Establishment and evaluation of an improved rat model of open abdomen

Introduction:This study aimed to establish an animal model of open abdomen(OA)through temporary abdominal closure via different techniques.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups:group A(OA with polypropylene mesh alone);group B(OA with polypro-pylene mesh combined with a patch);and group C(OA with polypropylene mesh and a sutured patch).Vital signs,pathophysiological changes,and survival rates were closely monitored in the rats for 7 days after surgery.Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing.Results:The results showed no significant difference in mortality rates among the three groups(p>0.05).However,rats in group B exhibited superior overall condi-tion,cleaner wounds,and a higher rate of wound healing compared to the other groups(p<0.05).Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups.Histopathological examinations revealed fibrous hyperpla-sia,inflammatory cell infiltration,neovascularization,and collagen deposition in all groups.Group B demonstrated enhanced granulation tissue generation,neovasculari-zation,and collagen deposition compared to the other groups(p<0.05).Conclusions:Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA.This model successfully replicated the patho-logical and physiological changes in postoperative patients with OA,specifically the progress of abdominal skin wound healing.It provides a practical and reliable animal model for OA research.

Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion(IR)injury.Inspired from the structure of native intestinal villi,we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on coaxial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold.The chip was featured on:(i)eight times the oxygen exchange efficiency compared with the conventional device,tri-gas incubator,(ii)implantation of intestinal organoid reproducing all types of intestinal epithelial cells,and(iii)bio-responsiveness to hypoxia and reoxygenation(HR)by presenting metabolism disorder,inflammatory reaction,and cell apoptosis.Strikingly,it was found for the first time that Olfactomedin 4(Olfm4)was the most significantly downregulated gene under a rapid HR condition by sequencing the RNA from the organoids.Mechanistically,OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation,thus it could be used as a therapeutic target.Altogether,this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo,and sets an example of next-generation multisysteminteractive organoid chip for finding precise therapeutic targets of IR injury.

GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity

Gasdermin B (GSDMB) has been reported to be associated with immune diseases in humans, but the detailed molecular mechanisms remain unsolved. The N-terminus of GSDMB by itself, unlike other gasdermin family proteins, does not induce cell death. Here, we show that GSDMB is highly expressed in the leukocytes of septic shock patients, which is associated with increased release of the gasdermin D (GSDMD) N-terminus. GSDMB expression and the accumulation of the N-terminal fragment of GSDMD are induced by the activation of the non-canonical pyroptosis pathway in a human monocyte cell line. The downregulation of GSDMB alleviates the cleavage of GSDMD and cell death. Consistently, the overexpression of GSDMB promotes GSDMD cleavage, accompanied by increased LDH release. We further found that GSDMB promotes caspase-4 activity, which is required for the cleavage of GSDMD in non-canonical pyroptosis, by directly binding to the CARD domain of caspase-4. Our study reveals a GSDMB-mediated novel regulatory mechanism for non-canonical pyroptosis and suggests a potential new strategy for the treatment of inflammatory diseases.

Biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules

Intestinal barriers play an important role in preventing intestinally derived diseases,and maintaining their function is a promising approach to prevent and treat those diseases.Here,inspired by the protection effect of intestinal barriers in live organisms and the mucosa adhesive property of sucralfate,we present a biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules.Benefiting from the flexible selectivity and precise control of microfluidic electrospray flows,the generated microcapsules were imparted with stomach-tolerant dietary-fibre shells and controllable released sucralfate cores,both of which could contribute to forming a continuous biomimetic intestinal barrier on the intestine.Through in vitro adhesive study,in vivo computed tomography(CT)imaging and in vivo imaging system(IVIS)methods,we have demonstrated that the microcapsule-derived biomimetic intestinal barrier can effectively block food fermentation in the gut,reduce generation of fat,decrease disease risk indexes,and prevent obesity.These features make the microfluidic encapsulated sucralfate microcapsules and their resultant biomimetic intestinal barrier an approach for treating obesity and other intestinal diseases.

Microfluidic Electrospray Niacin Metal-Organic Frameworks Encapsulated Microcapsules for Wound Healing

Niacin metal-organic frameworks(MOFs)encapsulated microcapsules with alginate shells and copper-/zinc-niacin framework cores were in situ synthesized by using a microfuidic electrospray approach for wound healing.As the alginate shells were bacteriaresponsively degradable,the niacin MOFs encapsulated microcapsules could intelligently,controllably,and programmably release calcium,copper,and zinc ions,depending on the degree of infections.Te released ions could not only kill microbes by destroying their membrane and inducing the outfow of nutrient substance,but also activate copper/zinc superoxide dismutase(Cu/ZnSOD)to eliminate oxygen free radicals and rescue the cells from oxidative stress injury.Furthermore,the simultaneously released niacin could promote hemangiectasis and absorption of functional metal ions.Tus,the niacin MOFs encapsulated microcapsules were imparted with outstanding antibacterial,antioxidant,and angiogenesis properties.Based on an in vivo study,we have also demonstrated that the chronic wound healing process of an infected full-thickness skin defect model could be signifcantly enhanced by using the niacin MOFs encapsulated microcapsules as therapeutic agent.Terefore,the microfuidic electrospray niacin MOFs encapsulated microcapsules are potential for clinical applications.

Marine-inspired molecular mimicry generates a drug-free, but immunogenic hydrogel adhesive protecting surgical anastomosis

Herein,we report the synthesis of a biomimic hydrogel adhesive that addresses the poor healing of surgical anastomosis.Dopamine-conjugated xanthan gum(Da-g-Xan)is fabricated using deep insights into the molecular similarity between mussels'adhesive and dopamine as well as the structural similarity between barnacle cement proteins and xanthan gum.The hydrogel mimics marine animals’adherence to wet tissue surfaces.Upon applying this adhesive to colonic anastomosis in a rat model,protective effects were shown by significantly improving the bursting pressure.Mechanistically,the architecture of Da-g-Xan hydrogel is maintained by dynamic intermolecular hydrogen bonds that allow the quick release of Da-g-Xan.The free Da-g-Xan can regulate the inflammatory status and induce type 2 macrophage polarization(M2)by specifically interacting with mannose receptors(CD206)revealed by RNA-sequencing and molecular binding assays.Consequently,an appropriate microenvironment for tissue healing is created by the secretion of chemokines and growth factors from M2 macrophages,strengthening the fibroblast migration and proliferation,collagen synthesis and epithelial vascularization.Overall,this study demonstrates an unprecedented strategy for generating an adhesive by synergistic mimicry inspired by two marine animals,and the results show that the Da-g-Xan adhesive augments native tissue regenerative responses,thus enabling enhanced recovery following surgical anastomosis.

Microfluidic generation of egg-derived protein microcarriers for 3D cell culture and drug delivery

Microcarriers have a demonstrated value for biomedical applications,in particular for drug delivery and three-dimensional cell culture.Attempts to develop this technique tend to focus on the fabrication of functional microparticles by using convenient methods with innovative but accessible materials.Inspired by the process of boiling eggs in everyday life,which causes the solidification of egg proteins,we present a new microfluidic‘‘cooking"approach for the generation of egg-derived microcarriers for cell culture and drug delivery.As the egg emulsion droplets are formed with exquisite precision during the microfluidic emulsification,the resultant egg microcarriers present highly monodisperse and uniform morphologies at the size range of hundred microns to one millimeter.Benefiting from the excellent biocompatibility of the egg protein components,the obtained microcarriers showed good performances of cell adherence and growth.In addition,after a freezing treatment,the egg microcarriers were shown to have interconnected porous structures throughout their whole sphere,could absorb and load different kinds of drugs or other active molecules,and work as microcarrier-based delivery systems.These features point to the potential value of the microfluidic egg microcarriers in biomedicine.

Damps’role in inflammatory bowel disease:a paradoxical player of mtDNA-STING signaling pathway in gut homeostasis

The inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis,are chronic,relapsing immune mediated disorders of the gastrointestinal homeostasis and intestinal inflammation[1].Failure to resolve mucosal inflammation and maintain gut barrier are notable shared clinical challenges in IBD,in particular when they activate immune cells within the gut lamia propria.Clinical trials and animal model studies aiming towards DAMPs have demonstrated that they can be effective therapeutic targets in mucosal inflammation of IBD.

Applications of four-dimensional printing in emerging directions:Review and prospects

Four-dimensional(4 D) printing technology is an extension of three-dimensional(3 D) printing technology that enables a 3 D-printed static structure to dynamically change its shape with time. Therefore, the resulting structure can undergo self-folding/unfolding assisted by some stimuli. This technology has made much initial progress in many industrial fields. Aiming to investigate the in-depth application value of4 D printing, this study reviews the recent research and application breakthroughs of 4 D printing in several emerging directions, including the simulation of plant and animal behaviors, smart tissue scaffolds and biomedical devices, food printing, digitalization of industrial art design, renewable energy, intelligent communication, soft electronics and robots, vehicle optimization, textile customization, and flexible machinery and mechanical structure. Based on the analyses of specific cases and processes, we present the current obstacles to large-scale applications and the future prospects.

GSDMB N-terminal assembles in plasma membrane to execute pyroptotic cell death

Human genome encodes six paralogous gasdermin genes:GSDMA,GSDMB,GSDMC,GSDMD,GSDME and DFNB59.1 Proteolytic cleavage of these gasdermin proteins liberates an N-terminal(NT)fragment from autoinhibition,which assembles in membrane to form pores and execute pyroptotic cell death in general.1 In contrast to other gasdermins,gasdermin B(GSDMB)is the only gasdermin gene that has not been identified in rodents.Zhou et al first shed light on the molecular mechanism by which cytotoxic lymphocyte-derived granzyme A(GZMA)cleaves GSDMB to execute pyroptosis in GSDMB-positive cells,especially in cancer cells.2 In this issue of Cell,Hansen et al reported a dynamic host pathogen S.flexneri prevents GSDMB-mediated lysis by secreting IpaH7.8,which targets and ubiquitinates GSDMB for 26S proteasome destruction.3 They showed that GSDMB implements bacteriocidic ability by recognition of the phospholipids on Gram-negative bacterial membranes rather than lysing host cells.Although their experimental design and data are clearly presented and straightforward,there are still some doubts to be clarified.