Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

PURPOSE: To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). METHODS: A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50 min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. RESULTS: The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. CONCLUSION: The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

Salmonella Enteritidis antitoxin DinJ inhibits NLRP3-dependent canonical inflammasome activation in macrophages.

The inflammasome is a pivotal component of the innate immune system, acting as a multiprotein complex that plays an essential role in detecting and responding to microbial infections. Salmonella Enteritidis have evolved multiple mechanisms to regulate inflammasome activation and evade host immune system clearance. Through screening S. Enteritidis C50336ΔfliC transposon mutant library, we found that the insertion mutant of dinJ increased inflammasome activation. In this study, we demonstrated the genetic connection between the antitoxin DinJ and the toxin YafQ in S. Enteritidis, confirming their co-transcription. The deletion mutant ΔfliCΔdinJ increased cell death and IL-1ß secretion in J774A.1 cells. Western blotting analysis further showed elevated cleaved Caspase-1 product (p10 subunits) and IL-1ß secretion in cells infected with ΔfliCΔdinJ compared to cells infected with ΔfliC. DinJ was found to inhibit canonical inflammasome activation using primary bone marrow-derived macrophages (BMDMs) from Casp-/- C57BL/6 mice. Furthermore, DinJ specifically inhibited NLRP3 inflammasome activation, as demonstrated in BMDMs from Nlrp3-/- and Nlrc4-/- mice. Fluorescence resonance energy transfer (FRET) experiments confirmed the translocation of DinJ into host cells during infection. Finally, we revealed that DinJ could inhibit the secretion of IL-1ß and IL-18 in vivo, contributing to S. Enteritidis evading host immune clearance. In summary, our findings provide insights into the role of DinJ in modulating the inflammasome response during S. Enteritidis infection, highlighting its impact on inhibiting inflammasome activation and immune evasion.

Transcription suppression of GABARAP mediated by lncRNA XIST-EZH2 interaction triggers caspase-11-dependent inflammatory injury in ulcerative colitis.

BACKGROUND: We have previously found that enhancer of zeste homolog 2 (EZH2) is correlated with inflammatory infiltration and mucosal cell injury in ulcerative colitis (UC). This study aims to analyze the role of X-inactive specific transcript (XIST), a possible interactive long non-coding RNA of EZH2, in UC and to explore the mechanisms. METHODS: C57BL/6N mice were treated with dextran sulfate sodium (DSS), and mouse colonic mucosal epithelial cells were treated with DSS and lipopolysaccharide (LPS) for UC modeling. The UC-related symptoms in mice, and the viability and apoptosis of mucosal epithelial cells were determined. Inflammatory injury in animal and cellular models were assessed through the levels of ACS, occludin, IL-1ß, IL-18, TNF-α, caspase-1, and caspase-11. Molecular interactions between XIST, EZH2, and GABA type A receptor-associated protein (GABARAP) were verified by immunoprecipitation assays, and their functions in inflammatory injury were determined by gain- or loss-of-function assays. RESULTS: XIST was highly expressed in DSS-treated mice and in DSS + LPS-treated mucosal epithelial cells. It recruited EZH2, which mediated gene silencing of GABARAP through H3K27me3 modification. Silencing of XIST alleviated body weight loss, colon shortening, and disease active index of mice and reduced inflammatory injuries in their colon tissues. Meanwhile, it reduced apoptosis and inflammation in mucosal epithelial cells. However, these alleviating effects were blocked by either EZH2 overexpression or GABARAP knockdown. Rescue experiments identified caspase-11 as a key effector mediating the inflammatory injury following GABARAP loss. CONCLUSION: This study suggests that the XIST-EZH2 interaction-mediated GABARAP inhibition activates caspase-11-dependent inflammatory injury in UC.

Melatonin, a phytohormone for enhancing the accumulation of high-value metabolites and stress tolerance in microalgae: Applications, mechanisms, and challenges.

High-value metabolites, such as carotenoids, lipids, and proteins, are synthesized by microalgae and find applications in various fields, including food, health supplements, and cosmetics. However, the potential of the microalgal industry to serve these sectors is constrained by low productivity and high energy consumption. Environmental stressors can not only stimulate the accumulation of secondary metabolites in microalgae but also induce oxidative stress, suppressing cell growth and activity, thereby resulting in a decrease in overall productivity. Using melatonin (MT) under stressful conditions is an effective approach to enhance the productivity of microalgal metabolites. This review underscores the role of MT in promoting the accumulation of high-value metabolites and enhancing stress resistance in microalgae under stressful and wastewater conditions. It discusses the underlying mechanisms whereby MT enhances metabolite synthesis and improves stress resistance. The review also offers new perspectives on utilizing MT to improve microalgal productivity and stress resistance in challenging environments.

Microevolution of Salmonella 4,[5],12:i:- derived from Salmonella enterica serovar Typhimurium through complicated transpositions.

Salmonella enterica subsp. enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-), derived from S. Typhimurium, has become the dominant serotype causing human salmonellosis. In this study, we define the genetic mechanism of the generation of Salmonella 4,[5],12:i:- from S. Typhimurium through complicated transpositions and demonstrate that Salmonella 4,[5],12:i:- displays more efficient colonization and survival abilities in mice than its parent S. Typhimurium strain. We identified intermediate strains carrying both resistance regions (RRs) and the fljAB operon for the generation of Salmonella 4,[5],12:i:-. The insertion of RR3 into the chromosomal hin-iroB site of S. Typhimurium produced RR3-S. Typhimurium as a primary intermediate. Salmonella 4,[5],12:i:- was then produced by replacing the fljAB operon and/or its flanking sequences through intramolecular transpositions mediated by IS26 and/or IS1R elements in RR3-S. Typhimurium, which was further confirmed both in vitro and in vivo. Overall, we demonstrate the molecular mechanism underlying the origin, generation, and advantage of RRs-Salmonella 4,[5],12:i:- from S. Typhimurium.

Efficient screening of adsorbed receptors for Salmonella phage LP31 and identification of receptor-binding protein.

The adsorption process is the first step in the lifecycle of phages and plays a decisive role in the entire infection process. Identifying the adsorption mechanism of phages not only makes phage therapy more precise and efficient but also enables the exploration of other potential applications and modifications of phages. Phage LP31 can lyse multiple Salmonella serotypes, efficiently clearing biofilms formed by Salmonella enterica serovar Enteritidis (S. Enteritidis) and significantly reducing the concentration of S. Enteritidis in chicken feces. Therefore, LP31 has great potential for many practical applications. In this study, we established an efficient screening method for phage infection-related genes and identified a total of 10 genes related to the adsorption process of phage LP31. After the construction of strain C50041ΔrfaL 58-358, it was found that the knockout strain had a rough phenotype as an O-antigen-deficient strain. Adsorption rate and transmission electron microscopy experiments showed that the receptor for phage LP31 was the O9 antigen of S. Enteritidis. Homology comparison and adsorption experiments confirmed that the tail fiber protein Lp35 of phage LP31 participated in the adsorption process as a receptor-binding protein. IMPORTANCE A full understanding of the interaction between phages and their receptors can help with the development of phage-related products. Phages like LP31 with the tail fiber protein Lp35, or a closely related protein, have been reported to effectively recognize and infect multiple Salmonella serotypes. However, the role of these proteins in phage infection has not been previously described. In this study, we established an efficient screening method to detect phage adsorption to host receptors. We found that phage LP31 can utilize its tail fiber protein Lp35 to adsorb to the O9 antigen of S. Enteritidis, initiating the infection process. This study provides a great model system for further studies of how a phage-encoded receptor-binding protein (RBP) interacts with its host's RBP binding target, and this new model offers opportunities for further theoretical and experimental studies to understand the infection mechanism of phages.

Comprehensive understanding of the regulatory mechanism by which selenium nanoparticles boost CO2 fixation and cadmium tolerance in lipid-producing green algae under recycled medium.

Recycled medium plus cadmium is a promising technique for reducing the cultivation cost and enhancing the yield of microalgae lipids. However, oxidative stress and cadmium toxicity significantly hinder the resulting photosynthetic efficiency, cell growth and cell activity. Herein, selenium nanoparticles (SeNPs) were used to increase the total biomass, biolipid productivity, and tolerance to cadmium. Wide-ranging analyses of photosynthesis, energy yield, fatty acid profiles, cellular ultrastructure, and oxidative stress biomarkers were conducted to examine the function of SeNPs in CO2 fixation and cadmium resistance in Ankistrodesmus sp. EHY. The application of 15 µM cadmium and 2 mg L-1 SeNPs further enhanced the algal biomass productivity and lipid productivity to 500.64 mg L-1 d-1 and 301.14 mg L-1 d-1, respectively. Moreover, the rates of CO2 fixation, chlorophyll synthesis and total nitrogen removal were similarly increased by the application of SeNPs. Exogenous SeNPs strengthened cell growth and cadmium tolerance by upregulating photosynthesis, the TCA cycle and the antioxidant system, reducing the uptake and translocation of cadmium, and decreasing the levels of reactive oxidative stress (ROS), extracellular polymeric substances (EPSs) and cellular Cd2+ level in EHY under recycled medium and cadmium stress conditions. Additionally, a maximum energy yield of 127.40 KJ L-1 and a lipid content of 60.15% were achieved in the presence of both SeNPs and cadmium stress. This study may inspire the efficient disposal of recycled medium and biolipid production while also filling the knowledge gaps regarding the mechanisms of SeNP functions in carbon fixation and cadmium tolerance in microalgae.

Salmonella Enteritidis T1SS protein SiiD inhibits NLRP3 inflammasome activation via repressing the mtROS-ASC dependent pathway.

Inflammasome activation is an essential innate immune defense mechanism against Salmonella infections. Salmonella has developed multiple strategies to avoid or delay inflammasome activation, which may be required for long-term bacterial persistence. However, the mechanisms by which Salmonella evades host immune defenses are still not well understood. In this study, Salmonella Enteritidis (SE) random insertion transposon library was screened to identify the key factors that affect the inflammasome activation. The type I secretion system (T1SS) protein SiiD was demonstrated to repress the NLRP3 inflammasome activation during SE infection and was the first to reveal the antagonistic role of T1SS in the inflammasome pathway. SiiD was translocated into host cells and localized in the membrane fraction in a T1SS-dependent and partially T3SS-1-dependent way during SE infection. Subsequently, SiiD was demonstrated to significantly suppress the generation of mitochondrial reactive oxygen species (mtROS), thus repressing ASC oligomerization to form pyroptosomes, and impairing the NLRP3 dependent Caspase-1 activation and IL-1ß secretion. Importantly, SiiD-deficient SE induced stronger gut inflammation in mice and displayed NLRP3-dependent attenuation of the virulence. SiiD-mediated inhibition of NLRP3 inflammasome activation significantly contributed to SE colonization in the infected mice. This study links bacterial T1SS regulation of mtROS-ASC signaling to NLRP3 inflammasome activation and reveals the essential role of T1SS in evading host immune responses.

Comparative genomic analysis reveals the potential transmission of Vibrio parahaemolyticus from freshwater food to humans.

Vibrio parahaemolyticus is an increasingly important foodborne pathogen that cause acute gastroenteritis in humans. However, the prevalence and transmission of this pathogen in freshwater food remains unclear. This study aimed to determine the molecular characteristics and genetic relatedness of V. parahaemolyticus isolates obtained from freshwater food, seafood, environmental, and clinical samples. A total of 138 (46.6%) isolates were detected from 296 food and environmental samples, and 68 clinical isolates from patients. Notably, V. parahaemolyticus was more prevalent in freshwater food (56.7%, 85/150) than in seafood (38.8%, 49/137). Virulence phenotype analyses revealed that the high motility of isolates from freshwater food (40.0%) and clinical isolates (42.0%) was higher than that of isolates from seafood (12.2%), whereas the biofilm-forming capacity of freshwater food isolates (9.4%) was lower than that of seafood (22.4%) and clinical isolates (15.9%). Virulence genes analysis showed that 46.4% of the clinical isolates contained the tdh gene encoding thermostable direct hemolysin (TDH) and only two freshwater food isolates contained the trh gene encoding TDH-related hemolysin (TRH). Multilocus sequence typing (MLST) analysis divided the 206 isolates into 105 sequence types (STs), including 56 (53.3%) novel STs. ST2583, ST469, and ST453 have been isolated from freshwater food and clinical samples. Whole-genome sequence (WGS) analyses revealed that the 206 isolates were divided into five clusters. Cluster II contained isolates from freshwater food and clinical samples, whereas the other clusters contained isolates from seafood, freshwater food, and clinical samples. In addition, we observed that ST2516 had the same virulence pattern, with a close phylogenetic relationship to ST3. The increased prevalence and adaption of V. parahaemolyticus in freshwater food is a potential cause of clinical cases closely related to the consumption of V. parahaemolyticus contaminated freshwater food.

The relationship between probiotics and retinopathy of prematurity in preterm infants: A population-based retrospective study in China.

Background: Retinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The purpose of our study was to analyze the association between the use of probiotics and retinopathy of prematurity. Methods: This study retrospectively collected clinical data of premature infants with gestational age <32 weeks and birth weight <1500 g admitted to the neonatal intensive care unit from January 1, 2019 to December 31, 2021 in Suzhou Municipal Hospital, China. Demographic and clinical data of the inclusion population were collected. The outcome was the occurrence of ROP. The chi-square test was used to compare categorical variables, while the t-test and the nonparametric Mann-Whitney U rank-sum test were used for continuous variables. Univariate and multivariate logistic regression were used to analyze the relationship between probiotics and ROP. Results: A total of 443 preterm infants met the inclusion criteria, of which 264 didn't receive probiotics and 179 were supplemented with probiotics. There were 121 newborns with ROP in the included population. The results of univariate analysis showed that the preterm infants with and without probiotics were significantly different in the gestational age, the birth weight, the one-minute Apgar score, the oxygen inhalation time, the acceptance rate of invasive mechanical ventilation, the prevalence of bronchopulmonary dysplasia, ROP and severe intraventricular hemorrhage and periventricular leukomalacia (P < 0.05). Unadjusted univariate logistic regression model result showed that probiotics (OR 0.383, 95% CI 0.240∼0.611) were the factors affecting ROP in preterm infants (P < 0.01). Multivariate logistic regression result (OR 0.575, 95% CI 0.333∼0.994) was consistent with univariate analysis (P < 0.05). Conclusion: This study showed that probiotic was associated with a reduced risk of ROP in preterm infants with gestational age of <32 weeks and birth weight of <1500 g, but more large-scale prospective studies are still needed.

The DNA adenine methylase of Salmonella Enteritidis promotes their intracellular replication by inhibiting arachidonic acid metabolism pathway in macrophages.

Macrophages can participate in immune responses by altering their metabolism, and play important roles in controlling bacterial infections. However, Salmonella Enteritidis can survive and proliferate in macrophages. After the deletion of DNA adenine methylase (Dam), the proliferation of Salmonella Enteritidis in macrophages decreased, the molecular mechanism is still unclear. After infecting macrophages with Salmonella Enteritidis wild type and dam gene deletion strains, intracellular metabolites were extracted and detected by non-targeted metabolomics and fatty acid targeted metabolomics. We found Dam had significant effects on arachidonic acid and related metabolic pathways in macrophages. The dam gene can promote the proliferation of Salmonella Enteritidis in macrophages by inhibiting the metabolic pathway of cytosolic phospholipase A2-mediated arachidonic acid production and conversion to prostaglandin E2 in macrophages, reducing the secretion of the pro-inflammatory factors IL-1ß and IL-6. In addition, inhibition of arachidonic acid-related pathways in macrophages by Arachidonyl trifluoromethyl ketone could restore the proliferation of dam gene deletion strains in macrophages. This study explored the role of Dam in the process of Salmonella Enteritidis invading host cells from the perspective of host cell metabolism, and provides new insights into the immune escape mechanism of Salmonella Enteritidis.

Transcriptome Analysis Reveals the Effect of Low NaCl Concentration on Osmotic Stress and Type III Secretion System in Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a moderately halophilic foodborne pathogen that is mainly distributed in marine and freshwater environments. The transition of V. parahaemolyticus between aquatic ecosystems and hosts is essential for infection. Both freshwater and host environments have low salinity. In this study, we sought to further investigate the effects of low salinity (0.5% NaCl) on the fitness and virulence of V. parahaemolyticus. We found that V. parahaemolyticus could survive in Luria-Bertani (LB) and M9 mediums with different NaCl concentrations, except for the M9 medium containing 9% NaCl. Our results further showed that V. parahaemolyticus cultured in M9 medium with 0.5% NaCl had a higher cell density than that cultured at other NaCl concentrations when it entered the stationary phase. Therefore, we compared the transcriptomes of V. parahaemolyticus wild type (WT) cultured in an M9 medium with 0.5% and 3% NaCl at the stationary phase using RNA-seq. A total of 658 genes were significantly differentially expressed in the M9 medium with 0.5% NaCl, including regulators, osmotic adaptive responses (compatible solute synthesis systems, transporters, and outer membrane proteins), and virulence factors (T3SS1 and T6SS1). Furthermore, a low salinity concentration in the M9 medium induced the expression of T3SS1 to mediate the cytotoxicity of V. parahaemolyticus to HeLa cells. Similarly, low salinity could also induce the secretion of the T3SS2 translocon protein VPA1361. These factors may result in the high pathogenicity of V. parahaemolyticus in low-salinity environments. Taken together, these results suggest that low salinity (0.5% NaCl) could affect gene expression to mediate fitness and virulence, which may contribute to the transition of V. parahaemolyticus between aquatic ecosystems and the host.

A low-cost technique for biodiesel production in Ankistrodesmus sp. EHY by using harvested microalgal effluent.

The present study aims to use Ankistrodesmus sp. EHY to develop a viable and economic lipid production strategy using recycling of harvested microalgal effluent. In comparison to the control, the highest lipid content (52.4 %) and productivity (250.72 mg L-1 d-1) were achieved when 40 % recycled medium was used. Consistent with the trend of lipid accumulation, the six key lipogenetic genes were upregulated, as well as reactive oxygen species (ROS), glutathione (GSH) and genes encoding antioxidant enzymes during cultivation in recycled medium. Moreover, the consumption of dissolved organic carbon (DOC) and the increased humic acid (HA) in the recycled medium might also be associated with lipid biosynthesis. The biodiesel parameters of alga biomass-derived lipids were fitted to the standard of commercial biodiesel. In conclusion, this study offers an economically viable strategy for microalgal biofuel production and wastewater treatment using recycling of harvested microalgal effluent.

CCCTC-Binding Factor Mediates the Transcription of Insulin-Like Growth Factor Binding Protein 5 Through EZH2 in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. Insulin-like growth factor binding protein 5 (IGFBP5) has been indicated to be related to various inflammation-related diseases. However, its association with UC remains largely unclear. AIMS: Here, we investigate the role of IGFBP5 in colonic mucosal epithelial cell injury in UC. METHODS: Differentially expressed genes in the colonic tissues of UC mice were screened using the Gene Expression Omnibus database, and IGFBP5 was identified. UC mice were developed using dextran sulfate sodium, and IGFBP5 expression in the colonic tissues of UC mice was confirmed by immunohistochemistry and RT-qPCR. The effects of IGFBP5 in vivo and in vitro were investigated by intraperitoneal injection of adeno-associated virus into UC mice or by transfection with an IGFBP5 overexpression plasmid into lipopolysaccharide-treated colonic mucosal epithelial cells. The mechanisms causing IGFBP5 deletion in UC were predicted by bioinformatics analysis and ChIP-qPCR and verified by rescue experiments. RESULTS: IGFBP5 was reduced in UC. IGFBP5 impaired the NFκB pathway in the colonic tissue of UC mice and ameliorated inflammatory infiltration and colonic mucosal cell injury. IGFBP5 depletion was associated with H3K27me3 modification, which was induced by EZH2. CTCF was responsible for recruiting EZH2 to the promoter region of IGFBP5. CTCF inhibition repressed UC progression by reducing H3K27me3 modification via the discouragement of the enrichment of EZH2 in the IGFBP5 promoter. CONCLUSIONS: CTCF modulates H3K27me3 modification of the IGFBP5 promoter by recruiting EZH2, thereby downregulating IGFBP5 to accentuate colonic mucosal epithelial cell injury in UC mice.

The Salmonella T3SS1 effector IpaJ is regulated by ItrA and inhibits the MAPK signaling pathway.

Invasion plasmid antigen J (IpaJ) is a protein with cysteine protease activity that is present in Salmonella and Shigella species. Salmonella enterica serovar Pullorum uses IpaJ to inhibit the NF-κB pathway and the subsequent inflammatory response, resulting in bacterial survival in host macrophages. In the present study, we performed a DNA pull-down assay and EMSA and identified ItrA, a new DeoR family transcriptional regulator that could control the expression of IpaJ by directly binding to the promoter of ipaJ. The deletion of itrA inhibited the transcription of ipaJ in Salmonella. Tn-Seq revealed that two regulators of Salmonella pathogenicity island 1 (SPI-1), namely HilA and HilD, regulated the secretion of IpaJ. The deletion of hilA, hilD or SPI-1 inhibited the secretion of IpaJ in both cultured medium and Salmonella-infected cells. In contrast, the strain with the deletion of ssrB (an SPI-2 regulator-encoding gene) displayed normal IpaJ secretion, indicating that IpaJ is an effector of the SPI-1-encoded type III secretion system (T3SS1). To further demonstrate the role of IpaJ in host cells, we performed quantitative phosphoproteomics and compared the fold changes in signaling molecules in HeLa cells infected with wild-type S. Pullorum C79-13 with those in HeLa cells infected with the ipaJ-deleted strain C79-13ΔpSPI12. Both phosphoproteomics and Western blot analyses revealed that p-MEK and p-ERK molecules were increased in C79-13ΔpSPI12- and C79-13ΔpSPI12-pipaJ(C45A)-infected cells; and Co-IP assays demonstrated that IpaJ interacts with Ras to reduce its ubiquitination, indicating that IpaJ can inhibit the activation of the MAPK signaling pathway.

Salmonella Enteritidis GalE Protein Inhibits LPS-Induced NLRP3 Inflammasome Activation.

Microbial infection can trigger the assembly of inflammasomes and promote secretion of cytokines, such as IL-1ß and IL-18. It is well-known that Salmonella modulates the activation of NLRC4 (NLR family CARD domain-containing protein 4) and NLRP3 (NLR family pyrin domain-containing 3) inflammasomes, however the mechanisms whereby Salmonella avoids or delays inflammasome activation remain largely unknown. Therefore, we used Salmonella Enteritidis C50336ΔfliC transposon library to screen for genes involved in modulating inflammasomes activation. The screen revealed the galactose metabolism-related gene galE to be essential for inflammasome activation. Here, we found that inflammasome activation was significantly increased in J774A.1 cells or wild-type bone marrow-derived macrophages (BMDMs) during infection by ΔfliCΔgalE compared to cells infected with ΔfliC. Importantly, we found that secretion of IL-1ß was Caspase-1-dependent, consistent with canonical NLRP3 inflammasome activation. Furthermore, the virulence of ΔfliCΔgalE was significantly decreased compared to ΔfliC in a mouse model. Finally, RNA-seq analysis showed that multiple signaling pathways related to the inflammasome were subject to regulation by GalE. Taken together, our results suggest that GalE plays an important role in the regulatory network of Salmonella evasion of inflammasome activation.

The Relationship Between Knowledge, Attitude, Practice, and Fall Prevention for Childhood in Shanghai, China.

Background: Early childhood fall is a pressing global public health problem and one of the leading causes of child injury. China has a high proportion of children and a high burden of illness from falls. Therefore, educational interventions to prevent childhood fall would be beneficial. Methods: We used the outcome of knowledge, attitude and practice questionnaire, which was conducted by Pudong New District of Shanghai Municipal Government, to summarize demographic and baseline characteristics grouped by intervention or not, and analyzed descriptive statistics of continuous and categorical variables. A logistic stepwise function model was established to study the influence of different covariables on the degree of injury, and AIC/BIC/AICC was used to select the optimal model. Finally, we carried out single-factor analysis and established a multifactor model by the stepwise function method. Results: Attitude and actual behavior scores had significant differences. The intervention and control groups had 20.79 ± 3.20 and 20.39 ± 2.89 attitude scores, respectively. Compared to the control group (5.97 ± 1.32), the intervention group had higher actual behavior scores (5.75 ± 1.50). In the univariate analysis results, fathers' education level, mothers' education level, actual behavior and what cares for children had a significant influence on whether children got injured. In multivariate analysis, attitude had a positive influence on whether injured [odds ratio: 1.13 (1.05-1.21), P < 0.001]. Conclusion: Educational intervention for children and their guardians can effectively reduce the risk of childhood falls, and changes in behavior and attitude are the result of educational influence. Education of childhood fall prevention can be used as a public health intervention to improve children's health.

Gamma-aminobutyric acid coupled with copper ion stress stimulates lipid production of green microalga Monoraphidium sp. QLY-1 through multiple mechanisms.

Induction of copper ion (Cu2+) stress is a method used to increase lipid accumulation in microalgae, but it decreases cell growth. In this work, the impacts of gamma-aminobutyric acid (GABA) coupled with Cu2+ stress on the biomass and oil yield in Monoraphidium sp. QLY-1 were investigated. Results suggested that the combined treatment of GABA and Cu2+ resulted in a higher lipid content (55.13%) than Cu2+ treatment (48.43%). Furthermore, GABA addition upregulated the levels of lipid-relevant genes, cellular GABA, ethylene (ETH), and antioxidant enzyme activities and alleviated oxidative damage caused by Cu2+ stress. The autophagy-relevant gene atg8 was also upregulated by GABA treatment. Further exploration indicated that cell autophagy induced the lipid content up to 58.09% with GABA and Cu2+ stress treatment. This investigation demonstrates that the coupling strategy can stimulate lipid production and shed light on the underlying mechanisms in lipid biosynthesis, cell autophagy, and stress response of microalgae.