Baoyuan decoction inhibits atherosclerosis progression through suppression peroxidized fatty acid and Src/MKK4/JNK pathway-mediated CD 36 expression.

BACKGROUND: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated. PURPOSE: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation. STUDY DESIGN AND METHODS: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages. RESULTS: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages. CONCLUSIONS: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.

An inactivated PDCoV vaccine induces robust neutralizing antibodies and immune protection in pigs lasting for three months.

Porcine deltacoronavirus (PDCoV), a novel enteropathogenic coronavirus, causes diarrhea mainly in suckling piglets and has the potential to infect humans. Whereas, there is no commercially available vaccine which can effectively prevent this disease. In this study, to ascertain the duration of immune protection of inactivated PDCoV vaccine, suckling piglets were injected subcutaneously with inactivated PDCoV vaccine using a prime/boost strategy at 3 and 17-day-old. Neutralizing antibody assay showed that the level of the inactivated PDCoV group was still ≥1:64 at three months after prime vaccination. The three-month-old pigs were orally challenged with PDCoV strain CZ2020. Two pigs in challenge control group showed mild to severe diarrhea at 10-11 day-post-challenge (DPC), while the inactivated PDCoV group had no diarrhea. High levels of viral shedding, substantial intestinal villus atrophy, and positive straining of viral antigens in ileum were detected in challenge control group, while the pigs in inactivated PDCoV group exhibited significantly reduced viral load, minor intestinal villi damage and negative straining of viral antigens. These results demonstrated that PDCoV was pathogenic against three-month-old pigs and inactivated PDCoV vaccine can provide effective protection in pigs lasting for three months.

Fluctuation of flavor quality in roasted duck: The consequences of raw duck preform's repetitive freeze-thawing.

This study aimed to investigate the changes in flavor quality of roasted duck during repetitive freeze-thawing (FT, -20 ℃ for 24 h, then at 4 ℃ for 24 h for five cycles) of raw duck preforms. HS-SPME/GC-MS analysis showed that more than thirty volatile flavor compounds identified in roasted ducks fluctuated with freeze-thawing of raw duck preforms, while hexanal, nonanal, 1-octen-3-ol, and acetone could as potential flavor markers. Compared with the unfrozen raw duck preforms (FT-0), repetitive freeze-thawing increased the protein/lipid oxidation and cross-linking of raw duck preforms by maintaining the higher carbonyl contents (1.40 âˆ¼ 3.30 nmol/mg), 2-thiobarbituric acid reactive substances (0.25 âˆ¼ 0.51 mg/kg), schiff bases and disulfide bond (19.65 âˆ¼ 30.65 µmol/g), but lower total sulfhydryl (73.37 âˆ¼ 88.94 µmol/g) and tryptophan fluorescence intensity. Moreover, A lower protein band intensity and a transformation from α-helixes to ß-sheets and random coils were observed in FT-3 âˆ¼ FT-5. The obtained results indicated that multiple freeze-thawing (more than two cycles) of raw duck preforms could be detrimental to the flavor quality of the roasted duck due to excessive oxidation and degradation.

A D-π-A-type ratiometric fluorescent probe to detect polarity changes and inhibition effect during ferroptosis.

To thoroughly understand ferroptosis's biological functions in living cells, it is crucial to investigate the polarity variations that occur during this unique Fe(II)-facilitated oxidative type of cell death. In this work, we report the development of a ratiometric probe (Po-P) to visualize the polarity changes in living cells and the inhibition effect during ferroptosis. The polarity-responsive fluorophore utilized by Po-P has a D-π-A-type structure. Based on theoretical calculations, ICT was proposed as the basis for Po-P's polarity-responsive mechanism. According to cell imaging results, Po-P had a desirable capacity for monitoring polarity fluctuations and erastin-induced ferroptosis. Furthermore, inhibition imaging revealed that dihydrolipoic acid (DHLA) could potentially prevent polarity changes that occur during erastin-induced ferroptosis, just as vitamin E (VE). We anticipate that the probe Po-P could be a valuable tool to quickly monitor polarity fluctuations and inhibition effects during ferroptosis and create new medications for treating disorders related to ferroptosis.

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection.

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders.

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.

Type II and IV toxin-antitoxin systems coordinately stabilize the integrative and conjugative element of the ICESa2603 family conferring multiple drug resistance in Streptococcus suis.

Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite their importance, the mechanism underlying the stable inheritance of ICEs, which is necessary for the acquisition of new traits in bacteria, remains poorly understood. Here, we identified SezAT, a type II toxin-antitoxin (TA) system, and AbiE, a type IV TA system encoded within the ICESsuHN105, coordinately promote ICE stabilization and mediate multidrug resistance in Streptococcus suis. Deletion of SezAT or AbiE did not affect the strain's antibiotic susceptibility, but their duple deletion increased susceptibility, mainly mediated by the antitoxins SezA and AbiEi. Further studies have revealed that SezA and AbiEi affect the genetic stability of ICESsuHN105 by moderating the excision and extrachromosomal copy number, consequently affecting the antibiotic resistance conferred by ICE. The DNA-binding proteins AbiEi and SezA, which bind palindromic sequences in the promoter, coordinately modulate ICE excision and extracellular copy number by binding to sequences in the origin-of-transfer (oriT) and the attL sites, respectively. Furthermore, AbiEi negatively regulates the transcription of SezAT by binding directly to its promoter, optimizing the coordinate network of SezAT and AbiE in maintaining ICESsuHN105 stability. Importantly, SezAT and AbiE are widespread and conserved in ICEs harbouring diverse drug-resistance genes, and their coordinated effects in promoting ICE stability and mediating drug resistance may be broadly applicable to other ICEs. Altogether, our study uncovers the TA system's role in maintaining the genetic stability of ICE and offers potential targets for overcoming the dissemination and evolution of drug resistance.

Bacterial and host factors involved in zoonotic Streptococcal meningitis.

Zoonotic streptococci cause several invasive diseases with high mortality rates, especially meningitis. Numerous studies elucidated the meningitis pathogenesis of zoonotic streptococci, some specific to certain bacterial species. In contrast, others are shared among different bacterial species, involving colonization and invasion of mucosal barriers, survival in the bloodstream, breaching the blood-brain and/or blood-cerebrospinal fluid barrier to access the central nervous system, and triggering inflammation of the meninges. This review focuses on the recent advancements in comprehending the molecular and cellular events of five major zoonotic streptococci responsible for causing meningitis in humans or animals, including Streptococcus agalactiae, Streptococcus equi subspecies zooepidemicus, Streptococcus suis, Streptococcus dysgalactiae, and Streptococcus iniae. The underlying mechanism was summarized into four themes, including 1) bacterial survival in blood, 2) brain microvascular endothelial cell adhesion and invasion, 3) penetration of the blood-brain barrier, and 4) activation of the immune system and inflammatory reaction within the brain. This review may contribute to developing therapeutics to prevent or mitigate injury of streptococcal meningitis and improve risk stratification.

Improving the Edible and Nutritional Quality of Roasted Duck Breasts through Variable Pressure Salting: Implications for Protein Anabolism and Digestion in Rats.

Variable pressure salting (VPS) is considered a novel salting approach to improve meat quality. This study aimed to investigate the effects of roasted duck's edible and nutritional quality after VPS through serum biochemical indicators and in vivo digestion properties in rats. The results show that roasted duck after VPS led to an increase in the total protein content (57.24 g/L) and blood glucose levels (6.87 mmol/L), as well as a decrease in the blood urea nitrogen content (11.81 mmol/L), in rats. Compared to rats fed base diets and roasted duck after static wet salting (SWS), those ingesting roasted duck after VPS exhibited higher values of apparent protein digestibility (51.24%), pepsin activity (2.40 U/mg), and trypsin activity (389.80 U/mg). Furthermore, VPS treatment improved the textural properties and microstructure of duck breasts shown by a higher immobilized water relaxation area and more ordered protein structures (α-helixes and ß-sheets). These improvements enhanced the protein anabolism capacity and in vivo digestion properties in rats. Therefore, VPS represents a beneficial salting method for promoting effective digestion and absorption in rats.

Acid-Responsive Aggregation of Gold Nanoparticles for the Photothermal Treatment of Bacterial Infections.

Photothermal therapy (PTT) is considered to be one of the promising methods to combat pathogenic bacteria. However, traditional PTT is prone to generate undesired temperature increase to surrounding normal tissues, which limits the application of PTT. Herein, an acid-responsive PTT system (Au nanoparticles system: AuNPs-S) was constructed based on the photothermal feature of spherical gold nanoparticles (AuNPs) and the low pH of the bacterial infected site. AuNPs-S is composed of two kinds of AuNPs: AuNPs modified with Asp-Asp-Asp-Asp-Asp-Cys (peptide A) were denoted as AuNPs-A; AuNPs modified with 2,3-dimethylmaleic anhydride (DA) grafted Lys-Gly-Gly-Lys-Gly-Gly-Lys-Cys (peptide B) were denoted as AuNPs-B/DA. AuNPs-B/DA with an acid-responsive moiety showed a charge-convertible feature. The negatively charged AuNPs-B/DA became positively charged AuNPs-B at low pH, aggregating with the negatively charged AuNPs-A via an electrostatic interaction, reaching the threshold to the interparticle plasmonic coupling effect among AuNPs, thereby killing bacteria precisely under the irradiation of near-infrared (NIR) light through the elevated temperature at the targeted area. This acid-responsive PTT strategy supplies an excellent mode for combating bacterial infections with no vital damage to normal tissues.

Establishment of tongue microbiota by 18 months of age and determinants of its microbial profile.

IMPORTANCE: Understanding the development of oral microbiota early in life and the factors that influence it is important for preventing the establishment of dysbiotic oral microbiota later in life. This study demonstrates that the tongue microbiota undergoes early development from 4 to 18 months of age and converges into two types of microbiota showing indications of adult characteristics, with either S. salivarius or Neisseria-dominance. Interestingly, their divergence was strongly determined by their weaning status and the dietary frequencies of sweetened beverages, snacks, and fruits, suggesting that dietary habits during this period might influence the establishment of the oral microbiota. These findings may contribute to the development of novel preventive strategies against oral microbiota-related diseases.

Characterization of aroma profiles of chinese four most famous traditional red-cooked chickens using GC-MS, GC-IMS, and E-nose.

The aroma profile of the four most popular types of red-cooked chickens in China was analyzed using a combination of gas chromatography-mass spectrometry (GC-MS), gas chromatography-ion mobility spectrometry (GC-IMS), and electronic nose (E-nose). Principal component analysis (PCA) demonstrated that the E-nose could successfully distinguish between the four types of red-cooked chickens. Additionally, a fingerprint was created using GC-IMS to examine the variations in volatile organic compounds (VOCs) distribution in the four chicken types. A total number of 84 and 62 VOCs were identified in the four types of red-cooked chickens using GC-MS and GC-IMS, respectively. Odor activity value (OAV) showed that 1-octen-3-ol, heptanal, hexanal, nonanal, octanal, eugenol, dimethyl trisulfide, anethole, anisaldehyde, estragole, and eucalyptol were the key volatile components in all samples. Furthermore, partial least squares-discriminant analysis (PLS-DA) demonstrated that (E, E)-2,4-decadienal, dimethyl trisulfide, octanal, eugenol, hexanal, (E)-2-nonenal, 1-octen-3-ol, butanal, ethyl acetate, ethyl acetate (D), nonanal, and heptanal could be used as markers to distinguish aroma of the four types of red-cooked chickens. Also, it is worth noting that levels of VOCs varied between chicken breast muscle and skin. The obtained results offer theoretical and technological support for flavor identification and control in red-cooked chickens to enhance their quality and encourage consumer consumption, which will be advantageous for the red-cooked chicken production chain.

Evaluation of new IPSS-Molecular model and comparison of different prognostic systems in patients with myelodysplastic syndrome.

A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes (MDS). Previous risk prognostic scoring systems did not integrate molecular abnormalities. The new IPSS-Molecular (IPSS-M) model, combing genomic profiling with hematologic and cytogenetic parameters, was recently developed to evaluate the associations with leukemia-free survival (LFS), leukemic transformation, and overall survival (OS). However, it has not yet been widely validated in clinics. This study aims to further validate the prognostic power of IPSS-M based on real-world data and to compare the prognostic value of different scoring systems in patients with MDS. IPSS-M Web calculator was used to calculate a tailored IPSS-M score of the enrolled patient (N = 255), and the risk category was defined correspondingly. We next compared the IPSS-M prognostic power to that of IPSS, IPSS-R, and WPSS. We found that IPSS-M risk classification was statistically significant for 3-year OS and LFS. Compared with other tools, IPSS-M was superior in sensitivity and accuracy for 3-year OS and LFS. The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS, but not LFS and leukemic transformation. The result of different treatment options indicated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) can result in a better OS than those without allo-HSCT. In conclusion, IPSS-M was a valuable tool for risk stratification compared with other risk prognostic scoring systems. However, more studies should be conducted to explore the appropriate treatment options for different groups stratified by IPSS-M.

Structural changes induced by ultrasound improve the ability of the myofibrillar protein to bind flavor compounds from spices.

Effects of ultrasound (UT) treatments on the structural, physicochemical, and functional properties of myofibrillar proteins (MPs), as well as their ability to bind to flavor compounds from spices, were investigated. The results demonstrated that UT treatment enhanced surface hydrophobicity, SH content, and absolute ζ-potential value of the MPs. Atomic force microscopy analysis displayed formation of MPs aggregates with small particle size in the UT-treated MPs samples. Meanwhile, UT treatment could improve the emulsifying properties and physical stability of MPs' emulsion. Additionally, the MPs gel network structure and stability significantly improved following UT treatment. Changes in the structural, physicochemical, and functional properties enhanced the ability of MPs to bind to flavor substances from spices depending on the duration of UT treatment. Furthermore, correlation analysis showed that the ability of myristicin, anethole, and estragole to bind to MPs was highly correlated with surface hydrophobicity, ζ-potential value, and α-helix content of MPs. The results of this study may help in understanding the relationship between the changes in MPs properties during the processing of meat products and their ability to bind to flavors from spices, thereby improving flavors retention and taste of processed meat products.

Synthesis of S-2-phenylchromane Derivatives and Evaluation of the Antiproliferative Properties as Apoptosis Inducers in Cancer Cell Lines.

BACKGROUND: Cancer remains one of the major health issues globally, where chemotherapy forms the main treatment mode for different types of cancers. Due to cancer cell ability to develop resistance, decreased clinical effectiveness of anticancer drugs can occur. Therefore, the need to synthesize novel antitumor drugs remains important. OBJECTIVE: The aim of our work consisted of synthesizing S-2-phenylchromane derivatives containing the tertiary amide or 1,2,3-triazole fragments with promising anticancer activity. METHODS: A series of S-2-phenylchromane derivatives were synthesized and evaluated for cytotoxic activity against three selected cancer cell lines (HGC-27 human gastric carcinoma cell line, Huh-7 epithelial-like tumorigenic cells, and A549 adenocarcinomic human alveolar basal epithelial cells) using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Hoechst staining was used to detect the effects of S-2-phenylchromane derivatives on apoptosis. The apoptosis percentages were detected by annexin V-fluoresceine isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay with flow cytometry. Expression levels of apoptosis-related proteins were detected by western blot. RESULTS: Cell line A549, consisting of adenocarcinomic human alveolar basal epithelial cells, displayed the highest sensitivity to the S-2-phenylchromane derivatives. Among these compounds, E2 showed the most potent antiproliferative activity against A549 cells with an IC50 value of 5.60 µM. Hoechst staining and flow cytometry analysis revealed apoptosis in A549 cells by compound E2. In addition, activation of the expression levels of caspase-3, caspase-7, and their substrate poly (ADP-ribose) polymerase (PARP) by E2 was detected by western blot. CONCLUSION: In summary, results point towards compound E2, an S-2-phenylchromane derivative, as a potential lead molecule in anticancer agents for human adenocarcinomic alveolar basal cells based on the induction of apoptosis.

Systematic Surveillance of an Emerging Picornavirus among Cattle and Sheep in China.

Emerging viruses are a constant threat to human and animal health. Boosepivirus is a novel picornavirus considered a gastrointestinal pathogen and has broken out in recent years. In 2020, we identified a strain of boosepivirus NX20-1 from Chinese calf feces and performed genetic characterization and evolutionary analysis. NX20-1 was closely related to the Japanese strain Bo-12-38/2009/JPN and belonged to Boosepivirus B. We found that 64 of 603 samples (10.6%) from 20 different provinces across the country were positive for boosepivirus by reverse transcription (RT)-PCR. Further, coinfection with other diarrheal pathogens was also present in 35 of these positive samples. Importantly, we found the prevalence of boosepivirus in sheep as well, indicating that Boosepivirus can infect different domestic animals. Our data suggest that boosepivirus is a potential diarrheal pathogen, but the pathogenicity and the mechanism of pathogenesis need further study. IMPORTANCE We identified a novel picornavirus, boosepivirus, for the first time in China. Genetic evolutionary analysis revealed that NX20-1 strain was closely related to the Japanese strain Bo-12-38/2009/JPN and belonged to Boosepivirus B. In addition, we found that the virus was prevalent in China with an overall positivity rate of 10.6% (64 of 603 samples), and there was significant coinfection with other pathogens. Importantly, we found the prevalence of boosepivirus in sheep as well, suggesting that boosepivirus has a risk of spillover and can be transmitted across species.

Structural characterization of a fucoidan from Ascophyllum nodosum and comparison of its protective effect against cellular oxidative stress with its analogues.

In the present study, a fucoidan fraction (ANP-3) was isolated from Ascophyllum nodosum, and the combined application of desulfation, methylation, HPGPC, HPLC-MSn, FT-IR, GC-MS, NMR, and Congo red test elucidated ANP-3 (124.5 kDa) as a triple-helical sulfated polysaccharide constituted by →2)-α-Fucp3S-(1→, →3)-α-Fucp2S4S-(1→, →3,6)-ß-Galp4S-(1→, →3,6)-ß-Manp4S-(1→, →3,6)-ß-Galp4S-(1→，→6)-ß-Manp-(1→, →3)-ß-Galp-(1→, α-Fucp-(1→, and α-GlcAp-(1→ residues. To better understand the relationship between the fucoidan structure of A. nodosum and protective effects against oxidative stress, two fractions ANP-6 and ANP-7 were used as contrast. ANP-6 (63.2 kDa) exhibited no protective effect against H2O2-induced oxidative stress. However, ANP-3 and ANP-7 with the same molecular weight of 124.5 kDa could protect against oxidative stress by down-regulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels and up-regulating total antioxidant capability (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities. Then metabolites analysis indicated that arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis metabolic pathways and metabolic biomarkers such as betaine were involved in the effects of ANP-3 and ANP-7. The better protective effect of ANP-7 compared to that of ANP-3 could be attributed to its relatively higher molecular weight, sulfate substitution and →6)-ß-Galp-(1→ content, and lower uronic acid content.

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Streptococcus suis Infection.

Streptococcus suis serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for large economic losses in pig production and a great threat to human health. Pentraxin 3 (PTX3) is an essential regulator of the innate immune response to bacterial pathogens; however, its role during SS2 infection is not fully understood. In this study, we found that the SS2 strain HA9801 induced a significant inflammatory response in the mouse air pouch model; this response was amplified by the treatment of exogenous PTX3 simultaneously in terms of the results of inflammatory cell recruitment and proinflammatory cytokine IL-6 production. In addition, PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801. The supplementation of exogenous PTX3 significantly reduced the bacterial loads in a dose-dependent manner in lungs, livers and bloods of SS2-infected mice compared to the samples with HA9801 infection alone; this finding indicated that PTX3 may facilitate the bacterial clearance through enhancing the host inflammatory response during SS2 infection. Both PTX3 and SS2 capsular polysaccharide (CPS2) were required for the robust inflammatory response, implying that the host PTX3 protein and SS2 surface CPS2 modulate the host innate immune response in concert. All of these results suggested that PTX3 is a potential novel biological agent for the SS2 infection; however, the recommended dose of PTX3 must be evaluated strictly to avoid inducing an excessive inflammatory response that can cause serious tissue injury and animal death.

Atomic-scale study clarifying the role of space-charge layers in a Li-ion-conducting solid electrolyte.

Space-charge layers are frequently believed responsible for the large resistance of different interfaces in all-solid-state Li batteries. However, such propositions are based on the presumed existence of a Li-deficient space-charge layer with insufficient charge carriers, instead of a comprehensive investigation on the atomic configuration and its ion transport behavior. Consequently, the real influence of space-charge layers remains elusive. Here, we clarify the role of space-charge layers in Li0.33La0.56TiO3, a prototype solid electrolyte with large grain-boundary resistance, through a combined experimental and computational study at the atomic scale. In contrast to previous speculations, we do not observe the Li-deficient space-charge layers commonly believed to result in large resistance. Instead, the actual space-charge layers are Li-excess; accommodating the additional Li+ at the 3c interstitials, such space-charge layers allow for rather efficient ion transport. With the space-charge layers excluded from the potential bottlenecks, we identify the Li-depleted grain-boundary cores as the major cause for the large grain-boundary resistance in Li0.33La0.56TiO3.

Porcine extraintestinal pathogenic Escherichia coli delivers two serine protease autotransporters coordinately optimizing the bloodstream infection.

Extraintestinal pathogenic Escherichia coli (ExPEC) is one of the leading causes of bloodstream infections in a broad spectrum of birds and mammals, thus poses a great threat to public health, while its underlying mechanism causing sepsis is not fully understood. Here we reported a high virulent ExPEC strain PU-1, which has a robust ability to colonize within host bloodstream, while induced a low level of leukocytic activation. Two serine protease autotransporters of Enterobacteriaceae (SPATEs), VatPU-1 and TshPU-1, were found to play critical roles for the urgent blood infection of strain PU-1. Although the Vat and Tsh homologues have been identified as virulence factors of ExPEC, their contributions to bloodstream infection are still unclear. In this study, VatPU-1 and TshPU-1 were verified to interact with the hemoglobin (a well-known mucin-like glycoprotein in red blood cell), degrade the mucins of host respiratory tract, and cleave the CD43 (a major cell surface component sharing similar O-glycosylated modifications with other glycoprotein expressed on leukocytes), suggesting that these two SPATEs have the common activity to cleave a broad array of mucin-like O-glycoproteins. These cleavages significantly impaired the chemotaxis and transmigration of leukocytes, and then inhibited the activation of diverse immune responses coordinately, especially downregulated the leukocytic and inflammatory activation during bloodstream infection, thus might mediate the evasion of ExPEC from immune clearance of blood leukocytes. Taken together, these two SPATEs play critical roles to cause a heavy bacterial load within bloodstream via immunomodulation of leukocytes, which provides a more comprehensive understanding how ExPEC colonize within host bloodstream and cause severe sepsis.