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Extracellular vesicles (EVs) are key mediators in the communication between cancer cells and their microenvironment, significantly influencing drug resistance. This review provides a comprehensive analysis of the roles of EVs in promoting drug resistance through mechanisms such as drug efflux, apoptosis resistance, autophagy imbalance, and tumor microenvironment modulation. Despite extensive research, details of EVs biogenesis, cargo selection, and specific pathways in EVs-mediated drug resistance are not fully understood. This review critically examines recent advancements, highlighting key studies that elucidate the molecular mechanisms of EVs functions. Additionally, innovative therapeutic strategies targeting EVs are explored, including inhibiting EVs biogenesis, engineering EVs for drug delivery, and identifying resistance-inhibiting molecules within EVs. By integrating insights from primary research and proposing new directions for future studies, this review aims to advance the understanding of EVs in cancer biology and foster effective interventions to mitigate drug resistance in cancer therapy.

Nanosilver is an environment-friendly, harmless alternative of traditional disinfectants which can be potentially applied in the sericulture industry. However, the effects of nanosilver on the intestinal bacterial community of the silkworms ( Bombyx mori L.) are unclear. In this study, Illumina MiSeq high-throughput sequencing technology was used to assess the intestinal bacterial community in both male and female silkworms while treated with different concentrations of nanosilver. We found that nanosilver significantly influenced the composition of silkworm intestinal bacterial community on the different taxonomic levels. Most conspicuously, the abundance of Firmicutes was increased by the treatment of 20 mg L −1 nanosilver but decreased by that of 100 mg L −1 nanosilver at the phylum level. The same trend was observed in Bacilli at the class level and in Enterococcus at the genus level. In some extreme cases, application of nanosilver eliminated the bacterium, e.g., Brevibacillus , but increased the population of several other bacteria in the host intestine, such as Blautia , Terrisporobacter , Faecalibacterium , and some bacteria could only be found in nanosilver treatment groups, e.g., Dialister . In addition, although nanosilver generally showed negative effects on the cocooning rate in a dose-dependent manner, we found that 20 mg L −1 nanosilver treatment significantly increased the body weight of silkworms and did not show negative effects on the survival rate. These results indicated that the intestinal bacteria community of silkworm larvae was significantly changed after nanosilver treatment which might consequently influence host growth and development.

It was assumed that dietary inclusion of Lactobacillus reuteri SL001 isolated from the gastric contents of rabbits could act as an alternative to feed antibiotics to improve the growth performance of broiler chickens. We randomly assigned 360 one-day-old AA white-feathered chicks in three treatments: basal diet (control), basal diet plus zinc bacitracin (antibiotic), and basal diet plus L. reuteri SL001 (SL001) treatment. The results showed the total BW gain and average daily gain (ADG) of broilers in SL001 treatment increased significantly (p < 0.05, respectively) compared with the control group from day 0 to 42. Moreover, we observed higher levels of immune globulins in both the SL001 group and the antibiotic group. Total antioxidant capacity and levels of antioxidant factors were also significantly increased (p ≤ 0.05, respectively) in the SL001 treatment group, while the interleukin 6, interleukin 4, creatinine, uric acid, total cholesterol, triglyceride, VLDL, LDL and malondialdehyde were remarkably decreased (p < 0.05, respectively). In the ileum of SL001 treatment broilers, the height of villi and the ratio of villi height to crypt depth were significantly increased (p < 0.05). Meanwhile, the crypt depth reduced (p < 0.01) and the ratio of villi height to crypt depth increased (p < 0.05) in the jejunum compared to the control. The abundance of microbiota increased in the gut of broilers supplemented with SL001. Dietary SL001 significantly increased the relative abundance of Actinobacteria in the cecal contents of broilers (p < 0.01) at the phylum level. In conclusion, L. reuteri SL001 supplementation promotes the growth performance of broiler chickens and exhibits the potential application value in the industry of broiler feeding.

•We constructed non-hemolytic rSLYP353L mutant with single amino acid substitute.•The non-hemolytic rSLYP353L elicited reduced inflammatory response in vivo.•Anti-SLYP353L antisera protected mice from acute death after infection with S. suis.•Infected mice death within 24h is not due to obvious pathological damage to organs.•Immunization with rSLYP353L caused reduced inflammatory response to S. suis infection. Streptococcus suis is a persistent global hazard in the swine industry and an emerging threat to public health. The high mortality in China following outbreaks of streptococcal toxic shock syndrome (STSS) underscores the urgency for effective prevention. A limited understanding of the pathogenesis of S. suis in STSS may explain the lack of biological products for prevention. Suilysin (SLY) is an important virulence factor in the pathogenesis of S. suis. To identify a candidate vaccine for S. suis-induced STSS, we constructed a recombinant non-hemolytic mutant of SLY that has hemagglutination activity, rSLYP353L, and evaluated its ability to induce inflammatory response and prevent fatal S. suis infection in mice. The rSLYP353L mutant, as compared with hemolytic rSLY, elicited lower levels of IL-6, KC and IL-10 at 3h and 5h post-treatment (p<0.05), indicating that hemolytic activity is associated with rSLY-mediated inflammation. Furthermore, passive immunization with anti-SLYP353L antisera protected mice from acute death after infection with S. suis SC84 (p<0.05). Effects were not due to protection against tissue damage, as S. suis SC84 caused no detectable histopathological lesions in mice within 24h. However, immunization with rSLYP353L caused significantly reduced levels of KC and IL-1β at 6 and 9h post-challenge and IL-6 at 9h post-challenge (p<0.05). In conclusion, rSLYP353L may provide a potential vaccine for protection against S. suis-induced STSS due to its reduction in proinflammatory response early in S. suis infection.

Epstein–Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB 23–431 . Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. Epstein–Barr virus (EBV) is involved in the development of some cancers including nasopharyngeal carcinoma. Here, the authors show that a direct interaction between the viral protein gB and a host protein, neuropilin 1, is required for EBV infection of nasopharyngeal epithelial cells.

Background Shiga toxin-producing Escherichia coli (STEC) is recognized as an important human diarrheal pathogen. Swine plays an important role as a carrier of this pathogen. In this study we determined the prevalence and characteristics of STEC from healthy swine collected between May 2011 and August 2012 from 3 cities/provinces in China. Results A total of 1003 samples, including 326 fecal, 351 small intestinal contents and 326 colon contents samples, was analyzed. Two hundred and fifty five samples were stx -positive by PCR and 93 STEC isolates were recovered from 62 stx -positive samples. Twelve O serogroups and 19 O:H serotypes including 6 serotypes (O100:H20/[H20], O143:H38/[H38], O87:H10, O172:H30/[H30], O159:H16, O9:H30/[H30]) rarely found in swine and ruminants were identified. All 93 STEC isolates harbored stx 2 only, all of which were stx 2e subtype including 1 isolate being a new variant of stx 2e . 53.76%, 15.05% and 2.15% STEC isolates carried astA , hlyA and ehxA respectively. Four STEC isolates harbored the high-pathogenicity island. Of the 15 adherence-associated genes tested, 13 ( eae , efa1 , iha , lpfA O113 , lpfA O157/OI-154 , lpfA O157/OI-141 , toxB , saa , F4, F5, F6, F17 or F41) were all absent while 2 ( paa and F18) were present in 7 and 4 STEC isolates respectively. The majority of the isolates were resistant to tetracycline (79.57%), nalidixic acid (78.49%), trimethoprim-sulfamethoxazole (73.12%) and kanamycin (55.91%). The STEC isolates were divided into 63 pulsed-field gel electrophoresis patterns and 21 sequence types (STs). Isolates of the same STs generally showed the same or similar drug resistance patterns. A higher proportion of STEC isolates from Chongqing showed multidrug resistance with one ST (ST3628) resistant to 14 antimicrobials. Conclusions Our results indicate that swine is a significant reservoir of STEC strains in China. Based on comparison by serotypes and sequence types with human strains and presence of virulence genes, the swine STEC may have a low potential to cause human disease.

Background. Streptococcus suis emerged to cause an unusual outbreak of streptococcal toxic-shock-like syndrome (STSLS) in 2005. The mechanisms involved are unknown. Methods. Clinical, laboratory, and epidemiologic data on patients infected with culture-confirmed S. suis were analyzed. The strain involved in the outbreak, “epidemic” strain ST7, was compared with both a classical highly pathogenic strain, ST1, and an intermediately pathogenic strain, ST25, to determine both its capacity to induce cytokines in experimentally infected mice and its genomic difference. Results. Of 38 patients infected with culture-confirmed S. suis, 14 presented with STSLS. During the early phase of the disease, serum levels of interleukin (IL)-1β, IL-6, IL-8, IL-12p70, interferon-γ, and tumor necrosis factor-α were more elevated in patients with STSLS than in those with meningitis only. Serum levels of proinflammatory cytokines were significantly higher in mice infected with ST7 than in those infected with either ST1 or ST25. Genomic comparisons with ST25 showed that ST1 had acquired 132 genomic islands, including 5 pathogenicity islands, and that ST7, the epidemic strain, had acquired an additional 5 genomic islands. Conclusion. Intermediately pathogenic strain ST25 has evolved to become highly pathogenic strain ST1, which, in turn, has more recently evolved to become epidemic strain ST7. ST7 has the ability to stimulate the production of massive amounts of proinflammatory cytokines, leading to STSLS.

Streptococcus suis is a persistent global hazard in the swine industry and an emerging threat to public health. The high mortality in China following outbreaks of streptococcal toxic shock syndrome (STSS) underscores the urgency for effective prevention. A limited understanding of the pathogenesis of S. suis in STSS may explain the lack of biological products for prevention. Suilysin (SLY) is an important virulence factor in the pathogenesis of S. suis. To identify a candidate vaccine for S. suis-induced STSS, we constructed a recombinant non-hemolytic mutant of SLY that has hemagglutination activity, rSLY(P353L), and evaluated its ability to induce inflammatory response and prevent fatal S. suis infection in mice. The rSLY(P353L) mutant, as compared with hemolytic rSLY, elicited lower levels of IL-6, KC and IL-10 at 3h and 5h post-treatment (p<0.05), indicating that hemolytic activity is associated with rSLY-mediated inflammation. Furthermore, passive immunization with anti-SLY(P353L) antisera protected mice from acute death after infection with S. suis SC84 (p<0.05). Effects were not due to protection against tissue damage, as S. suis SC84 caused no detectable histopathological lesions in mice within 24h. However, immunization with rSLY(P353L) caused significantly reduced levels of KC and IL-1β at 6 and 9h post-challenge and IL-6 at 9h post-challenge (p<0.05). In conclusion, rSLY(P353L) may provide a potential vaccine for protection against S. suis-induced STSS due to its reduction in proinflammatory response early in S. suis infection.

Recent research studies have revealed that probiotics such as Lactobacillus are good antibiotic alternatives in the poultry industry. We previously isolated Lactobacillus reuteri SL001 from the gastric contents of rabbits and proved that dietary inclusion of SL001 could positively improve the composition of the intestinal bacterial community in Alzheimer's disease model mice. In the present study, we explored the effects of dietary SL001 on growth performance, health-related parameters, intestinal morphology and microbiota of broiler chickens. Our results showed that SL001 supplementation in diets promoted the growth performance of broilers, strengthened immunity, and improved antioxidant stress as well as intestinal morphology and microbiota, implying its potential application in boiler feeding. It was assumed that dietary inclusion of Lactobacillus reuteri SL001 isolated from the gastric contents of rabbits could act as an alternative to feed antibiotics to improve the growth performance of broiler chickens. We randomly assigned 360 one-day-old AA white-feathered chicks in three treatments: basal diet (control), basal diet plus zinc bacitracin (antibiotic), and basal diet plus L. reuteri SL001 (SL001) treatment. The results showed the total BW gain and average daily gain (ADG) of broilers in SL001 treatment increased significantly (p < 0.05, respectively) compared with the control group from day 0 to 42. Moreover, we observed higher levels of immune globulins in both the SL001 group and the antibiotic group. Total antioxidant capacity and levels of antioxidant factors were also significantly increased (p ≤ 0.05, respectively) in the SL001 treatment group, while the interleukin 6, interleukin 4, creatinine, uric acid, total cholesterol, triglyceride, VLDL, LDL and malondialdehyde were remarkably decreased (p < 0.05, respectively). In the ileum of SL001 treatment broilers, the height of villi and the ratio of villi height to crypt depth were significantly increased (p < 0.05). Meanwhile, the crypt depth reduced (p < 0.01) and the ratio of villi height to crypt depth increased (p < 0.05) in the jejunum compared to the control. The abundance of microbiota increased in the gut of broilers supplemented with SL001. Dietary SL001 significantly increased the relative abundance of Actinobacteria in the cecal contents of broilers (p < 0.01) at the phylum level. In conclusion, L. reuteri SL001 supplementation promotes the growth performance of broiler chickens and exhibits the potential application value in the industry of broiler feeding.

The past decades have witnessed a boom in nanotechnology that has led to increasing production and application of silver nanoparticles (AgNPs) in the textile industry due to their antimicrobial properties. Increase in the manufacture and use of NPs inevitably has resulted in their increased release into aquatic environments resulting in the exposure of organisms living in these environments. Recently, the risk of exposure to NPs and the potential interaction with biological systems has received increasing attention. The present study investigated the potential effects of predator cues on the toxicity of environmentally relevant concentrations of AgNPs in Daphnia carinata at organismal and biochemical levels. The results of this study show that exposure to environmentally relevant concentrations of AgNPs can result in adverse effects on daphnids with 24- and 48-h LC 50 values of 3.56 and 1.75 μg/L, respectively. Furthermore, significant inhibition of reproduction was observed at concentrations as low as 0.5 μg/L. Exposure to predator cues alone resulted in an increase in reproduction and inhibition of superoxide dismutase activity in daphnids. However, coexposure to predator cues interacted in an antagonistic manner with AgNPs with a 24-h LC 50 value of 10.81 μg/L compared with 3.56 μg/L for AgNPs alone. In summary, AgNPs could pose risks to aquatic invertebrates at environmentally relevant concentrations. Interestingly, the presence of other factors, such as predator cues, moderated the effects of exposure to AgNPs. Therefore, there is a need to further investigate the potential interactions between NPs and biological factors that can modulate toxicity of NPs for application to the risk assessment of aquatic invertebrates.