Global epidemiology and genetic diversity of mcr-positive Klebsiella pneumoniae: A systematic review and genomic analysis.

The rapid increase of mcr-positive Klebsiella pneumoniae (K. pneumoniae) has received considerable attention and poses a major public health concern. Here, we systematically analyzed the global distribution of mcr-positive K. pneumoniae isolates based on published articles as well as publicly available genomes. Combining strain information from 78 articles and 673 K. pneumoniae genomes, a total of 1000 mcr-positive K. pneumoniae isolates were identified. We found that mcr-positive K. pneumoniae has disseminated widely worldwide, especially in Asia, with a higher diversity of sequence types (STs). These isolates were disseminated in 57 countries and were associated with 12 different hosts. Most of the isolates were found in China and were isolated from human sources. Moreover, MLST analysis showed that ST15 and ST11 accounted for the majority of mcr-positive K. pneumoniae, which deserve sustained attention in further surveillance programs. mcr-1 and mcr-9 were the dominant mcr variants in mcr-positive K. pneumoniae. Furthermore, a Genome-wide association study (GWAS) demonstrated that mcr-1- and mcr-9-producing genomes exhibited different antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), thereby indicating a distinct evolutionary path. Notably, the phylogenetic analysis suggested that certain mcr-positive K. pneumoniae genomes from various geographical areas and hosts harbored a high degree of genetic similarities (<20 SNPs), suggesting frequent cross-region and cross-host clonal transmission. Overall, our results emphasize the significance of monitoring and exploring the transmission and evolution of mcr-positive K. pneumoniae in the context of "One health".

In Situ Visualizing Carboxylesterase Activity in Type 2 Diabetes Mellitus Using an Activatable Endoplasmic Reticulum Targetable Proximity Labeling Far-Red Fluorescent Probe.

Carboxylesterase (CE), an enzyme widely present in organisms, is involved in various physiological and pathological processes. Changes in the levels of CEs in the liver may predict the presence of type 2 diabetes mellitus (T2DM). Here, a novel dicyanoisophorone (DCI)-based proximity-labeled far-red fluorescent probe DCI2F-Ac with endoplasmic reticulum targeting was proposed for real-time monitoring and imaging of the CEs activity. DCI2F-Ac featured very low cytotoxicity and biotoxicity and was highly selective and sensitive for CEs. Compared with traditional CEs probes, DCI2F-Ac was covalently anchored directly to CEs, thus effectively reducing the loss of in situ fluorescent signals due to diffusion. Through the "on-off" fluorescence signal readout, DCI2F-Ac was able to distinguish cell lines and screen for CEs inhibitors. In terms of endoplasmic reticulum (ER) stress, it was found that thapsigargin (Tg) induced upregulation of CEs levels but not tunicamycin (Tm), which was related to the calcium homeostasis of the ER. DCI2F-Ac could efficiently detect downregulated CEs in the livers of T2DM, and the therapeutic efficacy of metformin, acarbose, and a combination of these two drugs was assessed by tracking the fluctuation of CEs levels. The results showed that combining metformin and acarbose could restore CEs levels to near-normal levels with the best antidiabetic effect. Thus, the DCI2F-Ac probe provides a great opportunity to explore the untapped potential of CEs in liver metabolic disorders and drug efficacy assessment.

Regulating Sodium Deposition Behavior by a Triple-Gradient Framework for High-Performance Sodium Metal Batteries.

An efficient method for the synthesis of a self-supporting carbon framework (denoted Gra-GC-MoSe2) is proposed with a triple-gradient structure-in sodiophilic sites, pore volume, and electrical conductivity-which facilitates the highly efficient regulation of Na deposition. In situ and ex situ measurements, together with theoretical calculations, reveal that the gradient distribution of Se heteroatoms in MoSe2, and its derivatives tailor the sodiophilicity, while the gradient distribution of porous nanostructures homogenizes the Na+ diffusion. Therefore, Na deposition occurs from the bottom to the top of the Gra-GC-MoSe2 framework without dendrite formation. In addition, the gradient in electrical conductivity ensures the stripping process does not lead to dead Na. As a result, a Gra-GC-MoSe2 modified Na anode (Na@Gra-GC-MoSe2) shows impressive cycling stability with a high average Coulombic efficiency in an asymmetric cell. In symmetric cells, it also exhibits a long cycling life of 2000 h with a low polarization voltage and works stably even under a large capacity of 10 mAh cm-2. Moreover, a Na@Gra-GC-MoSe2|| Na3V2(PO4)3 full cell delivers a high energy density with an excellent cycling performance.

Global distribution and genetic characterization of blaOXA-positive plasmids in Escherichia coli.

In recent years, the emergence of blaOXA-encoding Escherichia coli (E. coli) poses a significant threat to human health. Here, we systematically analyzed the global geographic distribution and genetic characteristics of 328 blaOXA-positive E. coli plasmids based on NCBI database. Twelve blaOXA variants have been discovered, with blaOXA-1 (57.93%) being the most common, followed by blaOXA-10 (11.28%) and blaOXA-48 (10.67%). Our results suggested that blaOXA-positive E. coli plasmids were widespread in 40 countries, mainly in China, the United States, and Spain. MLST analysis showed that ST2, ST43, and ST471 were the top three host STs for blaOXA-positive plasmids, deserving continuing attention in future surveillance program. Network analysis revealed a correlation between different blaOXA variants and specific antibiotic resistance genes, such as blaOXA-1 and aac (6')-Ib-cr (95.79%), blaOXA-181 and qnrS1 (87.88%). The frequent detection of aminoglycosides-, carbapenems- and even colistin-related resistance genes in blaOXA-positive plasmids highlights their multidrug-resistant potential. Additionally, blaOXA-positive plasmids were further divided into eight clades, clade I-VIII. Each clade displayed specificity in replicon types and conjugative transfer elements. Different blaOXA variants were associated with specific plasmid lineages, such as blaOXA-1 and IncFII plasmids in clade II, and blaOXA-48 and IncL plasmids in clade I. Overall, our findings provide a comprehensive insight into blaOXA-positive plasmids in E. coli, highlighting the role of plasmids in blaOXA dissemination in E. coli.

Novel ratiometric electrochemical aptasensor based on broad-spectrum aptamer recognition for simultaneous detection of penicillin antibiotics in milk.

To effectively monitor multi-residues of penicillin antibiotics (PENs) in milk, we developed a novel ratiometric electrochemical aptasensor enabling simultaneous detection of PENs. The aptasensor employed a broad-spectrum aptamer as a recognition element, niobium carbide functionalized with methylene blue (Nb2C-MB) as a reference signal generator, and a ferrocene-labeled aptamer (Fc-Apt) as an output signal. Electrodes were modified with Fe-N-C doped carbon nanotubes (Fe-N-C-CNTs) to amplify detection signals further. During detection, Fc-Apt binding to PENs decreased Fc current intensity (IFc) and increased MB current intensity (IMB). The simultaneous detection of PENs was achieved using IMB/IFc as a quantitative signal. Under optimal conditions, a good linear relationship between IMB/IFc and antibiotic concentration was observed, indicating the aptasensor had a robustness. The limits of detection of aptasensor for four penicillin antibiotics and their mixed targets were 0.093-0.191 nM. This work provides a new approach to multi-residue detection of the same class of antibiotics.

Large-scale comparative analysis reveals phylogenomic preference of blaNDM-1 and blaKPC-2 transmission among Klebsiella pneumoniae.

blaNDM-1 and blaKPC-2 are responsible for the global increase in carbapenem-resistant Klebsiella pneumoniae, posing a great challenge to public health. However, the impact of phylogenetic factors on the dissemination of blaNDM-1 and blaKPC-2 is not yet fully understood. This study established a global dataset of 4051 blaNDM-1+ and 10,223 blaKPC-2+ K. pneumoniae genomes, and compared their transmission modes on a global scale. The results showed that blaNDM-1+ K. pneumoniae genomes exhibited a broader geographical distribution and higher sequence type (ST) richness than blaKPC-2+ genomes, indicating higher transmissibility of the blaNDM-1 gene. Furthermore, blaNDM-1+ genomes displayed significant differences in ST lineage, antibiotic resistance gene composition, virulence gene composition and genetic environments compared with blaKPC-2+ genomes, suggesting distinct dissemination mechanisms. blaNDM-1+ genomes were predominantly associated with ST147 and ST16, whereas blaKPC-2+ genomes were mainly found in ST11 and ST258. Significantly different accessory genes were identified between blaNDM-1+ and blaKPC-2+ genomes. The preference for blaKPC-2 distribution across certain countries, ST lineages and genetic environments underscores vertical spread as the primary mechanism driving the expansion of blaKPC-2. In contrast, blaNDM-1+ genomes did not display such a strong preference, confirming that the dissemination of blaNDM-1 mainly depends on horizontal gene transfer. Overall, this study demonstrates different phylogenetic drivers for the dissemination of blaNDM-1 and blaKPC-2, providing new insights into their global transmission dynamics.

Repurposing homoharringtonine for thyroid cancer treatment through TIMP1/FAK/PI3K/AKT signaling pathway.

Homoharringtonine (HHT), an alkaloid isolated from Cephalotaxus, is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.

GhVIM28, a negative regulator identified from VIM family genes, positively responds to salt stress in cotton.

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

Synthesis of dual models multivalent activatable aptamers based on HCR and RCA for ultrasensitive detection of Salmonella typhimurium.

Aptamers have superior structural properties and have been widely used in bacterial detection methods. However, the problem of low affinity still exists in complex sample detection. In contrast, hybridization chain reaction (HCR)-based model I and rolling circle amplification (RCA)-based model II multivalent activatable aptamers (multi-Apts) can fulfill the need for low-cost, rapid, highly sensitive and high affinity detection of S. typhimurium. In our research, two models of multi-Apts were designed. First, a monovalent activatable aptamer (mono-Apt) was constructed by fluorescence resonance energy transfer (FRET) with an S. typhimurium aptamer and its complementary chain of BHQ1. Next, the DNA scaffold was obtained by HCR and RCA, and the multi-Apts were obtained by self-assembly of the mono-Apt with a DNA scaffold. In model I, when target was presented, the complementary chain BHQ1 was released due to the binding of multi-Apts to the target and was subsequently adsorbed by UIO66. Finally, a FRET-based fluorescence detection signal was obtained. In mode II, the multi-Apts bound to the target, and the complementary chain BHQ1 was released to become the trigger chain for the next round of amplification of HCR with a fluorescence detection signal. HCR and RCA based multi-Apts were able to detect S. typhimurium as low as 2 CFU mL-1 and 1 CFU mL-1 respectively. Multi-Apts amplification strategy provides a new method for early diagnosis of pathogenic microorganisms in foods.

UIO66 low background signal and fluorescence synergism strategy for highly sensitive detection of Salmonella typhimurium.

Successful construction of a detection method for Salmonella typhimurium (S. typhimurium) based on the synergy of hybridization chain reaction (HCR) and fluorescence was realized in this paper. First, the aptamer modified with the quenching group Black Hole Quencher-1 acid (BHQ1) was immobilized on the magnetic beads in combination with the complementary chain of the aptamer modified with 6-carboxyfluorescein (6-FAM). Second, S. typhimurium and cDNA-6-FAM immobilized on magnetic beads competitively bound to the aptamer. Finally, the cDNA-6-FAM was released after magnetic separation acted as a promoter to trigger HCR amplification when the target presented. The fluorescence signal could be significantly improved by the combination of green SYBR Green I (SGI) and HCR long double-stranded DNA and the fluorescent synergy of 6-FAM and SGI. Because of the separation of target and its aptamer, the trigger strand was abstracted by magnetic separation. There was no HCR to generate long double-stranded DNA, and the fluorescence of excess hairpin/SGI could be adsorbed through UIO66 so that only a very low background signal was detected. This fluorescent sensor was capable of monitoring S. typhimurium in the range of 10-3.2 × 107 CFU mL-1 with a limit of detection as low as 1.5 CFU mL-1. Because of the excellent properties of the aptasensor and the validity of SGI fluorescence synergy, this HCR enzyme-free amplification strategy could be generalized to other areas.

Osteopontin promotes tumor growth and metastasis and GPX4-mediated anti-lipid peroxidation in triple-negative breast cancer by activating the PI3k/Akt/mTOR pathway.

PURPOSE: Triple-negative breast cancer (TNBC) features high aggressiveness, metastasis rate, drug resistance as well as poor prognosis. Osteopontin (OPN) is a key protein in the process of osteogenesis and has emerged as a new tumor marker in recent years. METHODS: Cell viability was tested with the CCK-8 kit. Transwell and wound healing were adopted to test cell invasive and migratory abilities. Tumor sphere formation was detected by tumor sphere formation assay. Human umbilical vein endothelial cell (HUVEC) tube formation assay was used to measure the angiogenesis of tumor cells. Western blot was applied for the estimation of the expression of cancer stem cell markers, angiogenesis-, signaling pathway-related proteins as well as OPN. Bioinformatics tools predicted OPN expression in breast cancer tissues. The levels of oxidative stress-related markers were assessed with ELISA. Following the overexpression of OPN in MD-MB-436 cells and the addition of the PI3K/AKT/mTOR pathway inhibitor LY294002, the aforementioned functional experiments were implemented again to investigate the mechanism. Finally, in vivo experiments of tumor-bearing mice were performed for further verification. RESULTS: The proliferative, invasive, migratory and tumor sphere formation capabilities as well as angiogenesis of TNBC cells were conspicuously increased in contrast to non-TNBC cell lines. OPN expression in TNBC tissues and cells was dramatically enhanced. OPN upregulation significantly elevated cell proliferative, invasive and migratory capabilities as well as tumor sphere formation and angiogenesis. The mechanism might be achieved by activating PI3K/AKT/mTOR signaling to regulate glutathione peroxidase 4 (GPX4)-mediated anti-lipid peroxidation. CONCLUSION: OPN promoted tumor sphere formation and angiogenesis in TNBC by activating the PI3K/AKT/mTOR pathway to regulate GPX4-mediated anti-lipid peroxidation levels.

Exploring correlations between microplastics, microorganisms, and water quality in an urban drinking water source.

The microplastic pollution in freshwater system is gradually becoming more severe, which has led to increasing attention on the distribution and potential harmful effects of microplastics. Moreover, microplastics may have an impact on river ecology and pose risks to ecosystems. Therefore, it is important to reveal this process. This study aimed to explore correlations between microplastics and free-living microorganisms in an urban drinking water source of Xiangjiang River by using multivariate statistical analysis. The results indicated that the abundance of microplastics (size 50 µm to 5 mm) in surface water and sediments ranged from 0.72 to 18.6 (mean ± SD: 7.32 ± 2.36) items L-1 and 26.3-302 (150 ± 75.6) items kg-1 dry weight (dw), respectively, suggesting potential microplastic pollution despite the protected status as a drinking water source. Higher microplastic abundances were observed in urban areas and the downstream of wastewater plants, with mostly granular shape, transparent and black color as well as 50-100 µm in size. The multivariate statistical analysis presented that the abundance of microplastics is not significantly correlated with water indicators, due to the complexity of the abundance data. The water indicators showed an obvious correlation with microplastics in colors of transparent and black, and smaller sizes of 50-100 µm. This is also true for microplastics and microorganisms in water and sediment. Proteobacteria was the main prokaryote in water and sediments, being positively correlated with 50-100 µm microplastics; while Chloroplastida was the dominated eukaryotes, presenting a weak correlation with smaller-size microplastics. Overall, when considering the properties of microplastics such as shape, color and size, the potential correlations with water indicators and microorganisms were more evident than abundance. This study provides new insights into the multivariate statistical analysis, explaining the potential correlations among microplastic properties, microorganisms and environmental factors in a river system.

Lithium Superionic Conductive Nanofiber-Reinforcing High-Performance Polymer Electrolytes for Solid-State Batteries.

Although composite solid-state electrolytes (CSEs) are considered promising ionic conductors for high-energy lithium metal batteries, their unsatisfactory ionic conductivity, low mechanical strength, poor thermal stability, and narrow voltage window limit their practical applications. We have prepared a new lithium superionic conductor (Li-HA-F) with an ultralong nanofiber structure and ultrahigh room-temperature ionic conductivity (12.6 mS cm-1). When it is directly coupled with a typical poly(ethylene oxide)-based solid electrolyte, the Li-HA-F nanofibers endow the resulting CSE with high ionic conductivity (4.0 × 10-4 S cm-1 at 30 °C), large Li+ transference number (0.66), and wide voltage window (5.2 V). Detailed experiments and theoretical calculations reveal that Li-HA-F supplies continuous dual-conductive pathways and results in stable LiF-rich interfaces, leading to its excellent performance. Moreover, the Li-HA-F nanofiber-reinforced CSE exhibits good heat/flame resistance and flexibility, with a high breaking strength (9.66 MPa). As a result, the Li/Li half cells fabricated with the Li-HA-F CSE exhibit good stability over 2000 h with a high critical current density of 1.4 mA cm-2. Furthermore, the LiFePO4/Li-HA-F CSE/Li and LiNi0.8Co0.1Mn0.1O2/Li-HA-F CSE/Li solid-state batteries deliver high reversible capacities over a wide temperature range with a good cycling performance.

Advances in signal amplification strategies applied in pathogenic bacteria apta-sensing analysis-A review.

Pathogenic bacteria are primarily kinds of food hazards that provoke serious harm to human health via contaminated or spoiled food. Given that pathogenic bacteria continue to reproduce and expand once they contaminate food, pathogenic bacteria of high concentration triggers more serious losses and detriments. Hence, it is essential to detect low-dose pollution at an early stage with high sensitivity. Aptamers, also known as "chemical antibodies", are oligonucleotide sequences that have attracted much attention owing to their merits of non-toxicity, small size, variable structure as well as easy modification of functional group. Aptamer-based bioanalysis has occupied a critical position in the field of rapid detection of pathogenic bacteria. This is attributed to the unique advantage of using aptamers as recognition elements in signal amplification strategies. The signal amplification strategy is an effective means to improve the detection sensitivity. Some diverse signal amplification strategies emphasize the synthesis and assembly of nanomaterials with signal amplification capabilities, while others introduce various nucleic acid amplification techniques into the detection system. This review focuses on a variety of signal amplification strategies employed in aptamer-based detection approaches to pathogenic bacteria. Meanwhile, we provided a detailed introduction to the design principles and characteristics of signal amplification strategies, as well as the improvement of sensor sensitivity. Ultimately, the existing issues and development trends of applying signal amplification strategies in apta-sensing analysis of pathogenic bacteria are critically proposed and prospected. Overall, this review discusses from a new perspective and is expected to contribute to the further development of this field.

Fluorescent aptasensor mediated with multiple ssDNA for sensitive detection of acetamiprid in vegetables based on magnetic Fe3O4/C-assisted separation.

Acetamiprid (ACE) is a highly effective broad-spectrum insecticide, and its widespread use is potentially harmful to human health and environmental safety. In this study, magnetic Fe3O4/carbon (Fe3O4/C), a derivative of metal-organic framework MIL-101 (Fe), was synthesized by a two-step calcination method. And a fluorescent sensing strategy was developed for the efficient and sensitive detection of ACE using Fe3O4/C and multiple complementary single-stranded DNA (ssDNA). By using aptamer with multiple complementary ssDNA, the immunity of interference of the aptasensor was improved, and the aptasensor showed high selectivity and sensitivity. When ACE was present, the aptamer (Apt) combined with ACE. The complementary strand of Apt (Cs1) combined with two short complementary strands of Cs1, fluorophore 6-carboxyfluorescein-labeled complementary strand (Cs2-FAM) and the other strand Cs3. The three strands formed a double-stranded structure, and fluorescence would not be quenched by Fe3O4/C. In the absence of ACE, Cs2-FAM would be in a single-chain state and would be adsorbed by Fe3O4/C, and the fluorescence of FAM would be quenched by Fe3O4/C via photoelectron transfer. This aptasensor sensitively detected ACE over a linear concentration range of 10-1000 nM with a limit of detection of 3.41 nM. The recoveries of ACE spiked in cabbage and celery samples ranged from 89.49% to 110.76% with high accuracy.

Novel electrochemiluminescence aptasensor based on AuNPs-ABEI encapsulated TiO2 nanorod for the detection of acetamiprid residues in vegetables.

Gold nanoparticles (AuNPs)@N-(4-aminobutyl)-N-ethylisoluminol (ABEI)@Titanium dioxide nanorods (TiO2NRs) were used as sensing materials to produce a unique encapsulated nanostructure aptasensor for the detection of acetamiprid residues in this work. ABEI, an analog of luminol, was extensively used as an electrochemiluminescence (ECL) reagent. The ECL mechanism of ABEI- hydrogen peroxide (H2O2) system had connections to a number of oxygen-centered free radicals. TiO2NRs improved ECL response with high electron transfer and a specific surface area. AuNPs were easy to biolabel and could catalyze H2O2 to enhance ECL signal. AuNPs were wrapped around TiO2NRs by utilizing the reduction property of ABEI to form wrapped modified nanomaterials. The sulfhydryl-modified aptamer bound to the nanomaterial by forming gold-sulfur (Au-S) bonds. The aptamer selectively bound to its target with the addition of acetamiprid, which caused a considerable decrease in ECL intensity and enabled quantitative detection of acetamiprid. The aptasensor showed good stability, repeatability and specificity with a broad detection range (1×10-2-1×103 nM) and a lower limit of detection (3 pM) for acetamiprid residues in vegetables. Overall, this aptasensor presents a simple and highly sensitive method for ECL detecting acetamiprid, with potential applications in vegetable safety monitoring.

Screening of broad-spectrum aptamer and development of electrochemical aptasensor for simultaneous detection of penicillin antibiotics in milk.

Penicillin antibiotics (PENs) play an important role in killing pathogenic bacteria. However, the residues of various penicillin antibiotics in milk gradually accumulate in the human body with the increase of milk intake, which causes direct harm to the human body. Aptamers can be used as recognition element of sensors. It is great significance to use broad-spectrum aptamers for simultaneous detection of PENs. In this study, we reported the screening and identification of DNA aptamers for PENs. The aptamers were screened by graphene oxide-systematic evolution of ligands by exponential enrichment (GO-SELEX). The broad-spectrum aptamers with high affinity and specificity were successfully obtained after 13 rounds of screening. The affinity and specificity of candidate aptamers were analyzed by a GO fluorescence competition method. Further sequence analysis revealed that a truncated 47 nt aptamer (P-11-1) had a higher affinity than the original 79 nt aptamer. The truncated aptamer P-11-1 was used as a recognition element, and an electrochemical aptasensor was prepared using gold nanoparticles (AuNPs) combined with ferroferric oxide-multi walled carbon nanotube (Fe3O4-MWCNTs) complex. The results showed that the developed aptasensor achieved the simultaneous detection of PENs in milk samples across a concentration range of 2 nM-10,000 nM, achieving a limit of detection of 0.667 nM. This methodology provided a simple and sensitive new thinking for antibiotic multi-residue detection.

Research progress on preparation methods and sensing applications of molecularly imprinted polymer-aptamer dual recognition elements.

The aptamer (Apt) and the molecularly imprinted polymer (MIP), as effective substitutes for antibodies, have received widespread attention from researchers because of their creation. However, the low stability of Apt in harsh detection environment and the poor specificity of MIP have hindered their development. Therefore, some researchers have attempted to combine MIP with Apt to explore whether the effect of "1 + 1 > 2" can be achieved. Since its first report in 2013, MIP-Apt dual recognition elements have become a highly focused research direction in the fields of biology and chemistry. MIP-Apt dual recognition elements not only possess the high specificity of Apt and the high stability of MIP in harsh detection environment, but also have high sensitivity and affinity. They have been successfully applied in medical diagnosis, food safety, and environmental monitoring fields. This article provides a systematic overview of three preparation methods for MIP-Apt dual recognition elements and their application in eight different types of sensors. It also provides effective insights into the problems and development directions faced by MIP-Apt dual recognition elements.

BMP4 up-regulated by 630 nm LED irradiation is associated with the amelioration of rheumatoid arthritis.

Rheumatoid arthritis (RA) is caused by inflammatory response of joints with cartilage and damage of synovium and bone erosion. In our previous studies, it has showed that irradiation of 630 nm LED reduce inflammation of synovial fibroblasts and cartilage and bone destruction in RA. However, the key genes and mechanism in ameliorating RA by irradiation of 630 nm LED remains unknown. In this study, human fibroblast-like synoviocytes (FLS) cell line MH7A and primary human RA-FLSs were treated with TNF-α and 630 nm LED irradiation with the different energy density. The mRNA sequencing was performed to screen the differentially expressed genes (DEGs). In all datasets, 10 DEGs were identified through screening. The protein interaction network analysis showed that 8 out of the 10 DEGs interacted with each other including IL-6, CXCL2, CXCL3, MAF, PGF, IL-1RL1, RRAD and BMP4. This study focused on BMP4, which is identified as important morphogens in regulating the development and homeostasis. CCK-8 assay results showed that 630 nm LED irradiation did not affect the cell viability. The qPCR and ELISA results showed that TNF-α stimulation inhibited BMP4 mRNA and protein level and irradiation of 630 nm LED increased the BMP4 mRNA and protein level in MH7A cells. In CIA and transgenic hTNF-α mice models, H&E staining showed that irradiation of 630 nm LED decreased the histological scores assessed from inflammation and bone erosion, while BMP4 expression level was up-regulated after 630 nm LED irradiation. Pearson correlation analysis shown that BMP4 protein expression was negatively correlated with the histological score of CIA mice and transgenic hTNF-α mice. These results indicated that BMP4 increased by irradiation of 630 nm LED was associated with the amelioration of RA, which suggested that BMP4 may be a potential targeting gene for photobiomodulation.

Melatonin receptor, GhCAND2-D5 motivated responding to NaCl signaling in cotton.

As a receptor for plant melatonin, CAND2/PMTR plays an important role in melatonin signaling. Most of the CANDs are membrane proteins and play indispensable roles in signal transduction. In this study, the CANDs from four cotton species were characterized, and the phylogenetic relationships, expression patterns, stress responses of cotton CANDs were analyzed by bioinformatics. Through the analysis of phylogenetic and protein structure, it was found that the CANDs in clade Ⅱ might function as cotton melatonin receptors, and most of the GhCANDs in clade Ⅱ were induced by melatonin. A putative cotton melatonin receptor, GhCAND2-D5, was functionally probed by gene silencing. The plants with silenced expression of this gene exhibited decreased salt tolerance. Protein interaction prediction identified that GhCAND2-D5 interacted with several membrane proteins and played an important role in melatonin signaling. This study provided a theoretical reference for further investigation of melatonin signaling in cotton.