal platforms to co-loaded paclitaxel and the autophagy inhibitor hydroxychloroquine. The results showed that the muti-functional liposomes can target to the pancreatic tumor and efficiently kill tumor cells and inhibit stroma fibrosis, thus improve the therapeutic effect in orthotopic pancreatic cancer models.

One-Step Synthesis of Au@Pt-Graphene Nanocomposites and Their Electrochemical Properties.

A nanocomposite of gold@platinum core-shell nanoparticles on reduced graphene oxide (Au@Ptgraphene) was synthesized by a one-step method and further fabricated into a nanohybrid electrode. This approach not only allows for better structural integration of different components on the electrode but also improves the electrochemical properties in terms of the electrocatalytic activity and capacitive performance. As employed in the electrochemical sensor, the Au@Pt-graphene-modified glassy carbon electrode (GCE) has a wide linear range from 0.5 µmol·L-1 to 22.3 mmol·L-1, a detection limit of 0.2 µmol·L-1, high selectivity, good reproducibility and long-term stability towards the nonenzymatic detection of hydrogen peroxide (H2O2). Furthermore, when used as a binder-free electrode in supercapacitors, this electrode exhibits a high specific capacitance of 345 F·g-1 at a current density of 1 A·g-1, and the specific capacitance retention remains at 96% after 1000 times cycles. These merits enable a versatile electrode material for electrochemical applications.

Electrostatic assembly of gold nanoparticles on black phosphorus nanosheets for electrochemical aptasensing of patulin.

An aptamer based impedimetric assay for the mycotoxin patulin (PAT) is described. A glassy carbon electrode (GCE) was modified with black phosphorus nanosheets (BP NSs) and modified with PAT aptamer by electrostatic attraction. Detection is based on the variations of electron transfer resistance at the modified electrode surface. This assay can detect PAT over a linear range that extends from 1.0 nM to 1.0 µM with a 0.3 nM detection limit. To improve the performance of the sensor, the BP NS-GCE was further modified with gold nanoparticles and then with thiolated PAT aptamer. This modified electrode, operated at an applied potential of 0.18 V (vs. Ag/AgCl), has a wider linear range (0.1 nM to 10.0 µM) and a lower detection limits (0.03 nM). Both assays were successfully applied to the analysis of (spiked) genuine food samples. Graphical abstract Black phosphorus nanosheets (BP NSs) were used to fabricate an aptamer based assay for patulin. To further improve the performance of the electrode, gold nanoparticles (AuNP) were placed on the surface of black phosphorus nanosheets (AuNP-BP NSs) by electrostatic attraction for patulin aptasensing.