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Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

The type I interferon (IFN-I) signaling pathway is an important part of the innate immune response and plays a vital role in controlling and eliminating pathogens. African swine fever virus (ASFV) encodes various proteins to evade the host’s natural immunity. However, the molecular mechanism by which the ASFV-encoded proteins inhibit interferon production remains poorly understood. In the present study, ASFV MGF360-11L inhibited cGAS, STING, TBK1, IKKε, IRF7 and IRF3-5D mediated activation of the IFN-β and ISRE promoters, accompanied by decreases in IFN-β, ISG15 and ISG56 mRNA expression. ASFV MGF360-11L interacted with TBK1 and IRF7, degrading TBK1 and IRF7 through the cysteine, ubiquitin–proteasome and autophagy pathways. Moreover, ASFV MGF360-11L also inhibited the phosphorylation of TBK1 and IRF3 stimulated by cGAS-STING overexpression. Truncation mutation analysis revealed that aa 167-353 of ASFV MGF360-11L could inhibit cGAS-STING-mediated activation of the IFN-β and ISRE promoters. Finally, the results indicated that ASFV MGF360-11L plays a significant role in inhibiting IL-1β, IL-6 and IFN-β production in PAM cells (PAMs) infected with ASFV. In short, these results demonstrated that ASFV MGF360-11L was involved in regulating IFN-I expression by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism by which the ASFV MGF360-11L protein antagonizes IFN-I-mediated antiviral activity, which will help to provide new strategies for the treatment and prevention of ASF.

Influenza remains a severe respiratory illness that poses significant global health threats. Recent studies have identified distinct microbial communities within the respiratory tract, from nostrils to alveoli. This research explores specific anti-influenza respiratory microbes using a mouse model supported by 16S rDNA sequencing and untargeted metabolomics. The study found that transferring respiratory microbes from mice that survived H9N2 influenza to antibiotic-treated mice enhanced infection resistance. Notably, the levels of Aeromicrobium were significantly higher in the surviving mice. Mice pre-treated with antibiotics and then inoculated with Aeromicrobium camelliae showed reduced infection severity, as evidenced by decreased weight loss, higher survival rates, and lower lung viral titres. Metabolomic analysis revealed elevated LysoPE (16:0) levels in mildly infected mice. In vivo and in vitro experiments indicated that LysoPE (16:0) suppresses inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2) expression, enhancing anti-influenza defences. Our findings suggest that Aeromicrobium camelliae could serve as a potential agent for influenza prevention and a prognostic marker for influenza outcomes.

Azo dyes such as Congo red can easily cause cancer when they come into contact or are absorbed by the human body, so it is urgent to find a fast and simple method for degrading Congo red. In order to better achieve this research goal, an ultrasonic method was used to degrade Congo red solution in a rotating flow field. The concentration of hydroxyl radical in the solution was significantly increased under the action of ultrasonic cavitation, chemical action of zero valent iron, and mechanochemistry. Under the strong oxidation of hydroxyl radical and the reduction of nano zero valent iron peeled off in the reaction process, the reaction speed is significantly accelerated and should promote the reaction. The effect of increasing stirring and adding iron powder particles on ultrasonic cavitation was studied by numerical simulation, and the yield of hydroxyl radical in the system was measured by fluorescence analysis. The experimental results show that, first, the rotating field formed by mixing increases the uniformity of ultrasonic sound field distribution and the amplitude of sound pressure, and it improves the cavitation intensity. In the effective dispersion area, the strong ultrasonic wave can form a temporary high-energy microenvironment in the suspension through cavitation, generate high strength shockwaves and micro jets, and thus significantly deagglomerate the iron powder aggregates. The addition of iron powder particles then provides a complementary Fenton reagent for the degradation reaction. The concentration of hydroxyl radicals in the solution was significantly increased by the synergy of the two actions. The degradation rate of Congo red reached more than 99% after 30 min of reaction.

Ubiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Lycorine, a natural alkaloid, has been indicated to have various physiological effects, including a potential effect against cancer. However, the anticancer effect of lycorine on osteosarcoma (OS) and the detailed molecular mechanisms involved remain unclear. The purpose of this study was to examine the effect of lycorine on human OS and elucidated it underlying mechanisms In vitro assays, OS cells were treated with lycorine at various concentrations. Then the cell proliferation, colony formation, cell cycle distribution, apoptosis, migration and invasion were assayed to detect the anticancer effect of lycorine on OS cell lines. Western blotting analysis was used to verify the expression of related proteins. In addition, the mouse xenograft model was performed to evaluate lycorine's therapeutic potential on OS in vivo. The in vitro results demonstrated that lycorine induced apoptosis and cell cycle arrest and suppressed the migration and invasion by suppressing constitutive signal transducers and activators of transcription 3 (STAT3) activation through enhancing the expression of SH2 domain-containing phosphatase 1 (SHP-1) and downregulating the expression of STAT3 target proteins. Moreover, our mouse xenograft model revealed that lycorine inhibited the tumor growth in vivo. These results demonstrated that the anti-OS effects of lycorine were at least partly due to the suppression of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2)/STAT3 pathway. Taken together, these results indicate that lycorine possesses the potential to be a promising candidate in clinical therapy for human OS in the future.

Background The Porcine Epidemic Diarrhea Virus (PEDV) is one of the major challenges facing the global pig farming industry, and vaccines and treatments have proven difficult in controlling its spread. Faecalibacterium prausnitzii ( F.prausnitzii ), a key commensal bacterium in the gut, has been recognized as a promising candidate for next-generation probiotics due to its potential wide-ranging health benefits. A decrease in F.prausnitzii abundance has been associated with certain viral infections, suggesting its potential application in preventing intestinal viral infections. In this study, we utilized a piglet model to examine the potential role of F.prausnitzii in PEDV infections. Results A piglet model of PEDV infection was established and supplemented with F.prausnitzii , revealing that F.prausnitzii mitigated PEDV infection. Further studies found that outer membrane vesicles (OMVs) are the main functional components of F.prausnitzii , and proteomics, untargeted metabolomics, and small RNA-seq were used to analyze the composition of OMVs. Exhaustion of the gut microbiota demonstrated that the function of Fp. OMVs relies on the presence of the gut microbiota. Additionally, metagenomic analysis indicated that Fp. OMVs altered the gut microbiota composition, enhancing the abundance of Faecalibacterium prausnitzii , Prevotellamassilia timonensis , and Limosilactobacillus reuteri . Untargeted metabolomics analysis showed that Fp. OMVs increased phosphatidylcholine (PC) levels, with PC identified as a key metabolite in alleviating PEDV infection. Single-cell sequencing revealed that PC altered the relative abundance of intestinal cells, increased the number of intestinal epithelial cells, and reduced necroptosis in target cells. PC treatment in infected IPEC-J2 and Vero cells alleviated necroptosis and reduced the activation of the RIPK1-RIPK3-MLKL signaling axis, thereby improving PEDV infection. Conclusion F.prausnitzii and its OMVs play a critical role in mitigating PEDV infections. These findings provide a promising strategy to ameliorate PEDV infection in piglets. C4Fezg3AfHMZLAw-1CksA_ Video Abstract Graphical Abstract

SARS-CoV-2, the pathogen of COVID-19, is spreading around the world. Different individuals infected with COVID-19 have different manifestations. It is urgent to determine the risk factors of disease progress of COVID-19. 364 patients diagnosed with COVID-19, who were admitted to Wuhan Pulmonary Hospital from February 3, 2020 to March 16, 2020, were divided into mild, ordinary, severe, and critical groups, according to Chinese novel coronavirus pneumonia diagnosis and treatment plan. Peripheral blood IL-6 and leukocyte characteristics were analyzed, to evaluate the correlation with the severity of COVID-19. The levels of peripheral blood IL-6 were 2.35 ± 0.46 pg/ml (mild), 6.48 ± 1.13 pg/ml (ordinary), 20.30 ± 5.15 pg/ml (severe), and 123.48 ± 44.31 pg/ml (critical). The leukocytes were 5.70 ± 0.41×10 9 /L (mild), 6.21 ± 0.14×10 9 /L (ordinary), 6.37 ± 0.26×10 9 /L (severe), and 10.03 ± 1.43×10 9 /L (critical). The lymphocytes were 1.46 ± 0.19×10 9 /L (mild), 1.89 ± 0.14×10 9 /L (ordinary), 1.26 ± 0.07×10 9 /L (severe), and 1.17 ± 0.23×10 9 /L (critical). The neutrophils were 3.63 ± 0.36×10 9 /L (mild), 3.78 ± 0.11×10 9 /L (ordinary), 4.47 ± 0.25×10 9 /L (severe), and 7.92 ± 1.19×10 9 /L (critical). The monocytes were 0.42 ± 0.05×10 9 /L (mild), 0.44 ± 0.01×10 9 /L (ordinary), 0.46 ± 0.02×10 9 /L (severe), and 0.78 ± 0.25×10 9 /L (critical). Conclusively, increase of peripheral blood IL-6 and decrease of lymphocytes can be used as the indicators of severe COVID-19. The increase of neutrophils and monocytes was noticed in critical cases of COVID-19, suggesting that the increase of neutrophils and monocytes should be considered as risk factors of critical cases of COVID-19. Peripheral blood IL-6 and leukocyte characteristics were also analyzed in different age groups. The increase of serum IL-6, decrease of lymphocytes, and increase of neutrophils were noticed in patients over 60 years old.

Background Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. Methods In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 10 2 live oocysts of coccidia. A total of 5 × 10 4 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. Results The results showed that the proportion of CD4 + and CD8 + T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased ( P  < 0.05). The relative body weight gains were increased and the number of oocysts per gram (OPG) was decreased after E. tenella challenge. Moreover, the lesion scores and histopathological cecum sections showed that recombinant L. plantarum can significantly relieve pathological damage in the cecum. The ACI was 170.89 in the recombinant L. plantarum group, which was higher than the 150.14 in the commercial vaccine group. Conclusions These above results indicate that L. plantarum expressing RON2 improved humoral and cellular immunity and enhanced immunoprotection against E. tenella . The protective efficacy was superior to that of vaccination with the commercial live oocyst vaccine. This study suggests that recombinant L. plantarum expressing the RON2 protein provides a promising strategy for vaccine development against coccidiosis. Graphical Abstract

Background Avian coccidiosis posts a severe threat to poultry production. In addition to commercial attenuated vaccines, other strategies to combat coccidiosis are urgently needed. Lactobacillus plantarum has been frequently used for expression of foreign proteins as an oral vaccine delivery system using traditional erythromycin resistance gene ( erm ). However, antibiotic selection markers were often used during protein expression and they pose a risk of transferring antibiotic resistance genes to the environment, and significantly restricting the application in field production. Therefore, a food-grade recombinant L. plantarum vaccine candidate would dramatically improve its application potential in the poultry industry. Results In this study, we firstly replaced the erythromycin resistance gene ( erm ) of the pLp_1261Inv-derived expression vector with a non-antibiotic, asd - alr fusion gene, yielding a series of non-antibiotic and reliable, food grade expression vectors. In addition, we designed a dual-expression vector that displayed two foreign proteins on the surface of L. plantarum using the anchoring sequences from either a truncated poly-γ-glutamic acid synthetase A (pgsA′) from Bacillus subtilis or the L. acidophilus surface layer protein ( SlpA ). EGFP and mCherry were used as marker proteins to evaluate the surface displayed properties of recombinant L. plantarum strains and were inspected by western blot, flow cytometry and fluorescence microscopy. To further determine its application as oral vaccine candidate, the AMA1 and EtMIC2 genes of E. tenella were anchored on the surface of L. plantarum strain. After oral immunization in chickens, the recombinant L. plantarum strain was able to induce antigen specific humoral, mucosal, and T cell-mediated immune responses, providing efficient protection against coccidiosis challenge. Conclusions The novel constructed food grade recombinant L. plantarum strain with double surface displayed antigens provides a potential efficient oral vaccine candidate for coccidiosis.