Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention

Entropy Analysis in Pipe Flow Subjected to External Heating

Abstract: In the present study, heat transfer and entropy analysis for flow through a pipe system is considered. The Reynolds number and the pipe wall temperature effects on entropy distribution and total entropy generation in the pipe are investigated. Numerical scheme employing a control volume approach is introduced when solving the governing equations. Steel is selected as pipe material, while water is used as fluid. It is found that increasing pipe wall temperature and Reynolds number increases the entropy production rate, in which case, entropy generation due to heat transfer dominates over that corresponding to fluid friction

Promoting intestinal IgA production in mice by oral administration with anthocyanins

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields

The synthesis of novel AIE emitters with the triphenylethene-carbazole skeleton and para-/meta-substituted arylboron groups and their application in efficient non-doped OLEDs

Four novel aggregation-induced emission (AIE)-active luminogens (p-DPDECZ, p-DBPDECZ, m-DPDECZ and m-DBPDECZ) with triphenylethene-carbazole skeleton and para-/meta-substituted arylboron groups have been synthesized. Their structures are fully characterized using elemental analysis, mass spectrometry and proton nuclear magnetic resonance spectroscopy. The thermal stabilities, photophysical properties, electronic structures, and electrochemical properties of these molecules are investigated systematically using thermal analysis, UV-vis absorption spectroscopy, fluorescence spectroscopy, theoretical calculation and electrochemical methods. The effects of donor–acceptor interaction and conjugation degree on the photoluminescent and electroluminescent properties of these compounds are investigated. The results show that these donor–AIE–acceptor type compounds exhibit good thermal stability and electrochemical stability as well as AIE properties. Non-doped fluorescent OLEDs fabricated by using para-linked p-DPDECZ as an emitting layer emits a green light with a turn-on voltage of 4.8 V, a maximum brightness of 30210 cd m-2 and a maximum current efficiency of 9.96 cd A-1. While the OLED prepared with meta-linked m-DBPDECZ exhibits efficient blue light emission with a maximum current efficiency of 4.49 cd A-1 and a maximum luminance of 16410 cd m-2. The electroluminescence properties of these compounds demonstrate their potential application in OLEDs

Present-day activity and seismic potential of the north Qinling fault, southern ordos block, central China, as revealed from GPS data and seismicity

The North Qinling Fault, located at the boundary of the North China Block and the South China Block, represents an important tectonic structure between the Weihe Basin and the Qinling Mountains, and controls the subsidence and expansion of the Weihe Basin. This fault has been highly active and has caused strong earthquakes since the Holocene and in a pre-seismic stage currently, as indicated by the many paleoearthquake traces found along it. To determine the present-day activity and seismic potential of the North Qinling Fault, by inverting GPS data, we produced fault locking depth, slip rate, and regional strain fields maps; moreover, based on seismicity, we produced a seismic b-value map. Combining this information with modern seismicity, we were able to comprehensively analyze the seismic potential of different fault segments. Our inversion of GPS data showed that the slip rate of the western segment of the fault (Qingjiangkou–Xitangyu) and the correspondent locking depth are 1.33 mm/a and 13.54 km, respectively, while the slip rate of the middle segment (Xitangyu–Fengyukou) and the correspondent locking depth are 0.45 mm/a and 8.58 km, respectively; finally, the slip rate of the eastern segment (Xitangyu–Daiyu) and the correspondent locking depth are 0.36 mm/a and 21.46 km, respectively. The locking depths of the western and middle segments of the fault are shallower than 90% of the seismic cutoff depth, while the locking depth of the eastern segment of the fault is similar to 90% of the seismic cutoff depth, indicating that “deep creep” occurs in the western and middle segments, while the eastern segment is locked. Modern small earthquakes have involved the western and middle segments of the fault, while the eastern segment has acted as a seismic gap with weak seismicity, characterized by a higher shear strain value and a lower b-value. These characteristics reflect the relationship between the locking depth and seismicity distribution. The results of our comprehensive analysis, combined with field geological surveys, show that the eastern segment of the North Qinling Fault has a strong seismic potential and is presently locked

Micro/Nano biomedical devices for point-of-care diagnosis of infectious respiratory diseases

Corona Virus Disease 2019 (COVID-19) has developed into a global pandemic in the last two years, causing significant impacts on our daily life in many countries. Rapid and accurate detection of COVID-19 is of great importance to both treatments and pandemic management. Till now, a variety of point-of-care testing (POCT) approaches devices, including nucleic acid-based test and immunological detection, have been developed and some of them has been rapidly ruled out for clinical diagnosis of COVID-19 due to the requirement of mass testing. In this review, we provide a summary and commentary on the methods and biomedical devices innovated or renovated for the quick and early diagnosis of COVID-19. In particular, some of micro and nano devices with miniaturized structures, showing outstanding analytical performances such as ultra-sensitivity, rapidness, accuracy and low cost, are discussed in this paper. We also provide our insights on the further implementation of biomedical devices using advanced micro and nano technologies to meet the demand of point-of-care diagnosis and home testing to facilitate pandemic management. In general, our paper provides a comprehensive overview of the latest advances on the POCT device for diagnosis of COVID-19, which may provide insightful knowledge for researcher to further develop novel diagnostic technologies for rapid and on-site detection of pathogens including SARS-CoV-2.Natural Environment Research Council (NERC): NE/R013349/

Critical contributions of protein cargos to the functions of macrophage‑derived extracellular vesicles

Background Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. Results Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. Conclusion This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs

P38 Mitogen-Activated Protein Kinase Inhibitor, FR167653, Inhibits Parathyroid Hormone Related Protein-Induced Osteoclastogenesis and Bone Resorption

p38 mitogen-activated protein kinase (MAPK) acts downstream in the signaling pathway that includes receptor activator of NF-κB (RANK), a powerful inducer of osteoclast formation and activation. We investigated the role of p38 MAPK in parathyroid hormone related protein (PTHrP)-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo. The ability of FR167653 to inhibit osteoclast formation was evaluated by counting the number of tartrate-resistant acid phosphatase positive multinucleated cells (TRAP-positive MNCs) in in vitro osteoclastgenesis assays. Its mechanisms were evaluated by detecting the expression level of c-Fos and nuclear factor of activated T cells c1 (NFATc1) in bone marrow macrophages(BMMs) stimulated with sRANKL and M-CSF, and by detecting the expression level of osteoprotegerin (OPG) and RANKL in bone marrow stromal cells stimulated with PTHrP in the presence of FR167653. The function of FR167653 on bone resorption was assessed by measuring the bone resorption area radiographically and by counting osteoclast number per unit bone tissue area in calvaria in a mouse model of bone resorption by injecting PTHrP subcutaneously onto calvaria. Whole blood ionized calcium levels were also recorded. FR167653 inhibited PTHrP-induced osteoclast formation and PTHrP-induced c-Fos and NFATc1 expression in bone marrow macrophages, but not the expression levels of RANKL and OPG in primary bone marrow stromal cells treated by PTHrP. Furthermore, bone resorption area and osteoclast number in vivo were significantly decreased by the treatment of FR167653. Systemic hypercalcemia was also partially inhibited. Inhibition of p38 MAPK by FR167653 blocks PTHrP-induced osteoclastogenesis in vitro and PTHrP-induced bone resorption in vivo, suggesting that the p38 MAPK signaling pathway plays a fundamental role in PTHrP-induced osteoclastic bone resorption

A Label-Free Microelectrode Array Based on One-Step Synthesis of Chitosan–Multi-Walled Carbon Nanotube–Thionine for Ultrasensitive Detection of Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) has been an extensively used tumor marker responsible for clinical early diagnosis of cervical carcinomas, and pancreatic, colorectal, gastric and lung cancer. Combined with micro-electro mechanical system (MEMS) technology, it is important to develop a novel immune microelectrode array (MEA) not only for rapid analysis of serum samples, but also for cell detection in vitro and in vivo. In this work, we depict a simple approach to modify chitosan–multi-walled carbon nanotubes–thionine (CS–MWCNTs–THI) hybrid film through one-step electrochemical deposition and the CS-MWCNTs-THI hybrid films are successfully employed to immobilize anti-CEA for fabricating simple, label-free, and highly sensitive electro-chemical immune MEAs. The detection principle of immune MEA was based on the fact that the increasing formation of the antigen-antibody immunocomplex resulted in the decreased response currents and the relationship between the current reductions with the corresponding CEA concentrations was directly proportional. Experimental results indicated that the label-free MEA had good selectivity and the limit of detection for CEA is 0.5 pg/mL signal to noise ratio (SNR) = 3. A linear calibration plot for the detection of CEA was obtained in a wide concentration range from 1 pg/mL to 100 ng/mL (r = 0.996). This novel MEA has potential applications for detecting CEA for the research on cancer cells and cancer tissue slices as well as for effective early diagnosis