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The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses. [Display omitted] • Tregs are especially recruited to peri-lymphatic region in tumor stroma by mregDCs • The Treg-mregDC-lymphatic niche sustains Treg activation • Activated Tregs hinder tumor antigen trafficking to dLNs and anti-tumor immunity • The crosstalk between Tregs and mregDCs predicts worse outcome in human cancers You et al. show that Tregs are specifically recruited to peri-lymphatic stroma region of colorectal cancer by mregDC forming Treg-mregDC-lymphatic niche, where they acquire activation signature and restrain the trafficking of the tumor antigens to the draining lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. [ABSTRACT FROM AUTHOR]

Ceramics-polymer nanocomposites consisting of core-shell structured BaTiO 3 @Al 2 O 3 (BT@Al 2 O 3 ) nanoparticles as the filler and poly(vinylidene fluoride) (PVDF) as the polymer matrix were fabricated by solution casting. At the same volume fraction, the BT@Al 2 O 3 /PVDF nanocomposites, with larger dielectric constant and higher energy density, outperformed the BT/PVDF nanocomposites. The 2.5 vol% BT@Al 2 O 3 /PVDF nanocomposites at 360 MV/m had a double more energy density than pure PVDF at 400 MV/m (6.19 vs. 2.30 J/cm 3 ), and a remarkably 42% lower remnant polarization than the 2.5 vol% BT/PVDF nanocomposites (0.99 vs. 1.69 μC/cm 2 at 300 MV/m). Such significant enhancement was closely related to the surface modification by Al 2 O 3 , which improved the insulation of BT nanoparticles and reduced the contrast of dielectric constant between the filler and the PVDF matrix. [ABSTRACT FROM AUTHOR]

• TLR4 was activated on the membrane of mononuclear macrophage after PHP treatment. • After PHP treatment, the intestinal mucosa was more complete. • The contents of ScFA increased after PHP treatment. • The type and abundance of intestinal flora in colitis mice were changed after PHP treatment. Radix Pseudostellariae , the root of Pseudostellaria heterophylla (Miq.) Pax , has historically been used as medicine food homology plant for thousand years in China. Herein, PHP, a water soluble polysaccharides from Radix Pseudostellariae , was isolated and identified by HPGPC, GC–MS, FT-IR, and scanning electron microscopy. Results showed that PHP (Mw = 1.07 × 104 kDa) mainly consisted of rhamnose, galacturonic acid, glucose, galactose, arabinose, fucose in a molar ratio of 0.055:0.208:0.306:0.055:0.753:0.594:0.014. It contained nine types of linkages, including → 6)-Gal p (A)-(1→, →6)-Gal p -(1→, →3)-Ara p -(1→, Gal p -(1→, →3)-Rha p -(1→, Glu p -(1→, →3)-Ara f -(1→, →2,3,4)-Man p -(1 → and → 3,4)-Fuc p -(1→. Morphology analysis showed that PHP took flakes with irregular size and properties. It significantly activated TLR4 in vivo. In DSS induced mouse-acute-colitis molds, PHP90-3a improved and the colon length was on ulcerative in mice. the production of IL-1β and TNF-α were decreased. The intestinal mucosa was more complete, there were much more goblet cells, and the infiltration of lymphocytes and neutrophils was significantly decreased. The content of SCFA increased, whereas acetic acid, propionic acid and butyric acid increased. 16S RNA sequencing and OTUs cluster analysis revealed that Bacteroides and Pseudomonas were the dominant intestinal flora. The analysis of community thermogram showed that the abundance ratio of Pseudomonas and Bacteroides (F/B) was significantly lower than the dominant group and significantly inhibited the levels of Verrucomicrobia and Akkermansia. Altogether, the data suggested that the anti-inflammatory activity might be implicated with the activation of TLR4 signal pathways, reducing IL-1β and TNF-α, and the regulation of mucosal immunity and the composition of intestinal flora. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The main problem addressed in this study is the anti-inflammatory effects of Magnolol-a natural extract and the main bioactive component from Magnolia. • U937 LO-2 cells culture and DSS-treated experimental mice were utilized to analyze inflammatory cytokines, proteins activation in MAPK, NF-κB signal pathways regulation, the phagocytosis immunoregulatory effects in vitro and in vivo with that permits analysis of Magnolol contributors to the inflammatory bowel diseases. • By studying living human cell lines, we identified Magnolol previously unknown contributions of enhancement of phagocytosis, specific pro-inflammatory factors IL-6 and IL-1β significantly depression, p-JNK, p-P38, p-IκBα and p-P65 were down-regulation. • We provide experimental evidence to show that Magnolol as a drug could be used to improve human inflammatory bowel disease and gain new insights into the mechanisms involved phagocytosis immunoregulatory effects, MAPK and NF-κB signal pathways. Abstract Magnolol is a natural extract and the main bioactive component from Chinese medicine-Magnolia. We speculate that it's functional action might be associated with the anti-inflammatory effects of magnolol. Herein, the main purpose was to elucidate the phagocytic immune function and anti-inflammatory activities associated. The toxicity of magnolol on U937 and LO-2 cells was assayed by MTT, flow cytometry and laser scanning confocal microscope was utilized to detect the phagocytosis effect on U937 cells, C57BL/6 mice and the follow-up hematoxylin-eosin staining methods were used to evaluate its bioactivity in vivo. The results showed that magnolol had dose dependent effects on enhancement of phagocytosis ability and significantly inhibited the NO production at the concentration range from10 to 40 μM. Furthermore, Magnolol significantly reduced the gene expression and protein release of IL-1β and TNF-α. However, the p-ERK1/2 in MAPK signaling pathway was not significantly affected by magnolol, whereas p-JNK and p-P38 were down-regulated. Magnolol also inhibited the expression of p-IκBα and p-P65 of NF-κB signaling pathways. The loss of body weight and the shorter length of colon were significantly improved in DSS-treated colitis C57BL/6 mice after the administration of magnolol. The cytokines of pro-inflammatory factors TNF-α, IL-6 and IL-1β attenuated significantly in a concentration dependent manner. The histopathological manifestations of 5–20 mg/kg after the treatment magnolol were markedly improved in the DSS-treated mice. These findings showed that magnolol exerted an anti-inflammatory effect through immunoregulatory phagocytosis, MAPK and NF-κB signaling pathways. Our results provide experimental evidence and theory basis for research on anti-inflammatory effects for magnolol as a potentially anti-inflammatory drug candidate. [ABSTRACT FROM AUTHOR]

• AMGs carried by cyanophages isolated in different environments are not the same. • Carrying of AMG in cyanophage is related to host and environment. • The AMGs carried by the cyanophages help them and their host adapt to the environment. Synechococcus dominate picocyanobacterial communities in coastal environments. However, only a few Synechococcus phages have been described from the coastal seas of the Northwest Pacific Ocean. Here a new Synechococcus phage, S-B43 was isolated from the Bohai Sea, a semi-closed coastal sea of the Northwest Pacific Ocean. S-B43 is a member of Myoviridae , containing 275 predicted open reading frames. Fourteen auxiliary metabolic genes (AMG) were identified from the genome of S-B43, including five photosynthetic associated genes and several AMGs related to its adaption to the high turbidity and eutrophic coastal environment with a low ratio of phosphorus to nitrogen (HNLP). The occurrences of 31 AMGs among 34 cyanophage genomes indicates that AMGs zwf , gnd , speD , petF and those coding for FECH and thioredoxin were more common in coastal areas than in the open ocean and AMGs pebS and ho1 were more prevalent in the open ocean. The occurrence of cyanophage AMGs in different environments might be a reflection of the environmental adaption of their hosts. This study contributes to our understanding of the interactions between cyanobacteria and cyanophages and their environmental adaption to the coastal environment. [ABSTRACT FROM AUTHOR]