WO3/Pt/PEG/SiO2 porous film for hydrogen sensing by the sol-gel method.

Tungsten oxide (W O 3) has been widely used in hydrogen sensing due to its stable chemical properties and high oxygen vacancy diffusion coefficient. However, the response of pure W O 3 to hydrogen is slow, and doping is an effective way to improve the hydrogen sensing performance of W O 3 materials. In this paper, W O 3/P t/P E G/S i O 2 porous film was prepared by the sol-gel method using tungsten powder, H 2 O 2 and C 2 H 5 O H as precursors, polyethylene glycol (PEG) as the pore-forming agent, and tetraethyl orthosilicate (TEOS) as the S i O 2 source material. The sensing properties of the W O 3 composite for hydrogen were characterized by a transmission optical fiber hydrogen sensing system made at home. The process parameters such as water bath time, aging time, W:PEG ratio, and W:TEOS ratio were optimized to improve the sensitivity and response time of the sensing film. The experimental results indicate that the sensitivity is 15.68%, the average response time is 45 s, and the repeatability is up to 98.74% in 16 consecutive tests. The linearity index R 2 is 0.9946 within the hydrogen concentration range of 5000 ppm to 50,000 ppm. The film responds only to H 2 when the concentration of interfering gases (C H 4, CO, C O 2) is 2000 ppm. The hydrogen sensing performance of the optimized film is significantly improved compared with that of the undoped film.

A facile, low-cost bimetallic iron-nickel MOF nanozyme-propelled ratiometric fluorescent sensor for highly sensitive and selective uric acid detection and its smartphone application.

As a kind of well-known disease biomarker, uric acid (UA) is closely associated with normal metabolism and health. Despite versatile nanozymes facilitating the analysis of UA, most previous works could only generate single-signal outputs with unsatisfactory detection performance. Exploring a novel ratiometric fluorescent UA sensor with high sensitivity, reliability and portable sensing ability based on facile, low-cost nanozymes is still challenging. Herein, we report the first metal-organic-framework (MOF) nanozyme-originated ratiometric fluorescent UA sensor based on Fe3Ni-MOF-NH2 propelled UA/uricase/o-phenylenediamine tandem catalytic reaction. Different from previous reports, the peroxidase-like property and fluorescence of Fe3Ni-MOF-NH2 were simultaneously employed. In the absence of UA, only the MOF's fluorescence at 430 nm (FI430) can be observed, while the addition of UA will initiate UA/uricase catalytic reaction, and the generated H2O2 could oxidize o-phenylenediamine into highly fluorescent 2,3-diaminophenazine (DAP) (emission at 565 nm, FI565) under the catalysis of the MOF nanozyme. Coincidently, MOF's fluorescence can be quenched by DAP via the inner filter effect, resulting in a low FI430 value and high FI565 value, respectively. Therefore, H2O2 and UA can be alternatively detected through monitoring the above contrary fluorescence changes. The limit of detection for UA is 24 nM, which is much lower than those in most previous works, and the lowest among nanozyme-based ratiometric fluorescent UA sensors reported to date. Moreover, the portable sensing of UA via smartphone-based RGB analysis was facilely achieved by virtue of the above nanozyme-propelled tandem catalytic system, and MOF nanozyme-based molecular contrary logic pairs were further implemented accordingly.

An intelligent ratiometric fluorescent assay based on MOF nanozyme-mediated tandem catalysis that guided by contrary logic circuit for highly sensitive sarcosine detection and smartphone-based portable sensing application.

As the well-known test-indicator for early prostate cancer (PCa), sarcosine (SA) is closely related to the differential pathological process, which makes its accurate determination increasingly significant. Herein, we for the first time expanded the peroxidase (POD)-like property of facile-synthesized Zn-TCPP(Fe) MOF to fluorescent substrates and exploited it to ratiometric fluorescent (RF) sensing. By harnessing the effective catalytic oxidation of MOF nanozyme toward two fluorescent substrates (Scopoletin, SC; Amplex Red, AR) with contrary changes, and target-responsive (SA + SOx)/MOF/(SC + AR) tandem catalytic reaction, we constructed the first MOF nanozyme-based RF sensor for the quantitative determination of SA. Superior to previous works, the operation of this RF sensor is under the guidance of AND-(AND^NAND) contrary logic circuit. The dual-channel binary output changes (from 1/0 to 0/1) not only enable the intelligent logical recognition of SA, bringing strengthened reliability and accuracy, but also manifest the proof-of-concept discrimination of PCa individuals and healthy ones. Through recording the fluorescence alterations of SC (F465) and AR (F585), two segments of linear relationships between ratiometric values (F585/F465) and varied contents of SA are realized successfully. The LOD for SA could reach to as low as 39.98 nM, which outperforms all nanozyme-originated SA sensors reported till now. Moreover, this sensor also demonstrates high selectivity and satisfactory performance in human serum samples. Furthermore, the portable sensing of SA is realized under the assistance of smartphone-based RGB analysis, demonstrating the potential of point-of-care diagnostics of PCa in the future.

Toward Minute-Level DNA Computing: An Ultrafast, Cost-Effective, and Universal System for Lighting Up Various Concurrent DNA Logic Nanodevices (CDLNs) and Concatenated Circuits.

DNA logic nanodevices are powerful tools for both molecular computing tasks and smart bioanalytical applications. Nevertheless, the hour-level operation time and high cost caused by the frequent redesign/reconstruction of gates, tedious strand-displacement reaction, and expensive labeled probes (or tool enzymes) in previous works are ineluctable drawbacks. Herein, we report an ultrafast and cost-effective system for engineering concurrent DNA logic nanodevices (CDLNs) by combining polythymine CuNCs with SYBR Green I (SG I) as universal dual-output producers. Particularly, benefiting from the concomitant minute-level quick response of both unlabeled illuminators and the exquisite strand-displacement-free design, all CDLNs including contrary logic pairs (YES∧NOT, OR∧NOR, and Even∧Odd number classifier), noncontrary ones (IDE∧IMP, OR∧NAND), and concatenated circuits are implemented in just 10 min via a "one-stone-two-birds" method, resulting in only 1/12 the operation time and 1/4 the cost needed in previous works, respectively. Moreover, all of them share the same threshold value, and the dual output can be easily visualized by the naked eye under a portable UV lamp, indicating the universality and practicality of this system. Furthermore, by exploiting the "positive/negative cross-verification" advantages of concurrent contrary logic, the smart in vitro analysis of the polyadenine strand and its polymerase is realized, providing novel molecular tools for the early diagnosis of cancer-related diseases.

ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer.

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis.

Serotonin (5-hydroxytryptamine or 5-HT) is a neuroendocrine peptide endowed with immunomodulatory functions. Regulatory B cells (Bregs) play an important role in maintaining intestinal immune homeostasis. We analyzed the differences of 5-HT and Bregs between peripheral blood of ulcerative colitis (UC) and healthy controls (HC). Besides, 5-HT-treated B cells were adoptively transferred into colitis mice to elucidate the role of 5-HT in regulating Bregs. The level of serum 5-HT and IL-10 in UC patients was lower and both were negatively correlated with disease activity. 5-HT7 receptor (5-HT7R) was higher expressed on Bregs in UC. 5-HT promoted IL-10 production in Bregs through the activation of STAT3. And adoptive transfer of 5-HT-treated B cells alleviated intestinal inflammation via inducing IL-10-producing B cells in mice. Our results suggest that 5-HT/5-HT7R signaling pathway facilitate functional Bregs in constraining inflammation in UC, which may be a new potential prospect in the treatment of UC.

Integration of G-Quadruplex and Pyrene as a Simple and Efficient Ratiometric Fluorescent Platform That Programmed by Contrary Logic Pair for Highly Sensitive and Selective Coralyne (COR) Detection.

The effective and accurate detection of the anticancer drug coralyne (COR) is highly significant for drug quality control, medication safety and good health. Although various COR sensors have been reported in recent years, previous ones can only exhibit single-signal output (turn ON or turn OFF) with poor reliability and anti-interference ability. Therefore, exploring novel platform with dual-signal response for COR detection is urgently needed. Herein, we reported the first ratiometric fluorescent platform for highly sensitive and selective COR detection by integrating G-quadruplex (G4) and Pyrene (Py) as signal probes and harnessing A-COR-A interaction. In the absence of COR, the platform shows a low fluorescence signal of PPIX (F642) and a high one of Py monomer (F383). With the addition of COR, two delicately designed poly-A ssDNAs will hybridize with each other via A-COR-A coordination to form complete G4, yielding the increased fluorescence signal of PPIX and the decreased one of Py due to the formation of Py excimer. Based on the above mechanism, we constructed a simple and efficient sensor that could realize the ratiometric fluorescent detection of COR with high sensitivity and selectivity. A linear relationship between F642/F383 and COR's concentration is obtained in the range from 1 nM to 8 µM. And the limit of detection of COR could reach to as low as 0.63 nM without any amplification, which is much lower than that of most COR sensors reported so far. Notably, the logical analysis of COR can be carried out under the control of a "YES-NOT" contrary logic pair, enabling the smart dual-channel response with an adequate S/N ratio and improved reliability and anti-interference ability. Moreover, this system also presents satisfactory performance in fetal bovine serum (FBS) samples.

Regulation of DNA-PK activity promotes the progression of TNBC via enhancing the immunosuppressive function of myeloid-derived suppressor cells.

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is engaged in DNA damage repair and is significantly expressed in triple negative breast cancer (TNBC). Inhibiting DNA-PK to reduce DNA damage repair provides a possibility of tumor treatment. NU7441, a DNA-PK inhibitor, can regulate the function and differentiation of CD4+ T cells and effectively enhance immunogenicity of monocyte-derived dendritic cells. However, the effect of NU7441 on the tumor progression activity of immunosuppressive myeloid-derived suppressor cells (MDSCs) in TNBC remains unclear. RESULTS: In this study, we found that NU7441 alone significantly increased tumor growth in 4 T1 (a mouse TNBC cell line) tumor-bearing mice. Bioinformatics analysis showed that DNA-PK and functional markers of MDSCs (iNOS, Arg1, and IDO) tended to coexist in breast cancer patients. The mutations of these genes were significantly correlated with lower survival in breast cancer patients. Moreover, NU7441 significantly decreased the percentage of MDSCs in peripheral blood mononuclear cells (PBMCs), spleen and tumor, but enhanced the immunosuppressive function of splenic MDSCs. Furthermore, NU7441 increased MDSCs' DNA-PK and pDNA-PK protein levels in PBMCs and in the spleen and increased DNA-PK mRNA expression and expression of MDSCs functional markers in splenic MDSCs from tumor-bearing mice. NU7441 combined with gemcitabine reduced tumor volume, which may be because gemcitabine eliminated the remaining MDSCs with enhanced immunosuppressive ability. CONCLUSIONS: These findings highlight that the regulation of DNA-PK activity by NU7441 promotes TNBC progression via enhancing the immunosuppressive function of MDSCs. Moreover, NU7441 combined with gemcitabine offers an efficient therapeutic approach for TNBC and merits deeper investigation.

An IoT-Based Breeding Egg Identification and Coding System for Selection of High-Quality Breeding Geese.

The selection of breeding geese requires the recording of egg production information to correspond to the identity of the breeding geese. However, due to the special physiological characteristics of breeding geese, manual recording in practice can affect the egg-laying performance of breeding geese and can also lead to problems of missing and confusing individual breeding goose data with the number of eggs laid by the geese. For contactless recording of breeding goose identity and egg production information for high-quality breeding, this paper proposes an Internet of things (IoT)-based breeding egg identification and coding method for the selection of high-quality breeding geese. At the sensing level, we deployed a radiofrequency identification (RFID)-based sensor. Each breeding goose wore a foot ring RFID tag on its leg, and the individual information was read by foot ring RFID readers placed at the bottom of the devices. Individual information was uploaded to the cloud server for database management through structured query language (MySQL). The target detection modules were mounted on top of the devices, and the breeding geese and eggs were detected in the delivery rooms by an improved single-shot multi-box detector (SSD) target detection algorithm. The egg body limit transmission device and contactless coding device were activated only in the case of breeding eggs, and the breeding goose information was printed on the egg bodies in the form of quick response codes (QR codes), which enabled the breeding egg information to correspond with the breeding goose information. An evaluative experiment was performed using a system for the selection of high-quality breeding geese, with web cameras and a cloud monitoring platform. The breeding geese were allowed 14 days to become accustomed to the experimental environment before monitoring began. The evaluative experiment results showed that the pass rate of egg body coding reached 98.25%, the improved SSD algorithm was 8.65% more accurate and 62.6 ms faster than traditional SSD, and the accuracy rate corresponding to the individual information of the breeding geese and the surface information of the goose eggs was 97.8%. The experimental results met the requirements of accurate marking of individual information of breeding geese, which can provide technical support for the selection of high-quality breeding geese.

Recent advancements in coralyne (COR)-based biosensors: Basic principles, various strategies and future perspectives.

As a kind of protoberberine alkaloid heterocyclic analogues, coralyne (COR) has been reported to exhibit superior antileukemic ability and used as anticancer drug agent. While, the severe hazards and side effects caused by unreasonable use have made its accurate detection more and more important. Although scientists have explored various methods to sense COR and other related targets, a systematical review which could not only elaborate recent developments and analyze current challenges of COR-based biosensors, but also present future perspective has not been reported and is urgently needed. In this review, we attempt to summarize latest advancements in COR-based biosensors in recent decade. Firstly, the operating principles, advantages and disadvantages of various strategies for COR detection (colorimetric, fluorescent, electrochemical and other ones) are comprehensively demonstrated and reviewed. Secondly, COR-assisted biosensors for detection of different non-COR targets (heparin, toxins, nucleic acids and other small molecules) are further discussed. Finally, we analyze current challenges and also suggest potential perspectives for this area.

The TOX subfamily: all-round players in the immune system.

The thymocyte selection-related HMG box protein (TOX) subfamily comprises evolutionarily conserved DNA-binding proteins, and is expressed in certain immune cell subsets and plays key roles in the development of CD4+ T cells, innate lymphoid cells (ILCs), T follicular helper (Tfh) cells, and in CD8+ T-cell exhaustion. Although its roles in CD4+ T and natural killer (NK) cells have been extensively studied, recent findings have demonstrated previously unknown roles for TOX in the development of ILCs, Tfh cells, as well as CD8+ T-cell exhaustion; however, the molecular mechanism underlying TOX regulation of these immune cells remains to be elucidated. In this review, we discuss recent studies on the influence of TOX on the development of various immune cells and CD8+ T-cell exhaustion and the roles of specific TOX family members in the immune system. Moreover, this review suggests candidate regulatory targets for cell therapy and immunotherapies.

CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis.

The overproduction of osteoclasts, leading to bone destruction in patients with rheumatoid arthritis (RA), is well established. However, little is known about the metabolic dysfunction of osteoclast precursors (OCPs) in RA. Herein, we show that increasing fatty acid oxidation (FAO) induces OCP fusion. Carnitine palmitoyltransferase IA (CPT1A), which is important for carnitine transportation and is involved in FAO in the mitochondria, is upregulated in RA patients. This metabolic change further increases the expression of clathrin heavy chain (CLTC) and clathrin light chain A (CLTA) by enhancing the binding of the transcription factor CCAAT/enhancer binding protein ß (C/EBPß) to the promoters of CLTA and CLTC. This drives clathrin-dependent endocytosis pathway, which attenuates fusion receptors in the cellular membrane and contributes to increased podosome structure formation. This study reveals a new mechanism through which FAO metabolism participates in joint destruction in RA and provides a novel therapeutic direction for the development of drugs against bone destruction in patients with RA.

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis.

Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.

Prediction of Targets of Curculigoside A in Osteoporosis and Rheumatoid Arthritis Using Network Pharmacology and Experimental Verification.

PURPOSE: Network pharmacology is considered to be the next-generation drug development model that uses bioinformatics to predict and identify multiple drug targets and interactions in diseases. Here, network pharmacology was used to investigate the mechanism by which Curculigoside A (CA) acts in rheumatoid arthritis (RA) and osteoporosis. METHODS: First, TCMSP and SwissADME were applied to predict the druggability of CA. Then, potential targets were identified from overlapping data in SwissTarget and TargetNet, and targets were analyzed using Genemania and DAVID6.8 to obtain information about the GO and KEGG pathways. Ultimately, the drug-target-pathway network was identified after using Cytoscape 3.0 for visualization. Besides, qPCR was used to validate the predicted five major genes targets (EGFR, MAP2K1, MMP2, FGFR1, and MCL1). RESULTS: The results of TCMSP and SwissADME demonstrated that CA exhibits good druggability; 26 potential protein targets were classified by SwissTarget and TargetNet. The results of Genemania and DAVID6.8 indicated that CA probably caused anti-osteoporosis and anti-RA effects by regulating some biological pathways, especially nitrogen metabolism, estrogen signaling pathway, Rap1 signaling pathway, and PI3K/Akt signaling pathway. Besides, the result of Cytoscape 3.0 showed that the 26 targets participate in osteoporosis and RA-related pathways, metabolism, and other physiological processes. In vitro induced inflammation cell model experiments, the qPCR results showed that CA pretreatment significantly decreased the expression of EGFR, MAP2K1, MMP2, FGFR1, and MCL1 genes. CONCLUSION: These results suggested that network pharmacology may provide possible mechanism of how CA exerts therapeutic effects in osteoporosis and RA.

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases.

Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.

Puma is an essential mediator of p53-dependent and -independent apoptotic pathways.

Puma encodes a BH3-only protein that is induced by the p53 tumor suppressor and other apoptotic stimuli. To assess its physiological role in apoptosis, we generated Puma knockout mice by gene targeting. Here we report that Puma is essential for hematopoietic cell death triggered by ionizing radiation (IR), deregulated c-Myc expression, and cytokine withdrawal. Puma is also required for IR-induced death throughout the developing nervous system and accounts for nearly all of the apoptotic activity attributed to p53 under these conditions. These findings establish Puma as a principal mediator of cell death in response to diverse apoptotic signals, implicating Puma as a likely tumor suppressor.