Interactions of Amino Group Functionalized Tetraphenylvinyl and DNA: A Label-Free "On-Off-On" Fluorescent Aptamer Sensor toward Ampicillin.

As a type of aggregation-induced emission (AIE) fluorescent probe, tetraphenylvinyl (TPE) or its derivatives are widely used in chemical imaging, biosensing and medical diagnosis. However, most studies have focused on molecular modification and functionalization of AIE to enhance the fluorescence emission intensity. There are few studies on the interaction between aggregation-induced emission luminogens (AIEgens) and nucleic acids, which was investigated in this paper. Experimental results showed the formation of a complex of AIE/DNA, leading to the quenching of the fluorescence of AIE molecules. Fluorescent test experiments with different temperatures proved that the quenching type was static quenching. The quenching constants, binding constants and thermodynamic parameters demonstrated that electrostatic and hydrophobic interactions promoted the binding process. Then, a label-free "on-off-on" fluorescent aptamer sensor for the detection of ampicillin (AMP) was constructed based on the interaction between the AIE probe and the aptamer of AMP. Linear range of the sensor is 0.2-10 nM with a limit of detection 0.06 nM. This fluorescent sensor was applied to detect AMP in real samples.

Oridonin Attenuates Thioacetamide-Induced Osteoclastogenesis Through MAPK/NF-κB Pathway and Thioacetamide-Inhibited Osteoblastogenesis Through BMP-2/RUNX2 Pathway.

Osteoporosis, an age-related metabolic bone disease, is mainly caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. At present, there are many osteoporosis drugs that can promote bone formation or inhibit bone resorption. However, there were few therapeutic drugs that can simultaneously promote bone formation and inhibit bone resorption. Oridonin (ORI), a tetracyclic diterpenoid compound isolated from Rabdosia rubescens, has been proved to have anti-inflammatory, anti-tumor effects. However, little is known about the osteoprotective effect of oridonin. Thioacetamide (TAA) is a common organic compound with significant hepatotoxicity. Recent studies have found that there was a certain association between TAA and bone injury. In this work, we investigated the effect and mechanism of ORI on TAA-induced osteoclastogenesis and inhibition of osteoblast differentiation. The results showed that TAA could promote the osteoclastogenesis of RAW264.7 by promoting the MAPK/NF-κB pathway, and also promoted p65 nuclear translocation and activated intracellular ROS generation, and ORI can inhibit these effects to inhibit TAA-induced osteoclastogenesis. Moreover, ORI can also promote the osteogenic differentiation pathway and inhibit adipogenic differentiation of BMSCs to promote bone formation. In conclusion, our results revealed that ORI, as a potential therapeutic drug for osteoporosis, could protect against TAA-induced bone loss and TAA-inhibited bone formation.

Monoclonal antibody based immunoassay: An alternative way for aquatic environmental selenium detection.

Environmental concerns about human health encouraged increasing methodological interest in selenium (Se), which is an essential non-metal trace element and varies within a narrow concentration range between essential and toxic. In this study, two types of long-armed Se haptens (Se-hapten-lc-NHS) were synthesized for the first time using active ester formalization. In producing monoclonal antibodies (mAbs), the derivatization of haptenized Se at para- (meta-) and ortho-sites showed different properties. Finally, a mAb derived from hybridoma 5A52 was confirmed to be capable of establishing an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA). There was a successful quantitative determination of Se4+ with a detection range of 17 to 207 pmol mL-1 and a limit of detection of approximately 3.9 pmol mL-1. The mAb was found to be remarkably sensitive and specific, with no evidence of cross-reactivity with other ions. The assay was validated for four kinds of Se forms in water samples and showed satisfactory recoveries between 80 % and 108 %, with coefficients of variation of 2.1 %-11 %. The method proposed in our study offers a useful protocol for the rapid screening of Se and provides an alternative solution for the analysis of Se in aquatic environments.

Matrine, a potential c-Myc inhibitor, suppresses ribosome biogenesis and nucleotide metabolism in myeloid leukemia.

Previous studies have shown that matrine, a natural compound extracted from the herb Sophora flavescens, has a good anti-leukemia effect, but its key target and mechanism remains unclear. Here, we found that only c-Myc could respond rapidly to matrine treatment in three myeloid leukemia cell lines, and matrine inhibited both transcription and translation of c-Myc. Ribosome biogenesis and nucleotide metabolism, the key downstream of c-Myc, were significantly suppressed after matrine treatment. Therefore, our results confirmed that matrine is a special c-Myc inhibitor which suppresses ribosome biogenesis and nucleotide metabolism by inhibiting c-Myc in myeloid leukemia. This study provides scientific basis for the development of matrine derivatives to c-Myc-driven cancers.

Salmonella enterica serovar Typhi influences inflammation and autophagy in macrophages.

Salmonella enterica serovar Typhi (S. Typhi) is a human enteropathogen that can survive in macrophages and cause systemic infection. Autophagy and inflammation are two important immune responses of macrophages that contribute to the elimination of pathogens. However, Salmonella has derived many strategies to evade inflammation and autophagy. This study investigated inflammation-related NF-κB signaling pathways and autophagy in S. Typhi-infected macrophages. RNA-seq and quantitative real-time PCR indicated that mRNA levels of NF-κB signaling pathway and autophagy-related genes were dynamically influenced in S. Typhi-infected macrophages. Western blots revealed that S. Typhi activated the NF-κB signaling pathway and induced the expression of inhibitor protein IκBζ. In addition, S. Typhi enhanced autophagy during early stages of infection and may inhibit autophagy during late stages of infection. Thus, we propose that S. Typhi can influence the NF-κB signaling pathway and autophagy in macrophages.

Development of quantum dot-linked immunosorbent assay (QLISA) and ELISA for the detection of sunset yellow in foods and beverages.

Sunset yellow (SY) is widely used as food colorant. Excess and illegal use of SY could pose potential health risk. Quantum dots have been successfully used in biological research due to the high photoluminescence and high resistance to photobleaching. To analyze SY efficiently, quantum dot-linked immunosorbent assay (QLISA) and enzyme-linked immunosorbent assay (ic-ELISA) were developed on the basis of generated monoclonal antibody. A carboxyl group was introduced to SY and coupled with carrier proteins to synthesize artificial antigen. Under the optimal conditions, inhibitory concentrations (IC50) of SY were 1.9 ng/mL (ic-ELISA) and 3.4 ng/mL (QLISA); the limits of detection (LODs) were 0.2 ng/mL (ic-ELISA) and 1.0 ng/mL (QLISA), respectively. Cross-reactivities of the mAb toward eight kinds of analogues were<0.01%. The recovery rates in spiked foods and beverages were 75.6%∼120.1% (ic-ELISA) and 74.0%∼114.1% (QLISA), respectively.

A new precursor to diversify BCN architectures with enhanced electromagnetic wave absorption.

Hexagonal BCN (h-BCN) is considered to be a promising dielectric ceramic material with a hybrid B-C-N structure and an electromagnetic wave (EMW) absorbing material with tenable properties. H-BCN bulk and microtube architectures are simultaneously synthesized by precursor pyrolysis method using BCl3, aniline (AN) and diethylenetriamine (DETA) as the raw material. By analyzing its electromagnetic parameters, the effective absorption bandwidth of the sample cracking at 900 °C with the proportion of raw materials (DETA:AN = 1:1) can be up to 7.2 GHz, and the minimum reflection loss can reach -43.6 dB at 7.92 GHz with a thickness of 3.5 mm. Moreover, the EMW absorbing property of the ceramic can be tuned by adjusting the ratio of monomers, pyrolysis temperature, and cooling rates.

hns mRNA downregulates the expression of galU and attenuates the motility of Salmonella enterica serovar Typhi.

Recently, multiple bifunctional RNAs have been discovered, which can both be translated into proteins and play regulatory roles. hns encodes the global gene silencing factor H-NS, which is widespread in Gram-negative bacteria. This study reported that hns mRNA of Salmonella enterica serovar Typhi (S. Typhi) was a bifunctional RNA that could act as an antisense RNA downregulating the expression of galU, the coding gene of uridine triphosphate-glucose-1-phosphate uridylyltransferase, and attenuating bacterial motility. galU, which is located at the opposite strand of hns, was identified to have a long 3'-untranslated region that overlapped with hns and could be processed to produce short RNA fragments. The overexpression of hns mRNA inhibited the expression of galU. The deletion of galU attenuated the motility of S. Typhi, while the complementation of galU nearly restored the phenotype. Overexpressing hns mRNA in the wild-type strain of S. Typhi inhibited the motility and the expression of flagellar genes, while overexpressing hns mRNA in the galU-deletion mutant did not influence bacterial motility. In conclusion, hns mRNA has been identified to be a new bifunctional RNA that attenuates the motility of S. Typhi by downregulating the expression of galU.

Interactions between Salmonella and host macrophages - Dissecting NF-κB signaling pathway responses.

Salmonella not only invades host cells, but also replicates intracellularly to cause a range of diseases, including gastroenteritis and systemic infections such as typhoid fever. The body's first line of defense against pathogens is the innate immune response system that can protect against Salmonella invasion and replication. Nuclear factor κB (NF-κB) is an important transcriptional regulator that plays an important role in host inflammatory responses to pathogens. Both the canonical and non-canonical NF-κB signaling pathways are activated by Salmonella in many different ways through its virulence factors, leading to the release of inflammatory factors and the activation of inflammatory responses in mammalian hosts. Equally, Salmonella, as an enteropathogen, has accordingly evolved strategies to disturb NF-κB activation, such as secreting some effector proteins by type III secretion systems as well as inducing host cells to express NF-κB pathway inhibitors, allowing it to colonize and persistently infect the hosts. This review focuses on how Salmonella activates NF-κB signaling pathway and the strategies used by Salmonella to interfere with the NF-κB pathway activation.

cGAS promotes sepsis in radiotherapy of cancer by up-regulating caspase-11 signaling.

Radiotherapy is the most common strategy in the treatment of cancer. However, radiation-induced acute complications, in particular sepsis, render patients in a life-threatening status or lead to delay of therapy that largely influences patients' overall responses. The understanding of sepsis in radiotherapy is currently scant and effective medicine is not available by far. Here, with WT mice as control, we challenged mice deficient to cGas, Caspase-11, Gsdmd or Asc with cecal ligation and puncture (CLP, a sepsis model) after a treatment of thorax irradiation. We found that radiation robustly upgraded caspase-11 pathway in irradiated region and consequently deteriorated lung injury and mortality in the sepsis model. cGas knockout markedly attenuated radiation-upgraded caspase-11 and restored sepsis. Deficiency of non-canonical inflammasome, caspase-11 and the downstream GSDMD, rather than an AIM2 inflammasome component, ASC, dramatically protected against radiation-promoted injury and mortality in septic mice. The protection may attribute to the inhibition of caspase-11-mediated pyroptosis in endothelial cells of the lung. Thus, blocking cGAS/caspase-11 signaling would be an adjuvant treatment strategy for preventing sepsis in radiotherapy of cancer.

A sensitive sandwich ELISA using a modified biotin-streptavidin amplified system for histamine detection in fish, prawn and crab.

Histamine poisoning from seafood is a significant public health and safety concern. To detect histamine sensitively and accurately, a novel competitive sandwich immunoassay using a modified biotin-streptavidin system coupling with polylysine was developed. Using this strategy, a sandwich ELISA with an IC50 value of 112.8 ng mL-1 and a broad linear range of 11.7-1500 ng mL-1 with a correlation coefficient of 0.9942 was validated. Without any sample derivatization procedure, the recovery of histamine ranged from 80.19% to 108.3% with a coefficient of variation of 1.43-11.7% in tuna, prawn and crab. The sandwich ELISA had a detectionlimit of 5.86 ng mL-1, which was 15-fold lower than an indirect competitive ELISA (ic-ELISA). This simple, sensitive and accurate method can be applied to detect histamine in routine seafood samples.

Flexible full two-dimensional memristive synapses of graphene/WSe2-xOy/graphene.

van der Waals heterostructures realized by stacking different two-dimensional materials offer the possibility to design new devices with atomic-level precision. The realization of memristive synapses based on full two-dimensional materials provides an avenue for developing neuromorphic computing systems with excellent mechanical flexibility in future. Herein, we first develop the flexible full two-dimensional memristive synapse of graphene/WSe2-xOy/graphene exhibiting stable volatile resistive switching. The oxidation of WSe2 through O2 plasma treatment plays a key role in improving the memristive performance of the devices. And the switching behavior is associated with the migration of oxygen vacancies at the graphene/WSe2-xOy interface. Versatile synaptic functions have been realized, including short-term plasticity, long-term plasticity, the transition from short-term plasticity to long-term plasticity and high-pass temporal filtering, with ultralow energy consumption of ∼16.1 pJ per spike. The flexible full two-dimensional devices fabricated on flexible polyimide substrate show excellent mechanical flexibility, including a good endurance against repeatable bending of 1000 times and a bending strain of 2.5%.

DNA damage/cGAS-triggered up-regulation of MALAT1 promotes undesirable inflammatory responses in radiotherapy of cancer.

Radiotherapy is the most common strategy for treating cancer. However, the radiation-induced inflammatory responses, acute or chronic, in the normal tissues of the irradiated region may result in undesirable side effects, such as lung injury and atherosclerosis. MALAT1 is believed to function in the onset, development, progression and metastasis of various cancers. Silencing MALAT1 may be a promising treatment for rescuing cancer. Nevertheless, whether MALAT1 promotes the radiation-induced undesirable inflammatory response is still uncovered. The present study reveals that radiation-induced DNA damage triggers cGAS signaling and subsequently increases the expression of MALAT1. Overexpression of MALAT1 inhibits the function of miR146a in the suppression of STAT1, which results in the boost of adhesion molecules and eventually induces acute lung injury and atherosclerosis. Thus, silencing MALAT1 may facilitate the reduction of radiation-induced acute and chronic complications in the radiotherapy of cancer.

HMS1 interacts with HMS1I to regulate very-long-chain fatty acid biosynthesis and the humidity-sensitive genic male sterility in rice (Oryza sativa).

Environment-sensitive genic male sterility (EGMS) lines are used widely in two-line hybrid breeding in rice (Oryza sativa). At present, photoperiod-sensitive genic male sterility (PGMS) lines and thermo-sensitive genic male sterility (TGMS) lines are predominantly used in two-line hybrid rice, with humidity-sensitive genic male sterility (HGMS) lines rarely being reported. Here, it is shown that HUMIDITY-SENSITIVE GENIC MALE STERILITY 1 (HMS1), encoding a ß-ketoacyl-CoA synthase, plays key roles in the biosynthesis of very-long-chain fatty acids (VLCFAs) and HGMS in rice. The hms1 mutant displayed decreased seed setting under low humidity, but normal seed setting under high humidity. HMS1 catalyzed the biosynthesis of the C26 and C28 VLCFAs, contributing to the formation of bacula and tryphine in the pollen wall, which protect the pollen from dehydration. Under low-humidity conditions, hms1 pollen showed poor adhesion and reduced germination on the stigmas, which could be rescued by increasing humidity. HMS1-INTERACTING PROTEIN (HMS1I) interacted with HMS1 to coregulate HGMS. Furthermore, both japonica and indica rice varieties with defective HMS1 exhibited HGMS, suggesting that hms1 potentially could be used in hybrid breeding. The results herein reveal the novel mechanism of VLCFA-mediated pollen wall formation, which protects pollen from low-humidity stress in rice, and has a potential use in hybrid crop breeding.

Multi-gate memristive synapses realized with the lateral heterostructure of 2D WSe2 and WO3.

The development of novel synaptic device architectures with a high order of synaptic plasticity can provide a breakthrough toward neuromorphic computing. Herein, through the thermal oxidation of two-dimensional (2D) WSe2, unique memristive synapses based on the lateral heterostructure of 2D WSe2 and WO3, with multi-gate modulation characteristics, are firstly demonstrated. An intermediate transition layer in the heterostructure is observed through transmission electron microscopy. Raman spectroscopy and detailed electrical measurements provide insights into the mechanism of memristive behavior, revealing that the protons injected into/removed from the intermediate transition layer account for the memristive behavior. This novel memristive synapse can be used to emulate two neuron-based synaptic functions, like post-synaptic current, short-term plasticity and long-term plasticity, with remarkable linearity, symmetry, and an ultralow energy consumption of ∼2.7 pJ per spike. More importantly, the synaptic plasticity between the drain and source electrodes can be effectively modulated by the gate voltage and visible light in a four-terminal configuration. Such multi-gate tuning of the synaptic plasticity cannot be accomplished by any previously reported multi-gate synaptic devices that only mimic two neuron-based synapses. This new synaptic architecture with electrical and optical modulation enables a realistic emulation of biological synapses whose synaptic plasticity can be additionally regulated by the surrounding astrocytes, greatly improving the recognition accuracy and processing capacity of artificial neuristors, and paving a new way for highly efficient neuromorphic computation devices.

X-rays induced IL-8 production in lung cancer cells via p38/MAPK and NF-κB pathway.

PURPOSE: It is reported inflammatory cytokine interleukin-8 (IL-8) could predict radiation-induced lung toxicity (RILT). RILT is believed to be a consequence of a cascade of cytokine production. It is considered that vascular endothelial cell and macrophages are the mainly source of cytokines. This study was investigated the production of IL-8 from cancer cells induced by X-rays may involve in the radiation-induced inflammation. MATERIALS AND METHODS: We analyzed IL-8 in human lung cancer cell lines after expose to X-rays, and we also detect IL-8 in HUVEC cells and THP1 cells as endothelial cell and macrophage model to identify the change in normal cells after expose. Furthermore, we added the inhibitors to the culture with or without radiation to identify the role of MAPK and NF-κB pathways on the radiation-induced secretion of IL-8. RESULTS: Radiation could induce IL-8 production both in non-lung cancer cells (HUVECs and THP1 cells) and in lung cancer cells (A549 cells, H446 cells, PC-9 cells). Simultaneously, radiation activated p38/MAPK and NF-κB signal pathways in lung cancer cells. Moreover, p38/MAPK inhibitor SB203580 and NF-κB inhibitor BAY11-7082 could block the IL-8 up-regulated by X-rays but JNK inhibitor SP600125, ERK inhibitor U0126, ROS Scavenger NAC could not inhibit this phenomenon. CONCLUSIONS: X-rays could induce IL-8 production in lung cancer cells, which may be related to the activation of p38/MAPK and NF-κB signaling pathway, providing a new point for elucidating the mechanism of radiation pneumonitis.

Multiple sites of soft-tissue metastases secondary to lung cancer: A case report.

RATIONALE: The prognosis of lung cancer is dismal, which has resulted in lung carcinoma being one of the leading causes of cancer-related deaths worldwide. Non-small cell lung cancer accounts for approximately 80% of all types of lung carcinoma. The skeletal system and central nervous system are the most common distal metastatic sites in patients with lung cancer, while cutaneous and soft tissues metastasis is rare. PATIENT CONCERNS: We report a case of concomitant metastasis in the nasal tip and suspected buttocks metastasis secondary to lung cancer, who complained of repeated cough and white sputum for 6 months. DIAGNOSE: Primary lung cancer was diagnosed by bronchoscopy and biopsy, lesion on nasal tip was confirmed by biopsy. Furthermore, PET-CT scan identified the untouchable buttocks lesion that could have been easily missed. INTERVENTIONS: This patient refused systemic treatments, but he chose traditional Chinese medicine at home. OUTCOMES: He died 6 months after the diagnosis. LESSONS: The possibility of metastasis of primary cancers should be considered when encountering soft-tissue neoplasm lesions, and a biopsy of the suspicious cutaneous lesions could likely aid in the histological identification of the primary cancer. PET-CT scan could be an effective supplementary tool for the diagnosis and evaluation of cancers.

Competitive immunoassay for analysis of bisphenol A in children's sera using a specific antibody.

Bisphenol A (BPA) has been reported as a potential estrogenic substance that could affect human health and reproduction. In this study, a monoclonal antibody (Mab) against BPA was produced after the immunization of Balb/c mice with a conjugate of 4,4-bis (4-hydroxyphenyl) valeric acid coupling with keyhole limpet hemocyanin (BVA-KLH). The obtained Mab showed higher affinity against BPA and lower cross-reactivity toward 4,4'-sulfonyldiphenol, diphenolic acid, hydroquinone, salicylic acid, and other common phenolic compounds. Basing on the Mab, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed. Under the optimal conditions, the limit of detection (LOD) was found to be 0.1 ng mL(-1) with the linear working range of 0.45-10.56 ng mL(-1). After sample extraction, the fortified serum samples were detected with intra- and inter-assay recovery ranges of 81.2-92.9 and 84.4-94.4 %, respectively. Then, 100 children's sera were screened by ic-ELISA. The result showed that 54 % of the serum samples were BPA-positive. The positive samples were purified by immuno-affinity column (IAC) and further confirmed by high-performance liquid chromatography (HPLC) with fluorescence detector measured at λ ex/λ em 228/310 nm in acetonitrile-water solution (v:v, 40:60). The analysis of the unknown samples showed that ic-ELISA agreed well with the HPLC results. It also revealed that the ELISA developed here could be a useful tool for screening BPA in children's sera before the validation of HPLC.

Novel surface dummy molecularly imprinted silica as sorbent for solid-phase extraction of bisphenol A from water samples.

A novel surface molecularly imprinted silica composite was prepared by a dummy-template imprinting strategy for the solid-phase extraction (SPE) of bisphenol A (BPA). 2,2-Bis(4-hydroxyphenyl) hexafluoropropane (BPAF) was chosen as the template molecule, and a hybrid technique was used for imprinting procedure. The imprinted silica was characterized by FT-IR spectroscopy, scanning electron microscope, thermo-gravimetric analysis, and nitrogen adsorption-desorption isotherms. The static binding test verified that the imprinted silica had much higher recognition ability for BPA than the non-imprinted silica, and the kinetic adsorption test presented the fast binding kinetics of the surface imprinted silica for BPA. When used as a SPE sorbent, the imprinted silica showed high extraction efficiencies and high enrichment factor for BPA. Based on the imprinted silica, a SPE-HPLC-UV method was developed and successfully applied to the detection of BPA in BPA-spiked lake water, tap water and drinking water samples with a high recovery of 97.3-106.0%, a RSD of 1.2-3.8% (n=3) and a limit of detection (S/N=3) of 0.3 ng/mL. The analysis results of a certified BPA sample also demonstrated the reliability of present method. The new surface dummy molecularly imprinted silica completely avoided the interference of the residual template molecules and greatly improved the binding kinetic of the target molecules. Therefore, it can be used as a good sorbent for SPE of BPA in environmental water samples.