A colorimetric and electrochemical dual-mode Hg2+ sensor utilizing oxidase-like activity arising from the combination of Hg2+ and palladium metal-organic framework@graphene.

Developing convenient and reliable methods for Hg2+ monitoring is highly important. Some precious metal nanomaterials with intriguing peroxidase-like activity have been used for highly sensitive Hg2+ detection. However, H2O2 must be added during these detections, which impedes practical applications of Hg2+ sensors due to its susceptible decomposition by environmental factors. Herein, we discovered that the combination of Hg2+ and palladium metal-organic framework@graphene (Pd-MOF@GNs) exhibits oxidase-like activity (OXD). In the absence of H2O2, this activity not only catalyzes the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) or o-phenylenediamine (OPD) to produce a color change but also enhances the electrical signals during OPD oxidation. Based on these properties, an effective and convenient dual-mode colorimetric and electrochemical sensor for Hg2+ has been developed. The colorimetric and amperometric linear relationships for Hg2+ were 0.045 µM-0.25 mM and 0.020 µM-2.0 mM, respectively. The proposed strategy shows good recovery in real sample tests, indicating promising prospects for multiple environmental sample detection of Hg2+ without relying on H2O2. The colorimetric and electrochemical dual-mode Hg2+ sensor is expected to hold great potentials in applications such as environmental monitoring, rapid field detection, and integration into smartphone detection of Hg2+.

[Mechanism of IL-17 Signaling Pathway in Spleen Inflammatory Response Induced by Altitude Hypoxia in Mice]. / IL-17ä¿¡å·é€šè·¯åœ¨é«˜åŽŸä½Žæ°§è¯±å¯¼å°é¼ è„¾è„ç‚Žç—‡ååº”çš„ä½œç”¨æœºåˆ¶.

Objective: To explore the mechanism of spleen tissue inflammatory response induced by altitude hypoxia in mice. Methods: C57BL/6 mice were randomly assigned to a plain, i.e., low-altitude, normoxia group and an altitude hypoxia group, with 5 mice in each group. In the plain normoxia group, the mice were kept in a normoxic environment at the altitude of 400 m above sea level (with an oxygen concentration of 19.88%). The mice in the altitude hypoxia group were kept in an environment at the altitude of 4200 m above sea level (with an oxygen concentration of 14.23%) to establish the animal model of altitude hypoxia. On day 30, spleen tissues were collected to determine the splenic index. HE staining was performed to observe the histopathological changes in the spleen tissues of the mice. Real time fluorogenic quantitative PCR (RT-qPCR) and Western blot were conducted to determine the mRNA and protein expressions of interleukin (IL)-6, IL-12, and IL-1ß in the spleen tissue of the mice. High-throughput transcriptome sequencing was performed with RNA sequencing (RNA-seq). KEGG enrichment analysis was performed for the differentially expressed genes (DEGs). The DEGs in the key pathways were verified by RT-qPCR. Results: Compared with the plain normoxia group, the mice exposed to high-altitude hypoxic environment had decreased spleen index (P<0.05) and exhibited such pathological changes as decreased white pulp, enlarged germinal center, blurred edge, and venous congestion. The mRNA and protein expression levels of IL-6, IL-12, and IL-1ß in the spleen tissue of mice in the altitude hypoxia group were up-regulated (P<0.05). According to the results of transcriptome sequencing and KEGG pathway enrichment analysis, 4218 DEGs were enriched in 178 enrichment pathways (P<0.05). DEGs were significantly enriched in multiple pathways associated with immunity and inflammation, such as T cell receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway (P<0.05) in the spleen of mice exposed to high-altitude hypoxic environment. Among them, IL-17 signaling pathway and the downstream inflammatory factors were highly up-regulated (P<0.05). Compared with the plain normoxia group, the mRNA expression levels of key genes in the IL-17 signaling pathway, including IL-17, IL-17R, and mitogen-activated protein kinase genes (MAPKs), and the downstream inflammatory factors, including matrix metallopeptidase 9 (MMP9), S100 calcium binding protein A8 gene (S100A8), S100 calcium binding protein A9 gene (S100A9), and tumor necrosis factor α (TNF-α), were up-regulated or down-regulated (P<0.05) in the altitude hypoxia group. According to the validation of RT-qPCR results, the mRNA expression levels of DEGs were consistent with the RNA-seq results. Conclusion: Altitude hypoxia can induce inflammatory response in the mouse spleen tissue by activating IL-17 signaling pathway and promoting the release of downstream inflammatory factors.

Triple Amplification Ratiometric Electrochemical Aptasensor for CA125 Based on H-Gr/SH-ß-CD@PdPtNFs.

A triple-amplified and ratiometric electrochemical aptasensor for CA125 was designed based on hemin-graphene/SH-ß-cyclodextrin@PdPt nanoflower (H-Gr/SH-ß-CD@PdPtNF) composites and an exonuclease I (Exo I)-assisted strategy. In the nanocomposite, hemin acts as an internal reference signal owing to the reversible heminox/heminred pair. PdPtNFs can significantly improve the electron transfer rate. SH-ß-CD can efficiently enrich quercetin probes through host-guest recognition and increase the second indicator signal. In the presence of CA125, due to the specific binding between the aptamer and CA125, the conformational change of dsDNA (designed by the CA125 aptamer and its complementary DNA) results in the release of quercetin embedded in dsDNA. Subsequently, the free quercetin and DNA fragments are enriched on the H-Gr/SH-ß-CD@PdPtNF-modified electrode. Thus, an enhanced oxidation peak from quercetin (IQ) and a reduced peak from hemin (Ihemin) can indicate the same biological identification event. In addition, the recycling amplification of CA125 by Exo I can effectively assist the increase of the quercetin signal. The value of IQ/Ihemin is linear with the concentration of CA125 in the range from 6.0 × 10-4 to 1.0 × 103 ng/mL, and the limit of detection is 1.4 × 10-4 ng/mL. The recovery of CA125 in human blood serum samples was from 99.2 to 104.4%. The proposed sensor is sensitive and reliable, which provides an avenue for the development of triple amplification and ratiometric signal strategies for detecting tumor markers in clinical diagnostics.

CuO nanorod-decorated hemin-graphene with enhanced peroxidase-mimicking performance for the colorimetric and electrochemical determination of 4-aminophenol with a smartphone.

The detection of 4-aminophenol (4-AP) is of critical importance due to its high toxicity, and the development of accurate, sensitive, and portable methods for this purpose is essential. Here, a facile colorimetric and electrochemical dual-mode sensor based on a CuO nanorod-decorated hemin-functionalized graphene nanocomposite (CuO/H-Gr) is successfully constructed for the detection of 4-AP. CuO/H-Gr exhibited superior peroxidase-mimicking activity, catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 and generating a colorimetric signal. The catalytic system was found to contain hydroxyl radicals, as revealed by reactive oxygen species trials. Meanwhile, TMB was found to be an electroactive indicator that could be oxidized on a glassy carbon electrode. In the presence of CuO/H-Gr and H2O2, an enhanced electrochemical signal of TMB was generated. Upon the addition of 4-AP, the catalytic performance of CuO/H-Gr in the oxidation of TMB was significantly reduced, leading to a decrease in colorimetric and electrochemical signals. Based on this, a dual-mode sensor for the detection of 4-AP was developed. The linear response ranges for colorimetric and electrochemical sensors are 1.00-200 µM and 0.0100-300 µM, with detection limits of 0.687 µM and 0.00756 µM, respectively. Real water samples were tested to estimate the feasibility of the dual-mode sensor, and the recoveries were found to be consistent with those obtained by high-performance liquid chromatography. In addition, a smartphone-based assay was used to evaluate the levels of 4-AP, which opened a new path for on-site detection.

Nickel hexacyanoferrate nanoparticle-decorated 3D rGO composites-based electrochemical sensing platform for detection of di-2-ethylhexyl phthalate.

A label-free and efficient electrochemical (EC) sensing platform for di-2-ethylhexyl phthalate (DEHP) was developed based on in situ probe nickel hexacyanoferrate nanoparticle (NiHCF NP)-decorated three-dimensional reduced graphene oxide (3D rGO) composites. NiHCF NPs in the composites as an in situ probe show a pair of well-defined peaks with good reversibility and stability. Coupling 3D rGO with NiHCF NPs not only improved the electron transfer capability of NiHCF NPs but also provided more sites for aptamer immobilization. The synthesized NiHCF NP-decorated 3D rGO composites were used to act as a substrate for the immobilization of anti-DEHP aptamer by the covalent bonding method. The designed EC sensing platform displays excellent sensing performance for DEHP with a low detection limit of 3.64 pg/L, and a linear working range of 0.01 - 1000 ng/L. The application of the sensing platform to actual environmental samples was studied and satisfactory results were obtained. Thus, the proposed EC sensing platform would provide a potential tool for efficient detection of pollutants in the environment.

Tailored Water-Soluble Covalent Organic Cages for Encapsulation of Pyrene and Information Encryption.

Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.

Integrative Analysis of Proteomics and Metabolism Reveals the Potential Roles of Arachidonic Acid Metabolism in Hypoxia Response in Mouse Spleen.

High altitude hypoxia stress is the key cause of high-altitude pulmonary edema and spleen contraction. The molecular mechanism of immune response of various tissue systems to hypoxia stress remains lacking. In this study, we applied proteomics combined with metabolomics to explore the key molecular profilings involved in high altitude hypoxia response in the spleen of mice. The results showed that 166 proteins were significantly up-regulated, and only 39 proteins were down-regulated. Bioinformatics analysis showed that mineral absorption, neuroactive ligand-receptor interaction, arachidonic acid metabolism, IL-17 signaling pathway and NOD-like preceptor signaling pathway were significantly enriched in the list of 166 upregulated differentially expressed proteins (DEPs). Among these metabolic pathways, the former three pathways were co-identified in KEGG terms from LC-MS/MS based metabolic analysis. We further found that both arachidonate 15-lipoxygenase and hematopoietic prostaglandin D synthase were upregulated by around 30% and 80% for their protein levels and mRNA levels, respectively. Most downstream metabolites were upregulated accordingly, such as prostaglandin A2 and D2. This study provides important evidence that arachidonic acid metabolism potentially promotes spleen hypoxia response through a combined analysis of proteomics and metabolism, which could bring new insights for the spleen targeted rational design upon arachidonic acid metabolism of new therapies.

Recent Perspectives on Rearrangement Reactions of Ylides via Carbene Transfer Reactions.

Among the available methods to increase the molecular complexity, sigmatropic rearrangements occupy a distinct position in organic synthesis. Despite being known for over a century sigmatropic rearrangement reactions of ylides via carbene transfer reaction have only recently come of age. Most of the ylide mediated rearrangement processes involve rupture of a σ-bond and formation of a new bond between π-bond and negatively charged atom followed by simultaneous redistribution of π-electrons. This minireview describes the advances in this research area made in recent years, which now opens up metal-catalyzed enantioselective sigmatropic rearrangement reactions, metal-free photochemical rearrangement reactions and novel reaction pathways that can be accessed via ylide intermediates.

Effects of water flow on performance of soil microbial fuel cells: Electricity generation, benzo[a]pyrene removal, microbial community and molecular ecological networks.

Soil microbial fuel cells with water flow (W-SMFCs) as a driven force of substrate transport were constructed. Electricity generation, benzo[a]pyrene (BaP) removal, microbial communities and microbial molecular ecological networks were compared between W-SMFCs and their control reactors (without water flow, C-SMFCs) in 240 days of operation. The W-SMFCs started up faster than C-SMFCs (37 days vs. 50 days) and output higher startup voltage (148.45 mV vs. 111.90 mV). The water flow caused higher removal efficiency of BaP at sites >1 cm from the anode (S > 1 cm) than at sites <1 cm from the anode (S < 1 cm) in W-SMFCs, whereas in C-SMFCs, the removal efficiency of BaP at S< 1 cm was higher than that at S> 1 cm. The removal efficiency of BaP at S> 1 cm in W-SMFCs was up to 1.7 times higher than that at S> 1 cm in C-SMFCs on the 91st day. After 240 days of operation, the biodegradation efficiency of absolute BaP amount was 45.95% in W-SMFCs, being 20% higher than that in C-SMFCs (38.17%). Moreover, the water flow caused highly tight interaction among the microbial species, which could be beneficial to BaP biodegradation. Conclusively, the water flow in soil was very beneficial for startup and biodegradation of BaP in SMFCs.

Interannual variation in riparian vegetation cover and its relationship with river flow under a high level of human intervention: an example from the Yongding River Basin.

Riparian vegetation cover is significantly affected by a river's hydrological conditions. Especially in arid and semiarid areas, low flow will degrade riparian vegetation, and recent, intensive human activities in the Yongding River Basin have caused a sharp decrease in river flow. We analyzed interannual change in riparian vegetation, river flow effects, and land use on vegetation coverage using the 40 years (1977-2016) of remote sensing images and river flow, combined with 38 years (1980-2018) of land use data. The normalized difference vegetation index (NDVI) was used to determine vegetation cover in five different categories: extremely low, low, medium, high, and extremely high based on the pixel dichotomy model. The weighted average was calculated to obtain vegetation cover trends. We show that riparian vegetation cover from four rivers increased. Compared with 1977, in 2016, combined high and extremely high vegetation covers at the Dongyang, Yang, Sanggan, and Yongding Rivers increased by 20.3%, 26.7%, 50.0%, and 39.2%, respectively. High (R = -0.976, P < 0.01) and extremely high (R = -0.762, P < 0.05) vegetation covers are negatively correlated with flow in the Yongding River. The high vegetation cover of the Sanggan River riparian zone is negatively correlated with river flow (R = -0.683, P < 0.05). In the Dongyang and Sanggan Rivers, land use analysis in the riparian zone showed that change in cultivated land, grassland, and forest were significantly correlated with high and extremely high vegetation cover. The abundant cultivated land and restoration activities are likely responsible for the increase of riparian vegetation cover as river flows decline.

Photochemical, Metal-Free Sigmatropic Rearrangement Reactions of Sulfur Ylides.

Sigmatropic rearrangement reactions constitute one of the most fundamental reactions of carbenes. While state-of-the-art synthetic methods require the use of expensive precious metal catalysts, the application of visible light for the photolysis of α-aryldiazoacetates is much less investigated and provides an operationally simple entry to carbenes under mild reaction conditions. Herein, we report on blue-light induced sigmatropic rearrangement reactions of sulfur compounds with α-aryldiazoacetates. This process, depending on the substitution pattern of the sulfide, opens up formal insertion reactions of carbenes into S-N, S-C, or C-H bonds.

Blue-Light-Induced Carbene-Transfer Reactions of Diazoalkanes.

Carbenes are very important reactive intermediates to access a variety of complex molecules and are applied widely in organic synthesis and drug discovery. Typically, their chemistry is accessed by the use of transition metal catalysts. Herein, we describe the application of low-energy blue light for the photochemical generation of carbenes from donor-acceptor diazoalkanes. This catalyst-free and operationally simple approach enables highly efficient cyclopropenation reactions with alkynes and the rearrangement of sulfides under mild reaction conditions, which can be utilized for both batch and continuous-flow processes.

Iodine-Mediated Difunctionalization of Imidazopyridines with Sodium Sulfinates: Synthesis of Sulfones and Sulfides.

Novel iodine-induced sulfonylation and sulfenylation of imidazopyridines have been described using sodium sulfinates as the sulfur source. This strategy enables highly selective difunctionalization of imidazo[1,2-a]pyridine to access sulfones and sulfides in good yields. A wide range of substrates and functional groups were well-tolerated under optimized conditions. Moreover, control experiments have been conducted, indicating a radical pathway involved in the reaction mechanisms.

Electrochemical prostate specific antigen aptasensor based on hemin functionalized graphene-conjugated palladium nanocomposites.

An electrochemical aptasensor is described for the detection of prostate specific antigen (PSA). The aptasensor is based on the use of hemin-functionalized graphene-conjugated palladium nanoparticles (H-Gr/PdNPs) deposited on a glassy carbon electrode. The nanocomposites integrate the high electrical conductivity of graphene with the easily functionalized surface chemistry of PdNPs and their excellent catalytic property. The hemin placed on graphene acts as both a protective agent and an in-situ redox probe. The PdNPs provide numerous binding sites for the immobilization of DNA-biotin via coordinative binding between Pd and amino groups. A sensitive and specific PSA assay was attained by immobilizing the PSA aptamer via biotin-streptavidin interaction. The resulting aptasensor has a linear response that covers the PSA concentration range from 0.025 to 205 ng·mL-1, with a 8 pg·mL-1 lower detection limit (at -0.362 V, scan rate: 0.1 mV·s-1, S/N = 3). The method was applied to the quantitation of PSA in spiked serum samples, giving recoveries ranging from 95.0 to 100.3%. Graphical abstract A signal amplified and approving electrochemical aptasensor was constructed for the determination of prostate specific antigen (PSA) based on the use of hemin-functionalized graphene conjugated to palladium nanoparticles (H-Gr/PdNPs). The sensor has a wide linear range, a relatively low detection limit, satisfying stability and high specificity.

Reactivity of p-Toluenesulfonylmethyl Isocyanide: Iron-Involved C-H Tosylmethylation of Imidazopyridines in Nontoxic Media.

A novel iron-involved tosylmethylation of imidazo[1,2-α]pyridines with p-toluenesulfonylmethyl isocyanide in a solvent mixture of H2O and PEG400 under an Ar atmosphere has been developed. This protocol provides a facile synthetic route for the functionalization of the imidazo[1,2-α]pyridine scaffold with broad substrate compatibility, which is less expensive and environmentally friendly. The current methodology could further enable regioselective C-H tosylmethylation of indole at the C3 position. Also, p-toluenesulfonylmethyl isocyanide was utilized as the tosylmethylating reagent for the first time.

Electrochemical Aptasensor for Myoglobin-Specific Recognition Based on Porphyrin Functionalized Graphene-Conjugated Gold Nanocomposites.

In this work, a novel electrochemical aptasensor was developed for sensitive and selective detection of myoglobin based on meso-tetra (4-carboxyphenyl) porphyrin-functionalized graphene-conjugated gold nanoparticles (TCPP-Gr/AuNPs). Due to its good electric conductivity, large specific surface area, and excellent mechanical properties, TCPP-Gr/AuNPs can act as an enhanced material for the electrochemical detection of myoglobin. Meanwhile, it provides an effective matrix for immobilizing myoglobin-binding aptamer (MbBA). The electrochemical aptasensor has a sensitive response to myoglobin in a linear range from 2.0 × 10-11 M to 7.7 × 10-7 M with a detection limit of 6.7 × 10-12 M (S/N = 3). Furthermore, the method has the merits of high sensitivity, low price, and high specificity. Our work will supply new horizons for the diagnostic applications of graphene-based materials in biomedicine and biosensors.

Aptamer-Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy.

Improving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer-targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug-loading capacity and demonstrates pH-responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.

Design of a dual-mode ratiometric fluorescent probe via MOF-on-MOF strategy for Al (III) and pH detection.

BACKGROUND: The construction of ratiometric fluorescent MOF sensors with integrated self-calibration and dual-channel detection can efficiently overcome the deficiencies of single-signal sensing. In this regard, the rational design of structurally functionalized MOFs is paramount for enhancing their performance in ratiometric fluorescent sensors. Lately, the concept of MOF-on-MOF design has garnered notable interest as a potential strategy for regulating the structural parameters of MOFs by integrating two or more distinct MOF types. Great efforts have been dedicated to exploring new MOF-on-MOF hybrids and developing their applications in diverse fields. Even so, these materials are still in the stage of advancement in the sensing field. RESULTS: Herein, a Zr-based metal-organic framework anchored on a rare-earth metal-organic framework (UiO-66(OH)2@Y-TCPP) was prepared for the ratiometric fluorescence detection toward Al (III) and pH. In this probe, the UiO-66(OH)2 featured hydroxyl active sites for Al (III), leading to a significant enhancement in fluorescence intensity upon the addition of Al (III), while the signal emitted by the red-emitting Y-TCPP, serving as the reference, remained constant. UiO-66(OH)2@Y-TCPP exhibited excellent selectivity for Al (III) sensing with a wider linear range of 0.1-1000 µM, and a lower detection limit of 0.06 µM. This probe has also been utilized for the quantitative determination of Al (III) in hydrotalcite chewable tablets with satisfactory results. In addition, the probe realized ratiometric pH sensing in the range of 7-13 using UiO-66(OH)2 as an interior reference. The paper-based probe strip was developed for visual pH sensing. By installing color recognition and processing software on a smartphone, real-time and convenient pH sensing could be achieved. SIGNIFICANCE: This is the first ratiometric fluorescent sensor for Al (III) and pH detection based on a MOF-on-MOF composite probe, which yields two different response modes. The detection results of Al (III) in hydrotalcite chewable tables and smartphone imaging for pH test paper demonstrate the practicability of the probe. This work opens up a new outlook on constructing a multi-functional application platform with substantial potential for employment in environmental and biological analysis tasks.

Engineering aptamers to enhance their interaction with protein target for selective inhibition of cell surface receptors.

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.

Photochemical α-amination of carbonyl groups with iodinanes.

We report on a photochemical reaction of silyl enol ethers with iminoiodinanes. This aza Rubottom reaction provides a direct access towards α-amino carbonyl compounds under catalyst free reaction conditions with light as the sole source of energy. Control experiments suggest the participation of triplet nitrene intermediates.