A bacteriophage against Citrobacter braakii and its synergistic effect with antibiotics.

A bacteriophage BD49 specific for Citrobacter braakii was screened out and purified by double-layer plate method. It consists of a polyhedral head of 93.1 ± 1.2 nm long and 72.9 ± 4.2 nm wide, tail fibers, collar, sheath and baseplate. The bacteriophage was identified by morphology observed with transmission electron microscope (TEM), whole genome sequencing carried out by Illumina next generation sequencing (NGS) technique, and gene annotation based on Clusters of Orthologous Groups of proteins (COG) database. It was identified primarily as a member of Caudovirales by morphology and further determined as Caudovirales, Myoviridae, and Citrobacter bacteriophage by alignment of its whole genome sequence with the NCBI database and establishment of phylogenetic tree. The bacteriophage showed good environmental suitability with optimal multiplicity of infection (MOI) of 0.01, proliferation time of 80 min, optimum living temperature of 30-40 °C, and living pH of 5-10. In addition, it exhibited synergistic effect with ciprofloxacin against C. braakii in antibacterial tests.

Zn2+ Binding Increases Parallel Structure in the Aß(16-22) Oligomer by Disrupting Salt Bridge in Antiparallel Structure.

The aggregation of monomeric amyloid ß protein (Aß) into oligomers and amyloid plaque in the brain is associated with Alzheimer's disease. The hydrophobic central core Aß16-22 has been widely studied due to its essential role in the fibrillization of full-length Aß peptides. Compared to the homogeneous antiparallel structure of Aß16-22 at the late stage, the early-stage prefibrillar aggregates contain varying proportions of different ß structures. In this work, we studied the appearance probabilities of various self-assembly structures of Aß16-22 and the effects of Zn2+ on these probabilities by replica exchange molecular dynamics simulations. It was found that at room temperature, Aß16-22 can readily form assembled ß-sheet structures in pure water, where a typical antiparallel arrangement dominates (24.8% of all sampled trimer structures). The addition of Zn2+ to the Aß16-22 solution will dramatically decrease the appearance probability of antiparallel trimer structures to 12.5% by disrupting the formation of the Lys16-Glu22 salt bridge. Meanwhile, the probabilities of hybrid antiparallel/parallel structures increase. Our simulation results not only reveal the competition between antiparallel and parallel structures in the Aß16-22 oligomers but also show that Zn2+ can affect the oligomer structures. The results also provide insights into the role of metal ions in the self-assembly of short peptides.

Azobenzene as a photoswitchable mechanophore.

Azobenzene has been widely explored as a photoresponsive element in materials science. Although some studies have investigated the force-induced isomerization of azobenzene, the effect of force on the rupture of azobenzene has not been explored. Here we show that the light-induced structural change of azobenzene can also alter its rupture forces, making it an ideal light-responsive mechanophore. Using single-molecule force spectroscopy and ultrasonication, we found that cis and trans para-azobenzene isomers possess contrasting mechanical properties. Dynamic force spectroscopy experiments and quantum-chemical calculations in which azobenzene regioisomers were pulled from different directions revealed that the distinct rupture forces of the two isomers are due to the pulling direction rather than the energetic difference between the two isomers. These mechanical features of azobenzene can be used to rationally control the macroscopic fracture behaviours of polymer networks by photoillumination. The use of light-induced conformational changes to alter the mechanical response of mechanophores provides an attractive way to engineer polymer networks of light-regulatable mechanical properties.

IFN-γ enhances the therapeutic efficacy of MSCs-derived exosome via miR-126-3p in diabetic wound healing by targeting SPRED1.

BACKGROUND AND AIMS: The traditional treatment of diabetic wounds is unsatisfactory. Exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) promote the healing of diabetic wounds. However, whether the exosomes secreted by interferon (IFN)-γ-pretreated BMSCs have an enhanced therapeutic effect on diabetic wound healing and the relevant mechanisms remain unclear. METHODS: In this study, we isolated exosomes from the corresponding supernatants of BMSCs with (IExos) or without IFN-γ treatment (NExos). Human umbilical vein endothelial cells (HUVECs) were used to investigate the proliferation, migration, and tube formation under different treatments in vitro. Diabetic mice were induced by intraperitoneal administration of streptozotocin, and a circular full-thickness dermal defect was then made on the back of each mouse, followed by a multisite subcutaneous injection of phosphate buffered saline or exosomes. Hematoxylin-eosin (H&E) staining, Masson's trichrome staining, and histological analysis were performed to assess the speed and quality of wound healing. RESULTS: NExos treatment accelerated the healing of diabetic wounds by promoting angiogenesis in vivo and in vitro, and IExos exhibited superior therapeutic efficiency. MicroRNA (miR)-126-3p was significantly increased in IExos, and exosomal miR-126-3p promoted angiogenesis and diabetic wound healing via its transfer to HUVECs. miR-126-3p regulates SPRED1 by directly targeting the 3'-UTR. Mechanistically, IFN-γ-pretreated BMSCs secreted miR-126-3p-enriched exosomes, which enhanced the function of HUVECs and promoted angiogenesis via the SPRED1/Ras/Erk pathway. CONCLUSION: Exosomal miR-126-3p secreted from IFN-γ-pretreated BMSCs exhibited higher therapeutic efficacy than NExos in diabetic wound healing by promoting angiogenesis via the SPRED1/Ras/Erk axis.

The Relationship between Executive Functions and Metacognition in College Students.

This study investigated the relationship between executive functions and metacognition. Both constructs have been well-studied, but little research has focused on their connections. The goal of the current investigation was to increase the understanding of the relationship between metacognition and executive functions by assessing the relationships between metacognitive monitoring accuracy and the three component executive functions (updating, inhibition, and shifting) among college students. Metacognitive monitoring accuracy was measured using a knowledge monitoring accuracy (KMA) test. The three components of executive functions, updating, inhibition, and shifting were measured, respectively, using the ABCD updating task, the Stroop color-word interference test, and the letter-number task. The Tower of Hanoi task was used to measure the complex executive functions (inhibition and updating). Correlation and regression analyses were performed to examine the relationships. The results indicate that updating is the only component executive function that significantly correlated with metacognitive monitoring, suggesting that metacognition-specifically, metacognitive monitoring-is associated with at least one component of executive functioning.

Screening quality markers (Q-markers) of Xiaoer Chaige Tuire Oral Liquid by in vitro sequential metabolism and in vivo biopharmaceutical analysis.

BACKGROUND: Xiaoer Chaige Tuire Oral Liquid (XCT) is a preparation composed of 7 traditional Chinese medicines including Bupleuri Radix, Puerariae Lobatae Radix, Scutellariae Radix, Gypsum Fibrosum, Artemisiae Annuae Herba, Paeoniae Radix Alba and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle in proportion. According to traditional Chinese medicine theory, it has the function of dispelling wind evil and relieving exterior syndrome, clearing summer heat and dampness, and reducing internal heat. So, it is indicated for pediatric upper respiratory tract infection caused by exogenous wind-heat. Modern pharmacological studies have indicated that XCT has a variety of activities such as anti-inflammation and antivirus. PURPOSE: To screen potential quality markers (Q-markers) of XCT by tracking in vivo bioactive compounds concomitantly using in vitro sequential metabolism and in vivo biopharmaceutical analysis. METHODS: In vitro metabolic models including artificial gastric juice, intestinal juice, intestinal microbiota, Caco-2 cell monolayer and liver S9 were employed to simulate metabolism of main compounds of XCT in the body. High performance liquid chromatography with diode-array detection (HPLC-DAD) was used to quantitatively determine main components of XCT preparation and its sequential metabolism samples. Ultra performance liquid chromatography with QExactive Orbitrap tandem mass spectrometry (UPLC-QExactive-HF-x-Orbitrap-MS) was used to qualitatively determine in vivo components of XCT preparation in rat plasma and metabolites obtained with liver S9 fraction of rats. RESULTS: Twenty-five compounds were identified from the preparation of XCT. Sequential in vitro metabolism studies indicated that most of these compounds except baicalin and baicalein were stable in artificial gastric juice, albiflorin, glycyrrhizic acid, gallic acid and baicalein were unstable in artificial intestinal juice, daidzin, liquiritin and genistin were hydrolyzed into their aglycones daidzein, liquiritigenin and genistein by intestinal microbiota, and 7 compounds thereout including benzoic acid, puerarin, 3'-methoxypuerarin, paeoniflorin, scopoletin, daidzein and liquiritigenin were shown to be well absorbed with Caco-2 cell monolayer model. These 7 compounds were demonstrated to be metabolized via hydroxylation and glycosylation by liver S9 system. Ten components of XCT preparation including puerarin, baicalin, wogonoside, benzoic acid, daidzein, baicalein, wogonin, oroxylin A, isoscopoletin and isoliquiritigenin were identified from rat plasma by in vivo biopharmaceutical analysis. Most of the compounds screened with both in vitro and in vivo metabolic studies were shown to be active against inflammation and influenza virus. CONCLUSIONS: A screening strategy for potential quality markers (Q-markers) of XCT preparation based on tracking in vivo bioactive compounds using the combination of in vitro sequential metabolism and in vivo biopharmaceutical analysis was established. With this strategy, a total of 12 compounds including puerarin, daidzein, benzoic acid, baicalin, baicalein, wogonoside, wogonin, oroxylin A, 3'-methoxypuerarin, paeoniflorin, scopoletin and liquiritigenin were screened to be potential Q-markers of XCT, which provides a material basis for quality control and development of XCT.

Dynamic behavior of the single-strand DNA molecules from the hydrophilic to hydrophobic regions on graphene oxide surface driven by heating.

Heating affects the interfacial properties of two-dimensional nanomaterials, especially when they interact with biomolecules. Here, we theoretically studied the dynamic processes driving single-strand DNA (ssDNA) molecules from the hydrophilic to hydrophobic regions on the graphene oxide (GO) surface by heating, as reported by recent experiments. This was accomplished by using multi-sample molecular dynamics simulations in the NVT ensemble, with the temperature increasing from 300 K to 350 K. When the temperature increased, the lifetime of hydrogen bonds between water molecule and oxygen-containing groups on the GO surface decreased from 10.04 ps to 6.86 ps, and the end-to-end distance of 4-mer and 8-mer ssDNA molecules also decreased. This indicated that heating facilitated the breaking/formation of hydrogen bonds and enhanced the flexibility of ssDNA molecules. By heating, active hydrogen bonding first led to unbalanced interactions between the ssDNA molecule and GO surface, and the enhanced flexibility allowed the ssDNA molecule to release stress by moving on the GO surface and relaxing its structure. The ssDNA molecule constantly adjusted its structure by a competition between intra and inter π-π stacking structures. With dynamic cooperation of hydrogen bonding and π-π stacking, the ssDNA molecule moved from the hydrophilic to hydrophobic regions. Our results offer fundamental interfacial science insights into the effects of heating on the interactions between biomolecules and two-dimensional nanomaterials.

Solution epitaxy of polarization-gradient ferroelectric oxide films with colossal photovoltaic current.

Solution growth of single-crystal ferroelectric oxide films has long been pursued for the low-cost development of high-performance electronic and optoelectronic devices. However, the established principles of vapor-phase epitaxy cannot be directly applied to solution epitaxy, as the interactions between the substrates and the grown materials in solution are quite different. Here, we report the successful epitaxy of single-domain ferroelectric oxide films on Nb-doped SrTiO3 single-crystal substrates by solution reaction at a low temperature of ~200 oC. The epitaxy is mainly driven by an electronic polarization screening effect at the interface between the substrates and the as-grown ferroelectric oxide films, which is realized by the electrons from the doped substrates. Atomic-level characterization reveals a nontrivial polarization gradient throughout the films in a long range up to ~500 nm because of a possible structural transition from the monoclinic phase to the tetragonal phase. This polarization gradient generates an extremely high photovoltaic short-circuit current density of ~2.153 mA/cm2 and open-circuit voltage of ~1.15 V under 375 nm light illumination with power intensity of 500 mW/cm2, corresponding to the highest photoresponsivity of ~4.306×10-3 A/W among all known ferroelectrics. Our results establish a general low-temperature solution route to produce single-crystal gradient films of ferroelectric oxides and thus open the avenue for their broad applications in self-powered photo-detectors, photovoltaic and optoelectronic devices.

Multicolor Chromism from a Single Chromophore through Synergistic Coupling of Mechanochromic and Photochromic Subunits.

We report a versatile mechanophore exhibiting a vividly detectable, light-regulable multicolor mechanochromism. Such optical features rely on the synergistic coupling of mechanochromic bis-rhodamine (Rh) and photochromic bisthienylethene (BTE). Poly(methyl acrylate)s incorporating this bis-mechanophore can be mechanically activated under sonication. The relative distribution of the two distinctly colored and fluorescent Rh ring-opening products is altered with different magnitudes of applied force. Orthogonal use of the photochromic reaction of the BTE core can strengthen the mechanochromism and gate the mechanofluorescence in polymers. Due to increased conjugation offered by the BTE linker, both force- and light-induced optical signals display high contrast. Combined DFT simulated and experimental results reveal that the three subunits (two Rhs and one BTE) in this chromophore are activated sequentially, thus generating switchable three-colored forms and gradient optical responses.

Clinical significance of tumor abnormal protein in patients with type 2 diabetes complicated with lung adenocarcinoma in situ.

BACKGROUND: To investigate the application value of tumor abnormal protein in patients with type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. MATERIALS AND METHODS: A total of 140 patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ (Group A), 160 patients with type 2 diabetes mellitus (Group B), and 120 healthy controls (Group C) were enrolled in the Department of Thoracic Surgery of the First Affiliated Hospital of Soochow University from November 2021 to December 2022. RESULTS: The total cholesterol level was higher in Group A than in Group B (p < 0.05) and Group C (p < 0.01), and it was higher in Group B than in Group C (p < 0.01). The comparison results of cholesterol level were similar to those of tumor abnormal protein, low-density lipoprotein cholesterol, and glycosylated hemoglobin among the three groups. The triglyceride level was higher in Group A than in Group B and Group C (both p < 0.01). Group A had a higher level of high-density lipoprotein cholesterol than Group C (p < 0.01). The fasting plasma glucose level was higher in Group A than in Group B and Group C (both, p < 0.01). These findings indicated that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. CONCLUSION: Therefore, detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

The study found that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. Detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

Cooperative and Geometry-Dependent Mechanochromic Reactivity through Aromatic Fusion of Two Rhodamines in Polymers.

The unique topological features of Piezo proteins underlie the lever-like cellular mechanotransduction mechanism. This knowledge inspires us to seek topological/geometric control of mechanochromophores with unprecedentedly amplified, synergistic changes in polymers to serve as ideal stress probes. Here, by judicious placement of two spirolactam rings into aminobenzopyranoxanthene, a series of stereo- and regio-isomeric rhodamine-like mechanophores are developed. With two labile bonds closely coupled into one rigidified scaffold, these π-fused bis-mechanophores enable mechanochromic polymers, featuring cooperative bond scission, low rupture force (lower than rhodamine), and geometry-controlled ring-opening reactivity. Sonication, single-molecule force spectroscopy experiments, and density functional theory calculations provide insight into the force-color relationship and rationalize how the difference in reactivity of the four isomeric mechanophores is affected by their molecular geometry and thermodynamic equilibrium. Our strategy based on the aromatic fusion of bis-mechanophore promises a modular approach to isomeric mechanophores for cooperative bond scission. Also, important insights into internal and external factors governing tandem mechanochemical reactions are gained.

Serum Tenascin-C and Alarin Levels Are Associated with Cardiovascular Diseases in Type 2 Diabetes Mellitus.

Background: Tenascin-C (TNC), an extracellular matrix glycoprotein, is elevated in inflammatory and cardiovascular pathologies, whereas alarin, a novel orexigenic peptide, participates in insulin resistance and glycometabolism. The roles of these molecules in individuals with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), clinical conditions associating with metabolic disorders, and chronic inflammation, remain controversial. Our study aimed at determining the potential role of TNC and alarin in CVD adult patients with T2DM. Methods: This was a cross-sectional study. Basic and clinical information for 250 patients with T2DM were analyzed. Based on their cardiovascular disease status, participants were assigned into the CVD and non-CVD groups. Serum TNC and alarin levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results: Serum TNC and alarin concentrations in the CVD group were significantly higher than those of the non-CVD group. Moreover, serum TNC levels were positively correlated with age, waist circumference, and waist-hip ratio; however, they were negatively correlated with TC, LDL-C, and eGFR levels. Alarin levels were positively correlated with BMI, waist circumference, and hip circumference. In logistic regression models, TNC and alarin were also established to be independent determinants for CVD in T2DM patients and their increases were associated with CVD severity. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values for TNC and alarin were 0.68 and 0.67, respectively. TNC and alarin were good predictors of CVD occurrence. When the cutoff value for TNC was 134.05 pg/mL, its sensitivity was 69.47% while its specificity was 61.29%. When the cutoff value for alarin was 142.69 pg/mL, sensitivity and specificity were 38.95% and 90.97%, respectively. Conclusion: Elevated TNC and alarin levels are independently associated with the occurrence and severity of CVD in T2DM individuals. Therefore, these two biomarkers are potential diagnostic and prognostic indicators for CVD in diabetics.

A newly isolated human intestinal strain deglycosylating flavonoid C-glycosides.

Glycosidic bond of C-glycosides is difficult to be broken due to its chemical stability. Screening specific microbe from microbiota is a practical way to deglycosylate these compounds. In this study, a new strain W974-1 which is capable of cleaving C-glycosidic bonds was isolated from human gut microbiota by spread plate method. It deglycosylates flavonoid 8-C-glycosides such as orientin and vitexin to their aglycones with the enzymes secreted outside the bacterial cells. This strain was identified as Enterococcus avium by 16S rDNA sequencing, physiological and biochemical characterization.

Influencing factors for hepatic fat accumulation in patients with type 2 diabetes mellitus.

BACKGROUND: Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide, which originates from the accumulation of triglyceride (TG) in the liver. Patients with type 2 diabetes mellitus (T2DM) are considered to have a predisposition to hepatic steatosis. However, the influencing factors for hepatic fat accumulation in T2DM patients remain unclear. AIM: To investigate the influencing factors for hepatic fat accumulation in T2DM patients. METHODS: We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University, who underwent MR mDIXON-Quant examination to quantify the hepatic fat fraction (HFF). According to body mass index (BMI), the patients were divided into normal weight, overweight, and obese groups. The differences in general statistics, biochemical parameters, islet function, and HFF were compared among the three groups. The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed. RESULTS: The HFF of T2DM patients gradually increased in the normal weight, overweight, and obese groups (P < 0.05). Spearman correlation analysis showed that in T2DM patients, HFF was negatively correlated with age and high-density lipoprotein cholesterol (P < 0.05), whereas it was positively correlated with BMI, waist-hip ratio, fasting plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, glutamyl transpeptidase, lactate dehydrogenase, albumin (ALB), uric acid (UA), total cholesterol, TG, low-density lipoprotein cholesterol (LDL-C), C-reactive protein, free triiodothyronine, fasting insulin, fasting C-peptide, and homeostasis model assessment of insulin resistance (P < 0.05). Multiple linear regression analysis showed significant positive influences of BMI, ALT, LDL-C, UA, and ALB on HFF in T2DM patients (P < 0.05). Binary logistic regression analysis showed that BMI, ALT, ALB, and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients, and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times (P < 0.05). CONCLUSION: The HFF of T2DM patients increases with BMI. Higher BMI, ALT, ALB, and LDL-C are independent risk factors for moderate to severe fatty liver in T2DM patients.

Characteristics and outcomes of COVID-19 infection in 45 patients with breast cancer: A multi-center retrospective study in Hubei, China.

BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.

Regulation of Free Fatty Acid Receptor 4 on Inflammatory Gene Induced by LPS in Large Yellow Croaker (Larimichthys crocea).

Free fatty acid receptor 4 (FFAR4) plays a key role in regulating the inflammatory response in mammals. The present study aimed to investigate the function of large yellow croaker FFAR4 on inflammation. In the present study, ffar4 was widely expressed in 10 tissues of large yellow croaker including gill, head kidney and spleen. Further studies showed that treatment of head kidney macrophages with agonists (TUG891 or GSK137647A) or overexpression of ffar4 reduced the mRNA expression of pro-inflammatory genes induced by LPS, and increased the expression of pparγ. Treatment of macrophages with antagonist AH7614 increased the mRNA expression of pro-inflammatory genes induced by LPS, and decreased the mRNA expression of pparγ. In order to verify the immunomodulatory effect of PPARγ, PPARγ was overexpressed in macrophages which significantly reduced the mRNA expression of pro-inflammatory genes il6, il1ß, il8, tnfα and cox2. Moreover, results of dual-luciferase assays showed that PPARγ downregulated the transcriptional activity of il6 and il1ß promoters. In conclusion, FFAR4 showed anti-inflammatory effects on LPS-induced inflammation in large yellow croaker.

Molecular identification of peptidoglycan recognition protein 5 and its functional characterization in innate immunity of large yellow croaker, Larimichthys crocea.

Fish peptidoglycan recognition proteins (PGRPs) play important roles in microbial recognition, and bacterial elimination. In the present study, a short-type PGRP from large yellow croaker, LcPGRP5 was cloned and its functions were characterized. LcPGRP5 gene encodes a protein containing conserved PGRP domain, but no signal peptide. Phylogenetic analysis shows that LcPGRP5 is clustered with other short PGRPs identified in other teleosts. LcPGRP5 is constitutively expressed in all tissues examined, with the highest expression being detected in the head kidney. Recombinant LcPGRP5 protein features amidase activity and bactericidal activity. Notably, LcPGRP5 could enhance the phagocytosis of the bacteria by large yellow croaker macrophage, with higher phagocytic capacity being observed in Staphylococcus aureus compared to Escherichia coli. Moreover, overexpression of LcPGRP5 suppresses pro-inflammatory effects elicited by bacterial exposure in the macrophage cell line. Overall, the present results clearly indicate the important roles of LcPGRP5 played in the innate immune responses against bacterial infection.

Semi-IPNs Reinforced with Silica Janus Nanoparticles and Their Stress Sensing with Mechanoluminescent Probe.

A series of nanocomposite elastomers are prepared by dispersing surface-modified silica Janus nanoparticles into semi-interpenetrating network (Semi-IPN) of polyurethane/polyethyl methacrylate. Benefiting from the hierarchically crosslinked structures that consist of physical interlocking mediated by hydrogen-bond-rich silica Janus nanoparticles and permanent crosslinking by Semi-IPN, these elastomers exhibit excellent mechanical properties. Moreover, the Janus nanosheet is found more effective in strengthening and toughening the Semi-IPN, in comparison to Janus hollow sphere. Since 1,2-dioxetane is covalently embedded in these elastomers as a mechanoluminescent stress probe, stress transfer between the polymer and Janus nanoparticles and the toughening mechanism can be illuminated, which offer exciting opportunities to study the failure process of complex polymer nanocomposites with high spatial and temporal resolution.

Polyunsaturated Fatty Acids Influence LPS-Induced Inflammation of Fish Macrophages Through Differential Modulation of Pathogen Recognition and p38 MAPK/NF-κB Signaling.

Polyunsaturated fatty acids (PUFAs) not only serve as essential nutrients but also function as modulators of the immune response in marine fish. However, their immunomodulatory mechanism is poorly understood given that the underlying regulation of the innate immune response in fish has not been fully elucidated. Hence, study of the innate immunity of fish could help elucidate the mechanism by which PUFAs affect the fish immune response. Here, we used combined transcriptome analysis and in vitro experimentation to study the mechanism of LPS-induced inflammation. Transcriptome profiling indicated that LPS elicited strong pro-inflammatory responses featuring high expression levels of pathogen recognition receptors (PRRs) and cytokines along with the activation of NF-κB and MAPK signaling pathways. The transcription factor p65 alone could increase the transcription of IL1ß by binding to the promoter of IL1ß, and this promoting effect disappeared after mutation or deletion of its binding sites. We then examined the effects of PUFAs on the levels of gene expression and the abundance of proteins of critical kinases associated with LPS-induced inflammation. We found that LA exerts pro-inflammatory response while ALA, EPA, and DHA induced anti-inflammatory effects by modulating the expression of PRRs, phosphorylation of IKK and p38, and the nuclear translocation of p65. Overall, this study advances our understanding of the regulatory mechanisms by which PUFAs regulate LPS-induced inflammation in a non-model fish species.