A CRISPR-Cas9-Mediated Large-Fragment Assembly Method for Cloning Genomes and Biosynthetic Gene Cluster.

The ability to clone large DNA fragments from genomes is valuable for both basic and applied research, such as the construction of synthetic genomes, and the expression of biosynthetic gene clusters (BGCs) for natural product discovery. Here, we report a fast and efficient platform for the direct capture of genome DNAs, by combining CRISPR and Gibson assembly. We demonstrate this method with the ability of cloning large DNA fragments ranging from 30 to 77 kb from various host genomes, achieving a near 100% cloning fidelity for DNA fragments below 50 kb. We next demonstrate this method by the cloning of a 40 kb fragment from Streptomyces ceruleus A3(2), which is rich in BGCs for natural products; and used this method cloning the 40 kb fengycin synthetic gene cluster from B. subtilis 168, encoding for a class of peptides with bioactivity. This method provides efficient and simple opportunities for assembling large DNA constructs from distant sources.

Ultrasensitive monitoring of PCB77 in environmental samples using a visible-driven photoelectrochemical sensing platform coupling with exonuclease I assisted in target recycling.

Due to the urgent need for detecting trace amounts of 3,3',4,4'-tetrachlorobiphenyl (PCB77) in the environment, we have developed an efficient and visible-driven photoelectrochemical (PEC) sensing platform based on carbon quantum dots (CQDs) modified titanium dioxide nanorods (TiO2 NRs), coupling with exonuclease I (Exo I) assisted in target recycling for significant signal amplification. CQDs/TiO2 NRs with high visible-light absorption ability and electron-hole separation efficiency is used as photoactive substrate for anchoring anti-PCB77 aptamer and its complementary DNA (cDNA). With the addition of PCB77, the specific interaction between PCB77 and its aptamer forces aptamer to separate from the electrode surface, resulting in an increase in photocurrent density. Adding Exo I in the test system, a self-catalytic target cycle was motivated, which significantly increased the PEC signal by more than twice, achieving signal amplification. The relationship between the photocurrent density changes and the concentrations of PCB77 are utilized to achieve quantitative detection of PCB77. The designed PEC sensing platform has good analytical performance with a detection limit as low as 0.33 pg L-1, high selectivity and stability. Moreover, the PEC sensor is successfully used to evaluate the content of PBC77 in the environment samples. The established sensing platform provides a simple and efficient method for detecting trace amounts of PCB77 in the environment.

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+.

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.

A novel ß-cyclodextrin-assisted enhancement strategy for portable and sensitive detection of miR-21 in human serum.

Benefiting from our discovery that ß-cyclodextrin (ß-CD) could enhance the catalytic activity of invertase through hydrogen bonding to improve detection sensitivity, a highly sensitive and convenient biosensor for the detection of miR-21 was proposed, which is based on the simplicity of reading signals from a personal glucose meter (PGM), combined with self-assembled signal amplification probes and the performance of ß-CD as an enhancer. In the presence of miR-21, magnetic nanoparticle coupled capture DNA (MNPs-cDNA) could capture it and then connect assist DNA/H1-invertase (aDNA/H1) and self-assembled signal amplification probes (H1/H2) in turn. As a result, a "super sandwich" structure was formed. The invertase on MNPs-cDNA could catalyze the hydrolysis of sucrose to glucose and this catalytic process could be enhanced by ß-CD. The PGM signal exhibited a linear correlation with miR-21 concentration within the range of 25 pmol L-1 to 3 nmol L-1, and the detection limit was as low as 5 pmol L-1 with high specificity. Moreover, the recoveries were 103.82-124.65% and RSD was 2.59-6.43%. Furthermore, the biosensor was validated for the detection of miR-21 in serum, and the results showed that miR-21 levels in serum samples from patients with Diffuse Large B-Cell Lymphoma (DLBCL) (n = 12) were significantly higher than those from healthy controls (n = 12) (P < 0.001). Therefore, the ingenious combination of PGM-based signal reading, self-assembled signal amplification probes and ß-CD as an enhancer successfully constructed a convenient, sensitive and specific biosensing method, which is expected to be applied to clinical diagnosis.

[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.

RNA-Seq-Based WGCNA and Association Analysis Reveal the Key Regulatory Module and Genes Responding to Salt Stress in Wheat Roots.

Soil salinization is the main abiotic stressor faced by crops. An improved understanding of the transcriptional response to salt stress in roots, the organ directly exposed to a high salinity environment, can inform breeding strategies to enhance tolerance and increase crop yield. Here, RNA-sequencing was performed on the roots of salt-tolerant wheat breeding line CH7034 at 0, 1, 6, 24, and 48 h after NaCl treatment. Based on transcriptome data, a weighted gene co-expression network analysis (WGCNA) was constructed, and five gene co-expression modules were obtained, of which the blue module was correlated with the time course of salt stress at 1 and 48 h. Two GO terms containing 249 differentially expressed genes (DEGs) related to osmotic stress response and salt-stress response were enriched in the blue module. These DEGs were subsequently used for association analysis with a set of wheat germplasm resources, and the results showed that four genes, namely a Walls Are Thin 1-related gene (TaWAT), an aquaporin gene (TaAQP), a glutathione S-transfer gene (TaGST), and a zinc finger gene (TaZFP), were associated with the root salt-tolerance phenotype. Using the four candidate genes as hub genes, a co-expression network was constructed with another 20 DEGs with edge weights greater than 0.6. The network showed that TaWAT and TaAQP were mainly co-expressed with fifteen interacting DEGs 1 h after salt treatment, while TaGST and TaZFP were mainly co-expressed with five interacting DEGs 48 h after salt treatment. This study provides key modules and candidate genes for understanding the salt-stress response mechanism in wheat roots.

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.

Genome-Wide Association Study of Arsenic Accumulation in Polished Rice.

The accumulation of arsenic (As) in rice poses a significant threat to food safety and human health. Breeding rice varieties with low As accumulation is an effective strategy for mitigating the health risks associated with arsenic-contaminated rice. However, the genetic mechanisms underlying As accumulation in rice grains remain incompletely understood. We evaluated the As accumulation capacity of 313 diverse rice accessions grown in As-contaminated soils with varying As concentrations. Six rice lines with low As accumulation were identified. Additionally, a genome-wide association studies (GWAS) analysis identified 5 QTLs significantly associated with As accumulation, with qAs4 being detected in both of the experimental years. Expression analysis demonstrated that the expression of LOC_Os04g50680, which encodes an MYB transcription factor, was up-regulated in the low-As-accumulation accessions compared to the high-As-accumulation accessions after As treatment. Therefore, LOC_Os04g50680 was selected as a candidate gene for qAs4. These findings provide insights for exploiting new functional genes associated with As accumulation and facilitating the development of low-As-accumulation rice varieties through marker-assisted breeding.

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.

Revealing the intrinsic peroxidase-like catalytic mechanism of O-doped CoS2 nanoparticles.

CoS2 nanoparticles (NPs) have shown promise as potential peroxidase (POD)-like catalysts, but the catalytic molecular mechanisms are largely unknown. Moreover, no study has adequately explored the influence of O-doping induced by the inevitable oxidation of CoS2 on their POD-like activity. Here, O-doped CoS2 NPs were prepared by a one-step method, and their intrinsic POD-like catalytic mechanism was investigated with a combined experimental and theoretical approach. The hydroxyl radical (˙OH) and the superoxide radical (O2˙-) have been found to play significant roles in the POD-like activity, and ˙OH is the major radical. The O-doping could reduce the transition-state energy barrier of H2O2 dissociation, thus promoting the decomposition of H2O2 to ˙OH and inducing the formation of O2˙-. Therefore, O-doping is an effective method for enhancing the catalytic activity of CoS2 NPs. Furthermore, due to the excellent oxidation property of ˙OH and O2˙-, this nanozyme exhibited efficient catalytic activity towards the degradation of organic dyes with H2O2. This manuscript provides a new inspiration for designing more promising anion-defective transition-metal sulfide nanozymes for different applications.

Efficient photoelectrochemical aptasensing of di-2-ethylhexyl phthalate in environmental samples based on N, S co-doped graphene quantum dots/TiO2 nanorods.

An efficient photoelectrochemical (PEC) sensing platform was developed for detection of di-2-ethylhexyl phthalate (DEHP) based on nitrogen and sulfur co-doped graphene quantum dots/TiO2 nanorods (N, S-GQDs/TiO2 NRs) coupling with exonuclease I (Exo I)-assisted target recycling for remarkable signal amplification. N, S-GQDs uniformly grown on TiO2 NRs by simple hydrothermal method showed high electron-hole separation efficiency and superior photoelectric performance, which was explored as the photoactive substrate for anchoring anti-DEHP aptamer and its complementary DNA (cDNA). With the addition of DEHP, aptamer molecules fell from the electrode surface owing to the specific recognition of aptamer to DEHP, resulting in the increment of photocurrent signal. At this moment, Exo I could stimulate aptamer hydrolysis in the aptamer-DEHP complexes, so that DEHP was released from the complexes to take part in the next reaction cycling, which remarkably increasing the photocurrent response and achieving signal amplification. The designed PEC sensing platform exhibited excellent analytical performance for DEHP with a low detection limit of 0.1 pg L-1. Also, its applications in real samples were further investigated in detail. Thus, the established method would provide a simple and efficient tool for DEHP or other pollutants monitoring in the environment.

Defect Damping-Enhanced Plasmonic Photothermal Conversion.

Significantly increasing the photothermal conversion of plasmonic nanostructured particles (PNPs) is a common goal for all applications of thermoplasmonics, but it is still in challenge, especially for PNPs with the morphology and composition required for a specific photothermal application. Here, we present a concept of defect-induced damping-enhanced photothermal conversion, which favors PNP intrinsic properties. A model of a defect-damped harmonic oscillator is established to depict photothermal conversion correlation with the structure of PNPs and is capable of accurately reproducing the optical performance of the PNPs with the local surface plasmon resonance far from the interband transition. The theoretical model analyses demonstrate that the defect-induced damping can significantly suppress the light scattering of the PNPs and effectively improve their photothermal conversion efficiency. Especially for the PNPs with a sufficiently large size (larger than ∼100 nm for Au and Ag), we show that defect-induced damping can significantly enhance their light absorption and photothermal performances. These are experimentally confirmed. Typically, defect-enriched Au nanostars with ∼100-150 nm profile size were fabricated and showed much higher photothermal performance and a big increment by 23% in photothermal conversion efficiency, compared with the normal (or defect-impoverished) counterpart. Furthermore, the in vitro and in vivo biological experiments demonstrate that this defect-enriched PNP can indeed exhibit significantly higher photothermal performance than the normal counterpart in cells and mouse tumors, which confirms the validity of the presented strategy in typical practical applications. This work provides a strategy to intrinsically and significantly enhance plasmonic photothermal conversion of PNPs with a sufficiently large size, which is not only suitable for PNPs with the morphology and composition required for specific applications but also can be combined with existing strategies to further increase their photothermal performance.

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.

[Contribution Analysis of External Source Pollution Load and Environmental Capacity Estimation of Reservoirs in Central Yunnan Plateau].

To explore the source of the pollution load and its contribution rate in the upper reaches of the plateau reservoir and to analyze the water environment capacity of the reservoir, we selected the Chaishitan Reservoir in the Yunnan Plateau as the research object, applied the pollutant discharge coefficient method to estimate the source of external pollution in the upstream basin of the reservoir, used the simultaneous monitoring data of hydrology and water quality to calculate pollution load into the reservoir, and used the eutrophication model to calculate the maximum capacity of TN and TP in the reservoir under different water quality target scenarios. The results showed that:① the main characteristic pollutants in Chaishitan Reservoir and the above basin were TN and TP. ② COD and TP in the upper reaches of the reservoir mainly came from rural non-point source pollution, with contribution rates of 49.40% and 50.11%, respectively; NH4+-N and TN mainly came from urban domestic pollution sources, with contribution rates of 45.76% and 33.77%, respectively. Among the contributions of rural non-point source pollution, the contribution rates of COD and TP in Luliang District were 34.82% and 36.82%, respectively. The contributions of COD, NH4+-N, TN, and TP to urban domestic pollution were the highest in Qilin District, all of which were up to 65%. ③ The inflows of COD, NH4+-N, TN, and TP were 28050.90, 2465.16, 4680.54, and 870.93 t·a-1, respectively. The inflow of TN and TP pollution load was 4637.80 t·a-1 and 125.04 t·a-1, respectively. ④ When the target of water quality was Class Ⅲ, and the requirements of the Water Function Zoning of Yunnan province were met, the environmental capacities of TN and TP were 1102.62 t·a-1 and 54.85 t·a-1, respectively. Rural non-point source pollution and urban domestic pollution sources were the main sources of pollution in the upper reaches of Chaishitan Reservoir, which were priority control sources. These research results can provide a scientific theoretical basis for pollution source treatment in the plateau reservoir basin.

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.

Highly Active Catalytic CO2 Hydrogenation to Lower Olefins via Spinel ZnGaOx Combined with SAPO-34.

A key primary method for creating a carbon cycle and carbon neutrality is the catalytic hydrogenation of CO2 into high value-added chemicals or fuels. In this work, ZnGaOx oxides were prepared by parallel co-precipitation and physically mixed with SAPO-34 molecular sieves prepared by hydrothermal synthesis to produce ZnGaOx /SAPO-34 bifunctional catalysts, which were evaluated for the catalytic synthesis of lower olefins (C2 = -C4 = ) from carbon dioxide hydrogenation. It was demonstrated that the reaction process requires oxygen defect activation, synergistic hydrogenation, and CO2 alkaline adsorption of ZnGaOx . The spinel structure of ZnGaOx has more abundant oxygen defects and alkaline adsorption sites than the ZnGaOx solid solution, which effectively enhances the catalytic performance. The CO2 conversion was 28.52%, the selectivity of C2 = -C4 = in hydrocarbons reached 70.01%, and the single-pass yield of C2 = -C4 = was 10.95% at 370 °C, 3.0 MPa, and 4800 mL/gcat /h.

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.

Design an efficient photoelectrochemical aptasensor for PCB72 based on CdTe@CdS core@shell quantum dots-decorated TiO2 nanotubes.

In this work, an efficient and novel photoelectrochemical (PEC) aptasensor for 2,3',5,5'-tetrachlorobiphenyl (PCB72) was constructed based on CdTe@CdS core@shell quantum dots (CdTe@CdS QDs)-decorated TiO2 nanotubes (TiO2 NTs). CdTe@CdS QDs were prepared by the combination of CdTe and CdS with a proper lattice mismatch. Due to their large band offsets, core@shell QDs can reduce undesirable carrier recombination, significantly improving their charge separation efficiency. Then the synthesized CdTe@CdS QDs were modified on TiO2 NTs (CdTe@CdS QDs/TiO2 NTs) through electrostatic adsorption method. The as-prepared composites exhibit a wide visible light absorption range, good PEC activity and high photoelectric conversion efficiency. Also, the PEC aptasensor prepared via the immobilization of anti-PCB72 aptamer on the composites exhibits outstanding analytical performance with high sensitivity and specificity for PCB72 under visible-light irradiation, achieving a detection limit as low as 0.03 ng/L. It was also applied to detect PCB72 in four different real environmental samples with satisfactory results.

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.