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Abstract Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that induces an NLRP3-dependent cytokine storm. NLRP3 inflammasome activation triggers not only an inflammatory response but also pyroptosis. However, the exact mechanism underlying S. suis-induced macrophage pyroptosis is not clear. Our results showed that SS2 induced the expression of pyroptosis-associated factors, including lactate dehydrogenase (LDH) release, propidium iodide (PI) uptake and GSDMD-N expression, as well as NLRP3 inflammasome activation and IL-1β secretion. However, GSDMD deficiency and NLRP3 inhibition using MCC950 attenuated the SS2-induced expression of pyroptosis-associated factors, suggesting that SS2 induces NLRP3-GSDMD-dependent pyroptosis. Furthermore, RACK1 knockdown also reduced the expression of pyroptosis-associated factors. In addition, RACK1 knockdown downregulated the expression of NLRP3 and Pro-IL-1β as well as the phosphorylation of P65. Surprisingly, the interaction between RACK1 and P65 was detected by co-immunoprecipitation, indicating that RACK1 induces macrophage pyroptosis by mediating the phosphorylation of P65 to promote the transcription of NLRP3 and pro-IL-1β. Similarly, NEK7 knockdown decreased the expression of pyroptosis-associated factors and ASC oligomerization. Moreover, the results of co-immunoprecipitation revealed the interaction of NEK7-RACK1-NLRP3 during SS2 infection, demonstrating that NEK7 mediates SS2-induced pyroptosis via the regulation of NLRP3 inflammasome assembly and activation. These results demonstrate the important role of RACK1 and NEK7 in SS2-induced pyroptosis. Our study provides new insight into SS2-induced cell death.

Tetracycline was reported to trigger intense lucigenin chemiluminescence (CL). Based on its significant quenching to lucigenin-tetracycline CL, procyanidin was detected. The mechanism of the lucigenin-tetracycline CL and its quenching by procyanidin were proposed. Under the optimum conditions, the calibration curve is linear in the range of 10-1000 nM for procyanidin with a detection limit of 4.4 nM. The RSD for nine replicate determinations of procyanidin was less than 1.7%. Moreover, this method was satisfactorily applied to the determination of procyanidin in human urine samples and health food capsule of grape seed. [ABSTRACT FROM AUTHOR]

Abstract Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen with the characteristics of high mortality and morbidity, which brings great challenges to prevent and control epidemic disease in the swine industry. Cathelicidins (CATH) are antimicrobial peptides with antimicrobial and immunomodulatory activities. In this study, bactericidal and anti-inflammatory effects of chicken cathelicidin-1 (CATH-1) were investigated in vitro and in vivo against SS2 infection. The results show that CATH-1 exhibited a better bactericidal effect compared to other species’ cathelicidins including chickens (CATH-2, -3, and -B1), mice (CRAMP) and pigs (PMAP-36 and PR-39), which rapidly killed bacteria in 20 min by a time-killing curve assay. Furthermore, CATH-1 destroyed the bacterial morphology and affected bacterial ultrastructure as observed under electron microscopy. Moreover, CATH-1 antibacterial activity in vivo shows that CATH-1 increased survival rate of SS2-infected mice by 60% and significantly reduced the bacterial load in the lungs, liver, spleen, blood, and peritoneal lavage as well as the release of SS2-induced inflammatory cytokines including IL-1α, IL-1β, IL-12, and IL-18. Importantly, CATH-1 did not show severe histopathological changes in mice. Further studies on the mechanism of anti-inflammatory activity show that CATH-1 not only reduced the inflammatory response through direct neutralization, but also by regulating the TLR2/4/NF-κB/ERK pathway. This study provides a scientific basis for the research and development of antimicrobial peptides as new antimicrobial agents.

Abstract Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.

Abstract Chicken cathelicidin-2 (CATH-2) as a host defense peptide has been identified to have potent antimicrobial and immunomodulatory activities. Here, we reported the mechanism by which CATH-2 modulates NLRP3 inflammasome activation. Our results show that CATH-2 and ATP as a positive control induced secretion of IL-1β and IL-1α in LPS-primed macrophages but did not affect secretion of IL-6, IL-12 and TNF-α. Furthermore, CATH-2 induced caspase-1 activation and oligomerization of apoptosis-associated speck-like protein containing a carboxy- terminal caspase recruitment domain (ASC), which is essential for NLRP3 inflammasome activation. However, CATH-2 failed to induce IL-1β secretion in Nlrp3−/−, Asc−/− and Casp1−/− macrophages. Notably, IL-1β and NLRP3 mRNA expression were not affected by CATH-2. In addition, CATH-2-induced NLRP3 inflammasome activation was mediated by K+ efflux but independent of the P2X7 receptor that is required for ATP-mediated K+ efflux. Gene interference of NEK7 kinase which has been identified to directly interact with NLRP3, significantly reduced IL-1β secretion and caspase-1 activation induced by CATH-2. Furthermore, confocal microscopy shows that CATH-2 significantly induced lysosomal leakage with the diffusion of dextran fluorescent signal. Cathepsin B inhibitors completely abrogated IL-1β secretion and caspase-1 activation as well as attenuating the formation of ASC specks induced by CATH-2. These results all indicate that CATH-2-induced activation of NLRP3 inflammasome is mediated by K+ efflux, and involves the NEK7 protein and cathepsin B. In conclusion, our study shows that CATH-2 acts as a second signal to activate NLRP3 inflammasome. Our study provides new insight into CATH-2 modulating immune response.

BackgroundHealth science popularization short video disseminates health information to the public in an understandable way about health information.ObjectiveTo investigate the preferences of Chinese residents for health science popularization short videos and provide suggestions for optimizing the production of short videos.MethodsAn online survey of Chinese people was conducted using a self-administered questionnaire, and a discrete choice experiment (DCE) was used to explore the public’s preferences for health science popularization short videos.ResultsA total of 618 respondents were included, of which 306 (45.51%) were male and 312 (50.49%) were female, 271 (43.85%) were aged 18–25, 239 (38.67%) were aged 26–60, and 108 (17.48%) were aged 60 and above. Whether the video is charged or not (46.891%) and the account subject (28.806%) were both considered important. The results of the DCE revealed that the participants considered video free of charge as the most significant attribute of health science popularization short videos (OR 3.433, 95% CI 3.243–3.633). Overall, participants preferred and were more willing to pay for health science popularization short videos with a hospital account subject (OR 1.192, 95% CI 1.116–1.274), with the form of graphic narration (OR 1.062, 95% CI 1.003–1.126), free of charge (OR 3.433, 95% CI 3.243–3.633), with the content that satisfies their needs (very much needed: OR 1.253, 95% CI 95% CI 1.197–1.311; generally needed: OR 1.078, 95% CI 1.029–1.129), with platform certification (OR 1.041, 95% CI 1.011–1.073), without commercial advertisements (OR 1.048, 95% CI 1.018–1.080), with simple-to-understand content (OR 1.071, 95% CI 1.040–1.104), and with video content that evokes fear or dread of illness in the viewer (OR 1.046, 95% CI 1.015–1.078).ConclusionParticipants favor free health popularization short videos, which are hospital accounts, with content that is illustrated, understandable, meets their needs, and can serve as a warning. In the future, the production of health popularization short videos should focus on improving the diversity and relevance of video content, making it as easy to understand to achieve good science popularization effects.

At present, most high-performance cellulose matrix composites only use cellulose as reinforcement material, which is an obstacle to maximize the advantages of nanocellulose in structure and properties. The development of new functional nanocomposites with cellulose as the main component can better meet people’s needs for high-performance and degradable composites, which requires a comprehensive and thorough understanding of cellulose. Considering the limitations of physical experiments, we performed molecular dynamics simulation of the uniaxial tensile behavior of the cellulose system at three different strain rates (10−4/ps, 10−5/ps, and 10−6/ps), and the stress-strain responses of cellulose systems at different strain rates are obtained. The effect of the strain rate on the mechanical properties of amorphous cellulose system during the tensile processes is analyzed. The deformation mechanism of cellulose amorphous system during the tensile processes is characterized by the energy changes of the different terms including dihedral angle torsion term, bond tensile term, angle bending term, and nonbond term. Structural evolution of the cellulose crystal system during the tensile processes is used to explain the failure mechanism of cellulose. The kinetic simulation results show that the mechanical properties of the cellulose amorphous system increase with the increase of strain rate. Compared with the strain rate of 10−5/ps, the elastic modulus of the system increases by 6.73 GPa at the strain rate 10−4/ps. During the tensile processes, cellulose amorphous region adapts to the applied load mainly through the stretching of the cellulose macromolecular chains, i.e., the deformation of bond lengths and bond angles, without any breakage of the molecular chains. The main causes of chain lengthening at different strain rates are different. The failure of cellulose is caused by the slip and rearrangement of some molecular chains in the crystal structure.

Phage therapy is an alternative approach to overcome the problem of multidrug resistance in bacteria. In this study, a bacteriophage named PZL-Ah152, which infects Aeromonas hydrophila, was isolated from sewage, and its biological characteristics and genome were studied. The genome contained 54 putative coding sequences and lacked known putative virulence factors, so it could be applied to phage therapy. Therefore, we performed a study to (i) investigate the efficacy of PZL-Ah152 in reducing the abundance of pathogenic A. hydrophila strain 152 in experimentally infected crucian carps, (ii) evaluate the safety of 12 consecutive days of intraperitoneal phage injection in crucian carps, and (iii) determine how bacteriophages impact the normal gut microbiota. The in vivo and in vitro results indicated that the phage could effectively eliminate A. hydrophila. Administering PZL-Ah152 (2 × 109 PFU) could effectively protect the fish (2 × 108 CFU/carp). Furthermore, a 12-day consecutive injection of PZL-Ah152 did not cause significant adverse effects in the main organs of the treated animals. We also found that members of the genus Aeromonas could enter and colonize the gut. The phage PZL-Ah152 reduced the number of colonies of the genus Aeromonas. However, no significant changes were observed in α-diversity and β-diversity parameters, which suggested that the consumed phage had little effect on the gut microbiota. All the results illustrated that PZL-Ah152 could be a new therapeutic method for infections caused by A. hydrophila.

With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.

Streptococcus pneumoniae is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against S. pneumoniae, but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6−/− mice in the lung had lower bacterial burdens after S. pneumoniae infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against S. pneumoniae infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6−/−) mice during S. pneumoniae infection. Also, NLRP6−/− mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6−/− neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during S. pneumoniae infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during S. pneumoniae infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection.

Citrobacter freundii refers to a fish pathogen extensively reported to be able to cause injury and high mortality. Phage therapy is considered a process to alternatively control bacterial infections and contaminations. In the present study, the isolation of a virulent bacteriophage IME-JL8 isolated from sewage was presented, and such bacteriophage was characterized to be able to infect Citrobacter freundii specifically. Phage IME-JL8 has been classified as the member of the Siphoviridae family, which exhibits the latent period of 30–40 min. The pH and thermal stability of phage IME-JL8 demonstrated that this bacteriophage achieved a pH range of 4–10 as well as a temperature range of 4, 25, and 37°C. As revealed from the results of whole genomic sequence analysis, IME-JL8 covers a double-stranded genome of 49,838 bp (exhibiting 47.96% G+C content), with 80 putative coding sequences contained. No bacterial virulence- or lysogenesis-related ORF was identified in the IME-JL8 genome, so it could be applicable to phage therapy. As indicated by the in vitro experiments, phage IME-JL8 is capable of effectively removing bacteria (the colony count decreased by 6.8 log units at 20 min), and biofilm can be formed in 24 h. According to the in vivo experiments, administrating IME-JL8 (1 × 107 PFU) was demonstrated to effectively protect the fish exhibiting a double median lethal dose (2 × 109 CFU/carp). Moreover, the phage treatment led to the decline of pro-inflammatory cytokines in carp with lethal infections. IME-JL8 was reported to induce efficient lysis of Citrobacter freundii both in vitro and in vivo, thereby demonstrating its potential as an alternative treatment strategy for infections attributed to Citrobacter freundii.

Performance degradation of cellulose and cellulose-based materials caused by water is an inevitable problem in application processes. In most studies, this was attributed to the fracture and rebuilding of the hydrogen bond network in the system; however, limited attention was paid to the movement, aggregation state, and specific property evolution of cellulose and water during this process. In this study, based on molecular dynamics simulations, the effects of moisture content on the microscopic properties of cellulose are investigated, including the mechanical properties, diffusion coefficient, glass transition temperature, microscopic motion of water molecules, and preferred hydration sites on cellulose. The results show that the mechanical properties of the system increase and then decrease as the water content in the system increases. When the moisture content is 4%, the mechanical properties of cellulose are the best, and the elastic modulus and shear modulus increase by 7.6% and 9.4%, respectively, compared with those of dry cellulose. The glass transition temperature of the system with 4% moisture content increases by 72 K compared with that of dry cellulose. The mean square displacement and diffusion coefficient of water in the system is affected by the water molecules’ polymerisation state and the free water content. In the entire range of water contents studied, hydroxyl groups O2, O3, and O6 of cellulose dominate the reaction with water compared with acetal oxygens O4 and O5. In the system with 4% moisture content, the number of water molecules around the glycosidic bonds O4 are the most minor and cause the least damage to the cellulose structure. A critical water content point of 4% is recommended, and this result is expected to provide a reference for maintaining the excellent and stable properties of cellulose and cellulose-based materials.

This study investigates the influence of sliding velocity and loading on the friction of chromium and amorphous cotton fibers using water molecules act as lubricants via molecular dynamics simulation. It is found that the movement of water molecules between the contact interfaces is mainly along the sliding-direction not than the loading-direction during the sliding process. The high sliding velocity or large loading will reduce the lubricating properties of water molecules and increase the average coefficient of friction in the stabilization. The sliding time before the stabilization increase with sliding velocity while decreases with loading. Moreover, the water-lubricants can reduce the damage to chromium, and the increase of sliding velocity is more easy to cause the damage than loading, so it is more important to choose a right sliding velocity.

Soft robotic grippers are able to carry out many tasks that traditional rigid-bodied grippers cannot perform but often have many limitations in terms of control and feedback. In this study, a Fin Ray effect inspired soft robotic gripper is proposed with its whole body directly 3D printed using soft material without the need of assembly. As a result, the soft gripper has a light weight, simple structure, is enabled with high compliance and conformability, and is able to grasp objects with arbitrary geometry. A force sensor is embedded in the inner side of the gripper, which allows the contact force required to grip the object to be measured in order to guarantee successful grasping and to provide the most suitable gripping force. In addition, it enables control and data monitoring of the gripper’s operating state at all times. Characterization and grasping demonstration of the gripper are given in the Experiment section. Results show that the gripper can be used in a wide range of scenarios and applications, such as the service robot and food industry.

Abstract In situ tissue regeneration approach aims to exploit the body’s own biological resources and reparative capability and recruit host cells by utilizing cell-instructive biomaterials. In order to immobilize and release bioactive factors in biomaterials, it is important to engineer the load effectiveness, release kinetics and cell recruiting capabilities of bioactive molecules by using suitable bonding strategies. Stromal cell-derived factor 1α (SDF-1α) is one of the most potent chemokines for stem cell recruitment, and SDF-1α-loaded scaffolds have been used for the regeneration of many types of tissues. This review summarizes the strategies to incorporate SDF-1α into scaffolds, including direct loading or adsorption, polyion complexes, specific heparin-mediated interaction and particulate system, which may be applied to the immobilization of other chemokines or growth factors. In addition, we discuss the application of these strategies in the regeneration of tissues such as blood vessel, myocardium, cartilage and bone.