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

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

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/

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

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

A CATIONIC POLYACRYLAMIDE DISPERSION SYNTHESIS BY DISPERSION POLYMERIZATION IN AQUEOUS SOLUTION

A cationic polyacrylamide (CPAM) dispersion, the copolymer of acrylamide (AM) and acryloyloxyethyltrimethyl ammonium chloride (DAC), has been synthesized through dispersion polymerization in aqueous ammonium sulfate ((NH4)2SO4) solution. The polymerization was initiated by tert-butyl hydroperoxide (TBHP) and ferrisulfas (FeSO4) using poly(dimethyl diallyl ammonium chloride) (PDMDAAC) as the stabilizer. At the optimal reaction conditions, the relative molecular weight of the CPAM dispersion was 4.2×106, its charge density was 2.2 mmol•g-1, its average particle size was 6.01 μm, and its stability and dissolvability were both excellent. The CPAM dispersion was characterized using Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and differential scanning calorimeter (DSC). Results indicated that the copolymerization was successful

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

Effects of Tree Age and Bole Section on Pulpwood of Korean Spruce (Picea koraiensis Nakai)

Korean spruce (Picea koraiensis Nakai) is one of the most important wood resources for pulp and paper industry. However, a long production cycle is required for spruce to obtain mature timber, which may negatively influence the biomass production. In this study, fiber morphology, chemical composition, and pulping properties of Korean spruce with different tree ages and vertical locations were investigated. The results show that, along with the increase of tree ages, the contents of extractives, lignin, and pentosan increase to different extents. There are also some differences of pulping properties with different tree ages. As a pulpwood, the Korean spruce with tree ages of around 22 to 32 years is more suitable for kraft pulping, compared to that with 32-46 years. In addition, the middle segment of the bole had better pulp strength properties than the upper or lower bole segments

Selective Recognition of 5-Hydroxytryptamine and Dopamine on a Multi-Walled Carbon Nanotube-Chitosan Hybrid Film-Modified Microelectrode Array

It is difficult to determine dopamine (DA) and 5-hydroxytryptamine (5-HT) accurately because of the interference of ascorbic acid (AA) in vitro, which has a high concentration and can be oxidized at a potential close to DA and 5-HT at a conventional electrode, combined with the overlapping voltammetric signal of DA and 5-HT at a bare electrode. Herein, chitosan (CS) was used as a stabilizing matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs) were modified onto the microelectrode array (MEA). The CS-MWCNT hybrid film-modified MEA was quite effective at simultaneously recognizing these species in a mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three well-defined oxidation peaks in differential pulse voltammetry (DPV) at −80 mV, 105 mV and 300 mV (versus Ag|AgCl), respectively. The linear responses were obtained in the range of 5 × 10−6 M to 2 × 10−4 M for DA (r = 0.996) and in the range of 1 × 10−5 M to 3 × 10−4 M for 5-HT (r = 0.999) using the DPV under the presence of a single substance. While DA coexisted with 5-HT in the interference of 3 × 10−4 M AA, the linear responses were obtained in the range of 1 × 10−5 M to 3 × 10−4 M for selective molecular recognition of DA (r = 0.997) and 5-HT (r = 0.997) using the DPV. Therefore, this proposed MEA was successfully used for selective molecular recognition and determination of DA and 5-HT using the DPV, which has a potential application for real-time determination in vitro experiments