Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.

Antimicrobial peptides act on the rumen the performance of castrated bulls

Background Many countries have already banned the use of antibiotics in animal husbandry,making it extremely difficult to maintain animal health in livestock breeding.In the livestock industry,there is an urgent need to develop alternatives to antibiotics which will not lead to drug resistance on prolonged use.In this study,eighteen castrated bulls were randomly divided into two groups.The control group(CK)was fed the basal diet,while the antimicrobial peptide group(AP)was fed the basal diet supplemented with 8 g of antimicrobial peptides in the basal diet for the experimental period of 270 d.They were then slaughtered to measure production performance,and the ruminal contents were isolated for metagenomic and metabolome sequencing analysis.Result The results showed that antimicrobial peptides could improve the daily weight,carcass weight,and net meat weight of the experimental animals.Additionally,the rumen papillae diameter and the micropapillary density in the AP were significantly greater than those in the CK.Furthermore,the determination of digestive enzymes and fermentation parameters showed that the contents of protease,xylanase,andβ-glucoside in the AP were greater than those in the CK.However,lipase content in the CK was greater than that in the AP.Moreover,the content of acetate,propionate,butyrate,and valerate was found to be greater in AP than those in CK.The metagenomic analysis annotated 1993 differential microorganisms at the species level.The KEGG enrichment of these microorganisms revealed that the enrichment of drug resistance-related pathways was dramatically decreased in the AP,whereas the enrichment of immune-related pathways was significantly increased.There was also a significant reduction in the types of viruses in the AP.187 probiotics with significant differences were found,135 of which were higher in AP than in CK.It was also found that the antimicrobial mechanism of the antimicrobial peptides was quite specific.Seven low-abundance microorganisms(Acinetobactersp.Ac1271,Aequorivita soesokkakensis,Bacillus lacisalsi,Haloferax larsenii,Lysinibacillussp.3DF0063,Parabacteroidessp.217,Streptomycessp.So13.3)were found to regulate growth performance of the bull negatively.Metabolome analysis identified 45 differentially differential metabolites that significantly different between the CK and the AP groups.Seven upregulated metabolites(4-pyridoxic acid,Ala-Phe,3-ureidopropionate,hippuric acid,terephthalic acid,L-alanine,uridine 5-monophosphate)improve the growth performance of the experimental animals.To detect the interactions between the rumen microbiome and metabolism,we associated the rumen microbiome with the metabolome and found that negative regulation between the above 7 microorganisms and 7 metabolites.Conclusions This study shows that antimicrobial peptides can improve the growth performance of animals while resisting viruses and harmful bacteria and are expected to become healthy alternatives to antibiotics.We demonstrated a new antimicrobial peptides pharmacological model.We demonstrated low-abundance microorganisms may play a role by regulating the content of metabolites.

High precision patternable liquid metal based conductor and adhesive substrate enabled stretchable hybrid systems

Stretchable hybrid systems have been attracting tremendous attention for their essential role in soft robotics,on-skin electronics,and implantable devices.Both rigid and soft functional modules are typically required in those devices.Consequently,ensuring stable electrical contact between rigid and soft modules is a vital part.Here,we propose a simple,universal,and scalable strategy for the stretchable hybrid system through a highly precise printable liquid metal particle-based conductor and adhesive fluorine rubber substrate.The properties of liquid metal particle-based conductors could be easily tuned to realize high-precision patterning,large-scale printing,and the ability to print on various substrates.Additionally,the fluorine rubber substrate could form strong interfacial adhesion with various components and materials through simply pressing and heating,hence enabling stable electrical contact.Furthermore,we prepared a stretchable hybrid light-emitting diode(LED)display system and employed it in on-skin visualization of pressure levels,which perfectly combined rigid and soft modules,thus demonstrating the promising potential applications in complex multifunctional stretchable hybrid systems for emerging technologies.

Recent advances in ultrathin materials and their applications in e-skin

Intelligent technologies based on artificial intelligence and big data hold great potential for health monitoring and human–machine capability enhancement.However,electronics must be connected to the human body to realize this vision.Thus,tissue or skin-like electronics with high stretchability and low stiffness mechanical properties are highly desirable.Ultrathin materials have attracted significant attention from the research community and the industry because of their high performance and flexibility.Over the past few years,considerable progress has been made in flexible ultrathin sensors and devices based on ultrathin materials.Here,we review the developments in this area and examine representative research progress in ultrathin materials fabrication and device construction.Strategies for the fabrication of stretchable ultrathin materials and devices are considered.The relationship between the thin-film structure and performance is emphasized and highlighted.Finally,the current capabilities and limitations of ultrathin devices were explored.

Identification of lipid droplets in gut bacteria

Dear Editor,The field of gut microbiota is progressing rapidly and thus,appellations like the last human organ,a separate organ,a forgotten organ,and a new organ have been applied to gut microbiota to emphasize its vital functions in our body(Chang and Kao,2019).Gut microbiota has been shown to play a central role in the regulation of human lipid metabolism and be associated with lipid metabolism disorders when aberrant,through composition and microbial metabolites.